[1]GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specifi c all-cause and cause-specifi c mortality for 240 causes of death, 1990–2013:
[2]a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015; 385: 117–71.
[3]Millett ER, Quint JK, Smeeth L, Daniel RM, Thomas SL. Incidence of community-acquired lower respiratory tract infections and pneumonia among older adults in the United Kingdom: a population-based study. PLoS One 2013; 8: e75131.
[4]Ochoa-Gondar O, Vila-Córcoles A, de Diego C, et al, for the EVAN-65 Study Group. The burden of community-acquired pneumonia in the elderly: the Spanish EVAN-65 study. BMC Public Health 2008; 8: 222.
[5]File TM Jr, Marrie TJ. Burden of community-acquired pneumonia in North American adults. Postgrad Med 2010; 122: 130–41
[6]Black RE, Cousens S, Johnson HL, et al, for the Child Health Epidemiology Reference Group of WHO and UNICEF. Global, regional, and national causes of child mortality in 2008: a systematic analysis. Lancet 2010; 375: 1969–87.
[7]Welte T, Torres A, Nathwani D. Clinical and economic burden of community-acquired pneumonia among adults in Europe. Thorax 2012; 67: 71–79.
[8]Drijkoningen JJ, Rohde GG. Pneumococcal infection in adults: burden of disease. Clin Microbiol Infect 2014; 20 (suppl 5): 45–51.
[9]Efferth T. From ancient herb to modern drug: artemisia annua and artemisinin for cancer therapy. Semin Cancer Biol. 2017;46:65–83. doi: 10.1016/j.semcancer.2017.02.009.
[10]Chen, Xin et al. 2002. “Effects of Shuanghuanglian and Qingkailing, Two Multi-Components of Traditional Chinese Medicinal Preparations, on Human Leukocyte Function.” Life sciences 70(24): 2897–2913.
[11]Li, Wei. 2002. “[The curative effect observation of shuanghuanglian and penicillin on acute tonsillitis].” Lin chuang er bi yan hou ke za zhi = Journal of clinical otorhinolaryngology 16(9): 475–76.
[12]Song, Z J et al. 2000. “Effects of Radix Angelicae Sinensis and Shuanghuanglian on a Rat Model of Chronic Pseudomonas Aeruginosa Pneumonia.” Chinese medical sciences journal = Chung-kuo i hsueh k’o hsueh tsa chih 15(2): 83–88.
[13]Zhang, Hongwei et al. 2013. “Chinese Medicine Injection Shuanghuanglian for Treatment of Acute Upper Respiratory Tract Infection: A Systematic Review of Randomized Controlled Trials.” Evidence-based complementary and alternative medicine : eCAM 2013: 987326.
[14]Howard LS, Sillis M, Pasteur MC, Kamath AV, Harrison BD. Microbiological profi le of community-acquired pneumonia in adults over the last 20 years. J Infect 2005; 50: 107–13.
[15]do Carmo Debur M, Raboni SM, Flizikowski FBZ, et al. Immunohistochemical assessment of respiratory viruses in necropsy samples from lethal and non-pandemic seasonal respiratory infections. J Clin Pathol 2010; 63: 930–34.
[16]Nicholls JM, Poon LLM, Lee KC, et al. Lung pathology of fatal severe acute respiratory syndrome. Lancet 2003; 361: 1773–78.
[17]Korteweg C, Jiang G. Pathology, molecular biology, and pathogenesis of avian infl uenza A (H5N1) infection in humans. Am J Pathol 2008; 172: 1155–70.
[18]World Health Organization WHO Guidelines for the Global Surveillance of Severe Acute Respiratory Syndrome (SARS) [(accessed on 8 October 2018)];2004 Oct; Updated Recommendations. Available online: http://www.who.int/mediacentre/factsheets/mers-cov/en/
[19]Mackay IM, Arden KE. MERS coronavirus: diagnostics, epidemiology and transmission. Virol J 2015;12(1):222.
[20]von Grotthuss M, Wyrwicz LS, Rychlewski L. mRNA cap‐1 methyltransferase in the SARS genome. Cell 2003; 113: 701–2.
[21]Lee, N. et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. N. Engl. J. Med. 348, 1986–1994 (2003).
[22]Booth, C. M. et al. Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. JAMA 289, 2801–2809 (2003).
[23]Poutanen, S. M. et al. Identification of severe acute respiratory syndrome in Canada. N. Engl. J. Med. 348, 1995–2005 (2003).
[24]So, L. K. et al. Development of a standard treatment protocol for severe acute respiratory syndrome. Lancet 361, 1615–1617 (2003).
[25]Tsang, K. W. et al. A cluster of cases of severe acute respiratory syndrome in Hong Kong. N. Engl. J. Med. 348, 1977–1985 (2003).
[26]Loutfy, M. R. et al. Interferon alfacon-1 plus corticosteroids in severe acute respiratory syndrome: a preliminary study. JAMA 290, 3222–3228 (2003).
[27]Zhao, Z. et al. Description and clinical treatment of an early outbreak of severe acute respiratory syndrome (SARS) in Guangzhou, PR China. J. Med. Microbiol. 52, 715–720 (2003).
[28]Chan, J. F. et al. Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus. J. Infect. 67, 606–616 (2013).
[29]Falzarano, D. et al. Inhibition of novel β coronavirus replication by a combination of interferon-α2b and ribavirin. Sci. Rep. 3, 1686 (2013).
[30]Hart, B. J. et al. Interferon-β and mycophenolic acid are potent inhibitors of Middle East respiratory syndrome coronavirus in cell-based assays. J. Gen. Virol. 95, 571–577 (2014).
[31]Falzarano, D. et al. Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. Nat. Med. 19, 1313–1317 (2013). The first application of a potential treatment option for MERS through the repurposing of IFNα2b and ribavirin in a non‑human primate model.
[32]Morgenstern, B., Michaelis, M., Baer, P. C., Doerr, H. W. & Cinatl, J. Ribavirin and interferon-β synergistically inhibit SARS-associated coronavirus replication in animal and human cell lines. Biochem. Biophys. Res. Commun. 326, 905–908 (2005).
[33]Falzarano, D. et al. Inhibition of novel β coronavirus replication by a combination of interferon-α2b and ribavirin. Sci. Rep. 3, 1686 (2013).
[34]Hart, B. J. et al. Interferon-β and mycophenolic acid are potent inhibitors of Middle East respiratory syndrome coronavirus in cell-based assays. J. Gen. Virol. 95, 571–577 (2014).
[35]Gong Y., Huang X., Wang D., Li M., Liu Z. (2017). Triptolide protects bone against destruction by targeting RANKL-mediated ERK/AKT signalling pathway in the collagen-induced rheumatoid arthritis. Biomed. Res. 28 4111–4116.
[36]Efferth T. From ancient herb to modern drug: artemisia annua and artemisinin for cancer therapy. Semin Cancer Biol. 2017;46:65–83. doi: 10.1016/j.semcancer.2017.02.009.
[37]Efferth T, Zacchino S, Georgiev MI, Liu L, Wagner H, Panossian AJ, et al. Nobel prize for artemisinin brings phytotherapy into the spotlight. Phytomedicine. 2015;22(13):1–4. doi: 10.1016/j.phymed.2015.10.003.
[38]Cai YY, Lin WP, Li AP, Xu JY. Combined effects of curcumin and triptolide on an ovarian cancer cell line. Asian Pac J Cancer Prev. 2013;14(7):4267–4271. doi: 10.7314/APJCP.2013.14.7.4267.
[39]Jose A, Labala S, Venuganti VVK. Co-delivery of curcumin and STAT3 siRNA using deformable cationic liposomes to treat skin cancer. J Drug Target.
[40]Ravindranathan P, Pasham D, Balaji U, Cardenas J, Gu JH, Toden S, et al. A combination of curcumin and oligomeric proanthocyanidins offer superior anti-tumorigenic properties in colorectal cancer.
[41]Sivanantham B, Sethuraman S, Krishnan UM. Combinatorial effects of curcumin with an anti-neoplastic agent on head and neck squamous cell carcinoma through the regulation of EGFR-ERK1/2 and apoptotic signaling pathways. Acs Comb Sci. 2016;18(1):22–35. doi: 10.1021/acscombsci.5b00043.
[42]Zou P, Zhang JR, Xia YQ, Kanchana K, Guo GL, Chen WB, et al. ROS generation mediates the anti-cancer effects of WZ35 via activating JNK and ER stress apoptotic pathways in gastric cancer. Oncotarget. 2015;6(8):5860–5876. doi: 10.18632/oncotarget.3333.
[43]Zhang J, Zhou F, Wu X, Zhang X, Chen Y, Zha BS, et al. Cellular pharmacokinetic mechanisms of adriamycin resistance and its modulation by 20(S)-ginsenoside Rh2 in MCF-7/Adr cells. Br J Pharmacol. 2012;165(1):120–134. doi: 10.1111/j.1476-5381.2011.01505.x.
[44]Lu Z, Xu H, Yu X, Wang Y, Huang L, Jin X, et al. 20(S)-Protopanaxadiol induces apoptosis in human hepatoblastoma HepG2 cells by downregulating the protein kinase B signaling pathway. Exp Ther Med. 2018;15(2):1277–1284.
[45]Liu Y, Fan D. Ginsenoside Rg5 induces apoptosis and autophagy via the inhibition of the PI3K/Akt pathway against breast cancer in a mouse model. Food Funct. 2018;9:5513–5527. doi: 10.1039/C8FO01122B.
[46]Wu Q, Deng J, Fan D, Duan Z, Zhu C, Fu R, et al. Ginsenoside Rh4 induces apoptosis and autophagic cell death through activation of the ROS/JNK/p53 pathway in colorectal cancer cells. Biochem Pharmacol. 2018;148:64–74. doi: 10.1016/j.bcp.2017.12.004.
[47]Leem DG, Shin JS, Kim KT, Choi SY, Lee MH, Lee KT. Dammarane-type triterpene ginsenoside-Rg18 inhibits human non-small cell lung cancer A549 cell proliferation via G1 phase arrest. Oncol Lett. 2018;15(4):6043–6049.
[48]Zeng D, Wang J, Kong P, Chang C, Li J, Li J. Ginsenoside Rg3 inhibits HIF-1α and VEGF expression in patient with acute leukemia via inhibiting the activation of PI3K/Akt and ERK1/2 pathways. Int J Clin Exp Pathol. 2014;7(5):2172–2178.
[49]Wang L, Gao S, Jiang W, Luo C, Xu M, Bohlin L, et al. Antioxidative dietary compounds modulate gene expression associated with apoptosis, DNA repair, inhibition of cell proliferation and migration. Int J Mol Sci. 2014;15(9):16226–16245. doi: 10.3390/ijms150916226.
[50]Kim YJ, Choi WI, Jeon BN, Choi KC, Kim K, Kim TJ, et al. Stereospecific effects of ginsenoside 20-Rg3 inhibits TGF-beta1-induced epithelial-mesenchymal transition and suppresses lung cancer migration, invasion and anoikis resistance. Toxicology. 2014;322:23–33. doi: 10.1016/j.tox.2014.04.002.
[51]Yang J, Yuan D, Xing T, Su H, Zhang S, Wen J, et al. Ginsenoside Rh2 inhibiting HCT116 colon cancer cell proliferation through blocking PDZ-binding kinase/T-LAK cell-originated protein kinase. J Ginseng Res. 2016;40(4):400–408. doi: 10.1016/j.jgr.2016.03.007.
[52]He NW, Zhao Y, Guo L, Shang J, Yang XB. Antioxidant, antiproliferative, and pro-apoptotic activities of a saponin extract derived from the roots of Panax notoginseng (Burk.) F.H. Chen. J Med Food. 2012;15(4):350–359. doi: 10.1089/jmf.2011.1801.
[53]Lu M, Fei Z, Zhang G. Synergistic anticancer activity of 20(S)-Ginsenoside Rg3 and Sorafenib in hepatocellular carcinoma by modulating PTEN/Akt signaling pathway. Biomed Pharmacother. 2018;97:1282–1288. doi: 10.1016/j.biopha.2017.11.006.
[54]Wang X, Sun YY, Zhao C, Qu FZ, Zhao YQ. 12-Chloracetyl-PPD, a novel dammarane derivative, shows anti-cancer activity via delay the progression of cell cycle G2/M phase and reactive oxygen species-mediate cell apoptosis. Eur J Pharmacol. 2017;798:49–56. doi: 10.1016/j.ejphar.2016.12.027.
[55]Lee IS, Uh I, Kim KS, Kim KH, Park J, Kim Y, et al. Anti-inflammatory effects of ginsenoside Rg3 via NF-kappaB pathway in A549 cells and human asthmatic lung tissue. J Immunol Res. 2016;2016:7521601.
[56]Chen G, Zhang J, Zhang H, Xiao Y, Kao X, Liu Y, et al. Anti-inflammatory effect of emodin on lipopolysaccharide-induced keratitis in Wistar rats. Int J Clin Exp Med. 2015;8(8):12382–12389. [PMC free article] [PubMed] [Google Scholar]
[57]Li Y, Xiong W, Yang J, Zhong J, Zhang L, Zheng J, et al. Attenuation of inflammation by emodin in lipopolysaccharide-induced acute kidney injury via inhibition of toll-like receptor 2 signal pathway. Iran J Kidney Dis. 2015;9(3):202–208. [PubMed] [Google Scholar]
[58]Chen GL, Zhang JJ, Kao X, Wei LW, Liu ZY. Emodin ameliorates lipopolysaccharides-induced corneal inflammation in rats. Int J Ophthalmol. 2015;8(4):665–669.
[59]Park SY, Jin ML, Ko MJ, Park G, Choi YW. Anti-neuroinflammatory effect of emodin in LPS-stimulated microglia: involvement of AMPK/Nrf2 activation. Neurochem Res. 2016;41(11):2981–2992. doi: 10.1007/s11064-016-2018-6.
[60]Yao WY, Zhou YF, Qian AH, Zhang YP, Qiao MM, Zhai ZK, et al. Emodin has a protective effect in cases of severe acute pancreatitis via inhibition of nuclear factor-kappa B activation resulting in antioxidation. Mol Med Rep. 2015;11(2):1416–1420. doi: 10.3892/mmr.2014.2789.
[61]Alisi A, Pastore A, Ceccarelli S, Panera N, Gnani D, Bruscalupi G, et al. Emodin prevents intrahepatic fat accumulation, inflammation and redox status imbalance during diet-induced hepatosteatosis in rats. Int J Mol Sci. 2012;13(2):2276–2289. doi: 10.3390/ijms13022276.
[62]Sharma R, Tiku AB. Emodin, an anthraquinone derivative, protects against gamma radiation-induced toxicity by inhibiting DNA damage and oxidative stress. Int J Radiat Biol. 2014;90(4):275–283. doi: 10.3109/09553002.2014.884292.
[63]Ma L, Yang Y, Yin Z, Liu M, Wang L, Chen L, et al. Emodin suppresses the nasopharyngeal carcinoma cells by targeting the chloride channels. Biomed Pharmacother. 2017;90:615–625. doi: 10.1016/j.biopha.2017.03.088.
[64]Li XX, Dong Y, Wang W, Wang HL, Chen YY, Shi GY, et al. Emodin as an effective agent in targeting cancer stem-like side population cells of gallbladder carcinoma. Stem Cells Develop. 2013;22(4):554–566. doi: 10.1089/scd.2011.0709.
[65]Haque E, Kamil M, Irfan S, Sheikh S, Hasan A, Nazir A, et al. Blocking mutation independent p53 aggregation by emodin modulates autophagic cell death pathway in lung cancer. Int J Biochem Cell Biol. 2018;96:90–95. doi: 10.1016/j.biocel.2018.01.014.
[66]Zhang X, Chen Y, Zhang T, Zhang Y. Inhibitory effect of emodin on human hepatoma cell line SMMC-7721 and its mechanism. Afr Health Sci. 2015;15(1):97–100. doi: 10.4314/ahs.v15i1.13.
[67]Ma YS, Weng SW, Lin MW, Lu CC, Chiang JH, Yang JS, et al. Antitumor effects of emodin on LS1034 human colon cancer cells in vitro and in vivo: roles of apoptotic cell death and LS1034 tumor xenografts model. Food Chem Toxicol. 2012;50(5):1271–1278. doi: 10.1016/j.fct.2012.01.033.
[68]Manimaran A, Buddhan R, Manoharan S. Emodin downregulates cell proliferation markers during DMBA induced oral carcinogenesis in Golden Syrian Hamsters. Afr J Tradit Complement Altern Med. 2017;14(2):83–91. doi: 10.21010/ajtcam.v14i2.10
[69]Lu J, Xu Y, Zhao Z, Ke X, Wei X, Kang J, et al. Emodin suppresses proliferation, migration and invasion in ovarian cancer cells by down regulating ILK in vitro and in vivo. OncoTargets Ther. 2017;10:3579–3589. doi: 10.2147/OTT.S138217.
[70]Cha TL, Chuang MJ, Tang SH, Wu ST, Sun KH, Chen TT, et al. Emodin modulates epigenetic modifications and suppresses bladder carcinoma cell growth. Mol Carcinog. 2015;54(3):167–177. doi: 10.1002/mc.22084.
[71]Deng G, Ju X, Meng Q, Yu ZJ, Ma LB. Emodin inhibits the proliferation of PC3 prostate cancer cells in vitro via the Notch signaling pathway. Mol Med Rep. 2015;12(3):4427–4433. doi: 10.3892/mmr.2015.3923.
[72]Sun Y, Wang X, Zhou Q, Lu Y, Zhang H, Chen Q, et al. Inhibitory effect of emodin on migration, invasion and metastasis of human breast cancer MDA-MB-231 cells in vitro and in vivo. Oncol Rep. 2015;33(1):338–346. doi: 10.3892/or.2014.3585.
[73]Chihara T, Shimpo K, Beppu H, Yamamoto N, Kaneko T, Wakamatsu K, et al. Effects of aloe-emodin and emodin on proliferation of the MKN45 human gastric cancer cell line. Asian Pac J Cancer Prev. 2015;16(9):3887–3891. doi: 10.7314/APJCP.2015.16.9.3887.
[74]Liu A, Chen H, Wei W, Ye S, Liao W, Gong J, et al. Antiproliferative and antimetastatic effects of emodin on human pancreatic cancer. Oncol Rep. 2011;26(1):81–89
[75]Qu W, Wang Y, Wu Q, Liu J, Hao D. Emodin inhibits HMGB1-induced tumor angiogenesis in human osteosarcoma by regulating SIRT1. Int J Clin Exp Med. 2015;8(9):15054–15064.
[76]Gao, Yuan et al. 2014. “Shuang-Huang-Lian Exerts Anti-Inflammatory and Anti-Oxidative Activities in Lipopolysaccharide-Stimulated Murine Alveolar Macrophages.” Phytomedicine : international journal of phytotherapy and phytopharmacology 21(4): 461–69.
[77]Gu, Naibing et al. 2012. “Shuanghuanglian Injection Downregulates Nuclear Factor-Kappa B Expression in Mice with Viral Encephalitis.” Neural regeneration research 7(33): 2592–99.
[78]Ma, Qinhai et al. 2017. “Comparative Study on the Antivirus Activity of Shuang-Huang-Lian Injectable Powder and Its Bioactive Compound Mixture against Human Adenovirus III In Vitro.” Viruses 9(4).
[79]Tang, Yuling et al. 2018. “Antiviral Effects of Shuanghuanglian Injection Powder against Influenza A Virus H5N1 in Vitro and in Vivo.” Microbial pathogenesis 121: 318–24.