Khasiat & Bukti Pendukung
Terpinen-4-ol, the main component of the essential oil of Melaleuca alternifolia (tea tree oil), suppresses inflammatory mediator production by activated human monocytes
Objective: To evaluate potential anti-inflammatory properties of tea tree oil, the essential oil steam distilled from the Australian native plant, Melaleuca alternifolia..
In Vitro Evaluation of Antioxidant and Antimicrobial Activities of Melaleuca alternifolia Essential Oil
BioMed Research International Volume 2018, Article ID 2396109. DOI:10.1155/2018/2396109
Xiaofeng Zhang1 Yanjun Guo1,2 Liying Guo1 Hui Jiang1 and Qianhua Ji1,2 *
1Fruit Tree Research Institute, Zhaoqing University, Zhaoqing, China
2College of Life Science, Zhaoqing University, Zhaoqing, China
*Correspondence
ABSTRACT
Objective: The in vitro antioxidant and antimicrobial activity of the essential oil from Melaleuca alternifolia was evaluated in this report.
Methods: The antioxidant potential of the essential oil from Melaleuca alternifolia was evaluated by the DPPH (2,2-diphenyl-1-picrylhydrazyl) method, thiobarbituric acid reactive species (TBARS) assay, and the hydroxyl radical scavenging activity method.
Results: The essential oil from Melaleuca alternifolia was able to reduce DPPH with an EC50 (concentration for 50% of maximal effect) of 48.35 𝜇g/ml, inhibit the lipid peroxidation with an IC50 (50% inhibitory concentration) of 135.9 𝜇g/ml, and eliminate hydroxyl radicals with an EC50 of 43.71 𝜇g/ml. Antimicrobial screening, minimum inhibitory concentration, and minimum bactericidal concentration assays showed that the essential oil from Melaleuca alternifolia inhibited strongly the growth of different types of microorganisms, including Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Penicillium italicum Wehmer, and Penicillium digitatum Sacc.
Conclusion: The essential oil of Melaleuca alternifolia possesses antioxidant and antimicrobial activity and could be suitable for use as a natural preservative ingredient in food, agriculture, and pharmaceutical industries.
Ringkasan: Hasil penelitian menunjukkan bahwa Melaleuca alternifolia mampu mengurangi DPPH, menghambat lipid peroksidasi, dan mengurangi radikal hidroksil.
Melaleuca alternifolia juga mampu menghambat pertumbuhan berbagai mikroorganisme, termasuk Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Penicillium italicum Wehmer, dan Penicillium digitatum Sacc.
Berdasarkan hasil pengujian tersebut, dapat dibuktikan bahwa Melaleuca alternifolia memiliki manfaat sebagai antioksidan dan antimikroba.
Anti-inflammatory effects of Melaleuca alternifolia essential oil on human polymorphonuclear neutrophils and monocytes
Objective and design: The fungicidal and bactericidal actions of the essential oil (EO) of Melaleuca alternifolia seem well established, but their anti-inflammatory and anti-oxidative effects remain unclear. In this study, we investigated in vitro…
Anti-inflammatory effects of Melaleuca alternifolia essential oil on human polymorphonuclear neutrophils and monocytes
Free Radical Research, 2004 Aug;38(8):805-11. DOI: 10.1080/1071576042000220247
Affiliations expand
ABSTRACT
Objective and design: The fungicidal and bactericidal actions of the essential oil (EO) of Melaleuca alternifolia seem well established, but their anti-inflammatory and anti-oxidative effects remain unclear. In this study, we investigated in vitro the possible role of whole Melaleuca alternifolia EO as a modulator of the oxidative response, i.e. reactive oxygen species (ROS) production, of leukocytes (monocytes and polymorphonuclear neutrophils (PMNs)) in humans.
Methods: Whole blood leukocytes from healthy human volunteers (n = 7), isolated from erythrocytes by haemolytic shock, were incubated for 30 min with Melaleuca alternifolia EO (0-0.1%) to determine their ROS production by flow cytometry with or without stimulation of cells. We compared the effects of 3 different stimulating agents acting differently on transductional pathways to stimulate the ROS production: a phorbol ester (PMA), formyl-methionyl-leucyl-phenylalanine (fMLP) and opsonised zymosan (OZ).
Results: As attested by the Krüskall-Wallis test, Melaleuca alternifolia EO at 0.1% directly stimulated ROS production by PMNs (x 8.7 vs. 0% EO, p < 0.05) and increased the intracellular ROS produced by monocytes. Whichever the stimulating agent used (PMA, fMLP or OZ), Melaleuca alternifolia EO decreased the intracellular ROS production at the dilution of 0.1% by PMNs and monocytes, more so with PMNs.
Conclusion: Melaleuca alternifolia EO may be both a direct active mediator of the bactericidal action of the circulating leukocytes and may be efficient in protecting the organism from an excess of ROS, through an anti-oxidant and radical scavenging activity.
Ringkasan: Melaleuca alternifolia essential oil (EO) diketahui memiliki aksi antifungi/antijamur dan antibakteri. Penelitian ini dilakukan untuk membuktikan apakah Melaleuca alternifolia EO juga memiliki efek antiinflamasi (antiradang) dan antioksidan, melalui pengamatan peran Melaleuca alternifolia pada respon oksidatif.
Penelitian ini membuktikan bahwa Melaleuca alternifolia EO (MAC) berpotensi menjadi mediator aktif aksi pembasmian bakteri dari leukosit yang bersirkulasi dan memiliki potensi melindungi organisme dari reactice oxygen species (ROS) berlebih melalui aktivitas antioksidan dan penangkalan radikal. Aktivitas antioksidan ini berpengaruh pada potensi pencegahan peradangan dalam tubuh makhluk hidup.
Potential Anti-inflammatory Effects of Melaleuca alternifolia Essential Oil on Human Peripheral Blood Leukocytes
Objective: The fungicidal and bactericidal actions of the essential oil (EO) of Melaleuca alternifolia seem well established, but their anti-inflammatory and antioxidative effects remain unclear. This study investigated in vitro the possible role of whole Melaleuca alternifolia EO as…
Potential Anti-inflammatory Effects of Melaleuca alternifolia Essential Oil on Human Peripheral Blood Leukocytes
Phytotherapy Research. 20, 364–370 (2006) DOI: 10.1002/ptr.1862
- Caldefie-Chézet1,2*, C. Fusillier1,2, T. Jarde1, H. Laroye1, M. Damez1,2, M-P. Vasson2,3
and J. Guillot1,2
1 Laboratoire de Botanique, Cryptogamie et Microbiologie, CRNH Auvergne, Clermont-Ferrand, France
2 Faculté de Pharmacie, 3Unite de Nutrition, Centre Jean-Perrin CRNH Auvergne, Clermont-Ferrand, France
ABSTRACT
Objective: The fungicidal and bactericidal actions of the essential oil (EO) of Melaleuca alternifolia seem well established, but their anti-inflammatory and antioxidative effects remain unclear. This study investigated in vitro the possible role of whole Melaleuca alternifolia EO as a modulator of the inflammatory/non-specific immune response by exploring the chemotaxis and kinetic radical oxygen species (ROS) production of leukocytes and cytokine secretion in peripheral blood mononuclear cells (PBMCs) in humans.
Method: The influence of Melaleuca alternifolia EO on the chemotaxis under agarose of isolated neutrophils (PMNs) was evaluated. The kinetics of ROS production by stimulated total circulating leukocytes was followed over 2 h by recording the fluorescence intensity of oxidized dihydrorhodamine 123. The effects of this EO on pro-(interleukin IL-2) and anti-(IL-4 and IL10) inflammatory cytokine secretions were determined by ELISA following incubation of PBMCs with the EO for 24 h.
Results: Melaleuca alternifolia EO was inefficient on the chemotaxis of PMNs. It exerted an antioxidant effect, reducing ROS production throughout the kinetic study. Melaleuca alternifolia EO inhibited PBMC proliferation, as revealed by a reduction in IL-2 secretion by stimulated lymphocytes. This EO at 0.1% directly increased the secretion of the anti-inflammatory cytokine IL-4 compared with IL-4 secretion without EO (18.5 ± 10.0 vs 3.3 ± 1, p < 0.05), and also increased IL-10 secretion at 0.01% (94.9 ± 38.7 vs 44.1 ± 18, ns).
Conclusion: Melaleuca alternifolia EO may not only act as an anti-inflammatory mediator through its antioxidant activity but may also efficiently protect the organism by reducing the proliferation of inflammatory cells without affecting their capacity to secrete anti-inflammatory cytokines.
Ringkasan: Melaleuca alternifolia EO memberikan efek antioksidan dengan mengurangi produksi reactive oxygen species (ROS) selama studi kinetik. Melaleuca alternifolia EO mampu :
- menghambat profilerasi/perbanyakan peripheral blood mononuclear cells (PBMCs) dengan cara mengurangi sekresi IL-2
- meningkatkan sekresi senyawa sitokin antiradang IL-4
- meningkatkan sekresi senyawa sitokin antiradang IL-10 pada konsentrasi Melaleuca alternifolia EO 0,01%
Melaleuca alternifolia EO tidak hanya berpotensi sebagai mediator antiradang melalui aktivitas antioksidan, namun juga melindungi organisme dengan mengurangi perbanyakan sel-sel radang tanpa mempengaruhi kapasitasnya dalam menghasilkan sitokin antiinflamasi. Hal ini menyebabkan Melaleuca alternifolia EO membantu mencegah terjadinya cytokine storm (badai sitokin).
In Vitro Evaluation of Antioxidant and Antimicrobial Activities of Melaleuca alternifolia Essential Oil
BioMed Research International Volume 2018, Article ID 2396109. DOI:10.1155/2018/2396109
Xiaofeng Zhang1 Yanjun Guo1,2 Liying Guo1 Hui Jiang1 and Qianhua Ji1,2 *
1Fruit Tree Research Institute, Zhaoqing University, Zhaoqing, China
2College of Life Science, Zhaoqing University, Zhaoqing, China
*Correspondence
ABSTRACT
Objective: The in vitro antioxidant and antimicrobial activity of the essential oil from Melaleuca alternifolia was evaluated in this report.
Methods: The antioxidant potential of the essential oil from Melaleuca alternifolia was evaluated by the DPPH (2,2-diphenyl-1-picrylhydrazyl) method, thiobarbituric acid reactive species (TBARS) assay, and the hydroxyl radical scavenging activity method.
Results: The essential oil from Melaleuca alternifolia was able to reduce DPPH with an EC50 (concentration for 50% of maximal effect) of 48.35 𝜇g/ml, inhibit the lipid peroxidation with an IC50 (50% inhibitory concentration) of 135.9 𝜇g/ml, and eliminate hydroxyl radicals with an EC50 of 43.71 𝜇g/ml. Antimicrobial screening, minimum inhibitory concentration, and minimum bactericidal concentration assays showed that the essential oil from Melaleuca alternifolia inhibited strongly the growth of different types of microorganisms, including Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Penicillium italicum Wehmer, and Penicillium digitatum Sacc.
Conclusion: The essential oil of Melaleuca alternifolia possesses antioxidant and antimicrobial activity and could be suitable for use as a natural preservative ingredient in food, agriculture, and pharmaceutical industries.
Ringkasan: Hasil penelitian menunjukkan bahwa Melaleuca alternifolia mampu mengurangi DPPH, menghambat lipid peroksidasi, dan mengurangi radikal hidroksil.
Melaleuca alternifolia juga mampu menghambat pertumbuhan berbagai mikroorganisme, termasuk Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Penicillium italicum Wehmer, dan Penicillium digitatum Sacc.
Berdasarkan hasil pengujian tersebut, dapat dibuktikan bahwa Melaleuca alternifolia memiliki manfaat sebagai antioksidan dan antimikroba.
Anti-inflammatory effects of Melaleuca alternifolia essential oil on human polymorphonuclear neutrophils and monocytes
Free Radical Research, 2004 Aug;38(8):805-11. DOI: 10.1080/1071576042000220247
Affiliations expand
ABSTRACT
Objective and design: The fungicidal and bactericidal actions of the essential oil (EO) of Melaleuca alternifolia seem well established, but their anti-inflammatory and anti-oxidative effects remain unclear. In this study, we investigated in vitro the possible role of whole Melaleuca alternifolia EO as a modulator of the oxidative response, i.e. reactive oxygen species (ROS) production, of leukocytes (monocytes and polymorphonuclear neutrophils (PMNs)) in humans.
Methods: Whole blood leukocytes from healthy human volunteers (n = 7), isolated from erythrocytes by haemolytic shock, were incubated for 30 min with Melaleuca alternifolia EO (0-0.1%) to determine their ROS production by flow cytometry with or without stimulation of cells. We compared the effects of 3 different stimulating agents acting differently on transductional pathways to stimulate the ROS production: a phorbol ester (PMA), formyl-methionyl-leucyl-phenylalanine (fMLP) and opsonised zymosan (OZ).
Results: As attested by the Krüskall-Wallis test, Melaleuca alternifolia EO at 0.1% directly stimulated ROS production by PMNs (x 8.7 vs. 0% EO, p < 0.05) and increased the intracellular ROS produced by monocytes. Whichever the stimulating agent used (PMA, fMLP or OZ), Melaleuca alternifolia EO decreased the intracellular ROS production at the dilution of 0.1% by PMNs and monocytes, more so with PMNs.
Conclusion: Melaleuca alternifolia EO may be both a direct active mediator of the bactericidal action of the circulating leukocytes and may be efficient in protecting the organism from an excess of ROS, through an anti-oxidant and radical scavenging activity.
Ringkasan: Melaleuca alternifolia essential oil (EO) diketahui memiliki aksi antifungi/antijamur dan antibakteri. Penelitian ini dilakukan untuk membuktikan apakah Melaleuca alternifolia EO juga memiliki efek antiinflamasi (antiradang) dan antioksidan, melalui pengamatan peran Melaleuca alternifolia pada respon oksidatif.
Penelitian ini membuktikan bahwa Melaleuca alternifolia EO (MAC) berpotensi menjadi mediator aktif aksi pembasmian bakteri dari leukosit yang bersirkulasi dan memiliki potensi melindungi organisme dari reactice oxygen species (ROS) berlebih melalui aktivitas antioksidan dan penangkalan radikal. Aktivitas antioksidan ini berpengaruh pada potensi pencegahan peradangan dalam tubuh makhluk hidup.
Potential Anti-inflammatory Effects of Melaleuca alternifolia Essential Oil on Human Peripheral Blood Leukocytes
Phytotherapy Research. 20, 364–370 (2006) DOI: 10.1002/ptr.1862
- Caldefie-Chézet1,2*, C. Fusillier1,2, T. Jarde1, H. Laroye1, M. Damez1,2, M-P. Vasson2,3
and J. Guillot1,2
1 Laboratoire de Botanique, Cryptogamie et Microbiologie, CRNH Auvergne, Clermont-Ferrand, France
2 Faculté de Pharmacie, 3Unite de Nutrition, Centre Jean-Perrin CRNH Auvergne, Clermont-Ferrand, France
ABSTRACT
Objective: The fungicidal and bactericidal actions of the essential oil (EO) of Melaleuca alternifolia seem well established, but their anti-inflammatory and antioxidative effects remain unclear. This study investigated in vitro the possible role of whole Melaleuca alternifolia EO as a modulator of the inflammatory/non-specific immune response by exploring the chemotaxis and kinetic radical oxygen species (ROS) production of leukocytes and cytokine secretion in peripheral blood mononuclear cells (PBMCs) in humans.
Method: The influence of Melaleuca alternifolia EO on the chemotaxis under agarose of isolated neutrophils (PMNs) was evaluated. The kinetics of ROS production by stimulated total circulating leukocytes was followed over 2 h by recording the fluorescence intensity of oxidized dihydrorhodamine 123. The effects of this EO on pro-(interleukin IL-2) and anti-(IL-4 and IL10) inflammatory cytokine secretions were determined by ELISA following incubation of PBMCs with the EO for 24 h.
Results: Melaleuca alternifolia EO was inefficient on the chemotaxis of PMNs. It exerted an antioxidant effect, reducing ROS production throughout the kinetic study. Melaleuca alternifolia EO inhibited PBMC proliferation, as revealed by a reduction in IL-2 secretion by stimulated lymphocytes. This EO at 0.1% directly increased the secretion of the anti-inflammatory cytokine IL-4 compared with IL-4 secretion without EO (18.5 ± 10.0 vs 3.3 ± 1, p < 0.05), and also increased IL-10 secretion at 0.01% (94.9 ± 38.7 vs 44.1 ± 18, ns).
Conclusion: Melaleuca alternifolia EO may not only act as an anti-inflammatory mediator through its antioxidant activity but may also efficiently protect the organism by reducing the proliferation of inflammatory cells without affecting their capacity to secrete anti-inflammatory cytokines.
Ringkasan: Melaleuca alternifolia EO memberikan efek antioksidan dengan mengurangi produksi reactive oxygen species (ROS) selama studi kinetik. Melaleuca alternifolia EO mampu :
- menghambat profilerasi/perbanyakan peripheral blood mononuclear cells (PBMCs) dengan cara mengurangi sekresi IL-2
- meningkatkan sekresi senyawa sitokin antiradang IL-4
- meningkatkan sekresi senyawa sitokin antiradang IL-10 pada konsentrasi Melaleuca alternifolia EO 0,01%
Melaleuca alternifolia EO tidak hanya berpotensi sebagai mediator antiradang melalui aktivitas antioksidan, namun juga melindungi organisme dengan mengurangi perbanyakan sel-sel radang tanpa mempengaruhi kapasitasnya dalam menghasilkan sitokin antiinflamasi. Hal ini menyebabkan Melaleuca alternifolia EO membantu mencegah terjadinya cytokine storm (badai sitokin).
In vivo activity of terpinene-4-ol, the main bioactive component of Melaleuca alternifolia Cheel (tea tree) oil against azole-suspectible and resistant human pathogenic Candida species
Objective: Recent investigations on the antifungal properties of essential oil of Melaleuca alternifolia Cheel (Tea Tree Oil, TTO) have been performed with reference to the treatment of vaginal candidiasis. However, there…
In vivo activity of terpinene-4-ol, the main bioactive component of Melaleuca alternifolia Cheel (tea tree) oil against azole-suspectible and resistant human pathogenic Candida species
BMC Infectious Diseases 2006, 6:158. DOI:10.1186/1471-2334-6-158
Francesca Mondello*1, Flavia De Bernardis1, Antonietta Girolamo1, Antonio Cassone1, Giuseppe Salvatore2
1 Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy
2 Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, Italy
* Corresponding author
ABSTRACT
Objective: Recent investigations on the antifungal properties of essential oil of Melaleuca alternifolia Cheel (Tea Tree Oil, TTO) have been performed with reference to the treatment of vaginal candidiasis. However, there is a lack of in vivo data supporting in vitro results, especially regarding the antifungal properties of TTO constituents. Thus, the aim of our study was to investigate the in vitro and the in vivo anti-Candida activity of two critical bioactive constituents of TTO, terpinen-4-ol and 1,8-cineole.
Methods: Oophorectomized, pseudoestrus rats under estrogen treatment were used for experimental vaginal infection with azole (fluconazole, itraconazole) -susceptible or -resistant strains of Candida albicans. All these strains were preliminarily tested for in vitro susceptibility to TTO, terpinen-4-ol and 1,8-cineole for their antifungal properties, using a modification of the CLSI (formerly NCCLS) reference M27-A2 broth micro-dilution method.
Results: In vitro minimal inhibitory concentrations (MIC90) values were 0.06% (volume/volume) for terpinen-4-ol and 4% (volume/volume) for 1,8-cineole, regardless of susceptibility or resistance of the strains to fluconazole and itraconazole. Fungicidal concentrations of terpinen-4-ol were equivalent to the candidiastatic activity. In the rat vaginal infection model, terpinen-4-ol was as active as TTO in accelerating clearance from the vagina of all Candida strains examined.
Conclusion: Our data suggest that terpinen-4-ol is a likely mediator of the in vitro and in vivo activity of TTO. This is the first in vivo demonstration that terpinen-4-ol could control Candida albicans vaginal infections. The purified compound holds promise for the treatment of vaginal candidiasis, and articularly the azole-resistant forms.
Ringkasan: Melaleuca alternifolia essential oil (EO) memiliki potensi manfaat sebagai antijamur terutama untuk vaginal kandidiasis. Studi ini bertujuan meneliti aktivitas senyawa utama dalam Melaleuca alternifolia EO, terutama terpinen-4-ol.
Terpinen-4-ol sama dengan Melaleuca alternifolia EO dalam mempercepat pembersihan vagina dari semua jenis Candida yang diperiksa. Terpinen-4-ol merupakan mediator dari aktivitas Melaleuca alternifolia EO untuk mengendalikan infeksi Candida albicans pada vagina, khususnya bentuk-bentuk lain yang resisten terhadap obat golongan azole.
Hal ini menunjukkan Melaleuca alternifolia berpotensi membantu pemulihan pada kondisi infeksi yang disebabkan oleh jenis-jenis Candida.
Melaleuca alternifolia Concentrate inhibits entry of influenza virus H1N1 into host cell by disturbing the uncoating
Objective: Influenza virus causes high morbidity of population infection annually an pandemic spread occasionally. Melaleuca alternifolia Concentrate (MAC) is an essential oil derived from a native Australian tea tree. Our aim was to investigate whether MAC has effect capable of inhibiting influenza virus infection in vitro and what mechanism does the MAC use to fight…
Melaleuca alternifolia Concentrate inhibits entry of influenza virus H1N1 into host cell by disturbing the uncoating
Molecules 2013, 18, 9550-9566; DOI:10.3390/molecules18089550
Xinghua Li1, Songwei Duan2, Cordia Chu3, Jun Xu4, Gucheng Zeng1, Alfred King-Yin Lam5, Junmei Zhou1, Yue Yin1, Danyun Fang1, Maxwell John Reynolds3, Huaiyu Gu2, Lifang Jiang1
1, 2, 4 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
3, 5 Griffith University, Queensland, Australia
ABSTRACT
Objective: Influenza virus causes high morbidity of population infection annually an pandemic spread occasionally. Melaleuca alternifolia Concentrate (MAC) is an essential oil derived from a native Australian tea tree. Our aim was to investigate whether MAC has effect capable of inhibiting influenza virus infection in vitro and what mechanism does the MAC use to fight the virus infection.
Methods: The antiviral activity of MAC was examined by its inhibition of cytopathic effects. The immunofluorescence, direct enzyme linked immunosorbent assay, electron microscopy and in silico prediction was performed to evaluate the interaction between MAC and the viral haemagglutinin.
Results: When the influenza virus was incubated with 0.010% MAC for one hour, no cytopathic effect on MDCK cells was found after the virus infection and no immunofluorescence signal was detected in the host cells. Electron microscopy showed that the virus treated with MAC retained its structural integrity. By computational simulations, we found that terpinen-4-ol, which is the major bioactive component of MAC, could combine with the membrane fusion site of haemagglutinin.
Conclusion: MAC could prevent influenza virus from entering the host cells by disturbing the normal viral membrane fusion procedure.
Ringkasan: Virus influenza pada kondisi endemik dan pandemik menjadi penyebab tingkat morbiditas (kematian) yang tinggi seperti virus H1N1 pada tahun 2009. Obat dan vaksin digunakan untuk menanggulangi kondisi ini, namun dapat terjadi resistensi virus influenza terhadap obat-obat antiinfluenza.
Hasil penelitian menunjukkan bahwa ekstrak herbal MAC memiliki efek melawan virus influenza. Efek tersebut dimungkinkan berasal dari senyawa utama dari Melaleuca alternifolia Concentrate (MAC) yaitu terpinen-4-ol yang dapat mencegah masuknya virus ke dalam sel inang dengan mengganggu prosedur fusi (penggabungan) membran virus normal, sehingga mencegah virus menginfeksi sel inang. Hal ini membuktikan bahwa Melaleuca alternifolia Concentrate (MAC) memiliki potensi sebagai antivirus, termasuk virus influenza.
Melaleuca alternifolia Concentrate (MAC): A Plant-Derived Anticancer Agent
Objective: Melaleuca oils are commonly used products, primarily utilised and investigated for their antimicrobial activity. Previous studies reported Melaleuca oils to exhibit anticancer activity in vitro against a range of cancer cell lines, including melanoma, liver, leukaemia, lung, breast, and prostate cancer. This thesis investigated the hypothesis that MAC represented an effective anticancer agent with…
Melaleuca alternifolia Concentrate (MAC): A Plant-Derived Anticancer Agent
Griffith Research Online. Thesis (PhD Doctorate), 2013. DOI:10.25904/1912/889
Clark, Amanda
School of Medical Science, Griffith University, Queensland, Australia.
ABSTRACT
Objective: Melaleuca oils are commonly used products, primarily utilised and investigated for their antimicrobial activity. Previous studies reported Melaleuca oils to exhibit anticancer activity in vitro against a range of cancer cell lines, including melanoma, liver, leukaemia, lung, breast, and prostate cancer. This thesis investigated the hypothesis that MAC represented an effective anticancer agent with immunomodulatory activity.
Methods: The mechanism by which MAC caused cell death was investigated. MAC was elucidated to induce apoptosis predominantly by activating the intrinsic mitochondrial pathway, while at lower concentrations MAC induced autophagy and cell cycle arrest in G0/1 phase.
Results: The exact nature of the antitumour immune cell response induced by MAC was found to be highly dependent upon the model of murine breast cancer examined. In the syngeneic 4T-1 model, MAC elevated the presence of the effector T cells, which were potentially activated by APC-like neutrophils, while at the same time reducing the presence of suppressor Treg cells. Conversely, in the spontaneous c-neu model, neutrophils formed the bulk of the tumour cell infiltrate, while the effector T cells were reduced. The discrepancies in the types of immune responses between the two models by MAC are likely based on the dramatically different tumour microenvironments.
Conclusion: MAC represented an effective anticancer agent capable of inducing apoptosis both in vitro and in vivo, and demonstrated significant anticancer potential in the pre-clinical breast cancer models, without obvious adverse side effects or toxicity.
Ringkasan: Melaleuca alternifolia Concentrate (MAC) berpotensi sebagai antikanker melalui induksi apoptosis (kematian sel terprogram), yang dibuktikan secara in vitro maupun in vivo dan menunjukkan potensi antikanker dalam penelitian pra-klinis kanker payudara, tanpa efek samping maupun toksisitas.
In vivo activity of terpinene-4-ol, the main bioactive component of Melaleuca alternifolia Cheel (tea tree) oil against azole-suspectible and resistant human pathogenic Candida species
BMC Infectious Diseases 2006, 6:158. DOI:10.1186/1471-2334-6-158
Francesca Mondello*1, Flavia De Bernardis1, Antonietta Girolamo1, Antonio Cassone1, Giuseppe Salvatore2
1 Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy
2 Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Rome, Italy
* Corresponding author
ABSTRACT
Objective: Recent investigations on the antifungal properties of essential oil of Melaleuca alternifolia Cheel (Tea Tree Oil, TTO) have been performed with reference to the treatment of vaginal candidiasis. However, there is a lack of in vivo data supporting in vitro results, especially regarding the antifungal properties of TTO constituents. Thus, the aim of our study was to investigate the in vitro and the in vivo anti-Candida activity of two critical bioactive constituents of TTO, terpinen-4-ol and 1,8-cineole.
Methods: Oophorectomized, pseudoestrus rats under estrogen treatment were used for experimental vaginal infection with azole (fluconazole, itraconazole) -susceptible or -resistant strains of Candida albicans. All these strains were preliminarily tested for in vitro susceptibility to TTO, terpinen-4-ol and 1,8-cineole for their antifungal properties, using a modification of the CLSI (formerly NCCLS) reference M27-A2 broth micro-dilution method.
Results: In vitro minimal inhibitory concentrations (MIC90) values were 0.06% (volume/volume) for terpinen-4-ol and 4% (volume/volume) for 1,8-cineole, regardless of susceptibility or resistance of the strains to fluconazole and itraconazole. Fungicidal concentrations of terpinen-4-ol were equivalent to the candidiastatic activity. In the rat vaginal infection model, terpinen-4-ol was as active as TTO in accelerating clearance from the vagina of all Candida strains examined.
Conclusion: Our data suggest that terpinen-4-ol is a likely mediator of the in vitro and in vivo activity of TTO. This is the first in vivo demonstration that terpinen-4-ol could control Candida albicans vaginal infections. The purified compound holds promise for the treatment of vaginal candidiasis, and articularly the azole-resistant forms.
Ringkasan: Melaleuca alternifolia essential oil (EO) memiliki potensi manfaat sebagai antijamur terutama untuk vaginal kandidiasis. Studi ini bertujuan meneliti aktivitas senyawa utama dalam Melaleuca alternifolia EO, terutama terpinen-4-ol.
Terpinen-4-ol sama dengan Melaleuca alternifolia EO dalam mempercepat pembersihan vagina dari semua jenis Candida yang diperiksa. Terpinen-4-ol merupakan mediator dari aktivitas Melaleuca alternifolia EO untuk mengendalikan infeksi Candida albicans pada vagina, khususnya bentuk-bentuk lain yang resisten terhadap obat golongan azole.
Hal ini menunjukkan Melaleuca alternifolia berpotensi membantu pemulihan pada kondisi infeksi yang disebabkan oleh jenis-jenis Candida.
Melaleuca alternifolia Concentrate inhibits entry of influenza virus H1N1 into host cell by disturbing the uncoating
Molecules 2013, 18, 9550-9566; DOI:10.3390/molecules18089550
Xinghua Li1, Songwei Duan2, Cordia Chu3, Jun Xu4, Gucheng Zeng1, Alfred King-Yin Lam5, Junmei Zhou1, Yue Yin1, Danyun Fang1, Maxwell John Reynolds3, Huaiyu Gu2, Lifang Jiang1
1, 2, 4 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
3, 5 Griffith University, Queensland, Australia
ABSTRACT
Objective: Influenza virus causes high morbidity of population infection annually an pandemic spread occasionally. Melaleuca alternifolia Concentrate (MAC) is an essential oil derived from a native Australian tea tree. Our aim was to investigate whether MAC has effect capable of inhibiting influenza virus infection in vitro and what mechanism does the MAC use to fight the virus infection.
Methods: The antiviral activity of MAC was examined by its inhibition of cytopathic effects. The immunofluorescence, direct enzyme linked immunosorbent assay, electron microscopy and in silico prediction was performed to evaluate the interaction between MAC and the viral haemagglutinin.
Results: When the influenza virus was incubated with 0.010% MAC for one hour, no cytopathic effect on MDCK cells was found after the virus infection and no immunofluorescence signal was detected in the host cells. Electron microscopy showed that the virus treated with MAC retained its structural integrity. By computational simulations, we found that terpinen-4-ol, which is the major bioactive component of MAC, could combine with the membrane fusion site of haemagglutinin.
Conclusion: MAC could prevent influenza virus from entering the host cells by disturbing the normal viral membrane fusion procedure.
Ringkasan: Virus influenza pada kondisi endemik dan pandemik menjadi penyebab tingkat morbiditas (kematian) yang tinggi seperti virus H1N1 pada tahun 2009. Obat dan vaksin digunakan untuk menanggulangi kondisi ini, namun dapat terjadi resistensi virus influenza terhadap obat-obat antiinfluenza.
Hasil penelitian menunjukkan bahwa ekstrak herbal MAC memiliki efek melawan virus influenza. Efek tersebut dimungkinkan berasal dari senyawa utama dari Melaleuca alternifolia Concentrate (MAC) yaitu terpinen-4-ol yang dapat mencegah masuknya virus ke dalam sel inang dengan mengganggu prosedur fusi (penggabungan) membran virus normal, sehingga mencegah virus menginfeksi sel inang. Hal ini membuktikan bahwa Melaleuca alternifolia Concentrate (MAC) memiliki potensi sebagai antivirus, termasuk virus influenza.
Melaleuca alternifolia Concentrate (MAC): A Plant-Derived Anticancer Agent
Griffith Research Online. Thesis (PhD Doctorate), 2013. DOI:10.25904/1912/889
Clark, Amanda
School of Medical Science, Griffith University, Queensland, Australia.
ABSTRACT
Objective: Melaleuca oils are commonly used products, primarily utilised and investigated for their antimicrobial activity. Previous studies reported Melaleuca oils to exhibit anticancer activity in vitro against a range of cancer cell lines, including melanoma, liver, leukaemia, lung, breast, and prostate cancer. This thesis investigated the hypothesis that MAC represented an effective anticancer agent with immunomodulatory activity.
Methods: The mechanism by which MAC caused cell death was investigated. MAC was elucidated to induce apoptosis predominantly by activating the intrinsic mitochondrial pathway, while at lower concentrations MAC induced autophagy and cell cycle arrest in G0/1 phase.
Results: The exact nature of the antitumour immune cell response induced by MAC was found to be highly dependent upon the model of murine breast cancer examined. In the syngeneic 4T-1 model, MAC elevated the presence of the effector T cells, which were potentially activated by APC-like neutrophils, while at the same time reducing the presence of suppressor Treg cells. Conversely, in the spontaneous c-neu model, neutrophils formed the bulk of the tumour cell infiltrate, while the effector T cells were reduced. The discrepancies in the types of immune responses between the two models by MAC are likely based on the dramatically different tumour microenvironments.
Conclusion: MAC represented an effective anticancer agent capable of inducing apoptosis both in vitro and in vivo, and demonstrated significant anticancer potential in the pre-clinical breast cancer models, without obvious adverse side effects or toxicity.
Ringkasan: Melaleuca alternifolia Concentrate (MAC) berpotensi sebagai antikanker melalui induksi apoptosis (kematian sel terprogram), yang dibuktikan secara in vitro maupun in vivo dan menunjukkan potensi antikanker dalam penelitian pra-klinis kanker payudara, tanpa efek samping maupun toksisitas.
Infectious Disease; Melaleuca alternifolia Concentrate (MAC) as a Causal Therapy of Dengue Infection
Objective: Dengue infection is distributed throughout the tropical areas around the world, including Indonesia. Dengue fever/ dengue haemorrhagic fever is a mosquito-borne disease caused by dengue virus of any serotype 1 (DEN1) to DEN4. Until now, therapy is based on pathophysiology. The aim of this study is evaluating the efficacy and safety of MAC for the treatmen…
Infectious Disease; Melaleuca alternifolia Concentrate (MAC) as a Causal Therapy of Dengue Infection
Korean Society of Internal Medicine Fall Conference Proceedings, Vol. 2014, Issue 1 (2014)
Nasronudin, M.I. Lusida, B. Rachman, M. Rusli, M. Isfandiari, E. Apryani, V. Arfijanto, P. Sudibyo, J.T. Tjahjana, Siswanto, M.J. Reynolds, U. F. Achmadi
ABSTRACT
Objective: Dengue infection is distributed throughout the tropical areas around the world, including Indonesia. Dengue fever/ dengue haemorrhagic fever is a mosquito-borne disease caused by dengue virus of any serotype 1 (DEN1) to DEN4. Until now, therapy is based on pathophysiology. The aim of this study is evaluating the efficacy and safety of MAC for the treatment of dengue infection.
Methods: This clinical trial phase III was designed to study the inhibitory property of MAC against dengue virus (DENV) activity. A double-blind, randomized, controlled trial method was approved by Ethical Committee of Dr. Soetomo Hospital. This study was conducted from January 2012 to November 2013. After a signed informed consent, 530 patients, fever on day-1 or day-2, suspected dengue infection according to WHO criteria, showed positive result either by NS-1, and or IgM - IgG, were recruited. The subjects were divided into 2 groups. Group I received WHO standard treatment and 300 mg - MAC twice daily orally for 7 days. Group II received WHO standard treatment only. History, physical examination and complete blood count were done every day. Laboratory test (liver function, kidney function, CD4, CD8, VCAM, viral load) were performed on the first, fourth and seventh days.
Results: The results showed that the quantity of virus significantly decreased in the treatment group (96.67%) compared to the control group (44.79%). Also showed that MAC did improve the immune system by increasing the value of CD8 (6.89%) and CD4 (9.95%). MAC provision does not interfere with the function of liver and kidney, and was well tolerated by the patients.
Conclusion: MAC has significant reduction of viral load level, may have immunomodulatory effects, prevent plasma leakage, no hepatotoxic and nephrotoxic effects. MAC efficacy as an antiviral agent against DENV infection has been very effectively illustrated.
Ringkasan: Demam berdarah merupakan penyakit yang disebabkan virus dengue serotype 1 (DEN1) hingga DEN4. Penelitian ini dilakukan untuk mengevaluasi efikasi dan keamanan Melaleuca alternifolia Concentrate (MAC). Penelitian yang dilakukan merupakan uji klinis fase 3 untuk melihat daya hambat MAC terhadap virus dengue (DENV).
Hasil penelitian menunjukkan jumlah virus menurun secara signifikan pada pasien yang menerima pengobatan standar WHO dan 300 mg MAC 2 x sehari selama 7 hari (96,67%) dibandingkan group control (44.79%). MAC juga terbukti meningkatkan sistem imun dengan meningkatkan jumlah CD8 dan CD4. MAC tidak mempengaruhi fungsi hati dan ginjal, serta dapat ditoleransi oleh pasien. Kesimpulan penelitian: MAC mampu menurunkan level viral load, berpotensi sebagai imunomodulator, mencegah kebocoran plasma darah, tidak hepatotoksik (tidak berbahaya bagi hati) dan tidak nefrotoksik (tidak berbahaya bagi ginjal). MAC terbukti berpotensi sebagai antivirus melawan infeksi virus dengue.
Immunomodulatory activity of Melaleuca alternifolia concentrate (MAC): Inhibition of LPS-induced NF-κB activation and cytokine production in myeloid cell lines
Objective: Melaleuca alternifolia concentrate (MAC) is a mixture predominantly composed of monoterpenoids and sesquiterpenes, refined from the essential oil of the tea tree by removing up to 99% of the more…
Immunomodulatory activity of Melaleuca alternifolia concentrate (MAC): Inhibition of LPS-induced NF-κB activation and cytokine production in myeloid cell lines
International Immunopharmacology 26 (2015) 257–264. DOI:10.1016/j.intimp.2015.03.034
- Lowa, A. M. Clarka, T. C. Chouc, T. C. Changc, M. Reynoldsa,b, S. J. Ralpha,⁎
a Griffith University, Gold Coast campus, Southport, Queensland, Australia
b 98 Alive Pty Ltd., PO Box 82, Underwood, QLD 4119, Australia
c National Defense Medical Center, Taipei, Taiwan
ABSTRACT
Objective: Melaleuca alternifolia concentrate (MAC) is a mixture predominantly composed of monoterpenoids and sesquiterpenes, refined from the essential oil of the tea tree by removing up to 99% of the more toxic, hydrophobic monoterpenes. MAC was examined here for its immunomodulatory effects on the human THP1 and murine RAW264.7 myeloid leukemic cell lines as models for macrophage-like cells.
Methods: Firstly, MAC levels were determined that did not affect either the survival or proliferation of these cell lines in vitro. Next, the levels of lipopolysaccharide (LPS)-induced production of cytokines (IL-6, TNFα, IL-10, GM-CSF, IFNγ and IL-3) were examined from the myeloid cell lines using multiplex assays.
Results: Many of the LPS-inducible cytokines produced by either cell lines could be significantly inhibited by MAC. Closer examination of the mechanism of action of MAC showed that it inhibited the LPS-induced activation of IκB phosphorylation and nuclear factor (NF)-κB signalling and translocation, inhibiting iNOS protein expression and NO production.
Conclusion: These results demonstrate that MAC exerts its immunomodulatory effects by inhibiting NF-κB signalling activation and levels of cytokine production by macrophage-like cell lines.
Ringkasan: Melaleuca alternifolia Concentrate (MAC) merupakan campuran yang utamanya terdiri atas monoterpenoid dan sesquiterpene, hasil pemurnian dari minyak esensial tea tree dengan menghilangkan hingga 99% monoterpene hidrofobik yang beracun (toxic).
Hasil penelitian menunjukkan bahwa MAC memberikan efek imunomodulator dengan menghambat aktivasi persinyalan NF-κB dan tingkat produksi sitokin.
In Vitro Evaluation of Antioxidant and Antimicrobial Activities of Melaleuca alternifolia Essential Oil
Objective: The in vitro antioxidant and antimicrobial activity of the essential oil from Melaleuca alternifolia was evaluated in this report.
Methods: The antioxidant potential of the essential oil from Melaleuca alternifolia was…
Terpinen-4-ol, the main component of the essential oil of Melaleuca alternifolia (tea tree oil), suppresses inflammatory mediator production by activated human monocytes
Inflammation Research 49 (2000) 619–626. DOI: 1023-3830/00/110619-08
- H. Hart1, C. Brand1, C. F. Carson2,T.V. Riley2, R. H. Prager3 and J. J. Finlay-Jones1
1 Department of Microbiology and Infectious Diseases, School of Medicine, Flinders University, Adelaide, Australia
2 Department of Microbiology, University of Western Australia, Nedlands, Australia
3 School of Chemistry, Physics and Earth Sciences, Flinders University, Adelaide, Australia
ABSTRACT
Objective: To evaluate potential anti-inflammatory properties of tea tree oil, the essential oil steam distilled from the Australian native plant, Melaleuca alternifolia.
Methods: The ability of tea tree oil to reduce the production in vitro of tumour necrosis factor-a (TNFa), interleukin (IL)-1b, IL-8, IL-10 and prostaglandin E2 (PGE2) by lipopolysaccharide (LPS)-activated human peripheral blood monocytes was examined. The processes carried out in the research are monocyte isolation and culture; measurement of toxicity of tea tree oil and its water soluble components; ELISAs for TNFα, IL-1β, IL-8 and IL-10; radioimmunoassay for PGE2, solubilizing tea tree oil in water; and analyse with GC/MS.
Results: Tea tree oil emulsified by sonication in a glass tube into culture medium containing 10% fetal calf serum (FCS) was toxic for monocytes at a concentration of 0.016% v/v. However, the water soluble components of tea tree oil at concentrations equivalent to 0.125% significantly suppressed LPS-induced production of TNFa, IL-1b and IL-10 (by approximately 50%) and PGE2 (by approximately 30%) after 40 h. Gas chromatography/ mass spectrometry identified terpinen-4-ol (42%), a-terpineol (3%) and 1,8-cineole (2%, respectively, of tea tree oil) as the water soluble components of tea tree oil. When these components were examined individually, only terpinen-4-ol suppressed the production after 40 h of TNFa, IL-1b, IL-8, IL-10 and PGE2 by LPS-activated monocytes.
Conclusion: The water-soluble components of tea tree oil can suppress pro-inflammatory mediator production by activated human monocytes.
______________________________________
Ringkasan
Melaleuca alternifolia merupakan tumbuhan asli Australia penghasil minyak esensial (essential oil/EO) yang diperoleh melalui proses distilasi. Melaleuca alternifolia EO mengandung lebih dari 100 senyawa yang diketahui memiliki potensi melawan bakteri dan jamur.
Salah satu kandungan dalam Melaleuca alternifolia EO adalah terpinen-4-ol yang dibuktikan dalam penelitian ini mampu menekan produksi mediator inflamasi (radang). Aktivitas tersebut menunjukkan potensi Melaleuca alternifolia EO selain sebagai antibakteri, antijamur, juga berpotensi mencegah terjadinya peradangan.
Infectious Disease; Melaleuca alternifolia Concentrate (MAC) as a Causal Therapy of Dengue Infection
Korean Society of Internal Medicine Fall Conference Proceedings, Vol. 2014, Issue 1 (2014)
Nasronudin, M.I. Lusida, B. Rachman, M. Rusli, M. Isfandiari, E. Apryani, V. Arfijanto, P. Sudibyo, J.T. Tjahjana, Siswanto, M.J. Reynolds, U. F. Achmadi
ABSTRACT
Objective: Dengue infection is distributed throughout the tropical areas around the world, including Indonesia. Dengue fever/ dengue haemorrhagic fever is a mosquito-borne disease caused by dengue virus of any serotype 1 (DEN1) to DEN4. Until now, therapy is based on pathophysiology. The aim of this study is evaluating the efficacy and safety of MAC for the treatment of dengue infection.
Methods: This clinical trial phase III was designed to study the inhibitory property of MAC against dengue virus (DENV) activity. A double-blind, randomized, controlled trial method was approved by Ethical Committee of Dr. Soetomo Hospital. This study was conducted from January 2012 to November 2013. After a signed informed consent, 530 patients, fever on day-1 or day-2, suspected dengue infection according to WHO criteria, showed positive result either by NS-1, and or IgM - IgG, were recruited. The subjects were divided into 2 groups. Group I received WHO standard treatment and 300 mg - MAC twice daily orally for 7 days. Group II received WHO standard treatment only. History, physical examination and complete blood count were done every day. Laboratory test (liver function, kidney function, CD4, CD8, VCAM, viral load) were performed on the first, fourth and seventh days.
Results: The results showed that the quantity of virus significantly decreased in the treatment group (96.67%) compared to the control group (44.79%). Also showed that MAC did improve the immune system by increasing the value of CD8 (6.89%) and CD4 (9.95%). MAC provision does not interfere with the function of liver and kidney, and was well tolerated by the patients.
Conclusion: MAC has significant reduction of viral load level, may have immunomodulatory effects, prevent plasma leakage, no hepatotoxic and nephrotoxic effects. MAC efficacy as an antiviral agent against DENV infection has been very effectively illustrated.
Ringkasan: Demam berdarah merupakan penyakit yang disebabkan virus dengue serotype 1 (DEN1) hingga DEN4. Penelitian ini dilakukan untuk mengevaluasi efikasi dan keamanan Melaleuca alternifolia Concentrate (MAC). Penelitian yang dilakukan merupakan uji klinis fase 3 untuk melihat daya hambat MAC terhadap virus dengue (DENV).
Hasil penelitian menunjukkan jumlah virus menurun secara signifikan pada pasien yang menerima pengobatan standar WHO dan 300 mg MAC 2 x sehari selama 7 hari (96,67%) dibandingkan group control (44.79%). MAC juga terbukti meningkatkan sistem imun dengan meningkatkan jumlah CD8 dan CD4. MAC tidak mempengaruhi fungsi hati dan ginjal, serta dapat ditoleransi oleh pasien. Kesimpulan penelitian: MAC mampu menurunkan level viral load, berpotensi sebagai imunomodulator, mencegah kebocoran plasma darah, tidak hepatotoksik (tidak berbahaya bagi hati) dan tidak nefrotoksik (tidak berbahaya bagi ginjal). MAC terbukti berpotensi sebagai antivirus melawan infeksi virus dengue.
Immunomodulatory activity of Melaleuca alternifolia concentrate (MAC): Inhibition of LPS-induced NF-κB activation and cytokine production in myeloid cell lines
International Immunopharmacology 26 (2015) 257–264. DOI:10.1016/j.intimp.2015.03.034
- Lowa, A. M. Clarka, T. C. Chouc, T. C. Changc, M. Reynoldsa,b, S. J. Ralpha,⁎
a Griffith University, Gold Coast campus, Southport, Queensland, Australia
b 98 Alive Pty Ltd., PO Box 82, Underwood, QLD 4119, Australia
c National Defense Medical Center, Taipei, Taiwan
ABSTRACT
Objective: Melaleuca alternifolia concentrate (MAC) is a mixture predominantly composed of monoterpenoids and sesquiterpenes, refined from the essential oil of the tea tree by removing up to 99% of the more toxic, hydrophobic monoterpenes. MAC was examined here for its immunomodulatory effects on the human THP1 and murine RAW264.7 myeloid leukemic cell lines as models for macrophage-like cells.
Methods: Firstly, MAC levels were determined that did not affect either the survival or proliferation of these cell lines in vitro. Next, the levels of lipopolysaccharide (LPS)-induced production of cytokines (IL-6, TNFα, IL-10, GM-CSF, IFNγ and IL-3) were examined from the myeloid cell lines using multiplex assays.
Results: Many of the LPS-inducible cytokines produced by either cell lines could be significantly inhibited by MAC. Closer examination of the mechanism of action of MAC showed that it inhibited the LPS-induced activation of IκB phosphorylation and nuclear factor (NF)-κB signalling and translocation, inhibiting iNOS protein expression and NO production.
Conclusion: These results demonstrate that MAC exerts its immunomodulatory effects by inhibiting NF-κB signalling activation and levels of cytokine production by macrophage-like cell lines.
Ringkasan: Melaleuca alternifolia Concentrate (MAC) merupakan campuran yang utamanya terdiri atas monoterpenoid dan sesquiterpene, hasil pemurnian dari minyak esensial tea tree dengan menghilangkan hingga 99% monoterpene hidrofobik yang beracun (toxic).
Hasil penelitian menunjukkan bahwa MAC memberikan efek imunomodulator dengan menghambat aktivasi persinyalan NF-κB dan tingkat produksi sitokin.
Terpinen-4-ol, the main component of the essential oil of Melaleuca alternifolia (tea tree oil), suppresses inflammatory mediator production by activated human monocytes
Inflammation Research 49 (2000) 619–626. DOI: 1023-3830/00/110619-08
- H. Hart1, C. Brand1, C. F. Carson2,T.V. Riley2, R. H. Prager3 and J. J. Finlay-Jones1
1 Department of Microbiology and Infectious Diseases, School of Medicine, Flinders University, Adelaide, Australia
2 Department of Microbiology, University of Western Australia, Nedlands, Australia
3 School of Chemistry, Physics and Earth Sciences, Flinders University, Adelaide, Australia
ABSTRACT
Objective: To evaluate potential anti-inflammatory properties of tea tree oil, the essential oil steam distilled from the Australian native plant, Melaleuca alternifolia.
Methods: The ability of tea tree oil to reduce the production in vitro of tumour necrosis factor-a (TNFa), interleukin (IL)-1b, IL-8, IL-10 and prostaglandin E2 (PGE2) by lipopolysaccharide (LPS)-activated human peripheral blood monocytes was examined. The processes carried out in the research are monocyte isolation and culture; measurement of toxicity of tea tree oil and its water soluble components; ELISAs for TNFα, IL-1β, IL-8 and IL-10; radioimmunoassay for PGE2, solubilizing tea tree oil in water; and analyse with GC/MS.
Results: Tea tree oil emulsified by sonication in a glass tube into culture medium containing 10% fetal calf serum (FCS) was toxic for monocytes at a concentration of 0.016% v/v. However, the water soluble components of tea tree oil at concentrations equivalent to 0.125% significantly suppressed LPS-induced production of TNFa, IL-1b and IL-10 (by approximately 50%) and PGE2 (by approximately 30%) after 40 h. Gas chromatography/ mass spectrometry identified terpinen-4-ol (42%), a-terpineol (3%) and 1,8-cineole (2%, respectively, of tea tree oil) as the water soluble components of tea tree oil. When these components were examined individually, only terpinen-4-ol suppressed the production after 40 h of TNFa, IL-1b, IL-8, IL-10 and PGE2 by LPS-activated monocytes.
Conclusion: The water-soluble components of tea tree oil can suppress pro-inflammatory mediator production by activated human monocytes.
______________________________________
Ringkasan
Melaleuca alternifolia merupakan tumbuhan asli Australia penghasil minyak esensial (essential oil/EO) yang diperoleh melalui proses distilasi. Melaleuca alternifolia EO mengandung lebih dari 100 senyawa yang diketahui memiliki potensi melawan bakteri dan jamur.
Salah satu kandungan dalam Melaleuca alternifolia EO adalah terpinen-4-ol yang dibuktikan dalam penelitian ini mampu menekan produksi mediator inflamasi (radang). Aktivitas tersebut menunjukkan potensi Melaleuca alternifolia EO selain sebagai antibakteri, antijamur, juga berpotensi mencegah terjadinya peradangan.
Acute and Subacute Toxicity Studies of Melaleuca alternifolia Concentrate (MAC) in the Laboratory Animals
Objective: Melaleuca alternifolia Concentrate (MAC) is an essential oil isolated from a native Australian plant. The preparation has een approved by Australian TGA for human usen at 25% concentrationas well as by US FDA as herbal medicine. Homever, the safety of…
Acute and Subacute Toxicity Studies of Melaleuca alternifolia Concentrate (MAC) in the Laboratory Animals
Research Report (2008). Gadjah Mada University.
Nurlailaa, S. Widyarinib
a Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Gadjah Mada University, Yogyakarta, Indonesia
b Department of Clinical Pathology, Faculty of Veterinary Medicine, Gadjah Mada University, Yogyakarta, Indonesia
ABSTRACT
Objective: Melaleuca alternifolia Concentrate (MAC) is an essential oil isolated from a native Australian plant. The preparation has een approved by Australian TGA for human usen at 25% concentrationas well as by US FDA as herbal medicine. Homever, the safety of MAC has not been studied thoroughly in laboratory animals.
Methods: Non-pathogenic, male Wistar rats and domestic male rabbits were used in the studies. For the acute toxicity study in the rats, the animals were administered orally 10% MAC solution at the single dose of 0 (vehicle), 5, 10, 20, or 40 g/kgbw, whereas that in rabbits, received a single dose of 0 (vehicle), 13.3, 16.7, or 20 g/kgbw of 10% MAC solution. Toxic signs were observed for at least 24 hours and recorded in relation to dose and time. Animal dying during the observation period, as well as rats surviving to the end of the observation period were autopsied. For the subacute toxicity study in the rats, the animals were administered orally 10% MAC solution at 0 (vehicle), 1.6, 3.15, or 6.3 g/kgbw for 28 consecutive days, and 5 animals per dosing group were kept alive without the administration of MAC solution for 7 days. The animals were then sacrified for biochemical and histopathological analyses according to WHO Guidelines.
Results: LD50 value is 21 g/kg bw (Wistar rats) and 15,6 g/kgbw (rabbits), which are classified as practically non-toxic. All organ examined appear normal at the daily dose of 1,6 g/kg/day for 28 days. Intestine and liver injuries occur dose-dependently starting from 3,15 g/kg/day. Kidney function appears normal. Increase levels of SGPT and SGOT are seen in vehicle and MAC groups. All the blood constituents are normal.
Conclusion: MAC is classified practically non-toxic. All organ examined and blood constituents are normal at the daily dose.
Ringkasan: Melaleuca alternifolia Concentrate (MAC) terbukti aman/tidak toksik. Pengujian toksisitas akut dan subakut terhadap MAC yang dilakukan oleh Fakultas Farmasi UGM menunjukkan bahwa organ maupun parameter darah yang diuji menunjukkan kondisi normal pada penggunaan dosis harian sesuai rekomendasi.
Pharmacokinetics of Terpinen-4-ol in Healthy Subjects After Administration of a Single and Multiple Oral of MAC
Objective: Melaleuca alternifolia Concentrate (MAC) has been reported to contain mainly terpinen-4-ol, have an antiinflammatory and antimicrobial in vitro studies found that MAC can inhibit the growth of DV 1, 2, 3 and 4 and ultimately kill the virus. Solution of…
Pharmacokinetics of Terpinen-4-ol in Healthy Subjects After Administration of a Single and Multiple Oral of MAC
Thesis S2, Faculty of Pharmacy (2009) Gadjah Mada University
Arifah Sri Wahyuni, Lukman Hakim, Sudibyo Martono
Faculty of Pharmacy, Gadjah Mada University
ABSTRACT
Objective: Melaleuca alternifolia Concentrate (MAC) has been reported to contain mainly terpinen-4-ol, have an antiinflammatory and antimicrobial in vitro studies found that MAC can inhibit the growth of DV 1, 2, 3 and 4 and ultimately kill the virus. Solution of 10% MAC has also been found to have oral LD50 values found in rats and rabbits are 21 and 15.6 g/kgbb respectively, which are classified as practically non-toxic. Pharmacokinetic in chicken have been found that Cmaks reach in 0,04 µg/mL plasma). The ultimate objective of the studies is to develop a standardized MAC preparation which contains a major active component terpinen-4-ol (60%) to be a phytopharmaca for the treatment of patients with dengue viral infection.
Methods: The study involves 29 healthy subjects (15 males and 14 females) who have fulfilled the inclusion criteria, and was done at Dr Sardjito Hospital, Yogyakarta following an ethical clearance released by the Faculty of Medicine, Gadjah Mada University. The subjects were allocated randomly into 3 groups of dose regimens of MAC capsules for dose safety studies (i.e. a single oral dose of 300 mg and 600 mg, and multiple oral doses of 300 mg, 3-times a day for 5 days. The determination of its major, active component (terpinen-4-ol) in serum and urine was done by a validated GC-FID method.
Results: Terpinen-4-ol in MAC is rapidly absorbed from the GI tract, and achieved satisfactory concentration in serum 15 minutes after ingestion, and maximum concentrations of 2.84 ng/ml (300 mg dose) and 5.15 ng/ml (600 mg dose) after 1- 2 hours of ingestion. Terpinen-4-ol is also widely distributed in the body with a slow elimination rate with elimination half-lives vary from 28.5 to 41.6 hours. Mean steady-state serum concentration of the compound after 300 mg MAC (3- times/day for 5 days) is 2.72 ng/ml (2.43 to 2.95 ng/ml). Terpinen-4-ol is slowly excreted into urine with average excretion rates of 177.78 ng/hour and 118.49 ng/hour after single oral doses of 300 mg and 600 mg, respectively.
Conclusion: Terpinen-4-ol in MAC is rapidly absorbed from the GI tract and widely distributed in the body with a slow elimination rate. Terpinen-4-ol excreted in an appreciable amount to inhibit the growth of micro-organisms in the urinary tract.
Ringkasan: Terpinen-4-ol dalam Melaleuca alternifolia Concentrate (MAC) diabsorbsi secara cepat dari saluran pencernaan dan mencapai konsentrasi yang memuaskan pada 15 menit setelah dikonsumsi. Terpinen-4-ol mencapai konsentrasi maksimum 2,84 ng/ml (dosis 300 mg) dan 5,15 ng/ml (dosis 600 mg) 1 – 2 jam setelah dikonsumsi. Terpinen-4-ol terdistribusi secara luas dalam tubuh dengan t1/2 eliminasi lambat berkisar antara 28,5 – 41,6 jam. Konsentrasi serum steady-state (jenuh) rata-rata untuk dosis 300 mg MAC 3 kali sehari selama 5 hari adalah 2,72 ng/ml (2,43 – 2,95 ng/ml). Terpinen-4-ol diekskresi secara lambat melalui urin dengan rata-rata kecepatan ekskresi 177,78 ng/jam untuk dosis 300 mg dan 118,49 ng/jam untuk dosis 600 mg.
Phase I Clinical Trial of Standardized Melaleuca alternifolia Concentrate (MAC) in Healthy Indonesian Subjects
Objective: Melaleuca alternifolia Concentrate (MAC) is an extract isolated from a native Australian plant, Melaleuca alternifolia (familia Myrtaceae). MAC shows various biology activity such as…
Phase I Clinical Trial of Standardized Melaleuca alternifolia Concentrate (MAC) in Healthy Indonesian Subjects
Research Report (2009) Research Centre of Biotechnology. Gadjah Mada University
- Wibowo1, L. Hakim2, T. Wibawa3, D. Priyambodo4, U. Intansari5, D. K. Nugroho6, Mulyadi6, S. Kadarinah7, S. Purwaningsih8, A. S. Wahyuni9, T. Azizah9
- Clinical Pharmacology and Neurology
- Pharmacokinetics
- Microbiology
- Internal medicine
- Clinical Pathology and Immunology
- General physician
- Hospital research organizer
- Chief of nurses
- Analytical chemistry
ABSTRACT
Objective: Melaleuca alternifolia Concentrate (MAC) is an extract isolated from a native Australian plant, Melaleuca alternifolia (familia Myrtaceae). MAC shows various biology activity such as antibacterial, antifungi, antiinflammatory and antiviral activities against Herpes Simpleks. In vitro studies found that MAC can inhibit the growth of dengue strain-1,2,3 and 4 and ultimately kill the virus. MAC has been reported to contain mainly terpinen-4-ol. Solution of MAC 10% has also been found to have oral LD50 values found in rats and rabbits are 21 and 15,6 g/kg bw respectively which are classified as practically nontoxic.
Methods: A recent subacute toxicity study in rats reveals that 10% MAC solution at the oral daily dose of 1,6 g/kg bw/day (7,5% oral LD50 value) given 28 days shows a good safety in various vital organ and blood constituents. The ultimate objective of this studies is to know safety of using capsules MAC in healthy subjects are seen from parameter vital sign, haematology, blood chemistry and routine urine. The study involves 29 healthy subjects were divided into 3 groups, each group was contained 5 males and 4-5 females who have fulfilled the inclusion and exclusion criteria It was done at RSUP. Dr Sardjito Hospital, Yogyakarta following an ethical clearance release by the Faculty of Medicine, Gadjah Mada University. The subjects were allocated randomly into 3 groups of dose regimen of MAC capsules. Group I-III were given single oral dose of 600 mg and 750 mg, and multiple oral doses of 300 mg, 3-times a day for 5 days respectively.
Results: During study subject was monitored against occurring probability of side effect. The 14th days after treatment of single oral dose and the 1st day after treatment of multiple oral dose finished, some parameters such as haematology, blood chemistry and routine urine were measured. Data were compared between before and after treatment of capsules MAC using statistic paired t test with level of confidence 95%.
Conclusion: The results of this studies showed that MAC single oral dose of 600 mg and 750 mg, and multiple oral doses of 300 mg, 3-times a day for 5 days, were well tolerated by the subjects, and it is unlikely to affect vital signs, haematology, vital organs such as liver, kidney and it did not cause crystalluria.
Ringkasan: Penelitian in vitro menunjukkan bahwa Melaleuca alternifolia Concentrate (MAC) mampu menghambat pertumbuhan dan akhirnya membunuh virus dengue strain 1, 2, 3 dan 4. Senyawa utama dalam MAC adalah terpinen-4-ol. Dari segi keamanannya, MAC 10% mempunyai LD50 oral sebesar 21 g/kgbb (tikus) dan 15,6 g/kgbb (kelinci), sehingga dikategorikan praktis tidak toksik. Dari uji toksisitas subakut selama 28 hari pada tikus jantan, MAC dosis 1,6 g/kgbb/hari (setara dengan 7,5% LD50 oral) aman terhadap berbagai organ dan komponen kimia darah dan hematologi.
Data yang diperoleh dibandingkan antara sebelum dan setelah perlakuan MAC menggunakan uji t berpasangan dengan taraf kepercayaan 95%. Hasil penelitian menunjukkan bahwa MAC dosis tunggal oral 600 mg dan 750 mg serta dosis berulang 300 mg sebanyak 3 x sehari selama 5 hari dapat ditoleransi dengan baik oleh subyek sehat. Pemberian MAC tidak berpengaruh pada tanda vital, gambaran hematologi, fungsi organ hepar dan ginjal serta tidak menyebabkan kristaluria.
Acute and Subacute Toxicity Studies of Melaleuca alternifolia Concentrate (MAC) in the Laboratory Animals
Research Report (2008). Gadjah Mada University.
Nurlailaa, S. Widyarinib
a Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Gadjah Mada University, Yogyakarta, Indonesia
b Department of Clinical Pathology, Faculty of Veterinary Medicine, Gadjah Mada University, Yogyakarta, Indonesia
ABSTRACT
Objective: Melaleuca alternifolia Concentrate (MAC) is an essential oil isolated from a native Australian plant. The preparation has een approved by Australian TGA for human usen at 25% concentrationas well as by US FDA as herbal medicine. Homever, the safety of MAC has not been studied thoroughly in laboratory animals.
Methods: Non-pathogenic, male Wistar rats and domestic male rabbits were used in the studies. For the acute toxicity study in the rats, the animals were administered orally 10% MAC solution at the single dose of 0 (vehicle), 5, 10, 20, or 40 g/kgbw, whereas that in rabbits, received a single dose of 0 (vehicle), 13.3, 16.7, or 20 g/kgbw of 10% MAC solution. Toxic signs were observed for at least 24 hours and recorded in relation to dose and time. Animal dying during the observation period, as well as rats surviving to the end of the observation period were autopsied. For the subacute toxicity study in the rats, the animals were administered orally 10% MAC solution at 0 (vehicle), 1.6, 3.15, or 6.3 g/kgbw for 28 consecutive days, and 5 animals per dosing group were kept alive without the administration of MAC solution for 7 days. The animals were then sacrified for biochemical and histopathological analyses according to WHO Guidelines.
Results: LD50 value is 21 g/kg bw (Wistar rats) and 15,6 g/kgbw (rabbits), which are classified as practically non-toxic. All organ examined appear normal at the daily dose of 1,6 g/kg/day for 28 days. Intestine and liver injuries occur dose-dependently starting from 3,15 g/kg/day. Kidney function appears normal. Increase levels of SGPT and SGOT are seen in vehicle and MAC groups. All the blood constituents are normal.
Conclusion: MAC is classified practically non-toxic. All organ examined and blood constituents are normal at the daily dose.
Ringkasan: Melaleuca alternifolia Concentrate (MAC) terbukti aman/tidak toksik. Pengujian toksisitas akut dan subakut terhadap MAC yang dilakukan oleh Fakultas Farmasi UGM menunjukkan bahwa organ maupun parameter darah yang diuji menunjukkan kondisi normal pada penggunaan dosis harian sesuai rekomendasi.
Pharmacokinetics of Terpinen-4-ol in Healthy Subjects After Administration of a Single and Multiple Oral of MAC
Thesis S2, Faculty of Pharmacy (2009) Gadjah Mada University
Arifah Sri Wahyuni, Lukman Hakim, Sudibyo Martono
Faculty of Pharmacy, Gadjah Mada University
ABSTRACT
Objective: Melaleuca alternifolia Concentrate (MAC) has been reported to contain mainly terpinen-4-ol, have an antiinflammatory and antimicrobial in vitro studies found that MAC can inhibit the growth of DV 1, 2, 3 and 4 and ultimately kill the virus. Solution of 10% MAC has also been found to have oral LD50 values found in rats and rabbits are 21 and 15.6 g/kgbb respectively, which are classified as practically non-toxic. Pharmacokinetic in chicken have been found that Cmaks reach in 0,04 µg/mL plasma). The ultimate objective of the studies is to develop a standardized MAC preparation which contains a major active component terpinen-4-ol (60%) to be a phytopharmaca for the treatment of patients with dengue viral infection.
Methods: The study involves 29 healthy subjects (15 males and 14 females) who have fulfilled the inclusion criteria, and was done at Dr Sardjito Hospital, Yogyakarta following an ethical clearance released by the Faculty of Medicine, Gadjah Mada University. The subjects were allocated randomly into 3 groups of dose regimens of MAC capsules for dose safety studies (i.e. a single oral dose of 300 mg and 600 mg, and multiple oral doses of 300 mg, 3-times a day for 5 days. The determination of its major, active component (terpinen-4-ol) in serum and urine was done by a validated GC-FID method.
Results: Terpinen-4-ol in MAC is rapidly absorbed from the GI tract, and achieved satisfactory concentration in serum 15 minutes after ingestion, and maximum concentrations of 2.84 ng/ml (300 mg dose) and 5.15 ng/ml (600 mg dose) after 1- 2 hours of ingestion. Terpinen-4-ol is also widely distributed in the body with a slow elimination rate with elimination half-lives vary from 28.5 to 41.6 hours. Mean steady-state serum concentration of the compound after 300 mg MAC (3- times/day for 5 days) is 2.72 ng/ml (2.43 to 2.95 ng/ml). Terpinen-4-ol is slowly excreted into urine with average excretion rates of 177.78 ng/hour and 118.49 ng/hour after single oral doses of 300 mg and 600 mg, respectively.
Conclusion: Terpinen-4-ol in MAC is rapidly absorbed from the GI tract and widely distributed in the body with a slow elimination rate. Terpinen-4-ol excreted in an appreciable amount to inhibit the growth of micro-organisms in the urinary tract.
Ringkasan: Terpinen-4-ol dalam Melaleuca alternifolia Concentrate (MAC) diabsorbsi secara cepat dari saluran pencernaan dan mencapai konsentrasi yang memuaskan pada 15 menit setelah dikonsumsi. Terpinen-4-ol mencapai konsentrasi maksimum 2,84 ng/ml (dosis 300 mg) dan 5,15 ng/ml (dosis 600 mg) 1 – 2 jam setelah dikonsumsi. Terpinen-4-ol terdistribusi secara luas dalam tubuh dengan t1/2 eliminasi lambat berkisar antara 28,5 – 41,6 jam. Konsentrasi serum steady-state (jenuh) rata-rata untuk dosis 300 mg MAC 3 kali sehari selama 5 hari adalah 2,72 ng/ml (2,43 – 2,95 ng/ml). Terpinen-4-ol diekskresi secara lambat melalui urin dengan rata-rata kecepatan ekskresi 177,78 ng/jam untuk dosis 300 mg dan 118,49 ng/jam untuk dosis 600 mg.
Phase I Clinical Trial of Standardized Melaleuca alternifolia Concentrate (MAC) in Healthy Indonesian Subjects
Research Report (2009) Research Centre of Biotechnology. Gadjah Mada University
- Wibowo1, L. Hakim2, T. Wibawa3, D. Priyambodo4, U. Intansari5, D. K. Nugroho6, Mulyadi6, S. Kadarinah7, S. Purwaningsih8, A. S. Wahyuni9, T. Azizah9
- Clinical Pharmacology and Neurology
- Pharmacokinetics
- Microbiology
- Internal medicine
- Clinical Pathology and Immunology
- General physician
- Hospital research organizer
- Chief of nurses
- Analytical chemistry
ABSTRACT
Objective: Melaleuca alternifolia Concentrate (MAC) is an extract isolated from a native Australian plant, Melaleuca alternifolia (familia Myrtaceae). MAC shows various biology activity such as antibacterial, antifungi, antiinflammatory and antiviral activities against Herpes Simpleks. In vitro studies found that MAC can inhibit the growth of dengue strain-1,2,3 and 4 and ultimately kill the virus. MAC has been reported to contain mainly terpinen-4-ol. Solution of MAC 10% has also been found to have oral LD50 values found in rats and rabbits are 21 and 15,6 g/kg bw respectively which are classified as practically nontoxic.
Methods: A recent subacute toxicity study in rats reveals that 10% MAC solution at the oral daily dose of 1,6 g/kg bw/day (7,5% oral LD50 value) given 28 days shows a good safety in various vital organ and blood constituents. The ultimate objective of this studies is to know safety of using capsules MAC in healthy subjects are seen from parameter vital sign, haematology, blood chemistry and routine urine. The study involves 29 healthy subjects were divided into 3 groups, each group was contained 5 males and 4-5 females who have fulfilled the inclusion and exclusion criteria It was done at RSUP. Dr Sardjito Hospital, Yogyakarta following an ethical clearance release by the Faculty of Medicine, Gadjah Mada University. The subjects were allocated randomly into 3 groups of dose regimen of MAC capsules. Group I-III were given single oral dose of 600 mg and 750 mg, and multiple oral doses of 300 mg, 3-times a day for 5 days respectively.
Results: During study subject was monitored against occurring probability of side effect. The 14th days after treatment of single oral dose and the 1st day after treatment of multiple oral dose finished, some parameters such as haematology, blood chemistry and routine urine were measured. Data were compared between before and after treatment of capsules MAC using statistic paired t test with level of confidence 95%.
Conclusion: The results of this studies showed that MAC single oral dose of 600 mg and 750 mg, and multiple oral doses of 300 mg, 3-times a day for 5 days, were well tolerated by the subjects, and it is unlikely to affect vital signs, haematology, vital organs such as liver, kidney and it did not cause crystalluria.
Ringkasan: Penelitian in vitro menunjukkan bahwa Melaleuca alternifolia Concentrate (MAC) mampu menghambat pertumbuhan dan akhirnya membunuh virus dengue strain 1, 2, 3 dan 4. Senyawa utama dalam MAC adalah terpinen-4-ol. Dari segi keamanannya, MAC 10% mempunyai LD50 oral sebesar 21 g/kgbb (tikus) dan 15,6 g/kgbb (kelinci), sehingga dikategorikan praktis tidak toksik. Dari uji toksisitas subakut selama 28 hari pada tikus jantan, MAC dosis 1,6 g/kgbb/hari (setara dengan 7,5% LD50 oral) aman terhadap berbagai organ dan komponen kimia darah dan hematologi.
Data yang diperoleh dibandingkan antara sebelum dan setelah perlakuan MAC menggunakan uji t berpasangan dengan taraf kepercayaan 95%. Hasil penelitian menunjukkan bahwa MAC dosis tunggal oral 600 mg dan 750 mg serta dosis berulang 300 mg sebanyak 3 x sehari selama 5 hari dapat ditoleransi dengan baik oleh subyek sehat. Pemberian MAC tidak berpengaruh pada tanda vital, gambaran hematologi, fungsi organ hepar dan ginjal serta tidak menyebabkan kristaluria.
A Randomized, Double Blind, Placebo Controlled, Parallel Study of 150 mg and 300 mg of MAC (Melaleuca alternifolia Concentrate) as Cellular Immunity Enhancer in Healthy Subjects
Objective: To evaluate the efficacy and safety of 150 mg and 300 mg MAC as cellular immunity enhancer in comparison with…
A Randomized, Double Blind, Placebo Controlled, Parallel Study of 150 mg and 300 mg of MAC (Melaleuca alternifolia Concentrate) as Cellular Immunity Enhancer in Healthy Subjects
Clinical Study Report (2014) Equilab International
Frans D. Suyatna, Danang Agung Yunaidi
Equilab International
ABSTRACT
Objective: To evaluate the efficacy and safety of 150 mg and 300 mg MAC as cellular immunity enhancer in comparison with placebo in healthy subjects.
Methods: This study is randomized, double blind, placebo controlled, parallel study. Duration of this study is 10 weeks, with 120 subjects.
Results: After four weeks daily administration of 150 mg MAC and 300 mg MAC, the level of CD4 increased 4.7-5.1% and 0.6-3.4% from baseline respectively. A number of 0-2.5% and 0-2.9% subjects experienced the decrease of CD4 until below of lower limit of normal value (LLN) after 4 weeks daily administration of 150 mg MAC and 300 mg MAC respectively. In placebo group, it was found 0-5.7% of subjects. There was no subject (0%) had the decrease of CD8, CD19 and NK cell until below of its normal range after the treatment of both of MAC and placebo, in the other hand the level still kept in homeostatic condition during the treatment. There was no clinically difference of vital sign values before, during and after the treatment of MAC. Hematology, liver function parameter (AST, ALT), fasting blood glucose, and renal function parameter (ureum and creatinine) before and after 8 weeks of MAC supplementation still in normal range, even 2 weeks after the stopping of MAC supplementation.
Conclusion: Melaleuca alternifolia Concentrate (MAC) indicates can maintain the adequate number of lymphocyte subsets availability in healthy subjects until 4 weeks daily administration.
Ringkasan: Pada subjek sehat, Terpinen-4-ol meningkatkan CD4 dari kondisi baseline, hanya sebagian kecil subyek mengalami penurunan CD4 pada pemberian Avimac maupun pada placebo. Pemberian Avimac tidak menurunkan CD8, CD19 dan sel NK, justru menjaga agar selalu dalam kondisi homeostatis selama diberi perlakuan. Tidak ada perbedaan secara klinis pada kondisi sebelum, saat dan setelah pemberian MAC. Parameter hematologi, fungsi urin (AST, ALT), gula darah puasa, dan fungsi ginjal pada kondisi sebelum dan setelah pemberian 8 minggu Avimac masih dalam rentang normal, bahkan hingga 2 minggu setelah pemberian Avimac dihentikan.
Melaleuca alternifolia Concentrate (MAC) mampu menjaga ketersediaan limfosit dalam jumlah cukup pada subjek sehat, hingga 4 minggu pemberian Avimac.
A Randomized, Open Label, Controlled Study to Evaluate Efficacy and Tolerability of the Administration of MAC Oil as Adjuvant Treatment in Mild or Moderate COVID-19 Patients who Receive the Standard Treatment
Objective: COVID-19 has been declared a world pandemic by WHO. MAC oil capsule is a herbal medicinal product that contains the active ingredient MAC oil, which is an isolate and extract from the Melaleuca alternifolia…
Immune-boosting role of vitamins D, C, E, zinc, selenium and omega-3 fatty acids: Could they help against COVID-19?
Maturitas 143 (2021) 1–9. DOI: 10.1016/j.maturitas.2020.08.003
- Shakoora, J. Feehanb,c, A. S. Al Dhaheria, H. I. Alia, C. Platata, L. C. Ismaild, V. Apostolopoulosb, L. Stojanovskaa,b*
a College of Food and Agriculture, United Arab Emirates University, United Arab Emirates
b Institute for Health and Sport, Victoria University, Melbourne, Australia
c Department of Medicine, Western Health, The University of Melbourne, Melbourne, Australia
d College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
ABSTRACT
Objective: The world is currently in the grips of the coronavirus disease (COVID-19) pandemic, caused by the SARS-CoV-2 virus, which has mutated to allow human-to-human spread. COVID-19 affects the immune system by producing a systemic inflammatory response, or cytokine release syndrome. Patients with COVID-19 have shown a high level of pro-inflammatory cytokines and chemokines. Key dietary components such as vitamins C, D, E, zinc, selenium and the omega 3 fatty acids have well-established immunomodulatory effects, with benefits in infectious disease. Some of these nutrients have also been shown to have a potential role in the management of COVID-19.
Methods: To identify COVID-19, specific literature, title/abstract searches were conducted in the ‘PubMed,’ ‘Google Scholar’ and ‘Science Direct’ databases. Search terms included ‘COVID- 19’, ‘SARS-CoV-2’, ‘coronavirus’, ‘nutrient’, ‘vitamin’, and ‘mineral’, with filters identifying only studies published since 2020. 211 non-duplicate records were identified and underwent title and abstract screening. A total of 35 relevant studies specifically on COVID-19 and nutrition or diet components were identified. Studies were excluded based on relevance to the topic, with letters to the editor and commentaries also removed. Four published pre-prints are also discussed where relevant and are specifically identified in the manuscript. Included papers with relevant data are summarized.
Results: Adequate levels of vitamins C, D and E are crucial during COVID-19 to reduce symptom burden and lessen the duration of respiratory infection. Research also supports a role for minerals such as zinc as they have antiviral effects and may improve immune responses and suppress viral replication. Therefore, the consumption of adequate amounts of vitamins and minerals through diet is essential to ensure the proper functioning of the immune system.
Conclusion: Vitamins C, D, E, zinc, selenium and omega-3 fatty acids have a feasible role in the support of immune system and the possible benefits to those suffering from COVID-19.
Ringkasan: Covid-19 yang disebabkan oleh virus SARS-CoV-2 mempengaruhi sistem imun melalui respon inflamasi sistemik atau sindrom pelepasan sitokin. Komponen vitamin C, D, E, mineral zinc, selenium, dan omega 3 diketahui memiliki efek imunomodulator dan berperan dalam pemulihan dari Covid- 19.
Banyak penelitian menunjukkan bahwa vitamin C, D, E, mineral zinc, selenium, dan omega 3 dalam jumlah yang cukup dapat mengurangi gejala dan mempersingkat durasi infeksi saluran pernafasan. Penelitian juga membuktikan bahwa zinc memiliki efek antivirus, berpotensi meningkatkan respon imun, dan menekan replikasi virus.
Immune-boosting role of vitamins D, C, E, zinc, selenium and omega-3 fatty acids: Could they help against COVID-19?
Objective: The world is currently in the grips of the coronavirus disease (COVID-19) pandemic, caused by the SARS-CoV-2 virus, which has mutated to allow human-to-human spread. COVID-19 affects the immune system by…
Immune-boosting role of vitamins D, C, E, zinc, selenium and omega-3 fatty acids: Could they help against COVID-19?
Maturitas 143 (2021) 1–9. DOI: 10.1016/j.maturitas.2020.08.003
- Shakoora, J. Feehanb,c, A. S. Al Dhaheria, H. I. Alia, C. Platata, L. C. Ismaild, V. Apostolopoulosb, L. Stojanovskaa,b*
a College of Food and Agriculture, United Arab Emirates University, United Arab Emirates
b Institute for Health and Sport, Victoria University, Melbourne, Australia
c Department of Medicine, Western Health, The University of Melbourne, Melbourne, Australia
d College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
ABSTRACT
Objective: The world is currently in the grips of the coronavirus disease (COVID-19) pandemic, caused by the SARS-CoV-2 virus, which has mutated to allow human-to-human spread. COVID-19 affects the immune system by producing a systemic inflammatory response, or cytokine release syndrome. Patients with COVID-19 have shown a high level of pro-inflammatory cytokines and chemokines. Key dietary components such as vitamins C, D, E, zinc, selenium and the omega 3 fatty acids have well-established immunomodulatory effects, with benefits in infectious disease. Some of these nutrients have also been shown to have a potential role in the management of COVID-19.
Methods: To identify COVID-19, specific literature, title/abstract searches were conducted in the ‘PubMed,’ ‘Google Scholar’ and ‘Science Direct’ databases. Search terms included ‘COVID- 19’, ‘SARS-CoV-2’, ‘coronavirus’, ‘nutrient’, ‘vitamin’, and ‘mineral’, with filters identifying only studies published since 2020. 211 non-duplicate records were identified and underwent title and abstract screening. A total of 35 relevant studies specifically on COVID-19 and nutrition or diet components were identified. Studies were excluded based on relevance to the topic, with letters to the editor and commentaries also removed. Four published pre-prints are also discussed where relevant and are specifically identified in the manuscript. Included papers with relevant data are summarized.
Results: Adequate levels of vitamins C, D and E are crucial during COVID-19 to reduce symptom burden and lessen the duration of respiratory infection. Research also supports a role for minerals such as zinc as they have antiviral effects and may improve immune responses and suppress viral replication. Therefore, the consumption of adequate amounts of vitamins and minerals through diet is essential to ensure the proper functioning of the immune system.
Conclusion: Vitamins C, D, E, zinc, selenium and omega-3 fatty acids have a feasible role in the support of immune system and the possible benefits to those suffering from COVID-19.
Ringkasan: Covid-19 yang disebabkan oleh virus SARS-CoV-2 mempengaruhi sistem imun melalui respon inflamasi sistemik atau sindrom pelepasan sitokin. Komponen vitamin C, D, E, mineral zinc, selenium, dan omega 3 diketahui memiliki efek imunomodulator dan berperan dalam pemulihan dari Covid- 19.
Banyak penelitian menunjukkan bahwa vitamin C, D, E, mineral zinc, selenium, dan omega 3 dalam jumlah yang cukup dapat mengurangi gejala dan mempersingkat durasi infeksi saluran pernafasan. Penelitian juga membuktikan bahwa zinc memiliki efek antivirus, berpotensi meningkatkan respon imun, dan menekan replikasi virus.
A Randomized, Double Blind, Placebo Controlled, Parallel Study of 150 mg and 300 mg of MAC (Melaleuca alternifolia Concentrate) as Cellular Immunity Enhancer in Healthy Subjects
Clinical Study Report (2014) Equilab International
Frans D. Suyatna, Danang Agung Yunaidi
Equilab International
ABSTRACT
Objective: To evaluate the efficacy and safety of 150 mg and 300 mg MAC as cellular immunity enhancer in comparison with placebo in healthy subjects.
Methods: This study is randomized, double blind, placebo controlled, parallel study. Duration of this study is 10 weeks, with 120 subjects.
Results: After four weeks daily administration of 150 mg MAC and 300 mg MAC, the level of CD4 increased 4.7-5.1% and 0.6-3.4% from baseline respectively. A number of 0-2.5% and 0-2.9% subjects experienced the decrease of CD4 until below of lower limit of normal value (LLN) after 4 weeks daily administration of 150 mg MAC and 300 mg MAC respectively. In placebo group, it was found 0-5.7% of subjects. There was no subject (0%) had the decrease of CD8, CD19 and NK cell until below of its normal range after the treatment of both of MAC and placebo, in the other hand the level still kept in homeostatic condition during the treatment. There was no clinically difference of vital sign values before, during and after the treatment of MAC. Hematology, liver function parameter (AST, ALT), fasting blood glucose, and renal function parameter (ureum and creatinine) before and after 8 weeks of MAC supplementation still in normal range, even 2 weeks after the stopping of MAC supplementation.
Conclusion: Melaleuca alternifolia Concentrate (MAC) indicates can maintain the adequate number of lymphocyte subsets availability in healthy subjects until 4 weeks daily administration.
Ringkasan: Pada subjek sehat, Terpinen-4-ol meningkatkan CD4 dari kondisi baseline, hanya sebagian kecil subyek mengalami penurunan CD4 pada pemberian Avimac maupun pada placebo. Pemberian Avimac tidak menurunkan CD8, CD19 dan sel NK, justru menjaga agar selalu dalam kondisi homeostatis selama diberi perlakuan. Tidak ada perbedaan secara klinis pada kondisi sebelum, saat dan setelah pemberian MAC. Parameter hematologi, fungsi urin (AST, ALT), gula darah puasa, dan fungsi ginjal pada kondisi sebelum dan setelah pemberian 8 minggu Avimac masih dalam rentang normal, bahkan hingga 2 minggu setelah pemberian Avimac dihentikan.
Melaleuca alternifolia Concentrate (MAC) mampu menjaga ketersediaan limfosit dalam jumlah cukup pada subjek sehat, hingga 4 minggu pemberian Avimac.
Immune-boosting role of vitamins D, C, E, zinc, selenium and omega-3 fatty acids: Could they help against COVID-19?
Maturitas 143 (2021) 1–9. DOI: 10.1016/j.maturitas.2020.08.003
- Shakoora, J. Feehanb,c, A. S. Al Dhaheria, H. I. Alia, C. Platata, L. C. Ismaild, V. Apostolopoulosb, L. Stojanovskaa,b*
a College of Food and Agriculture, United Arab Emirates University, United Arab Emirates
b Institute for Health and Sport, Victoria University, Melbourne, Australia
c Department of Medicine, Western Health, The University of Melbourne, Melbourne, Australia
d College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
ABSTRACT
Objective: The world is currently in the grips of the coronavirus disease (COVID-19) pandemic, caused by the SARS-CoV-2 virus, which has mutated to allow human-to-human spread. COVID-19 affects the immune system by producing a systemic inflammatory response, or cytokine release syndrome. Patients with COVID-19 have shown a high level of pro-inflammatory cytokines and chemokines. Key dietary components such as vitamins C, D, E, zinc, selenium and the omega 3 fatty acids have well-established immunomodulatory effects, with benefits in infectious disease. Some of these nutrients have also been shown to have a potential role in the management of COVID-19.
Methods: To identify COVID-19, specific literature, title/abstract searches were conducted in the ‘PubMed,’ ‘Google Scholar’ and ‘Science Direct’ databases. Search terms included ‘COVID- 19’, ‘SARS-CoV-2’, ‘coronavirus’, ‘nutrient’, ‘vitamin’, and ‘mineral’, with filters identifying only studies published since 2020. 211 non-duplicate records were identified and underwent title and abstract screening. A total of 35 relevant studies specifically on COVID-19 and nutrition or diet components were identified. Studies were excluded based on relevance to the topic, with letters to the editor and commentaries also removed. Four published pre-prints are also discussed where relevant and are specifically identified in the manuscript. Included papers with relevant data are summarized.
Results: Adequate levels of vitamins C, D and E are crucial during COVID-19 to reduce symptom burden and lessen the duration of respiratory infection. Research also supports a role for minerals such as zinc as they have antiviral effects and may improve immune responses and suppress viral replication. Therefore, the consumption of adequate amounts of vitamins and minerals through diet is essential to ensure the proper functioning of the immune system.
Conclusion: Vitamins C, D, E, zinc, selenium and omega-3 fatty acids have a feasible role in the support of immune system and the possible benefits to those suffering from COVID-19.
Ringkasan: Covid-19 yang disebabkan oleh virus SARS-CoV-2 mempengaruhi sistem imun melalui respon inflamasi sistemik atau sindrom pelepasan sitokin. Komponen vitamin C, D, E, mineral zinc, selenium, dan omega 3 diketahui memiliki efek imunomodulator dan berperan dalam pemulihan dari Covid- 19.
Banyak penelitian menunjukkan bahwa vitamin C, D, E, mineral zinc, selenium, dan omega 3 dalam jumlah yang cukup dapat mengurangi gejala dan mempersingkat durasi infeksi saluran pernafasan. Penelitian juga membuktikan bahwa zinc memiliki efek antivirus, berpotensi meningkatkan respon imun, dan menekan replikasi virus.
Immune-boosting role of vitamins D, C, E, zinc, selenium and omega-3 fatty acids: Could they help against COVID-19?
Maturitas 143 (2021) 1–9. DOI: 10.1016/j.maturitas.2020.08.003
- Shakoora, J. Feehanb,c, A. S. Al Dhaheria, H. I. Alia, C. Platata, L. C. Ismaild, V. Apostolopoulosb, L. Stojanovskaa,b*
a College of Food and Agriculture, United Arab Emirates University, United Arab Emirates
b Institute for Health and Sport, Victoria University, Melbourne, Australia
c Department of Medicine, Western Health, The University of Melbourne, Melbourne, Australia
d College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
ABSTRACT
Objective: The world is currently in the grips of the coronavirus disease (COVID-19) pandemic, caused by the SARS-CoV-2 virus, which has mutated to allow human-to-human spread. COVID-19 affects the immune system by producing a systemic inflammatory response, or cytokine release syndrome. Patients with COVID-19 have shown a high level of pro-inflammatory cytokines and chemokines. Key dietary components such as vitamins C, D, E, zinc, selenium and the omega 3 fatty acids have well-established immunomodulatory effects, with benefits in infectious disease. Some of these nutrients have also been shown to have a potential role in the management of COVID-19.
Methods: To identify COVID-19, specific literature, title/abstract searches were conducted in the ‘PubMed,’ ‘Google Scholar’ and ‘Science Direct’ databases. Search terms included ‘COVID- 19’, ‘SARS-CoV-2’, ‘coronavirus’, ‘nutrient’, ‘vitamin’, and ‘mineral’, with filters identifying only studies published since 2020. 211 non-duplicate records were identified and underwent title and abstract screening. A total of 35 relevant studies specifically on COVID-19 and nutrition or diet components were identified. Studies were excluded based on relevance to the topic, with letters to the editor and commentaries also removed. Four published pre-prints are also discussed where relevant and are specifically identified in the manuscript. Included papers with relevant data are summarized.
Results: Adequate levels of vitamins C, D and E are crucial during COVID-19 to reduce symptom burden and lessen the duration of respiratory infection. Research also supports a role for minerals such as zinc as they have antiviral effects and may improve immune responses and suppress viral replication. Therefore, the consumption of adequate amounts of vitamins and minerals through diet is essential to ensure the proper functioning of the immune system.
Conclusion: Vitamins C, D, E, zinc, selenium and omega-3 fatty acids have a feasible role in the support of immune system and the possible benefits to those suffering from COVID-19.
Ringkasan: Covid-19 yang disebabkan oleh virus SARS-CoV-2 mempengaruhi sistem imun melalui respon inflamasi sistemik atau sindrom pelepasan sitokin. Komponen vitamin C, D, E, mineral zinc, selenium, dan omega 3 diketahui memiliki efek imunomodulator dan berperan dalam pemulihan dari Covid- 19.
Banyak penelitian menunjukkan bahwa vitamin C, D, E, mineral zinc, selenium, dan omega 3 dalam jumlah yang cukup dapat mengurangi gejala dan mempersingkat durasi infeksi saluran pernafasan. Penelitian juga membuktikan bahwa zinc memiliki efek antivirus, berpotensi meningkatkan respon imun, dan menekan replikasi virus.