期刊首页 优先出版 当期阅读 过刊浏览 作者中心 关于期刊 English

《工程(英文)》 >> 2020年 第6卷 第10期 doi: 10.1016/j.eng.2020.08.009

中药治疗新冠病毒肺炎的科学基础

State Key Laboratory of Quality Research in Chinese Medicine & Macau Institute for Applied Research in Medicine and Health & Faculty of Chinese Medicine, Macau University of Science and Technology, Macao 999078, China

收稿日期: 2020-04-13 修回日期: 2020-07-15 录用日期: 2020-08-10 发布日期: 2020-09-05

下一篇 上一篇

摘要

新近暴发的新冠病毒肺炎(COVID-19)已成为危害全球健康的紧急事件。现有证据表明,新冠病毒(SARS-CoV-2)与其他冠状病毒(如SARS-CoV和MERS-CoV)的基因序列具有相似性。因此, 针对现存冠状病毒的引发疾病的机制研究和在治疗SARS时所取得的经验和教训,可咨今天对抗新冠病毒引发疾病的参考。COVID-19患者的临床病理特征提示患者在病情进展过程中通常会经历五个发展阶段:大量病毒感染、免疫系统抑制、细胞因子风暴、多器官损伤及后期的肺纤维化样改变, 严重者常导致死亡。早期阻断疾病进展是取得治疗成功的关键。但是,目前尚无针对COVID-19的 特效药物或疫苗,世界卫生组织(WHO)正敦促尽快建立新型预防和治疗策略。传统中医药(TCM) 对于疫病的防治的实践已经积累了几千年的有用经验,它通过整体调节机体功能发挥疗效。在此次疫情中,中医药作为替代治疗或与西药联合使用,在疫情防控中发挥了重要的作用。本文总结了此次抗疫过程中中国国家和省级机构推荐使用的中药复方和中成药的潜在用途和治疗机制,以期发现其治疗COVID-19的潜在科学内涵。同时,整合应用多种组学及转化医学技术开展基础与临床研究有望进一步证实中药复方的治疗机制。

图片

图1

图2

参考文献

[ 1 ] Guan W, Ni Z, Hu Y, Liang W, Ou C, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382(18):1708–20. 链接1

[ 2 ] Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395(10229):1054–62. 链接1

[ 3 ] World Health Organization. Coronavirus disease 2019 (COVID-19) situation report—33. Geneva: World Health Organization; 2020. 链接1

[ 4 ] Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 2020;382(8):727–33. 链接1

[ 5 ] National Health Commission of the People’s Republic of China, State Administration of Traditional Chinese Medicine. Diagnosis and treatment protocol for novel coronavirus pneumonia (trial version 7) [Internet]. Beijing: National Health Commission of the People’s Republic of China; 2020 Mar 3 [cited 2020 Mar 3]. Available from: http://www.nhc.gov.cn/yzygj/s7653p/ 202003/46c9294a7dfe4cef80dc7f5912eb1989/files/ce3e6945832a438eaae415 350a8ce964.pdf. Chinese. 链接1

[ 6 ] Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, et al. A new coronavirus associated with human respiratory disease in China. Nature 2020;579 (7798):265–9. 链接1

[ 7 ] Jiang S, Xia S, Ying T, Lu L. A novel coronavirus (2019-nCoV) causing pneumonia-associated respiratory syndrome. Cell Mol Immunol 2020;17 (5):554. 链接1

[ 8 ] Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterization and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020;395(10224):565–74. 链接1

[ 9 ] Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020;579(7798):270–3. 链接1

[10] Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med 2005;11(8):875–9. 链接1

[11] Ferrario CM, Jessup J, Chappell MC, Averill DB, Brosnihan KB, Tallant EA, et al. Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2. Circulation 2005;111 (20):2605–10. 链接1

[12] Hamming I, Cooper ME, Haagmans BL, Hooper NM, Korstanje R, Osterhaus AD, et al. The emerging role of ACE2 in physiology and disease. J Pathol 2007;212 (1):1–11. 链接1

[13] Ziegler CGK, Allon SJ, Nyquist SK, Mbano IM, Miao VN, Tzouanas CN, et al. SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues. Cell 2020;181(5):1016–35. 链接1

[14] Gembardt F, Sterner-Kock A, Imboden H, Spalteholz M, Reibitz F, Schultheiss HP, et al. Organ-specific distribution of ACE2 mRNA and correlating peptidase activity in rodents. Peptides 2005;26(7):1270–7. 链接1

[15] Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020;181(2):271–80. 链接1

[16] Kuba K, Imai Y, Ohto-Nakanishi T, Penninger JM. Trilogy of ACE2: a peptidase in the renin-angiotensin system, a SARS receptor, and a partner for amino acid transporters. Pharmacol Ther 2010;128(1):119–28. 链接1

[17] Rolling updates on coronavirus disease (COVID-19) [Internet]. Geneva: World Health Organization; c2020 [updated 2020 Jul 31; cited 2020 Jul 3]. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/ events-as-they-happen.

[18] Liang W, Guan W, Chen R, Wang W, Li J, Xu K, et al. Cancer patients in SARSCoV-2 infection: a nationwide analysis in China. Lancet Oncol 2020;21 (3):335–7. 链接1

[19] Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020;395(10229):1033–4. 链接1

[20] Rismanbaf A, Zarei S. Liver and kidney injuries in COVID-19 and their effects on drug therapy; a letter to editor. Arch Acad Emerg Med 2020;8(1):e17. 链接1

[21] Jiang WY. Therapeutic wisdom in traditional Chinese medicine: a perspective from modern science. Trends Pharmacol Sci 2005;26(11):558–63. 链接1

[22] Yuan R, Lin Y. Traditional Chinese medicine: an approach to scientific proof and clinical validation. Pharmacol Ther 2000;86(2):191–8. 链接1

[23] Hao PP, Jiang F, Chen YG, Yang J, Zhang K, Zhang MX, et al. Traditional Chinese medication for cardiovascular disease. Nat Rev Cardiol 2015;12(2):115–22. 链接1

[24] Seong RK, Kim JA, Shin OS. Wogonin, a flavonoid isolated from Scutellaria baicalensis, has anti-viral activities against influenza infection via modulation of AMPK pathways. Acta Virol 2018;62(1):78–85. 链接1

[25] Chu M, Xu L, Zhang M, Chu Z, Wang Y. Role of Baicalin in anti-influenza virus A as a potent inducer of IFN-c. BioMed Res Int 2015;2015:263630. 链接1

[26] Wei W, Du H, Shao C, Zhou H, Lu Y, Yu L, et al. Screening of antiviral components of Ma Huang Tang and investigation on the ephedra alkaloids efficacy on influenza virus type A. Front Pharmacol 2019;10:961. 链接1

[27] Yu Y, Zhang Y, Wang S, Liu W, Hao C, Wang W. Inhibition effects of patchouli alcohol against influenza a virus through targeting cellular PI3K/Akt and ERK/ MAPK signaling pathways. Virol J 2019;16(1):163. 链接1

[28] Lau KM, Lee KM, Koon CM, Cheung CSF, Lau CP, Ho HM, et al. Immunomodulatory and anti-SARS activities of Houttuynia cordata. J Ethnopharmacol 2008;118(1):79–85. 链接1

[29] Zhang D, Zhang B, Lv JT, Sa RN, Zhang XM, Lin ZJ. The clinical benefits of Chinese patent medicines against COVID-19 based on current evidence. Pharmacoll Res 2020;157:104882. 链接1

[30] Deng Y, Liu B, He Z, Liu T, Zheng R, Yang A, et al. Study on active compounds from Huoxiang Zhengqi Oral Liquid for prevention of coronavirus disease 2019 (COVID-19) based on network pharmacology and molecular docking. Chin Tradit Herbal Drugs 2020;51(5):1113–22. 链接1

[31] Jo S, Kim S, Shin DH, Kim MS. Inhibition of SARS-CoV 3CL protease by flavonoids. J Enzyme Inhib Med Chem 2020;35(1):145–51. 链接1

[32] Li R, Hou Y, Huang J, Pan W, Ma Q, Shi Y, et al. Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2). Pharmacol Res 2020;156:104761. 链接1

[33] Kao ST, Liu CJ, Yeh CC. Protective and immunomodulatory effect of flos Lonicerae japonicae by augmenting IL-10 expression in a murine model of acute lung inflammation. J Ethnopharmacol 2015;168:108–15. 链接1

[34] Tao W, Su Q, Wang H, Guo S, Chen Y, Duan J, et al. Platycodin D attenuates acute lung injury by suppressing apoptosis and inflammation in vivo and in vitro. Int Immunopharmacol 2015;27(1):138–47. 链接1

[35] Fu PK, Yang CY, Tsai TH, Hsieh CL. Moutan cortex radicis improves lipopolysaccharide-induced acute lung injury in rats through antiinflammation. Phytomedicine 2012;19(13):1206–15. 链接1

[36] Hu M, Liu Y, Wang L, Wang J, Li L, Wu C. Purification, characterization of two polysaccharides from Pinelliae Rhizoma Praeparatum cum Alumine and their anti-inflammatory effects on mucus secretion of airway epithelium. Int J Mol Sci 2019;20(14):3553. 链接1

[37] Xu Y, Ming TW, Gaun TKW, Wang S, Ye B. A comparative assessment of acute oral toxicity and traditional pharmacological activities between extracts of Fritillaria cirrhosae Bulbus and Fritillaria pallidiflora Bulbus. J Ethnopharmacol 2019;238:111853. 链接1

[38] Yu P, Cheng S, Xiang J, Yu B, Zhang M, Zhang C, et al. Expectorant, antitussive, anti-inflammatory activities and compositional analysis of Aster tataricus. J Ethnopharmacol 2015;164:328–33. 链接1

[39] Yu X, Tang L, Wu H, Zhang X, Luo H, Guo R, et al. Trichosanthis Fructus: botany, traditional uses, phytochemistry and pharmacology. J Ethnopharmacol 2018;224:177–94. 链接1

[40] Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020;323(11):1061–9. 链接1

[41] Szodoray P, Nakken B, Barath S, Csipo I, Nagy G, El-Hage F, et al. Altered Th17 cells and Th17/regulatory T-cell ratios indicate the subsequent conversion from undifferentiated connective tissue disease to definitive systemic autoimmune disorders. Hum Immunol 2013;74(12):1510–8. 链接1

[42] Peng S, Hang N, Liu W, Guo W, Jiang C, Yang X, et al. Andrographolide sulfonate ameliorates lipopolysaccharide-induced acute lung injury in mice by downregulating MAPK and NF-jB pathways. Acta Pharm Sin B 2016;6(3):205–11. 链接1

[43] Song Y, Yao C, Yao Y, Han H, Zhao X, Yu K, et al. XueBiJing injection versus placebo for critically III patients with severe community-acquired pneumonia: a randomized controlled trial. Crit Care Med 2019;47(9):e735–43. 链接1

[44] Chen Y, Nie Y, Luo Y, Lin F, Zheng Y, Cheng G, et al. Protective effects of naringin against paraquat-induced acute lung injury and pulmonary fibrosis in mice. Food Chem Toxicol 2013;58:133–40. 链接1

[45] Cui W, Li L, Li D, Mo X, Zhou W, Zhang Z, et al. Total glycosides of Yupingfeng protects against bleomycin-induced pulmonary fibrosis in rats associated with reduced high mobility group box 1 activation and epithelial-mesenchymal transition. Inflamm Res 2015;64(12):953–61. 链接1

[46] Xia H, Diebold D, Nho R, Perlman D, Kleidon J, Kahm J, et al. Pathological integrin signaling enhances proliferation of primary lung fibroblasts from patients with idiopathic pulmonary fibrosis. J Exp Med 2008;205(7):1659–72. 链接1

[47] Stewart AG, Thomas B, Koff J. TGF-b: master regulator of inflammation and fibrosis. Respirology 2018;23(12):1096–7. 链接1

[48] Somogyi V, Chaudhuri N, Torrisi SE, Kahn N, Müller V, Kreuter M. The therapy of idiopathic pulmonary fibrosis: what is next? Eur Respir Rev 2019;28 (153):190021. 链接1

[49] Li L, Li D, Xu L, Zhao P, Deng Z, Mo X, et al. Total extract of Yupingfeng attenuates bleomycin-induced pulmonary fibrosis in rats. Phytomedicine 2015;22(1):111–9. 链接1

[50] Wu H, Li Y, Wang Y, Xu D, Li C, Liu M, et al. Tanshinone IIA attenuates bleomycin-induced pulmonary fibrosis via modulating angiotensinconverting enzyme 2/angiotensin-(1–7) axis in rats. Int J Med Sci 2014;11 (6):578–86. 链接1

[51] Dong J, Ma Q. Osteopontin enhances multi-walled carbon nanotube-triggered lung fibrosis by promoting TGF-b1 activation and myofibroblast differentiation. Part Fibre Toxicol 2017;14(1):18. 链接1

[52] Chiang CK, Sheu ML, Lin YW, Wu CT, Yang CC, Chen MW, et al. Honokiol ameliorates renal fibrosis by inhibiting extracellular matrix and proinflammatory factors in vivo and in vitro. Br J Pharmacol 2011;163 (3):586–97. 链接1

[53] Weng TI, Wu HY, Kuo CW, Liu SH. Honokiol rescues sepsis-associated acute lung injury and lethality via the inhibition of oxidative stress and inflammation. Intensive Care Med 2011;37(3):533–41. 链接1

[54] Huang YF, Bai C, He F, Xie Y, Zhou H. Review on the potential action mechanisms of Chinese medicines in treating coronavirus disease 2019 (COVID-19). Pharmacol Res 2020;158:104939. 链接1

[55] Wang WY, Xie Y, Zhou H, Liu L. Contribution of traditional Chinese medicine to the treatment of COVID-19. Phytomedicine 2020. In press.

[56] Kiemer L, Lund O, Brunak S, Blom N. Coronavirus 3CLpro proteinase cleavage sites: possible relevance to SARS virus pathology. BMC Bioinf 2004;5(1):72. 链接1

[57] Thiel V, Ivanov KA, Putics Á, Hertzig T, Schelle B, Bayer S, et al. Mechanisms and enzymes involved in SARS coronavirus genome expression. J Gen Virol 2003;84(9):2305–15. 链接1

[58] Li G, De Clercq E. Therapeutic options for the 2019 novel coronavirus (2019- nCoV). Nat Rev Drug Discov 2020;19(3):149–50. 链接1

[59] Hao P, Jiang F, Cheng J, Ma L, Zhang Y, Zhao Y. Traditional Chinese medicine for cardiovascular disease: evidence and potential mechanisms. J Am Coll Cardiol 2017;69(24):2952–66. 链接1

[60] Wan S, Yi Q, Fan S, Lv J, Zhang X, Guo L, et al. Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP). 2020. medRxiv:2020.02.10.20021832.

[61] Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395 (10223):497–506. 链接1

[62] Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med 2020;46(5):846–8. 链接1

[63] Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;395(10223):507–13. 链接1

[64] Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med 2020;180 (7):1–11. 链接1

[65] Zhang W, Zhao Y, Zhang F, Wang Q, Li T, Liu Z, et al. The use of antiinflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): the perspectives of clinical immunologists from China. Clin Immunol 2020;214:108393. 链接1

[66] Ware LB. Pathophysiology of acute respiratory distress syndrome. In: Webb A, Angus D, Finfer S, Gattinoni L, Singer M, editors. Oxford textbook of critical care. Oxford: Oxford University Press; 2016. p. 497–500. 链接1

[67] Chai X, Hu L, Zhang Y, Han W, Lu Z, Ke A, et al. Specific ACE2 expression in cholangiocytes may cause liver damage after 2019-nCoV infection. 2020. bioRxiv:2020.02.03.931766.

[68] Xu YH, Dong JH, An WM, Lv XY, Yin XP, Zhang JZ, et al. Clinical and computed tomographic imaging features of novel coronavirus pneumonia caused by SARS-CoV-2. J Infect 2020;80(4):394–400. 链接1

[69] Yuen MF, Tam S, Fung J, Wong DKH, Wong BCY, Lai CL. Traditional Chinese medicine causing hepatotoxicity in patients with chronic hepatitis B infection: a 1-year prospective study. Aliment Pharmacol Ther 2006;24(8):1179–86. 链接1

[70] Kam PC, Liew S. Traditional Chinese herbal medicine and anaesthesia. Anaesthesia 2002;57(11):1083–9. 链接1

[71] McLean-Tooke A, Moore I, Lake F. Idiopathic and immune-related pulmonary fibrosis: diagnostic and therapeutic challenges. Clin Transl Immunol 2019;8 (11):e1086. 链接1

[72] Otoupalova E, Smith S, Cheng G, Thannickal VJ. Oxidative stress in pulmonary fibrosis. Compr Physiol 2020;10(2):509–47. 链接1

[73] Divya T, Dineshbabu V, Soumyakrishnan S, Sureshkumar A, Sudhandiran G. Celastrol enhances Nrf2 mediated antioxidant enzymes and exhibits anti-fibrotic effect through regulation of collagen production against bleomycin-induced pulmonary fibrosis. Chem Biol Interact 2016;246:52–62. 链接1

[74] Nakahira K, Pabon Porras MA, Choi AM. Autophagy in pulmonary diseases. Am J Respir Crit Care Med 2016;194(10):1196–207. 链接1

[75] Chen C, Wang J, Chen J, Zhou L, Wang H, Chen J, et al. Morusin alleviates mycoplasma pneumonia via the inhibition of Wnt/b-catenin and NF-jB signaling. Biosci Rep 2019;39(6):BRS20190190. 链接1

[76] Williamson JD, Sadofsky LR, Hart SP. The pathogenesis of bleomycin-induced lung injury in animals and its applicability to human idiopathic pulmonary fibrosis. Exp Lung Res 2015;41(2):57–73. 链接1

[77] Kitamura H, Cambier S, Somanath S, Barker T, Minagawa S, Markovics J, et al. Mouse and human lung fibroblasts regulate dendritic cell trafficking, airway inflammation, and fibrosis through integrin avb8-mediated activation of TGFb. J Clin Invest 2011;121(7):2863–75. 链接1

[78] Weng T, Ko J, Masamha CP, Xia Z, Xiang Y, Chen NY, et al. Cleavage factor 25 deregulation contributes to pulmonary fibrosis through alternative polyadenylation. J Clin Invest 2019;129(5):1984–99. 链接1

[79] Borok Z. Role for a3 integrin in EMT and pulmonary fibrosis. J Clin Invest 2009;119(1):7–10. 链接1

[80] Sato N, Takasaka N, Yoshida M, Tsubouchi K, Minagawa S, Araya J, et al. Metformin attenuates lung fibrosis development via NOX4 suppression. Respir Res 2016;17(1):107. 链接1

[81] Kheirollahi V, Wasnick RM, Biasin V, Vazquez-Armendariz AI, Chu X, Moiseenko A, et al. Metformin induces lipogenic differentiation in myofibroblasts to reverse lung fibrosis. Nat Commun 2019;10(1):2987. 链接1

[82] Rangarajan S, Bone NB, Zmijewska AA, Jiang S, Park DW, Bernard K, et al. Metformin reverses established lung fibrosis in a bleomycin model. Nat Med 2018;24(8):1121–7. 链接1

相关研究