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1 Chinese Natural Medicines and Tuberculosis WENHONG ZHANG YING ZHANG

2 Outline Introduction to Chinese natural medicine Chinese natural medicine and tuberculosis Chinese natural medicine and HDT of tuberculosis

3 Traditional Chinese Medicine Traditional Chinese Medicine is based on Yin-Yang and the five element theory (metal, wood, water, fire and earth). Explain human body s physiology, pathology, diagnosis, prevention and cure Herbal medicine, acupuncture, Tui Na, Qigong ---Regulate Yin- Yang ---> balance

The ingredients work in harmony to help a person s body Drug combo

5 Chinese Natural Herbs Herbs are a vital part of Chinese healing. Each ingredient has unique characteristics (pathogen or host). The ingredients work in harmony to help a person s body Drug combo Herbs can help boost Qi and balance Yin/Yang. Some Chinese herbs can be purchased in the US.

6 Modernization of TCM Traditional Chinese Medicine has been to some degree modernized by transforming the plants and ingredients to soluble granules and tablets. Modern formulations in pills and sachets Investigation of the active ingredients in TCM has produced: Artemisinin ( 青蒿素 ), which is now widely used in treatment of malaria ( 疟疾 ).

8 Out line Chinese natural medicine Chinese natural medicine and tuberculosis Chinese natural medicine and HDT of tuberculosis

9 Tong, Y., Jia, Q., & Sun, Y. (2009). A renal tuberculosis case: could Chinese medicine play a role?. The Journal of Alternative and Complementary Medicine, 15(8),

10 Compound preparations of Chinese herbs used in TB treatment Medication 肺泰胶囊肺痨宁合剂抗痨胶囊肺痨康 Ingredient 苦荬菜黄芩百部枇杷叶栝楼川贝母北沙参太子参南沙参生地黄熟地黄玄参麦冬黄精五昧子当归白芍牡丹皮女贞子茯苓黄芪陈皮甘草矮地茶百部穿破石五指毛桃白及桑白皮蒸百部白及天冬川贝紫河车 [1] 郭晓燕, 张惠勇. 中医药治疗耐药肺结核的研究进展 [J]. 时珍国医国药,2010,21(8):

11 Clinical trials of Chinese traditional medicine regimens in the treatment of TB Medication Combined replenishing qi to nourish yin methods, eliminating blood stasis method[1] Year Sample size Control group 3DThLAZ/ 15DTh Treated group Chinese herbs added Followup time (month) Sputum negative conversion rate % vs 56.3% Effective rate of chest X ray 73.5% vs 53.1% Ingredient 太子参, 玄参, 南沙参, 黄芪, 车前草, 胡颓叶, 海蛤壳, 款冬花, 黄芩, 丹参, 百部二冬琼玉汤 [2] HREZ/4 HR Chinese herbs added 3 56% vs 38% 72% vs 48% 天门冬麦门冬南沙参生地黄太子参黄芪五昧子百合山萸肉阿胶山药蜂蜜茯苓甘草加减保真汤 [3] H 3 R 3 Z 3 E 3 Chinese herbs added % vs.75.0% 86.5% vs 50.0% 鱼腥草山药茯苓, 生地黄丹参知母百部, 麦冬党参黄芪白术赤芍柴胡黄柏, 甘草五味子 Xiaoshui Powder[4] HREZ Xiaoshui Powder added 2 Hydrothorax disappearance time (26.0±3.8) vs (42.0±1.2) day 76.0% vs 20.9% 生黄芪丹参茯苓党参枸杞子夏枯草甘草泽泻车前子桃仁生白术北沙参葶苈子生薏苡仁百部桂枝猪苓当归 [1] 张晔敏, 鹿振辉, 郭晓燕等. 益气滋阴行瘀抗痨法联合化疗长疗程治疗耐多药肺结核的随机对照临床研究 [J]. 上海中医药杂志,2012,46(9):44-46 [2] 逄金岐, 李同霞. 二冬琼玉汤加减辅助治疗初期肺结核的临床观察 [J]. 中国中西医结合杂志,2008,28(9): [3] 郝小萍, 杜雨华, 杜正新等. 加减保真汤配合抗痨强化期治疗复治菌阳肺结核 37 例临床观察 [J]. 中国中西医结合杂志,2007,27(5): [4] 荣学东, 刘伟娟, 郭新美. 消水散辅助治疗结核性胸腔残余积液疗效观察. 中国中西医结合杂志,2007,27(10);

12 Outline Chinese natural medicine Chinese natural medicine and tuberculosis Chinese natural medicine and HDT of tuberculosis

13 COMMONLY USED HERBS Ranunculus ternatus 猫抓草 Prunella vulgaris 夏枯草 Stemona sessilifolia 百部 Euphorbia fischeriana 狼毒 Allium sativum 大蒜 Sophora flavescens 苦参

14 Astragala 黄芪 Liquorice 甘草 Curcuma 姜科植物与姜黄 Anemarrhena asphodeloides 知母花与知母

15 Herb Effective component Effect on bacteria Effect on human body Ternatolide Induction of GLS expression and bactericidal activity Ranunculus ternatus Sophora flavescens Allium sativum Matrine Allicin Bactericidal activity Inhibition of DNA replication and protein synthesis of M. tuberculosis to exert bactericidal effect Coptidis Rhizoma Berberine Bacteriostasis Euphorbia fischeriana Fischeriana A and B Bacteriostasis Ottelia alismoides Humulus lupulus Anemone chinensis Herbs with antibacterial and immune regulatory effect Hunmulone and lupulone Bacteriostasis or bactericidal effect Bacteriostasis Bacteriostasis Enhanced function of cytotoxic T lymphocyte Immunity enhancement, anti inflammation and hepatoprotective effect Hepatoprotective effect Immunity enhancement and hepatoprotective effect Cordyceps sinensis Adenosine, aspartic acid et al and multivitamins Immunity enhancement and symptom alleviation Astragala Salvia miltiorrhiza [1] 刘秋琼, 高玉桥. 中药治疗肺结核的研究进展 [J]. 中药材,2007,30(11): [2] 邓郡, 曾建国, 欧艳. 中成药治疗结核病概况 [J]. 湖南中医杂志,2011,27(3): Promotion of T cell proliferation and regulation of the immunity Decrease of the level of endothelium 1(ET 1) and nitric oxide(no)

16 extracts of Radix Ranunculi Ternati( 猫爪草 ), Radix Sophorae Flavescentis( 苦参 ), Prunella Vulgaris L.( 夏枯草 )and Stellera Chamaejasme L( 狼毒 )are capable of enhancing cell mediated immunity in rats by upregulating gene transcription Lu, J., Ye, S., Qin, R., Deng, Y., & Li, C. P. (2013). Effect of Chinese herbal medicine extracts on cell mediated immunity in a rat model of tuberculosis induced by multiple drug resistant bacilli. Molecular medicine reports, 8(1),

17 Lu, J., Ye, S., Qin, R., Deng, Y., & Li, C. P. (2013). Effect of Chinese herbal medicine extracts on cell mediated immunity in a rat model of tuberculosis induced by multiple drug resistant bacilli. Molecular medicine reports, 8(1),

18 Xu, H. D., You, C. G., Zhang, R. L., Gao, P., & Wang, Z. R. (2007). Effects of Astragalus polysaccharides and astragalosides on the phagocytosis of Mycobacterium tuberculosis by macrophages. Journal of international medical research, 35(1),

19 Autophagy: Therapeutic Target for Tuberculosis Autophagy is initiated by the nucleation of an isolation membrane (phagophore). The phagophore elongates and closes on itself to form an autophagosome. Fusionofanautophagosome with a lysosome forms an autolysosome and, where the acid hydrolases in the lysosome, breaks down the inner membrane and cytoplasmic contents. During Mycobacterium tuberculosis infection, autophagy represents not only an antimicrobial mechanism for the clearance of the intracellular pathogen, but also prevents excessive inflammation, avoiding the adverse effects on host. Li W, He J, Xie L, Chen T, Xie J. Cell Physiol Biochem. 2013;31(1):

Curcumin, a natural compound derived from the curry spice with low toxicity in normal cells, could efficiently reduce the accumulation of A53T α

20 Curcumin, a natural compound derived from the curry spice with low toxicity in normal cells, could efficiently reduce the accumulation of A53T α synuclein through downregulation of the mtor/p70s6k signaling and recovery of autophagy which was suppressed. J Neuroimmune Pharmacol (2013) 8:

21 Curcumin plus ADM led to mitochondrial fragmentation, reduction of mitochondrial membrane potential, as well as activation of autophagy. These findings suggest the combined treatment of curcumin with ADM might be an optional chemotherapeutic method for HCC. European Journal of Pharmaceutical Sciences 43 (2011)

Real time quantitative RT PCR revealed that the expression levels of Bax gene, an apoptosis related molecule, and Beclin 1 gene which plays a key role in autophagy were higher in matrine

22 Real time quantitative RT PCR revealed that the expression levels of Bax gene, an apoptosis related molecule, and Beclin 1 gene which plays a key role in autophagy were higher in matrine treatment group than in control group, indicating that Beclin 1 is involved in matrine induced autophagy and the pro apoptotic mechanism. World J Gastroenterol 2010 September 14; 16(34):

23 Bactericidal Effect of Chinese Natural Medicine

24 Friis Møller, A., Chen, M., Fuursted, K., Christensen, S. B., & Kharazmi, A. (2002). In vitro antimycobacterial and antilegionella activity of licochalcone A from Chinese licorice roots. Planta medica, 68(05),

25 CONCLUSIONS /FUTURE DIRECTIONS Efforts are underway to eradicate TB from both Drugs (Yang) and Host (Yin): Chinese Natural Medicine as a potential source for developing new agents against TB Some herbal regimens appear to work alone or improve TB therapy, further evaluation needed Mechanisms of HDT against TB complex, some herbs determined; More HDT mechanisms associated with Chinese Natural Medicine remains to be uncovered. Insights may help develop effective treatment against TB.

Microsoft Word - 360145.doc

Microsoft Word - 360145.doc 项目批准号 81273814 归口管理部门申请代码收件日期 H2716 360145 y 国家自然科学基金委员会资助项目计划书资助类别 : 面上项目亚类说明 : 非连续资助类项目附注说明 : 项目名称 : 益气养肺法拮抗 bfgf 对肺癌微环境介导化疗