June19 Unitedkingdom  2021 

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Abstract Volume: 2 Issue: 6 ISSN:

Andrographis Paniculata, A Promising Medicinal Plant Fighting Against SARS-CoV-2

Attapon Cheepsattayakorn1,2* Ruangrong Cheepsattayakorn3 Chawapon  Kidhirunkul1

  1. Faculty of Medicine, Western University, Pathumtani Province, Thailand.
  2. 10th Zonal Tuberculosis and Chest Disease Center, Chiang Mai, Thailand.
  3. Department of Pathology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.

*Corresponding Author: Attapon Cheepsattayakorn, 10th Zonal Tuberculosis and Chest Disease Center, 143 Sridornchai Road Changklan Muang Chiang Mai 50100 Thailand.


Received Date: May 03, 2021

Publication Date: June 01, 2021

Andrographis Paniculata, A Promising Medicinal Plant Fighting Against SARS-CoV-2

Andrographis paniculata (Green chiretta) (Figure 1), a medicinal plant, known as “ Indian echinacea ” is an herb used in traditional Chinese medicine and ayurveda. Andrographis paniculata is native to India and Sri Lanka but is naturalized in many tropical countries, such as Thailand, Malaysia, Java, and Borneo where it grows isolated patches on roadside, near drain, in between wall cracks, lowlands, hillside, coastlines, and other cultivated or disturbed areas, such as wastelands. It is a bitter-tasting herb rich in compounds known as andrographolides, a major bioactive phytoconstituent found in various parts of Andrographis paniculata, particularly in the leaves [1-5] that is hypothesized to have antiviral, anti-inflammatory, and antioxidant properties. The chemical name of andrographolide is 3α, 14, 15, 18-tetrahydroxy-5β, 9βH, 10α-labda-8, 12-dien-16-oic acid γ-lactone with its molecular formula and weight are C20H30O5 and 350.4 (C 68.54 %, H 8.63 %, and O 22.83 %), respectively [1-5].

This herb is said to act as a natural immune-booster [6]. Other major bioactive compounds are flavonoids, polyphenols, and diterpenoids [7]. Andrographis paniculata is commonly known as the “ King of bitters ”. In Thailand, it is known as “ Fah-Thalai-Jone ”. In China, it is known as “ Chuan-Xin-Lian ”. In India, it is known as “ Kalmegh ”. In Japan, it is known as “ Senshinren ”. In Malaysia, it is known as “ Hempedu bumi ”. In Scandinavian countries, it is known as “ green chiretta ” [8]. In mice, the extract and purified andrographolide were reported to stimulate an innate immune response [9]. In murine immature dendritic cells with experimental autoimmune encephalomyelitis, andrographolide inhibited NF-kappa B activation [10]. In murine-T cells stimulated with concanavalin A in vitro, andrographolide reduces IFN-γ and IL-2 production [11]. Furthermore, in macrophages stimulated by lipopolysaccharide, andrographolide inhibits the production of IL-12 and TNF-α [12]. Andrographis paniculata, 25 µg/mL of ethanolic extract and 5 µg/mL of andrographolide effectively exhibits the expression of Epstein-Barr virus (EBV) lytic protein, Rta, Zta, and EA-D, during the viral lytic cycle in P3HR1 cells 13]. A previous study demonstrated that Andrographis paniculata has the most inhibitory effects against dengue type 1-infectd Vero E6 cells [14]. Andrographis paniculata also has antibacterial, antimalarial, insects-larvicidal and -ovicidal, renoprotective, hepatoprotective, antihyperglycemic, hypolipidemic, antifertility, antioxidant, anti-inflammatory, anticancer, anti-platelet aggregation, anti-NF-kappa B (NF-kB) transcription, and antipyretic and anti-analgesic effects [15]. Pre- and post-treatments of the extract of Andrographis paniculata after surgical procedures and operations, particularly angioplasty procedures, significantly prevent the blood vessel constriction, demonstrated by an increase of blood-clotting time, hence reducing the risk of subsequent closing blood vessels [16]. Several previous studies demonstrated antidiarrheal [17] and anti-HIV effects of Andrographis paniculata [18].

A previous study on 152 Thai adults with pharyngotonsillitis demonstrated that Andrographis paniculata at a dose of 6 g/day for 7 days relieved the symptoms of sore throat and fever similar to the efficiency of acetaminophen [19]. A previous study conducted by Ca?ceres and colleagues demonstrated that 4-days treatment of Andrographis paniculata extract SHA-10 decreased the intensity of the symptoms of sore throat (OR = 2.3; 95 % CI : 1.69-3.14), sleeplessness (OR = 1.71; 95 % CI : 1.38-2.11), and tiredness (OR = 1.28; 95 % CI : 1.07-1.53), compared with control group [20]. A previous study in mice challenged with ADP (700 mg/kg) can markedly lowering the mortality rate from 90 % to 60 % that were treated with andrographolide concentrations of 22 µg/kg and 55 µg/kg, respectively, confirming the effects of andrographolide on prevention of thromboembolism [21]. Andrographis paniculata is most widely used to treat cold and flu symptoms and is also used to treat other diseases and symptoms, such as human immunodeficiency-virus infection (HIV)/acquired immunodeficiency syndrome (AIDS), infections, parasitic infestations, sinus infections, cancer, rheumatoid arthritis, hepatic problems, cardiac diseases, anorexia, allergies, ulcers, and skin diseases. Nevertheless, there is not enough scientific evidence to support the use of Andrographis paniculata for most of these health benefits. Some preliminary studies demonstrated that Andrographis paniculata may offer the health benefits, such as upper respiratory tract infections and ulcerative colitis [22].

Andrographis paniculata may trigger adverse side effects like fatigue, headache, nausea, diarrhea, and allergic reaction. Andrographis paniculata should not be administered intravenously due to possible acute renal injury. Individuals using some medications, such as anti-hypertensive medicines, chemotherapy drugs, blood-thinning drugs, etc. should consult a clinician before using Andrographis paniculata. Little is known about the safety of using Andrographis paniculata. There is no single recommended dose of Andrographis paniculata due to various dose studies. Some previous studies revealed that for relief of sore throat, a dose of 3-6 grams Andrographis paniculata was used once a day. For ulcerative colitis, Andrographis paniculata extract, 1,200-1,800 milligrams was used once a day for eight weeks. For common cold, a combination product (4-5.6 milligrams Andrographolide and 400 milligrams Siberian ginseng) was used three times daily, whereas another previous study demonstrated using Andrographis extract (KalmCold) 200 milligrams once a day for 5 days [22].

Recently, some Asian countries claimed that Andrographis paniculata may kill the COVID-19 and they will initiate studies on this issue in 2020 as soon as possible. Meanwhile a joint research team of the Shanghai Institute of Materia Medica and Shanghai Tech University conducted a research and demonstrated that Chinese herbal medicines, such as Radix Sophorae Tonkinensis and Rhizoma Polygoni Cuspidati may contain ingredients against COVID-19. Until now, it has been difficult to get the polymerase complex that contains multiple proteins to function in a test tube [18]. A recent study in Thailand conducted by Sa-ngiamsuntorn et al in human lung epithelial cells demonstrated that Andrographis paniculata extract and its major component andrographolide expressed anti-SARS-CoV-2 (COVID-19) activity at 25TCID50 in SARS-CoV-2 infected Calu-3 cells by significant inhibition of the production of infectious virions with the IC50of 0.036 µg/mL and 0.034 µM, respectively [23].

 In conclusion, various experimental and clinical pharmacological actions of andrographolide include anti-inflammatory, anti-hyperglycemic, anti-hypoglycemic, anti-cancer, antioxidant, anti-viral, particularly SARS-CoV-2 (COVID-19) and HIV. Favorable cytotoxicity profiles and potent anti-SARS-CoV-2 activities promote further development of Andrographis paniculata extract and andrographolide for monotherapy or in effectively combined drug regimens against SARS-CoV-2 (COVID-19).

 

Bibliography

  1. Fujita T, Fujitani R, Takeda Y, et al. “On the diterpenoids of Andrographis paniculata : X-ray crystallographic analysis of andrographolide and structure determination of new minor diterpenoids”. Chemical and Pharmaceutical Bulletin 1984; 32 (6) : 2117-2125.
     
  2. Medforth CJ, Chang RS, Chen GQ, Olmstead MM, Smith KM. “A conformational study of diterpenoid lactones isolated from the Chinese medicinal herb Andrographis paniculata”. Journal of the Chemical Society, Perkin Tranactions 1990; 2 (6) : 1011-1016.
     
  3. Rajani M, Shrivastava N, Ravishankara MN. “A rapid method for isolation of andrographolide from Andrographis paniculata Nees (Kalmegh)”. Pharmaceutical Biology 2000; 38 (3) : 204-209.
     
  4. Du Q, Jerz G, Winterhalter P. “Separation of andrographolide from the leaves of Andrographis paniculata using high-speed counter-current chromatography”. Journal of Chromatography 2003; 984 (1) : 147-151.
     
  5. Cui L, Qiu F, Yao X. “Isolation and identification of seven glucuronide conjugates of andrographolide in human urine”. Drug Metabolism and Disposition 2005; 33 (4) : 555-562.
     
  6. Yim E. "New STRAITSTIMES. “ Bitter but medicinal ”. Published online on September 27, 2014. Available at : www.nst.com.my>news>2015/09>bitter-medicinal (accessed on March 28, 2020).
     
  7. Chao W-W, et al. “ Isolation and identification of bioactive compounds in Andrographis paniculata (Chuanxinlian) ”. BMC Chinese Medicine 5 (2020) : 17. Available at http://www.cmjournal.org/content/5/1/17 ; cmjournal.biomedcentral.com>articles (accessed on March 28, 2020).
     
  8. Gautret P, et al. “ Hydroxychloroquine and Azithromycin as a  treatment of COVID-19 : preliminary results of an open-label non randomized clinical trial ”. medRxivpreprint. 25 pages. DOI :  10.1016/j.ijantimicag.2020.105949 Available at www.medrxiv.org>content>2020.03.16.20037135v1 (accessed on March 28, 2020).
     
  9. Kumar RA, Sridevi K, Kumar NV, Nanduri S, Rajagopal S. “Anticancer and immunostimulatory compounds from Andrographis paniculata”. Journal of Ethnopharmacology 2004; 92 (2-3) : 291-295.
     
  10. Iruretagoyena MI, Tobar JA, Gonza?lez PA, et al. “Andrographolide interferes with T cell activation and reduces experimental autoimmune encephalomyelitis in the mouse”. The Journal of Pharmacology and Experimental Therapeutics 2005; 312 (1) : 366-372.
     
  11. Burgos RA, Caballero EE, Sa?nchez NS, Schroeder RA, Wikman GK, Hancke JL. “Testicular toxicity assessment of Andrographis paniculata dried extract in rats”. Journal of Ethnopharmacology 1997; 58 (3) : 219-224.
     
  12. Qin LH, Kong L, Shi GJ, Wang ZT, Ge BX. “Andrographolide inhibits the production of TNF-α and interleukin-12 in lipopolysaccharide-stimulated macrophages : role of mitogen-activated protein kinases”. Biological and Pharmaceutical Bulletin 2006; 29 (2) : 220-224.
     
  13. Lin TP, Chen SY, Duh PD, Chang LK, Liu YN. “Inhibition of the Epstein-Barr virus lytic cycle by andrographolide”. Biological and Pharmaceutical Bulletin 2008; 31 (11) : 2018-2023.
     
  14. Tang LIC, Ling APK, Koh RY, Chye SM, Voon KGL. “Screening of anti-dengue activity in methanolic extracts of medicinal plants”. BMC Compelmentary and Alternative Medicine 2012; 12 (3) : 1-10.
     
  15. Jayakumar T, Hsieh CY, Lee JJ, Sheu JR. “Experimental and clinical pharmacology of Andrographis paniculata and its major bioactive phytoconstituent andrographolide. Evidence-Based Complementary and Alternative Medicine 2013”, Volume 2013, Article ID 846740, 16 pages. DOI : http://dx.doi.org/10.1155/2013/846740
     
  16. Wang HW, Zhao HY, Xiang SQ. Effects of Andrographis paniculata component on nitric oxide, endothelin and lipid peroxidation in experimental atherosclerotic rabbits. Zhongguo Zhong Xi Yi Jie He Za Zhi 1997; 17 (9) : 547-549.
     
  17. Susan EA and Mays A. Pharmacology. In : The Merck Vetrinary Manual,p. 1638, Merck and Co., New York, NY, USA, 9th edition, 2005.
     
  18. Safadi El Y, Paillarte JC, Laumond G, et al. 5-modified-2??-dU and 2?-dC as mutagenic anti-HIV-1 proliferation agents : synthesis and activity. Journal of Medicinal Chemistry 2010; 53 (4) : 1534-1545.
     
  19. Thamlikitkul V, Theerapong S, Boonroj P, et al. Efficacy of Andrographis paniculata, nees for pharyngotonsillitis in adults. Journal of the Medical Association of Thailand 1991; 74 (10) : 437-442.
     
  20. Ca?ceres DD, Hancke JL, Burgos RA, Sandberg F, Wikman GK. Use of visual analogue scale measurements (VAS) to assess the effectiveness of standardized Andrographis paniculata extract SHA-10 in reducing the symptoms of common cold. A randomized double blind-placebo study. Phytomedicine 1999; 6 (4) : 217-223.
     
  21. Suo XB, Zhang H, Wang YQ. HPLC determination of andrographolide in rat whole blood : study on pharmacokinetics of andrographolide incorporated in liposomes and tablets. Biomedical Chromatography 2007; 21 (7) : 730-734.
     
  22. Wong C. verywellhealth. “ The health benefits of Andrographis, compounds in the Chinese herb may fight inflammation ”. Updated on November 30, 2019. Available at : www.verywellhealth.com>...>HolisticHealth>Supplements (accessed on March 28, 2020).
     
  23. Sa-ngiamsuntorn K, Suksatu A, Pewkliang Y, Thongsri P, Kanjanasirirat P, Manopwisedjaroen 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. Journal of Natural products 2016; 79 (3) : 629-661.

 

Volume 2 Issue 6 June 2021

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Figure 1