"Ya-Hok-Sing: bioactive substance components, in vitro toxicity, and a " by Khareeyoh Asae, Oratai Neamsuvan et al.
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Abstract

Background: Ya-Hok-Sing is a traditional Thai polyherbal medicine used by Singhanakhon healers, Thailand. This study aimed to provide scientific evidence supporting the traditional use of Ya-Hok-Sing as an anti-fever remedy.

Methods: The chemical fingerprinting and in vitro toxicity of Ya-Hok-Sing were investigated using the Liquid Chromatography-Quadrupole time-of-flight-Mass spectrometry (LC-QTOF-MS) method and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The clinical efficacy of Ya-Hok-Sing for fever relief was examined using a case series of five patients following treatment from a traditional Thai healer.

Results: The mass-spectrometry-total ion chromatogram (MS‑TIC) for Ya-Hok-Sing revealed the presence of thirty-six compounds, including twenty-one phenolics and fifteen organic acids. Ya-Hok-Sing was non-toxic at the highest tested concentration of 80 µg/mL in vero cells and mouse fibroblast cells. The results of the case series indicated that three patients out of five tested positive for COVID-19. The two remaining patients were diagnosed with influenza by a traditional healer. For the first two days, each patient took 90 mL of Ya-Hok-Sing every three hours. Starting on day 3, each patient took Ya-Hok-Sing three times daily (90 mL each) before meals for one week. All patients improved clinically after three to five days and recovered from fever and co-morbidities by six to nine days. Quality of life assessment showed that the patients had better mean quality of life scores after treatment (106.40 ± 7.90), compared to before treatment (62.00 ± 5.34).

Conclusion: Our findings supported the folk medicinal properties of Ya-Hok-Sing for the treatment of fever.

Keywords: Ya-Hok-Sing, Chemical fingerprinting, Toxicity, Thailand

References

[1] A-sae K, Sakulkeo O, Neamsuvan, O. Botanical and microscopic characteristics and uses of Polyalthia suberosa (Roxb.): a case study from Wat Vas, Singhanakhon District, Songkhla Province. Proceedings of the the 3rd National Conference in Traditional Thai Medicine; 2021 May 5-7; Songkhla: Prince of Songkla University: 2021. p. 47-55.

[2] National Drug Committee. The National List of Essential Medicines A.D. 2022 of Thailand: List of Herbal Medicinal Products. Nonthaburi: Herbal Products Division; 2022.

[3] Booranasubkajorn S, Kanlaya H, Huabprasert S, Lumlerdkij N, Akarasereenont P, Tripatara P. The effect of Thai herbal Ha-Rak formula (HRF) on LPS-induced systemic inflammation in wistar rats. Siriraj Med J. 2017;69(6):356-62. [cited 2024 Apr. 3]. Available from: https://he02.tci-thaijo.org/index.php/sirirajmedj/article/view/106179.

[4] Somwong P, Moriyasu M, Suttisri R. Chemical constituents from the roots of Clerodendrum indicum and Clerodendrum villosum. Biochem Sys Ecol. 2015;63:153-6. http://dx.doi.org/10.1016/j.bse.2015.10.005

[5] Jongchanapong A, Singharachai C, Palanuvej C, Ruangrungsi N, Towiwat P. Antipyretic and antinociceptive effects of Ben-cha-Lo-Ka-Wi-Chian remedy. J Health Res 2010;24(1):15-22. [cited 2024 Apr. 3]. Available from: https://he01.tci-thaijo.org/index.php/jhealthres/article/view/156632

[6] Nutmakul T, Pattanapanyasat K, Soonthornchareonnon N, Shiomi K, Mori M, Prathanturarug S. Antiplasmodial activities of a Thai traditional antipyretic formulation, Bencha-Loga-Wichian: a comparative study between the roots and their substitutes, the stems. J Ethnopharmacol. 2016;193:125-32. doi: 10.1016/j.jep.2016.07.013.

[7] Juckmeta T, Itharat A. Anti-inflammatory and antioxidant activities of Thai traditional remedy called “Ya-ha-rak”. J Health Res. 2012;26(4):205-10. [cited 2024 Apr. 3]. Available from: https://he01.tci-thaijo.org/index.php/jhealthres/article/view/85440

[8] Development of the World Health Organization WHOQOL-BREF quality of life assessment. The WHOQOL Group. Psychol Med. 1998 May;28(3):551-8. doi: 10.1017/s0033291798006667.

[9] Ministry of Public Health, Bureau of Drug and Narcotics. Thai Herbal Pharmacopoeia. Nonthaburi, Thailand: Bureau of Drug and Narcotics; 2020.

[10] Singharachai C, Palanuvej C, Kiyohara H, Yamada H, Ruangrungsi N. Safety evaluation of Thai traditional medicine remedy: Ben-Cha-Lo-Ka-Wi-Chian. J Health Res 2011;25(2):83-90. [cited 2024 Apr. 3]. Available from: https://he01.tci-thaijo.org/index.php/jhealthres/article/view/80059.

[11] Taechowisan T, Suttichokthanakorn S, Phutdhawong WS. Antibacterial and cytotoxicity activities of phenylbutanoids from Zingiber cassumunar Roxb. J App Pharm Sci 2018;8(7):121-7. DOI: 10.7324/JAPS.2018.8719.

[12] Sriwiriyajan S, Ninpesh T, Sukpondma Y, Nasomyon T, Graidist P. Cytotoxicity screening of plants of genus Piper in breast cancer cell lines. Trop J Pharm Res 2014;13(6):921-8. http://dx.doi.org/10.4314/tjpr.v13i6.14

[13] Ahmed F, Urooj A. Cardioprotective activity of standardized extract of Ficus racemosa stem bark against doxorubicin-induced toxicity. Pharm Biol. 2012 Apr;50(4):468-73. doi: 10.3109/13880209.2011.

[14] Chunthorng-Orn J, Pipatrattanaseree W, Juckmeta T, Dechayont B, Phuaklee P, Itharat A. Quality evaluation and pectolinarigenin contents analysis of Harak Remedy in Thailand. J Health Sci Altern Med. 2019;1(1): 25-33. [cited 2024 Apr. 3]. Available from: https://he01.tci-thaijo.org/index.php/jhealthscialternmed/article/view/167999.

[15] Plaza M, Amigo-Benavent M, del Castillo MD, Ibáñez E, Herrero M. Facts about the formation of new antioxidants in natural samples after subcritical water extraction. Food Res Inter 2010;43(10):2341-8. doi:10.1016/j.foodres.2010.07.036.

[16] Jaime A, Remsberg CM, Takemoto JK, Vega-Villa KR, Andrews PK, Sayre CL, et al. Polyphenols and flavonoids: an overview. In: Davies NM, Yáñez JA. Flavonoid Pharmacokinetics: Methods of Analysis, Preclinical and Clinical Pharmacokinetics, Safety, and Toxicology. New Jersey: John Wiley & Sons; 2013, p. 1-69.

[17] Kadam D, Palamthodi S, Lele SS. LC-ESI-Q-TOF-MS/MS profiling and antioxidant activity of phenolics from L. Sativum seedcake. J Food Sci Technol. 2018 Mar;55(3):1154-1163. doi: 10.1007/s13197-017-3031-8.

[18] Patel DK, Patel K, Kumar R, Gadewar M, Tahilyani V. Pharmacological and analytical aspects of bergenin: a concise report. Asian Pac J Trop Dis 2012;2(2):163-7. https://doi.org/10.1016/S2222-1808(12)60037-1.

[19] Afsar T, Khan MR, Razak S, Ullah S, Mirza B. Antipyretic, anti-inflammatory and analgesic activity of Acacia hydaspica R. Parker and its phytochemical analysis. BMC Complement Altern Med. 2015 Apr 29;15:136. doi: 10.1186/s12906-015-0658-8.

[20] Díaz-Gómez R, López-Solís R, Obreque-Slier E, Toledo-Araya H. Comparative antibacterial effect of gallic acid and catechin against Helicobacter pylori. LWT-Food Sci Technol. 2013;54(2):331-5. https://doi.org/10.1016/j.lwt.2013.07.012.

[21] Guo Y, Liu Y, Zhang Z, Chen M, Zhang D, Tian C, Liu M, Jiang G. The Antibacterial Activity and Mechanism of Action of Luteolin Against Trueperella pyogenes. Infect Drug Resist. 2020 Jun 10;13:1697-1711. doi: 10.2147/IDR.S253363.

[22] Garcia M, Puerta R, Martinez S, Saenz M. Analgesic, antipyretic and anti-inflammatory effects of Achillea ageratum. Phytother Res 1997;11(5):376-9.

[23] Ahmed EM, Desoukey SY, Fouad MA, Kamel MS. Chemical and biological studies of Russelia equisetiformis (SCH.&CHAM.) aerial parts. J App Pharm 2016;8. http://dx.doi.org/10.21065/19204159.

[24] Marzouk MS, Moharram FA, El Dib RA, El-Hossary DG. Novel macrocyclic monoterpene glycosides from bioactive extract of Parkinsonia aculeata L. Cell Biochem Biophys. 2013 Apr;65(3):301-13. doi: 10.1007/s12013-012-9433-3.

[25] Saravanan S, Arunachalam K, Parimelazhagan T. Antioxidant, analgesic, anti-inflammatory and antipyretic effects of polyphenols from Passiflora subpeltata leaves-A promising species of Passiflora. Indust Crops Prod. 2014;54:272-80. https://doi.org/10.1016/j.indcrop.2014.01.038.

[26] Gowda D, Muguli G, Deshpande R, Paramesh R. Phytochemical and pharmacological actions of Triphala: Ayurvedic formulation-a review. Inter J Pharm Sci Rev Res 2012;15:61-5.

[27] Ren X, Bao Y, Zhu Y, Liu S, Peng Z, Zhang Y, Zhou G. Isorhamnetin, Hispidulin, and Cirsimaritin Identified in Tamarix ramosissima Barks from Southern Xinjiang and Their Antioxidant and Antimicrobial Activities. Molecules. 2019 Jan 22;24(3):390. doi: 10.3390/molecules24030390.

[28] Panthong A, Kanjanapothi D, Taesotikul T, Wongcome T, Reutrakul V. Anti-inflammatory and antipyretic properties of Clerodendrum petasites S. Moore. J Ethnopharmacol. 2003 Mar;85(1):151-6. doi: 10.1016/s0378-8741(02)00368-9.

[29] Cheriet T, Ben-Bachir B, Thamri O, Seghiri R, Mancini I. Isolation and Biological Properties of the Natural Flavonoids Pectolinarin and Pectolinarigenin-A Review. Antibiotics (Basel). 2020 Jul 16;9(7):417. doi: 10.3390/antibiotics9070417.

[30] Bai J, Wu Y, Wang X, Liu X, Zhong K, Huang Y, et al. In vitro and in vivo characterization of the antibacterial activity and membrane damage mechanism of quinic acid against Staphylococcus aureus. J Food Saf. 2018;38(1):e12416. https://doi.org/10.1111/jfs.12416

[31] Aouey B, Samet AM, Fetoui H, Simmonds MSJ, Bouaziz M. Anti-oxidant, anti-inflammatory, analgesic and antipyretic activities of grapevine leaf extract (Vitis vinifera) in mice and identification of its active constituents by LC-MS/MS analyses. Biomed Pharmacother. 2016 Dec;84:1088-1098. doi: 10.1016/j.biopha.2016.10.033.

[32] El-Mekkawy S, Shahat AA, Alqahtani AS, Alsaid MS, Abdelfattah MAO, Ullah R, et al. A Polyphenols-Rich Extract from Moricandia sinaica Boiss. Exhibits Analgesic, Anti-Inflammatory and Antipyretic Activities In Vivo. Molecules. 2020 Oct 30;25(21):5049. doi: 10.3390/molecules25215049.

[33] Mokbel MS, Hashinaga F. Antibacterial and antioxidant activities of banana (Musa, AAA cv. Cavendish) fruits peel. Am J Biochem Biotechnol 2005;1(3):125-31. https://doi.org/10.3844/ajbbsp.2005.125.131.

[34] Dahiya DD, Tembare R, Gurav S, G.P S, Mani T. An review of phytochemical constituents and pharmacological activity of Plumeria species. Int J Curr Pharm Res 2012; 4:1-6.

[35] Afifi MS, Salama OM, Gohar AA, Marzouk AM. Iridoids with antimicrobial activity from Plumeria alba L. Bull Pharm Sci 2006;29(1):215-23. doi: 10.21608/bfsa.2006.65194.

[36] Kaithwas G, Mukherjee A, Chaurasia AK, Majumdar DK. Anti-inflammatory, analgesic and antipyretic activities of Linum usitatissimum L. (flaxseed/linseed) fixed oil. Indian J Exp Biol. 2011 Dec;49(12):932-8.

[37] Dilika F, Bremner PD, Meyer JJ. Antibacterial activity of linoleic and oleic acids isolated from Helichrysum pedunculatum: a plant used during circumcision rites. Fitoterapia. 2000 Aug;71(4):450-2. doi: 10.1016/s0367-326x(00)00150-7.

[38] Shah AS, Alagawadi KR. Anti-inflammatory, analgesic and antipyretic properties of Thespesia populnea Soland ex. Correa seed extracts and its fractions in animal models. J Ethnopharmacol. 2011 Oct 11;137(3):1504-9. doi: 10.1016/j.jep.2011.08.038.

[39] Dantas da Silva LL, Nascimento M, Siqueira Silva DH, Furlan M, da Silva Bolzani V. Antibacterial activity of a stearic acid derivative from Stemodia foliosa. Planta Med. 2002 Dec;68(12):1137-9. doi: 10.1055/s-2002-36346.

[40] Seubnooch P, Wattanarangsan J, Thamsermsang O, Booranasubkajorn S, Laohapand T, Akarasereenont P. Chemical profiling of an antipyretic drug, Thai herbal Harak formula, by liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Siriraj Med J. 2018;70(2):159-68. [cited 2024 Apr. 3]. Available from: https://he02.tci-thaijo.org/index.php/sirirajmedj/article/view/127514.

[41] Tuchinda P, Pohmakotr M, Reutrakul V, Thanyachareon W, Sophasan S, Yoosook C, Santisuk T, Pezzuto JM. 2-substituted furans from Polyalthia suberosa. Planta Med. 2001 Aug;67(6):572-5. doi: 10.1055/s-2001-16469.

[42] Akter F, Tania SA, Muslim T, Rahman MA. Phytochemical studies and fatty acid analysis of the stems of Polyalthia suberosa (Roxb.). J Pharmacogn Phytochem 2019;8(4):1744-7.

[43] Bhattacharya S, Roy B. Preliminary investigation on antipyretic activity of cuscuta reflexa in rats. J Adv Pharm Technol Res. 2010 Jan;1(1):83-7.

[44] Nunomura R, Oliveira VG, Da Silva SL, Nunomura SM. Characterization of bergenin in Endopleura uchi bark and its anti-inflammatory activity. J Brazil Chem Soc 2009;20:1060-4. https://doi.org/10.1590/S0103-50532009000600009

[45] Aladejana EB. Biological properties of polyherbal formulations: a review of their antimicrobial, anti-inflammatory, antioxidant, and toxicological activities. Pharmacog J 2023;15(5):933-63. DOI:10.5530/pj.2023.15.178

[46] Juckmeta T, Itharat A. Anti-inflammatory and antioxidant activities of Thai traditional remedy called “Ya-Ha-Rak”. J Health Res 2017;26(4):205-10. [cited 2024 Apr. 3]. Available from: https://he01.tci-thaijo.org/index.php/jhealthres/article/view/85440

[47] Palo T, Thaworn A, Charoenkij P, Thamsermsang O, Chotewuttakorn S, Tripatara P, et al. The Effects of Thai Herbal Ha-Rak Formula on COX Isoform Expression in Human Umbilical Vein Endothelial Cells Induced by IL-1β. Evid Based Complement Alternat Med. 2017; 2017:9383272. doi: 10.1155/2017/9383272.

[48] Hwang JH, Ma JN, Park JH, Jung HW, Park YK. Anti-inflammatory and antioxidant effects of MOK, a polyherbal extract, on lipopolysaccharide‑stimulated RAW 264.7 macrophages. Int J Mol Med. 2019 Jan;43(1):26-36. doi: 10.3892/ijmm.2018.3937.

[49] Subin P, Sabuhom P, Naladta A, Luecha P, Nualkaew S, Nualkaew N. An Evaluation of the Anti-Inflammatory Effects of a Thai Traditional Polyherbal Recipe TPDM6315 in LPS-Induced RAW264.7 Macrophages and TNF-α-Induced 3T3-L1 Adipocytes. Curr Issues Mol Biol. 2023 Jun 5;45(6):4891-4907. doi: 10.3390/cimb45060311.

[50] Nyemb J, Djankou M, Talla E, Tchinda A, Ngoudjou D. Antimicrobial, α-glucosidase and alkaline phosphatase inhibitory activities of bergenin, the major constituent of Cissus populnea roots. Med Chem (Los Angeles) 2018;8:426-30. DOI:10.4172/2161-0444.1000492

[51] Nayaka HB, Londonkar RL, Umesh MK, Tukappa A. Antibacterial Attributes of Apigenin, Isolated from Portulaca oleracea L. Int J Bacteriol. 2014;2014:175851. doi: 10.1155/2014/175851.

[52] Patel K, Gadewar M, Tahilyani V, Patel DK. A review on pharmacological and analytical aspects of diosmetin: a concise report. Chin J Integr Med. 2013 Oct;19(10):792-800. doi: 10.1007/s11655-013-1595-3.

[53] van Tonder A, Joubert AM, Cromarty AD. Limitations of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay when compared to three commonly used cell enumeration assays. BMC Res Notes. 2015 Feb 20;8:47. doi: 10.1186/s13104-015-1000-8.

[54] Chanthavong V, Shrestha B, Thairat S, Srithavaj T, Thaweboon S. Biological properties and active components of Ocimum. Asia Pac J Sci Technol. 2021;27(3): APST-27-03-07. [cited 2024 Apr. 3]. Available from: https://so01.tci-thaijo.org/index.php/APST/article/view/257477

[55] Jeena K, Liju VB, Kuttan R. Antitumor and cytotoxic activity of ginger essential oil (Zingiber officinale Roscoe). Int J Pharm Sci. 2015;7(8):341-4.

[56] Akter F, Muslim T, Rahman MA. Phytochemical screening and biological studies of the stems of Polyalthia suberosa (Roxb.). J Pharmacogn Phytochem 2020;9(2):682-6.

[57] Yasmen N, Aziz M, Tajmim A, Akter M, Hazra AK, Rahman S. Analgesic and anti-inflammatory activities of diethyl ether and n-hexane extract of Polyalthia suberosa leaves. Evid Based Complement Alternat Med 2018; 5617234. https://doi.org/10.1155/2018/56172342018.

[58] Sireeratawong S, Lertprasertsuke N, Srisawat U, Thuppia A, Ngamjariyawat A, Suwanlikhid N, et al. Acute and subchronic toxicity study of the water extract from Tiliacora triandra (Colebr.) Diels in rats. Songklanakarin J Sci Technol 2008;30(5). 611-9.

[59] Yadav RK, Nandy BC, Maity S, Sarkar S, Saha S. Phytochemistry, pharmacology, toxicology, and clinical trial of Ficus racemosa. Pharmacogn Rev. 2015 Jan-Jun;9(17):73-80. doi: 10.4103/0973-7847.156356.

[60] Phomarat S, Kantawong S, Chalom K. Investigation on the outbreak of influenza in behavior modification camp on drug users, Mueang District, Lamphun Province. Lanna Pub Health J 2021;17(1):1-11.[ in Thai].

[61] Alimohamadi Y, Holakouie-Naieni K, Sepandi M, Taghdir M. Effect of Social Distancing on COVID-19 Incidence and Mortality in Iran Since February 20 to May 13, 2020: An Interrupted Time Series Analysis. Risk Manag Healthc Policy. 2020 Sep 23;13:1695-1700. doi: 10.2147/RMHP.S265079.

[62] Lomarat T, Nakphan T. Evalution on efficacy of favipiravir for treatment of Covid-19 at Kutkhaopun Hospital Ubonratchathani Province. J Health Environ Ed 2022;7(2):8-16. [in Thai].

[63] Chen C, Zhang Y, Huang J, Yin P, Cheng Z, Wu J, et al. Favipiravir Versus Arbidol for Clinical Recovery Rate in Moderate and Severe Adult COVID-19 Patients: A Prospective, Multicenter, Open-Label, Randomized Controlled Clinical Trial. Front Pharmacol. 2021 Sep 2;12:683296. doi: 10.3389/fphar.2021.683296.

[64] Thubthawee P. Influenza and currently licensed anti-influenza drugs. Thai J Pharm Prac 2021;13(3):714-727.

[65] Whitley RJ, Hayden FG, Reisinger KS, Young N, Dutkowski R, Ipe D, Mills RG, Ward P. Oral oseltamivir treatment of influenza in children. Pediatr Infect Dis J. 2001 Feb;20(2):127-33. doi: 10.1097/00006454-200102000-00002.

[66] Puangkaew N, Udompittayasan J, Sukdang K, Rattanama P, Hlong N. A study of herbal folk medicine wisdom to treat the flu: case study of Mr. Jitr Boonluang, Wang Wiset District, Trang Province. Thai J Pub Health Health Sci 2021;4(3):111-22.

[67] Jongchanapong A, Singharachai C, Palanuvej C, Ruangrungsi N, Towiwat P. Antipyretic and antinociceptive effects of Ben-Cha-Lo-Ka-Wi-Chian remedy. J Health Res 2010; 24(1):15-22. [cited 2024 Apr. 3]. Available from: https://he01.tci-thaijo.org/index.php/jhealthres/article/view/156632.

[68] Yang J, Jit M, Zheng Y, Feng L, Liu X, Wu JT, et al. The impact of influenza on the health related quality of life in China: an EQ-5D survey. BMC Infect Dis. 2017 Oct 16;17(1):686. doi: 10.1186/s12879-017-2801-2.

[69] Panyasai K, Kitisri C. Effectiveness of health promotion programs for quality of life basic need among the elderly. PHJBUU 2017;12(2):65-74.

[70] Natarajan A, Shetty A, Delanerolle G, Zeng Y, Zhang Y, Raymont V, et al. A systematic review and meta-analysis of long COVID symptoms. Syst Rev. 2023 May 27;12(1):88. doi: 10.1186/s13643-023-02250-0.

[71] Kobayashi H, de Mejía E. The genus Ardisia: a novel source of health-promoting compounds and phytopharmaceuticals. J Ethnopharmacol. 2005 Jan 15;96(3):347-54. doi: 10.1016/j.jep.2004.09.037.

[72] Bukhari S, Feuerherm A, Boulfrad F, Zlatković B, Johansen B, Simic N. Anti-inflammatory and antioxidant activities of Sclerochloa dura (Poaceae). J Serb Chem Soc. 2014; 79(7): 779-791. doi: 10.2298/JSC131202003B.

[73] Lawrence R, Tripathi P, Jeyakumar E. Isolation, Purification and Evaluation of Antibacterial Agents from Aloe vera. Braz J Microbiol. 2009 Oct;40(4):906-15. doi: 10.1590/S1517-838220090004000023.

[74] Zhou M, Xie Z, Guan W, Zhang J. Comparative analysis of bioactive constituents and pharmacological activities from different parts of Nauclea officinalis. Biomed Chromatogr. 2021 Dec;35(12):e5214. doi: 10.1002/bmc.5214.

[75] Rahman MM, Lopa SS, Sadik G, Harun-Or-Rashid, Islam R, Khondkar P, et al. Antibacterial and cytotoxic compounds from the bark of Cananga odorata. Fitoterapia. 2005 Dec;76(7-8):758-61. doi: 10.1016/j.fitote.2005.08.011.

[76] Li Y, Yang Y, Kang X, Li X, Wu Y, Xiao J, et al. Study on The Anti-Inflammatory Effects of Callicarpa nudiflora Based on The Spectrum-Effect Relationship. Front Pharmacol. 2022 Jan 27;12:806808. doi: 10.3389/fphar.2021.806808.

[77] Syafni N, Putra DP, Arbain D. 3, 4-dihydroxybenzoic acid and 3, 4-dihydroxybenzaldehyde from the fern Trichomanes chinense L.; isolation, antimicrobial and antioxidant properties. Indones J Chem. 2012;12(3):273-8. https://doi.org/10.22146/ijc.21342

[78] Chen C, Zhang Y, Huang J, Yin P, Cheng Z, Wu J, et al. Favipiravir versus arbidol for clinical recovery rate in moderate and severe adult COVID-19 patients: a prospective, multicenter, open-label, randomized controlled clinical trial. Front Pharmacol. 2021 Sep 2;12:683296. doi: 10.3389/fphar.2021.683296.

[79] Liu YL, He WJ, Mo L, Shi MF, Zhu YY, Pan S, et al. Antimicrobial, anti-inflammatory activities and toxicology of phenylethanoid glycosides from Monochasma savatieri Franch. ex Maxim. J Ethnopharmacol. 2013 Sep 16;149(2):431-7. doi: 10.1016/j.jep.2013.06.042.

[80] Sarfraz A, Javeed M, Shah MA, Hussain G, Shafiq N, Sarfraz I, et al. Biochanin A: a novel bioactive multifunctional compound from nature. Sci Total Environ. 2020 Jun 20;722:137907. doi: 10.1016/j.scitotenv.2020.137907.

[81] Osawa K, Yasuda H, Morita H, Takeya K, Itokawa H. Macrocarpals H, I, and J from the Leaves of Eucalyptus globulus. J Nat Prod. 1996 Sep;59(9):823-7. doi: 10.1021/np9604994.

[82] Xie C, Kang J, Burris R, Ferguson ME, Schauss AG, Nagarajan S, Wu X. Açaí juice attenuates atherosclerosis in ApoE deficient mice through antioxidant and anti-inflammatory activities. Atherosclerosis. 2011 Jun;216(2):327-33. doi: 10.1016/j.atherosclerosis.2011.02.035.

[83] Sucharitha A, Devi PUM. Antimicrobial properties of chilli lipoxygenase products. Afr J Microbiol Res 2010;4(9):748-52.

[84] Mohri S, Takahashi H, Sakai M, Takahashi S, Waki N, Aizawa K, et al. Wide-range screening of anti-inflammatory compounds in tomato using LC-MS and elucidating the mechanism of their functions. PLoS One. 2018 Jan 12;13(1):e0191203. doi: 10.1371/journal.pone.0191203.

[85] Shikov AN, Pozharitskaya ON, Makarov VG, Makarova MN. Anti-inflammatory effect of Pinus sibirica oil extract in animal models. J Nat Med. 2008 Oct;62(4):436-40. doi: 10.1007/s11418-008-0254-z.

[86] Bhattacharyya R, Medhi KK, Borkataki S. Phytochemical analysis of Drymaria cordata (L.) Willd. ex Schult. (whole plant) used by tea tribes of erstwhile Nagaon district of Assam, India. Int J Pharm Sci Res. 2019;10:4264-9. DOI: 10.13040/IJPSR.0975-8232.10(9).4264-69.

[87] Paul A, Vibhuti A, Raj V. Evaluation of antiviral activity of Andrographis paniculata and Tinospora cordifolia using in silico and in vitro assay against DENV-2. J Pharmacogn Phytochem. 2021;10:486-96. DOI: 10.22271/phyto.2021.v10.i2f.13847

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