Inflammatory Cytokines and Metabolite Changes after High Dose of Andrographis paniculata Extract: A Preliminary Study in Mild COVID-19 Case Patients

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Suthatip Mahajaroensiri
Manmas Vannabhum
Pornvimol Leethong
Kulthanit Wanaratna
Nitapa Inchai
Wararath Chueawiang
Natchaya Ziangchin
Titchaporn Palo
Phornnapa Chareonkij
Pravit Akarasereenont


The Coronavirus disease which began in 2019 (COVID-19) was declared a global pandemic. It can increase inflammatory cytokines leading to organ failure. Efforts are being made to find drugs to treat or alleviate the severity. Andrographis paniculata (AP) is an herbal remedy for the respiratory system (cool tonic) in Thai traditional medicine theory. AP extracts have been reported to show potent inhibitory effects against SARS-CoV-2. The study aimed to investigate inflammatory cytokine changes and metabolomics profiling after high-dose AP extract had been given to patients with mild cases of COVID-19. Five patients received a high dose of AP extract (andrographolide 180 mg/day) for five consecutive days. The results showed that inflammatory cytokines related to COVID-19 infection tended to decrease. The metabolite profile showed a decrease of inflammatory metabolites and nucleotides. Moreover, the severity of the clinical symptoms was decreased within three days, especially cough. Side effects were not found by comparing the blood chemical analysis to pre-treatment controls. Therefore, a high dose of AP could be safely used in mild case COVID-19 patients. However, the absence of a placebo control meant that levels of pro-inflammatory cytokines and metabolite biomarkers related to clinical symptoms could not be determined. Therefore, further studies with comparative groups are needed and the number of patients studied should be increased.


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Felsenstein S, Herbert JA, McNamara PS, Hedrich CM. COVID-19: Immunology and treatment options. Clin Immunol. 2020; 215: 108448.

Boechat JL, Chora I, Morais A, Delgado L. The immune response to SARS-CoV-2 and COVID-19 immunopathology–current perspectives. Pulmonology. 2021;27(5):423-437.

Kanjanasirirat P, Suksatu A, Manopwised-jaroen S, Munyoo B, Tuchinda P, Jeara-wuttanakul K, et al. High-content screening of Thai medicinal plants reveals Boesenbergia rotunda extract and its component Panduratin A as anti-SARS-CoV-2 agents. Sci Rep. 2020;10(1):19963.

Ragab D, Salah Eldin H, Taeimah M, Khattab R, Salem R. The COVID-19 cytokine storm; What we know so far. Front Immunol. 2020;11:1446.

Blanco-Melo D, Nilsson-Payant BE, Liu W-C, Uhl S, Hoagland D, Møller R, et al. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell. 2020;181(5):1036-1045.e9.

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.

Liu K, Fang YY, Deng Y, Liu W, Wang MF, Ma JP, et al. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chin Med J (Engl). 2020;133(9):1025-1031.

Wenjun W, Xiaoqing L, Sipei W, Puyi L, Liyan H, Yimin L, et al. The definition and risks of cytokine release syndrome-like in 11 COVID-19-infected pneumonia critically ill patients: Disease Characteristics and Retrospective Analysis. medRxiv. 2020.02. 26.20026989.

Asim M, Sathian B, Banerjee I, Robinson J. A contemporary insight of metabolomics approach for COVID-19: Potential for novel therapeutic and diagnostic targets. Nepal J Epidemiol. 2020;10(4):923-927.

Pang Z, Zhou G, Chong J, Xia J. Comprehensive meta-analysis of COVID-19 global metabolomics datasets. Metabolites. 2021;11(1):44.

Traditional Thai medicine and the four body elements 2021 [cited June, 2021 25]. Available from: thai-massage-four-body-elements/.

Hu X-Y, Wu R-H, Logue M, Blondel C, Lai LYW, Stuart B, et al. Andrographis paniculata (Chuān Xīn Lián) for symptomatic relief of acute respiratory tract infections in adults and children: A systematic review and meta-analysis. Plos One. 2017;12(8): e0181780.

Chen J-X, Xue H-J, Ye W-C, Fang B-H, Liu Y-H, Yuan S-H, et al. Activity of Andrographolide and its derivatives against influenza virus in vivo and in vitro. Biol Pharm Bull. 2009;32(8):1385-1391.

Lee JC, Tseng CK, Young KC, Sun HY, Wang SW, Chen WC, et al. Andrographolide exerts anti-hepatitis C virus activity by up-regulating haeme oxygenase-1 via the p38 MAPK/Nrf2 pathway in human hepatoma cells. Br J Pharmacol. 2014;171(1):237-252.

Wintachai P, Kaur P, Lee RCH, Ramphan S, Kuadkitkan A, Wikan N, et al. Activity of andrographolide against chikungunya virus infection. Sci Rep. 2015;5:14179.

Gupta S, Mishra KP, Ganju L. Broad-spectrum antiviral properties of andro-grapholide. Arch Virol. 2017;162(3):611-623.

Ding Y, Chen L, Wu W, Yang J, Yang Z, Liu S. Andrographolide inhibits influenza A virus-induced inflammation in a murine model through NF-κB and JAK-STAT signaling pathway. Microbes Infect. 2017;19(12):605-615.

Ajaya Kumar R, Sridevi K, Vijaya Kumar N, Nanduri S, Rajagopal S. Anticancer

and immunostimulatory compounds from Andrographis paniculata. J Ethnophar-macol. 2004; 92(2-3):291-295.

Radhika P, Annapurna A, Rao SN. Immunostimulant, cerebroprotective & nootropic activities of Andrographis paniculata leaves extract in normal & type 2 diabetic rats. Indian J Med Res. 2012; 135(5):636-641.

Chandrasekaran CV, Gupta A, Agarwal A. Effect of an extract of Andrographis paniculata leaves on inflammatory and allergic mediators in vitro. J Ethnophar-macol. 2010;129(2):203-207.

Shen YC, Chen CF, Chiou WF. Andro-grapholide prevents oxygen radical production by human neutrophils: possible mechanism(s) involved in its anti-inflammatory effect. Br J Pharmacol. 2002;135(2):399-406.

Dai Y, Chen SR, Chai L, Zhao J, Wang Y, Wang Y. Overview of pharmacological activities of Andrographis paniculata and its major compound andrographolide. Crit Rev Food Sci Nutr. 2019;59(sup1): S17-S29.

Gupta S, Choudhry MA, Yadava JNS, Srivastava V, Tandon JS. Antidiarrhoeal Activity of Diterpenes of Andrographis paniculata (Kal-Megh) against Escherichia coli enterotoxin in in vivo models. Int J Crude Drug Res.1990; 28(4):273-283.

Hossain MS, Urbi Z, Sule A, Hafizur Rahman KM. Andrographis paniculata (Burm. f.) Wall. ex Nees: a review of ethnobotany, phytochemistry, and pharma-cology. The Scientific World Journal. 2014; 2014:274905.

Mussard E, Cesaro A, Lespessailles E, Legrain B, Berteina-Raboin S, Toumi H. Andrographolide, a natural antioxidant: an update. Antioxidants (Basel). 2019 Nov 20;8(12):571.

Zhou J, Zhang S, Ong CN, Shen HM. Critical role of pro-apoptotic Bcl-2 family members in andrographolide-induced apoptosis in human cancer cells. Biochem Pharmacol. 2006;72(2):132-144.

Yu BC, Chang CK, Su CF, Cheng JT. Mediation of β-endorphin in andro-grapholide-induced plasma glucose-lowering action in type I diabetes-like animals. Naunyn Schmiedebergs Arch Pharmacol. 2008;377(4-6):529-540.

Koteswara Rao Y, Vimalamma G, Rao CV, Tzeng YM. Flavonoids and androgra-pholides from Andrographis paniculata. Phytochemistry. 2004;65(16):2317-2321.

Sa-Ngiamsuntorn K, Suksatu A, Pewkliang Y, Thongsri P, Kanjanasirirat P, Manop-wisedjaroen S, et al. Anti-SARS-CoV-2 activity of Andrographis paniculata extract and its major component andrographolide in human lung epithelial cells and cytotoxicity evaluation in major organ cell representatives. J Nat Prod. 2021;84(4): 1261-1270.

Enmozhi SK, Raja K, Sebastine I, Joseph J. Andrographolide as a potential inhibitor of SARS-CoV-2 main protease: an in silico approach. J Biomol Struct Dyn. 2021;39(9):3092-3098.

Murugan NA, Pandian CJ, Jeyakanthan J. Computational investigation on Andro-graphis paniculata phytochemicals to evaluate their potency against SARS-CoV-2 in comparison to known antiviral compounds in drug trials. J Biomol Struct Dyn. 2021;39(12):4415-4426.

Chantrakul C, Punkrut W, Boontaeng N, Petcharoen S, Riewpaiboon W. Efficacy of Andrographis paniculata, nees for pharyngotonsillitis in adults. J Med Assoc Thai. 1991;74(10):437-442.

Costela-Ruiz VJ, Illescas-Montes R, Puerta-Puerta JM, Ruiz C, Melguizo-Rodríguez L. SARS-CoV-2 infection: The role of cytokines in COVID-19 disease. Cytokine Growth Factor Rev. 2020;54:62-75.

Pérez-Cabezas B, Ribeiro R, Costa I, Esteves S, Teixeira AR, Reis T, et al. IL-2 and IFN-γ are biomarkers of SARS-CoV-2 specific cellular response in whole blood stimulation assays. medRxiv. 2021.01.04. 20248897.

Shi H, Wang W, Yin J, Ouyang Y, Pang L, Feng Y, et al. The inhibition of IL-2/IL-2R gives rise to CD8+ T cell and lymphocyte decrease through JAK1-STAT5 in critical patients with COVID-19 pneumonia. Cell Death Dis. 2020; 11(6):429.

Archambault A-S, Zaid Y, Rakotoarivelo V, Dore E, Dubuc I, Martin C, et al. Lipid storm within the lungs of severe COVID-19 patients: Extensive levels of cyclooxygenase and lipoxygenase-derived inflammatory metabolites. MedRxiv. 2020.12.04.20242115.

Das UN. Bioactive lipids in COVID-19-further evidence. Arch Med Res. 2021; 52(1):107-120.

Song JW, Lam SM, Fan X, Cao WJ, Wang SY, Tian H, et al. Omics-driven systems interrogation of metabolic dys-regulation in COVID-19 pathogenesis. Cell Metab. 2020;32(2):188-202.e5.

Shi D, Yan R, Lv L, Jiang H, Lu Y, Sheng J, et al. The serum metabolome of COVID-19 patients is distinctive and predictive. Metabolism. 2021;118:154739.