The Role of Adaptogens in Prophylaxis and Treatment of Viral Respiratory Infections

Alexander Panossian, Thomas Brendler, Alexander Panossian, Thomas Brendler

Abstract

The aim of our review is to demonstrate the potential of herbal preparations, specifically adaptogens for prevention and treatment of respiratory infections, as well as convalescence, specifically through supporting a challenged immune system, increasing resistance to viral infection, inhibiting severe inflammatory progression, and driving effective recovery. The evidence from pre-clinical and clinical studies with Andrographis paniculata, Eleutherococcus senticosus, Glycyrrhiza spp., Panax spp., Rhodiola rosea, Schisandra chinensis, Withania somnifera, their combination products and melatonin suggests that adaptogens can be useful in prophylaxis and treatment of viral infections at all stages of progression of inflammation as well as in aiding recovery of the organism by (i) modulating innate and adaptive immunity, (ii) anti-inflammatory activity, (iii) detoxification and repair of oxidative stress-induced damage in compromised cells, (iv) direct antiviral effects of inhibiting viral docking or replication, and (v) improving quality of life during convalescence.

Keywords: Andrographis; Eleutherococcus; Glycyrrhiza; Panax; Rhodiola; Schisandra; Withania; adaptogens; melatonin; viral infection.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic diagram of reported effects of adaptogenic plants elucidated in animal and cell culture models: (i) modulatory effects on immune response (blue block), (ii) anti-inflammatory activity (green bock), (iii) detoxification and repair of oxidative stress-induced damage in compromised cells (brown block), and (iv) direct antiviral effect via infraction with viral docking or replication (red block).
Figure 2
Figure 2
Schematic diagram of various phases of immune and inflammatory responses to SARS-CoV-2 infection and stages of COVID-19 progression with and without considering potential effects of adaptogenic plants on prevention, infection, inflammation, and recovery phases of viral infection.

References

    1. Azkur A.K., Akdis M., Azkur D., Sokolowska M., van de Veen W., Brüggen M.C., O’Mahony L., Gao Y., Nadeau K., Akdis C.A. Immune response to SARS-CoV-2 and mechanisms of immunopathological changes in COVID-19. Allergy. 2020;75:1564–1581. doi: 10.1111/all.14364.
    1. Tay M.Z., Poh C.M., Rénia L., MacAry P.A., Ng L.F.P. The trinity of COVID-19: Immunity, inflammation and intervention. Nat. Rev. Immunol. 2020;20:363–374. doi: 10.1038/s41577-020-0311-8.
    1. Vardhana S.A., Wolchok J.D. The many faces of the anti-COVID immune response. J. Exp. Med. 2020;217 doi: 10.1084/jem.20200678.
    1. Li G., Fan Y., Lai Y., Han T., Li Z., Zhou P., Pan P., Wang W., Hu D., Liu X., et al. Coronavirus infections and immune responses. J. Med. Virol. 2020;92:424–432. doi: 10.1002/jmv.25685.
    1. Schijns V., Lavelle E.C. Prevention and treatment of COVID-19 disease by controlled modulation of innate immunity. Eur. J. Immunol. 2020;50:932–938. doi: 10.1002/eji.202048693.
    1. Lega S., Naviglio S., Volpi S., Tommasini A. Recent Insight into SARS-CoV2 Immunopathology and Rationale for Potential Treatment and Preventive Strategies in COVID-19. Vaccines. 2020;8:224. doi: 10.3390/vaccines8020224.
    1. Yang R., Liu H., Bai C., Wang Y., Zhang X., Guo R., Wu S., Wang J., Leung E., Chang H., et al. Chemical composition and pharmacological mechanism of Qingfei Paidu Decoction and Ma Xing Shi Gan Decoction against Coronavirus Disease 2019 (COVID-19): In silico and experimental study. Pharmacol. Res. 2020;157:104820. doi: 10.1016/j.phrs.2020.104820.
    1. Sakurai A., Sasaki T., Kato S., Hayashi M., Tsuzuki S.-I., Ishihara T., Iwata M., Morise Z., Doi Y. Natural History of Asymptomatic SARS-CoV-2 Infection. N. Engl. J. Med. 2020 doi: 10.1056/NEJMc2013020.
    1. Alberts B., Johnson A., Lewis J., Raff M., Roberts K., Walter P. Molecular Biology of the Cell. 4th ed. Garland Science; New York, NY, USA: 2002. Innate immunity.
    1. Efferth T., Koch E. Complex Interactions between Phytochemicals. The Multi-Target Therapeutic Concept of Phytotherapy. Curr. Drug Targets. 2011;12:122–132. doi: 10.2174/138945011793591626.
    1. Panossian A., Seo E.-J., Efferth T. Novel molecular mechanisms for the adaptogenic effects of herbal extracts on isolated brain cells using systems biology. Phytomedicine. 2018;50:257–284. doi: 10.1016/j.phymed.2018.09.204.
    1. Panossian A. Understanding adaptogenic activity: Specificity of the pharmacological action of adaptogens and other phytochemicals. Ann. N. Y. Acad. Sci. 2017;1401:49–64. doi: 10.1111/nyas.13399.
    1. Lazarev N.V., Ljublina E.I., Rozin M.A. State of nonspecific resistance. Patol. Fiziol. Experim. Ter. 1959;3:16–21.
    1. Brekhman I., Dardymov I. New substances of plant origin which increase nonspecific resistance. Annu. Rev. Pharmacol. 1969;9:419–430. doi: 10.1146/annurev.pa.09.040169.002223.
    1. Wagner H., Nörr H., Winterhoff H. Plant adaptogens. Phytomedicine. 1994;1:63–76. doi: 10.1016/S0944-7113(11)80025-5.
    1. Yang Y.M., Noh K., Han C.Y., Kim S.G. Transactivation of Genes Encoding for Phase II Enzymes and Phase III Transporters by Phytochemical Antioxidants. Molecules. 2010;15:6332–6348. doi: 10.3390/molecules15096332.
    1. Pooladanda V., Thatikonda S., Godugu C. The current understanding and potential therapeutic options to combat COVID-19. Life Sci. 2020;254:117765. doi: 10.1016/j.lfs.2020.117765.
    1. Khodadadi E., Maroufi P., Khodadadi E., Esposito I., Ganbarov K., Espsoito S., Yousefi M., Zeinalzadeh E., Kafil H.S. Study of combining virtual screening and antiviral treatments of the Sars-CoV-2 (Covid-19) Microb. Pathog. 2020;146:104241. doi: 10.1016/j.micpath.2020.104241.
    1. Mani J.S., Johnson J.B., Steel J.C., Broszczak D.A., Neilsen P.M., Walsh K.B., Naiker M. Natural product-derived phytochemicals as potential agents against coronaviruses: A review. Virus Res. 2020;284:197989. doi: 10.1016/j.virusres.2020.197989.
    1. Mirza M.U., Froeyen M. Structural elucidation of SARS-CoV-2 vital proteins: Computational methods reveal potential drug candidates against main protease, Nsp12 polymerase and Nsp13 helicase. J. Pharm. Anal. 2020 doi: 10.1016/j.jpha.2020.04.008.
    1. Saber-Ayad M., Saleh M.A., Abu-Gharbieh E. The Rationale for Potential Pharmacotherapy of COVID-19. Pharmaceuticals. 2020;13:96. doi: 10.3390/ph13050096.
    1. Wu C., Liu Y., Yang Y., Zhang P., Zhong W., Wang Y., Wang Q., Xu Y., Li M., Li X., et al. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm. Sin. B. 2020;10:766–788. doi: 10.1016/j.apsb.2020.02.008.
    1. Zhou H., Fang Y., Xu T., Ni W.-J., Shen A.-Z., Meng X.-M. Potential therapeutic targets and promising drugs for combating SARS-CoV-2. Br. J. Pharmacol. 2020;177:3147–3161. doi: 10.1111/bph.15092.
    1. Kamitani W., Narayanan K., Huang C., Lokugamage K., Ikegami T., Ito N., Kubo H., Makino S. Severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene expression by promoting host mRNA degradation. Proc. Natl. Acad. Sci. USA. 2006;103:12885–12890. doi: 10.1073/pnas.0603144103.
    1. Kuba K., Imai Y., Rao S., Gao H., Guo F., Guan B., Huan Y., Yang P., Zhang Y., Deng W., et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury. Nat. Med. 2005;11:875–879. doi: 10.1038/nm1267.
    1. Li W., Moore M.J., Vasilieva N., Sui J., Wong S.K., Berne M.A., Somasundaran M., Sullivan J.L., Luzuriaga K., Greenough T.C., et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426:450–454. doi: 10.1038/nature02145.
    1. Li M.-Y., Li L., Zhang Y., Wang X.-S. Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infect. Dis Poverty. 2020;9:1–7. doi: 10.1186/s40249-020-00662-x.
    1. Hamid S., Mir M.Y., Rohela G.K. Novel coronavirus disease (COVID-19): A pandemic (epidemiology, pathogenesis and potential therapeutics) N. Microbes N. Infect. 2020;35:100679. doi: 10.1016/j.nmni.2020.100679.
    1. Yi Y., Lagniton P.N.P., Ye S., Li E., Xu R.-H. COVID-19: What has been learned and to be learned about the novel coronavirus disease. Int. J. Biol. Sci. 2020;16:1753–1766. doi: 10.7150/ijbs.45134.
    1. Peron J.P.S., Nakaya H. Susceptibility of the Elderly to SARS-CoV-2 Infection: ACE-2 Overexpression, Shedding, and Antibody-dependent Enhancement (ADE) Clinics. 2020;75 doi: 10.6061/clinics/2020/e1912.
    1. Cinatl J., Morgenstern B., Bauer G., Chandra P., Rabenau H., Doerr H.W. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet. 2003;361:2045–2046. doi: 10.1016/S0140-6736(03)13615-X.
    1. Hoever G., Baltina L., Michaelis M., Kondratenko R., Baltina L., Tolstikov G.A., Doerr H.W., Cinatl J. Antiviral Activity of Glycyrrhizic Acid Derivatives against SARS−Coronavirus. J. Med. Chem. 2005;48:1256–1259. doi: 10.1021/jm0493008.
    1. Fiore C., Eisenhut M., Krausse R., Ragazzi E., Pellati D., Armanini D., Bielenberg J. Antiviral effects of Glycyrrhiza species. Phytother. Res. 2008;22:141–148. doi: 10.1002/ptr.2295.
    1. Cui Q., Du R., Anantpadma M., Schafer A., Hou L., Tian J., Davey R.A., Cheng H., Rong L. Identification of Ellagic Acid from Plant Rhodiola rosea L. as an Anti-Ebola Virus Entry Inhibitor. Viruses. 2018;10:152. doi: 10.3390/v10040152.
    1. Glatthaar-Saalmüller B., Sacher F., Esperester A. Antiviral activity of an extract derived from roots of Eleutherococcus senticosus. Antivir. Res. 2001;50:223–228. doi: 10.1016/S0166-3542(01)00143-7.
    1. Wang X.-Q., Li H.-Y., Liu X.-Y., Zhang F.-M., Li X., Piao Y.-A., Xie Z.-P., Chen Z.-H., Li X. The anti-respiratory syncytial virus effect of active compound of Glycyrrhiza GD4 in vitro. Zhong Yao Cai. 2006;29:692–694.
    1. Lee J.S., Ko E.-J., Hwang H.S., Lee Y.-N., Kwon Y.-M., Kim M.-C., Kang S.-M. Antiviral activity of ginseng extract against respiratory syncytial virus infection. Int. J. Mol. Med. 2014;34:183–190. doi: 10.3892/ijmm.2014.1750.
    1. 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;19:605–615. doi: 10.1016/j.micinf.2017.08.009.
    1. Yu B., Dai C.Q., Jiang Z.Y., Li E.Q., Chen C., Wu X.L., Chen J., Liu Q., Zhao C.L., He J.X., et al. Andrographolide as an anti-H1N1 drug and the mechanism related to retinoic acid-inducible gene-I-like receptors signaling pathway. Chin. J. Integr. Med. 2014;20:540–545. doi: 10.1007/s11655-014-1860-0.
    1. Ko H.-C., Wei B.-L., Chiou W.-F. The effect of medicinal plants used in Chinese folk medicine on RANTES secretion by virus-infected human epithelial cells. J. Ethnopharmacol. 2006;107:205–210. doi: 10.1016/j.jep.2006.03.004.
    1. Fedorov Y.V., Vasilyeva O.A., Vasilyev N.V. Effect of some stimulants of plant origin on the development of antibodies and immunomorphological reactions during acarid-borne encephalitis. Cent. Nerv. Syst. Stimul. 1966;1:99–105.
    1. Protasova S.F., Zykov M.P. New Data on Eleutherococcus, Proceedings of the II International Symposium on Eleutherococcus, Moscow, USSR, 1984. Far East Academy of Sciences of the USSR; Vladivostok, USSR: 1986. Antiviral effect of Eleutherococcus in experimental influenza infection; pp. 123–126.
    1. Yan W., Chen J., Wei Z., Wang X., Zeng Z., Tembo D., Wang Y., Wang X. Effect of eleutheroside B1 on non-coding RNAs and protein profiles of influenza A virus-infected A549 cells. Int. J. Mol. Med. 2020;45:753–768. doi: 10.3892/ijmm.2020.4468.
    1. Yan W., Zheng C., He J., Zhang W., Huang X.A., Li X., Wang Y., Wang X. Eleutheroside B1 mediates its anti-influenza activity through POLR2A and N-glycosylation. Int. J. Mol. Med. 2018;42:2776–2792. doi: 10.3892/ijmm.2018.3863.
    1. Wolkerstorfer A., Kurz H., Bachhofner N., Szolar O.H.J. Glycyrrhizin inhibits influenza A virus uptake into the cell. Antivir. Res. 2009;83:171–178. doi: 10.1016/j.antiviral.2009.04.012.
    1. Choi J.-G., Jin Y.-H., Lee H., Oh T.W., Yim N.-H., Cho W.-K., Ma J.Y. Protective Effect of Panax notoginseng Root Water Extract against Influenza A Virus Infection by Enhancing Antiviral Interferon-Mediated Immune Responses and Natural Killer Cell Activity. Front. Immunol. 2017;8:1542. doi: 10.3389/fimmu.2017.01542.
    1. Dong W., Farooqui A., Leon A.J., Kelvin D.J. Inhibition of influenza A virus infection by ginsenosides. PLoS ONE. 2017;12:e0171936. doi: 10.1371/journal.pone.0171936.
    1. Kim E.-H., Kim S.-W., Park S.-J., Kim S., Yu K.-M., Kim S.G., Lee S.H., Seo Y.-K., Cho N.-H., Kang K., et al. Greater Efficacy of Black Ginseng (CJ EnerG) over Red Ginseng against Lethal Influenza A Virus Infection. Nutrients. 2019;11:1879. doi: 10.3390/nu11081879.
    1. Lee J.S., Hwang H.S., Ko E.-J., Lee Y.-N., Kwon Y.-M., Kim M.-C., Kang S.-M. Immunomodulatory Activity of Red Ginseng against Influenza A Virus Infection. Nutrients. 2014;6:517–529. doi: 10.3390/nu6020517.
    1. Wang Y., Jung Y.-J., Kim K.-H., Kwon Y., Kim Y.-J., Zhang Z., Kang H.-S., Wang B.-Z., Quan F.-S., Kang S.-M. Antiviral Activity of Fermented Ginseng Extracts against a Broad Range of Influenza Viruses. Viruses. 2018;10:471. doi: 10.3390/v10090471.
    1. Xu M.L., Kim H.J., Choi Y.R., Kim H.-J. Intake of Korean red ginseng extract and saponin enhances the protection conferred by vaccination with inactivated influenza a virus. J. Ginseng Res. 2012;36:396–402. doi: 10.5142/jgr.2012.36.4.396.
    1. Yin S.Y., Kim H.J., Kim H.-J. A Comparative Study of the Effects of Whole Red Ginseng Extract and Polysaccharide and Saponin Fractions on Influenza A (H1N1) Virus Infection. Biol. Pharm. Bull. 2013;36:1002–1007. doi: 10.1248/bpb.b13-00123.
    1. Yoo D.G., Kim M.C., Park M.K., Song J.M., Quan F.S., Park K.M., Cho Y.K., Kang S.M. Protective Effect of Korean Red Ginseng Extract on the Infections by H1N1 and H3N2 Influenza Viruses in Mice. J. Med. Food. 2012;15:855–862. doi: 10.1089/jmf.2012.0017.
    1. Jeong H.J., Ryu Y.B., Park S.-J., Kim J.H., Kwon H.-J., Kim J.H., Park K.H., Rho M.-C., Lee W.S. Neuraminidase inhibitory activities of flavonols isolated from Rhodiola rosea roots and their in vitro anti-influenza viral activities. Bioorganic Med. Chem. 2009;17:6816–6823. doi: 10.1016/j.bmc.2009.08.036.
    1. Utsunomiya T., Kobayashi M., Pollard R.B., Suzuki F. Glycyrrhizin, an active component of licorice roots, reduces morbidity and mortality of mice infected with lethal doses of influenza virus. Antimicrob. Agents Chemother. 1997;41:551. doi: 10.1128/AAC.41.3.551.
    1. Park E.H., Yum J., Ku K.B., Kim H.M., Kang Y.M., Kim J.C., Kim J.A., Kang Y.K., Seo S.H. Red Ginseng-containing diet helps to protect mice and ferrets from the lethal infection by highly pathogenic H5N1 influenza virus. J. Ginseng Res. 2014;38:40–46. doi: 10.1016/j.jgr.2013.11.012.
    1. Sornpet B., Potha T., Tragoolpua Y., Pringproa K. Antiviral activity of five Asian medicinal pant crude extracts against highly pathogenic H5N1 avian influenza virus. Asian Pac. J. Trop. Med. 2017;10:871–876. doi: 10.1016/j.apjtm.2017.08.010.
    1. Michaelis M., Geiler J., Naczk P., Sithisarn P., Ogbomo H., Altenbrandt B., Leutz A., Doerr H.W., Cinatl J. Glycyrrhizin inhibits highly pathogenic H5N1 influenza A virus-induced pro-inflammatory cytokine and chemokine expression in human macrophages. Med. Microbiol. Immunol. 2010;199:291–297. doi: 10.1007/s00430-010-0155-0.
    1. Panraksa P., Ramphan S., Khongwichit S., Smith D.R. Activity of andrographolide against dengue virus. Antivir. Res. 2017;139:69–78. doi: 10.1016/j.antiviral.2016.12.014.
    1. Ramalingam S., Karupannan S., Padmanaban P., Vijayan S., Sheriff K., Palani G., Krishnasamy K.K. Anti-dengue activity of Andrographis paniculata extracts and quantification of dengue viral inhibition by SYBR green reverse transcription polymerase chain reaction. AYU. 2018;39:87–91. doi: 10.4103/ayu.AYU_144_17.
    1. Wintachai P., Kaur P., Lee R.C.H., Ramphan S., Kuadkitkan A., Wikan N., Ubol S., Roytrakul S., Chu J.J.H., Smith D.R. Activity of andrographolide against chikungunya virus infection. Sci. Rep. 2015;5:14179. doi: 10.1038/srep14179.
    1. Diwaker D., Mishra K.P., Ganju L., Singh S.B. Rhodiola inhibits dengue virus multiplication by inducing innate immune response genes RIG-I, MDA5 and ISG in human monocytes. Arch. Virol. 2014;159:1975–1986. doi: 10.1007/s00705-014-2028-0.
    1. Wang H., Ding Y., Zhou J., Sun X., Wang S. The in vitro and in vivo antiviral effects of salidroside from Rhodiola rosea L. against coxsackievirus B3. Phytomedicine. 2009;16:146–155. doi: 10.1016/j.phymed.2008.07.013.
    1. Jain J., Narayanan V., Chaturvedi S., Pai S., Sunil S. In Vivo Evaluation of Withania somnifera–Based Indian Traditional Formulation (Amukkara Choornam), Against Chikungunya Virus–Induced Morbidity and Arthralgia. J. Evid. Based Integr. Med. 2018;23 doi: 10.1177/2156587218757661.
    1. Enmozhi S.K., 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. 2020:1–7. doi: 10.1080/07391102.2020.1760136.
    1. Zhang D.-H., Wu K.-L., Zhang X., Deng S.-Q., Peng B. In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus. J. Integr. Med. 2020;18:152–158. doi: 10.1016/j.joim.2020.02.005.
    1. Murck H. Symptomatic Protective Action of Glycyrrhizin (Licorice) in COVID-19 Infection? Front. Immunol. 2020;11:1239. doi: 10.3389/fimmu.2020.01239.
    1. Shao Z.-J., Zheng X.-W., Feng T., Huang J., Chen J., Wu Y.-Y., Zhou L.-M., Tu W.-W., Li H. Andrographolide exerted its antimicrobial effects by upregulation of human β-defensin-2 induced through p38 MAPK and NF-κB pathway in human lung epithelial cells. Can. J. Physiol. Pharmacol. 2012;90:647–653. doi: 10.1139/y2012-050.
    1. Xiong W.-B., Shao Z.-J., Xiong Y., Chen J., Sun Y., Zhu L., Zhou L.-M. Dehydroandrographolide enhances innate immunity of intestinal tract through up-regulation the expression of hBD-2. Daru J. Pharm. Sci. 2015;23:37. doi: 10.1186/s40199-015-0119-4.
    1. Gao H., Wang J. Andrographolide inhibits multiple myeloma cells by inhibiting the TLR4/NF-κB signaling pathway. Mol. Med. Rep. 2016;13:1827–1832. doi: 10.3892/mmr.2015.4703.
    1. Kim A.-Y., Shim H.-J., Shin H.-M., Lee Y.J., Nam H., Kim S.Y., Youn H.-S. Andrographolide suppresses TRIF-dependent signaling of toll-like receptors by targeting TBK1. Int. Immunopharmacol. 2018;57:172–180. doi: 10.1016/j.intimp.2018.02.019.
    1. Han S.B., Yoon Y.D., Ahn H.J., Lee H.S., Lee C.W., Yoon W.K., Park S.K., Kim H.M. Toll-like receptor-mediated activation of B cells and macrophages by polysaccharide isolated from cell culture of Acanthopanax senticosus. Int. Immunopharmacol. 2003;3:1301–1312. doi: 10.1016/S1567-5769(03)00118-8.
    1. Lee S., Lee H.H., Shin Y.S., Kang H., Cho H. The anti-HSV-1 effect of quercetin is dependent on the suppression of TLR-3 in Raw 264.7 cells. Arch. Pharmacal Res. 2017;40:623–630. doi: 10.1007/s12272-017-0898-x.
    1. Lee S.A., Lee S.H., Kim J.Y., Lee W.S. Effects of glycyrrhizin on lipopolysaccharide-induced acute lung injury in a mouse model. J. Thorac. Dis. 2019;11:1287–1302. doi: 10.21037/jtd.2019.04.14.
    1. Peng L.N., Li L., Qiu Y.F., Miao J.H., Gao X.Q., Zhou Y., Shi Z.X., Xu Y.L., Shao D.H., Wei J.C., et al. Glycyrrhetinic acid extracted from Glycyrrhiza uralensis Fisch. induces the expression of Toll-like receptor 4 in Ana-1 murine macrophages. J. Asian Nat. Prod. Res. 2011;13:942–950. doi: 10.1080/10286020.2011.603305.
    1. Schröfelbauer B., Raffetseder J., Hauner M., Wolkerstorfer A., Ernst W., Szolar Oliver H.J. Glycyrrhizin, the main active compound in liquorice, attenuates pro-inflammatory responses by interfering with membrane-dependent receptor signalling. Biochem. J. 2009;421:473–482. doi: 10.1042/BJ20082416.
    1. Wang Q., Shen J., Yan Z., Xiang X., Mu R., Zhu P., Yao Y., Zhu F., Chen K., Chi S., et al. Dietary Glycyrrhiza uralensis extracts supplementation elevated growth performance, immune responses and disease resistance against Flavobacterium columnare in yellow catfish (Pelteobagrus fulvidraco) Fish. Shellfish Immunol. 2020;97:153–164. doi: 10.1016/j.fsi.2019.12.048.
    1. Ahn H., Han B.-C., Kim J., Kang S.G., Kim P.-H., Jang K.H., So S.H., Lee S.-H., Lee G.-S. Nonsaponin fraction of Korean Red Ginseng attenuates cytokine production via inhibition of TLR4 expression. J. Ginseng Res. 2019;43:291–299. doi: 10.1016/j.jgr.2018.03.003.
    1. Ahn J.Y., Choi I.S., Shim J.Y., Yun E.K., Yun Y.S., Jeong G., Song J.Y. The immunomodulator ginsan induces resistance to experimental sepsis by inhibiting Toll-like receptor-mediated inflammatory signals. Eur. J. Immunol. 2006;36:37–45. doi: 10.1002/eji.200535138.
    1. Kim T.-W., Joh E.-H., Kim B., Kim D.-H. Ginsenoside Rg5 ameliorates lung inflammation in mice by inhibiting the binding of LPS to toll-like receptor-4 on macrophages. Int. Immunopharmacol. 2012;12:110–116. doi: 10.1016/j.intimp.2011.10.023.
    1. Nakaya T.A., Kita M., Kuriyama H., Iwakura Y., Imanishi J. Panax ginseng Induces Production of Proinflammatory Cytokines via Toll-like Receptor. J. Interferon Cytokine Res. 2004;24:93–100. doi: 10.1089/107999004322813336.
    1. Nguyen C.T., Luong T.T., Lee S.Y., Kim G.L., Kwon H., Lee H.-G., Park C.-K., Rhee D.-K. Panax ginseng aqueous extract prevents pneumococcal sepsis in vivo by potentiating cell survival and diminishing inflammation. Phytomedicine. 2015;22:1055–1061. doi: 10.1016/j.phymed.2015.07.005.
    1. Paik S., Choe J.H., Choi G.-E., Kim J.-E., Kim J.-M., Song G.Y., Jo E.-K. Rg6, a rare ginsenoside, inhibits systemic inflammation through the induction of interleukin-10 and microRNA-146a. Sci. Rep. 2019;9:4342. doi: 10.1038/s41598-019-40690-8.
    1. Mishra K.P., Ganju L., Chanda S., Karan D., Sawhney R.C. Aqueous extract of Rhodiola imbricata rhizome stimulates Toll-like receptor 4, granzyme-B and Th1 cytokines in vitro. Immunobiology. 2009;214:27–31. doi: 10.1016/j.imbio.2008.04.001.
    1. Mishra K.P., Ganju L., Singh S.B. Anti-cellular and immunomodulatory potential of aqueous extract of Rhodiola imbricata rhizome. Immunopharmacol. Immunotoxicol. 2012;34:513–518. doi: 10.3109/08923973.2011.638307.
    1. Shan Y., Jiang B., Yu J., Wang J., Wang X., Li H., Wang C., Chen J., Sun J. Protective Effect of Schisandra chinensis Polysaccharides Against the Immunological Liver Injury in Mice Based on Nrf2/ARE and TLR4/NF-κB Signaling Pathway. J. Med. Food. 2019;22:885–895. doi: 10.1089/jmf.2018.4377.
    1. Sun K., Huang R., Yan L., Li D.-T., Liu Y.-Y., Wei X.-H., Cui Y.-C., Pan C.-S., Fan J.-Y., Wang X., et al. Schisandrin Attenuates Lipopolysaccharide-Induced Lung Injury by Regulating TLR-4 and Akt/FoxO1 Signaling Pathways. Front. Physiol. 2018;9:1104. doi: 10.3389/fphys.2018.01104.
    1. Zhao T., Feng Y., Li J., Mao R., Zou Y., Feng W., Zheng D., Wang W., Chen Y., Yang L., et al. Schisandra polysaccharide evokes immunomodulatory activity through TLR 4-mediated activation of macrophages. Int. J. Biol. Macromol. 2014;65:33–40. doi: 10.1016/j.ijbiomac.2014.01.018.
    1. Maitra R., Porter M.A., Huang S., Gilmour B.P. Inhibition of NFκB by the natural product Withaferin A in cellular models of Cystic Fibrosis inflammation. J. Inflamm. 2009;6:15. doi: 10.1186/1476-9255-6-15.
    1. Kang J.-W., Koh E.-J., Lee S.-M. Melatonin protects liver against ischemia and reperfusion injury through inhibition of toll-like receptor signaling pathway. J. Pineal Res. 2011;50:403–411. doi: 10.1111/j.1600-079X.2011.00858.x.
    1. Kim S.W., Kim S., Son M., Cheon J.H., Park Y.S. Melatonin controls microbiota in colitis by goblet cell differentiation and antimicrobial peptide production through Toll-like receptor 4 signalling. Sci. Rep. 2020;10:2232. doi: 10.1038/s41598-020-59314-7.
    1. Kowalewska M., Herman A.P., Szczepkowska A., Skipor J. The effect of melatonin from slow-release implants on basic and TLR-4-mediated gene expression of inflammatory cytokines and their receptors in the choroid plexus in ewes. Res. Vet. Sci. 2017;113:50–55. doi: 10.1016/j.rvsc.2017.09.003.
    1. Lucas K., Maes M. Role of the Toll Like Receptor (TLR) Radical Cycle in Chronic Inflammation: Possible Treatments Targeting the TLR4 Pathway. Mol. Neurobiol. 2013;48:190–204. doi: 10.1007/s12035-013-8425-7.
    1. Xu X., Wang G., Ai L., Shi J., Zhang J., Chen Y.-X. Melatonin suppresses TLR9-triggered proinflammatory cytokine production in macrophages by inhibiting ERK1/2 and AKT activation. Sci. Rep. 2018;8:15579. doi: 10.1038/s41598-018-34011-8.
    1. Panossian A., Davtyan T., Gukassyan N., Gukasova G., Mamikonyan G., Gabrielian E., Wikman G. Effect of Andrographolide and Kan Jang—Fixed combination of extract SHA-10 and extract SHE-3—On proliferation of human lymphocytes, production of cytokines and immune activation markers in the whole blood cells culture. Phytomedicine. 2002;9:598–605. doi: 10.1078/094471102321616409.
    1. Zykov M.P., Protasova S.F. New Data on Eleutherococcus, Proceedings of the 2nd International Symposium on Eleutherococcus, Moscow, 1984. Far East Academy of Sciences of the USSR; Vladivostok, USSR: 1986. Prospects of immunostimulating vaccination against influenza including the use of Eleutherococcus and other preparations of plant origin; pp. 118–122.
    1. Bohn B., Nebe C.T., Birr C. Flow-cytometric studies with eleutherococcus senticosus extract as an immunomodulatory agent. Arzneim. Forsch. 1987;37:1193–1196.
    1. Bohn B., Nebe C.T., Birr C. Immunopharmacological effects of eleutherococcus senticosus extract as determined by quantitative flow cytometry. Int. J. Immunopharmacol. 1988;10:67. doi: 10.1016/0192-0561(88)90326-8.
    1. Kupin V.I., Polevaya E.S., Sorokin A.M. New Data on Eleutherococcus, Proceedings of the 2nd International Symposium on Eleutherococcus, Moscow, 1984. Far East Academy of Sciences of the USSR; Vladivostok, USSR: 1986. Increased immunologic reactivity of lymphocytes in oncologic patients treated with Eleutherococcus extract; pp. 216–220.
    1. Wacker A. Über die Interferon induzierende und immunstimulierende Wirkung von Eleutherococcus. Erfahrungsheilkunde. 1983;32:339–343.
    1. Wacker A., Eichler A., Lodemann E. New Data on Eleutherococcus, Proceedings of the 2nd International Symposium on Eleutherococcus, Moscow, 1984. Far East Academy of Sciences of the USSR; Vladivostok, USSR: 1986. The molecular mechanism of virus inhibition by Eleutherococcus; pp. 13–15.
    1. Wacker A., Eilmes H.G. Virushemmung mit Eleutherokokk Fluid-Extrakt. Erfahrungsheilkunde. 1978;27:346–351.
    1. Kour K., Pandey A., Suri K.A., Satti N.K., Gupta K.K., Bani S. Restoration of stress-induced altered T cell function and corresponding cytokines patterns by Withanolide A. Int. Immunopharmacol. 2009;9:1137–1144. doi: 10.1016/j.intimp.2009.05.011.
    1. Malik F., Singh J., Khajuria A., Suri K.A., Satti N.K., Singh S., Kaul M.K., Kumar A., Bhatia A., Qazi G.N. A standardized root extract of Withania somnifera and its major constituent withanolide-A elicit humoral and cell-mediated immune responses by up regulation of Th1-dominant polarization in BALB/c mice. Life Sci. 2007;80:1525–1538. doi: 10.1016/j.lfs.2007.01.029.
    1. Khan B., Ahmad S.F., Bani S., Kaul A., Suri K.A., Satti N.K., Athar M., Qazi G.N. Augmentation and proliferation of T lymphocytes and Th-1 cytokines by Withania somnifera in stressed mice. Int. Immunopharmacol. 2006;6:1394–1403. doi: 10.1016/j.intimp.2006.04.001.
    1. Khan S., Malik F., Suri K.A., Singh J. Molecular insight into the immune up-regulatory properties of the leaf extract of Ashwagandha and identification of Th1 immunostimulatory chemical entity. Vaccine. 2009;27:6080–6087. doi: 10.1016/j.vaccine.2009.07.011.
    1. Chao W.-W., Kuo Y.-H., Hsieh S.-L., Lin B.-F. Inhibitory effects of ethyl acetate extract of Andrographis paniculata on NF-κB trans-activation activity and LPS-induced acute inflammation in mice. Evid. Based Complementary Altern. Med. 2011;2011:254531. doi: 10.1093/ecam/nep120.
    1. Panossian A., Hambartsumyan M., Panosyan L., Abrahamyan H., Mamikonyan G., Gabrielyan E., Amaryan G., Astvatsatryan V., Wikman G. Plasma nitric oxide level in familial Mediterranean fever and its modulations by Immuno-Guard. Nitric Oxide. 2003;9:103–110. doi: 10.1016/j.niox.2003.08.005.
    1. Jin L., Schmiech M., El Gaafary M., Zhang X., Syrovets T., Simmet T. A comparative study on root and bark extracts of Eleutherococcus senticosus and their effects on human macrophages. Phytomedicine. 2020;68:153181. doi: 10.1016/j.phymed.2020.153181.
    1. Panossian A.G. Adaptogens: Tonic Herbs for Fatigue and Stress. Altern. Complementary Ther. 2003;9:327–331. doi: 10.1089/107628003322658610.
    1. Chen S., Li X., Wang Y., Mu P., Chen C., Huang P., Liu D. Ginsenoside Rb1 attenuates intestinal ischemia/reperfusion-induced inflammation and oxidative stress via activation of the PI3K/Akt/Nrf2 signaling pathway. Mol. Med. Rep. 2019;19:3633–3641. doi: 10.3892/mmr.2019.10018.
    1. Iqbal H., Rhee D.-K. Ginseng alleviates microbial infections of the respiratory tract: A review. J. Ginseng Res. 2020;44:194–204. doi: 10.1016/j.jgr.2019.12.001.
    1. Zhou F., Wang M., Ju J., Wang Y., Liu Z., Zhao X., Yan Y., Yan S., Luo X., Fang Y. Schizandrin A protects against cerebral ischemia-reperfusion injury by suppressing inflammation and oxidative stress and regulating the AMPK/Nrf2 pathway regulation. Am. J. Transl. Res. 2019;11:199–209.
    1. Vanden Berghe W., Sabbe L., Kaileh M., Haegeman G., Heyninck K. Molecular insight in the multifunctional activities of Withaferin, A. Biochem. Pharmacol. 2012;84:1282–1291. doi: 10.1016/j.bcp.2012.08.027.
    1. Sánchez-López A.L., Ortiz G.G., Pacheco-Moises F.P., Mireles-Ramírez M.A., Bitzer-Quintero O.K., Delgado-Lara D.L.C., Ramírez-Jirano L.J., Velázquez-Brizuela I.E. Efficacy of Melatonin on Serum Pro-inflammatory Cytokines and Oxidative Stress Markers in Relapsing Remitting Multiple Sclerosis. Arch. Med. Res. 2018;49:391–398. doi: 10.1016/j.arcmed.2018.12.004.
    1. Schmolz M.W., Sacher F., Aicher B. The synthesis of Rantes, G-CSF, IL-4, IL-5, IL-6, IL-12 and IL-13 in human whole-blood cultures is modulated by an extract from Eleutherococcus senticosus L. roots. Phytother. Res. 2001;15:268–270. doi: 10.1002/ptr.746.
    1. Maurya S.P., Das B.K., Singh R., Tyagi S. Effect of Withania somnifer on CD38 expression on CD8+ T lymphocytes among patients of HIV infection. Clin. Immunol. 2019;203:122–124. doi: 10.1016/j.clim.2019.04.003.
    1. Kishore V., Yarla N.S., Zameer F., Nagendra Prasad M.N., Santosh M.S., More S.S., Rao D.G., Dhananjaya B.L. Inhibition of Group IIA Secretory Phospholipase A2 and its Inflammatory Reactions in Mice by Ethanolic Extract of Andrographis paniculata, a Well-known Medicinal Food. Pharmacogn. Res. 2016;8:213–216. doi: 10.4103/0974-8490.182916.
    1. Li Y., Zhao H., Wang Y., Zheng H., Yu W., Chai H., Zhang J., Falck J.R., Guo A.M., Yue J., et al. Isoliquiritigenin induces growth inhibition and apoptosis through downregulating arachidonic acid metabolic network and the deactivation of PI3K/Akt in human breast cancer. Toxicol. Appl. Pharmacol. 2013;272:37–48. doi: 10.1016/j.taap.2013.05.031.
    1. Wang Y., Wang S., Bao Y., Li T., Chang X., Yang G., Meng X. Multipathway Integrated Adjustment Mechanism of Glycyrrhiza Triterpenes Curing Gastric Ulcer in Rats. Pharm. Mag. 2017;13:209–215. doi: 10.4103/0973-1296.204550.
    1. Xie C., Li X., Wu J., Liang Z., Deng F., Xie W., Zhu M., Zhu J., Zhu W., Geng S., et al. Anti-inflammatory Activity of Magnesium Isoglycyrrhizinate Through Inhibition of Phospholipase A2/Arachidonic Acid Pathway. Inflammation. 2015;38:1639–1648. doi: 10.1007/s10753-015-0140-2.
    1. Cha T.W., Kim M., Kim M., Chae J.S., Lee J.H. Blood pressure-lowering effect of Korean red ginseng associated with decreased circulating Lp-PLA 2 activity and lysophosphatidylcholines and increased dihydrobiopterin level in prehypertensive subjects. Hypertens. Res. 2016;39:449–456. doi: 10.1038/hr.2016.7.
    1. Irfan M., Kim M., Rhee M.H. Anti-platelet role of Korean ginseng and ginsenosides in cardiovascular diseases. J. Ginseng Res. 2020;44:24–32. doi: 10.1016/j.jgr.2019.05.005.
    1. Kim D.Y., Ro J.Y., Lee C.H. 20(S)-Protopanaxatriol inhibits release of inflammatory mediators in immunoglobulin E-mediated mast cell activation. J. Ginseng Res. 2015;39:189–198. doi: 10.1016/j.jgr.2014.11.001.
    1. Shin J.-H., Kwon H.-W., Rhee M.H., Park H.-J. Inhibitory effects of thromboxane A2 generation by ginsenoside Ro due to attenuation of cytosolic phospholipase A2 phosphorylation and arachidonic acid release. J. Ginseng Res. 2019;43:236–241. doi: 10.1016/j.jgr.2017.12.007.
    1. Bawa A.S., Khanum F. Anti-inflammatory activity of Rhodiola rosea—“A second-generation adaptogen”. Phytother. Res. 2009;23:1099–1102. doi: 10.1002/ptr.2749.
    1. Ohkura Y., Mizoguchi Y., Morisawa S., Takeda S., Aburada M., Hosoya E. Effect of Gomisin A (TJN-101) on the Arachidonic Acid Cascade in Macrophages. Jpn. J. Pharmacol. 1990;52:331–336. doi: 10.1254/jjp.52.331.
    1. Lizano S., Domont G., Perales J. Natural phospholipase A2 myotoxin inhibitor proteins from snakes, mammals and plants. Toxicon. 2003;42:963–977. doi: 10.1016/j.toxicon.2003.11.007.
    1. Machiah D.K., Gowda T.V. Purification of a post-synaptic neurotoxic phospholipase A2 from Naja naja venom and its inhibition by a glycoprotein from Withania somnifera. Biochimie. 2006;88:701–710. doi: 10.1016/j.biochi.2005.12.006.
    1. Madhusudan M., Zameer F., Naidu A., Dhananjaya B.L., Hegdekatte R. Evaluating the inhibitory potential of Withania somnifera on platelet aggregation and inflammation enzymes: An in vitro and in silico study. Pharm. Biol. 2016;54:1936–1941. doi: 10.3109/13880209.2015.1123729.
    1. Chao W.-W., Kuo Y.-H., Li W.-C., Lin B.-F. The production of nitric oxide and prostaglandin E2 in peritoneal macrophages is inhibited by Andrographis paniculata, Angelica sinensis and Morus alba ethyl acetate fractions. J. Ethnopharmacol. 2009;122:68–75. doi: 10.1016/j.jep.2008.11.029.
    1. Panossian A., Seo E.-J., Efferth T. Effects of anti-inflammatory and adaptogenic herbal extracts on gene expression of eicosanoids signaling pathways in isolated brain cells. Phytomedicine. 2019;60:152881. doi: 10.1016/j.phymed.2019.152881.
    1. Amroyan E., Gabrielian E., Panossian A., Wikman G., Wagner H. Inhibitory effect of andrographolide from Andrographis paniculata on PAF-induced platelet aggregation. Phytomedicine. 1999;6:27–31. doi: 10.1016/S0944-7113(99)80031-2.
    1. Burgos R.A., Hidalgo M.A., Monsalve J., LaBranche T.P., Eyre P., Hancke J.L. 14-deoxyandrographolide as a platelet activating factor antagonist in bovine neutrophils. Planta Med. 2005;71:604–608. doi: 10.1055/s-2005-871264.
    1. Jung K.Y., Kim D.S., Oh S.R., Lee I.S., Lee J.J., Park J.D., Kim S.I., Lee H.-K. Platelet Activating Factor Antagonist Activity of Ginsenosides. Biol. Pharm. Bull. 1998;21:79–80. doi: 10.1248/bpb.21.79.
    1. Teng C.-M., Kuo S.-C., Ko F.-N., Lee J.-C., Lee L.-G., Chen S.-C., Huang T.-F. Antiplatelet actions of panaxynol and ginsenosides isolated from ginseng. Biochim. Biophys. Acta Gen. Subj. 1989;990:315–320. doi: 10.1016/S0304-4165(89)80051-0.
    1. Jung K.Y., Lee I.S., Oh S.R., Kim D.S., Lee H.K. Lignans with platelet activating factor antagonist activity from Schisandra chinensis (Turcz.) Baill. Phytomedicine. 1997;4:229–231. doi: 10.1016/S0944-7113(97)80072-4.
    1. Lee I.S., Jung K.Y., Oh S.R., Park S.H., Ahn K.S., Lee H.-K. Structure-Activity Relationships of Lignans from Schisandra chinensis as Platelet Activating Factor Antagonists. Biol. Pharm. Bull. 1999;22:265–267. doi: 10.1248/bpb.22.265.
    1. Chiou W.-F., Chen C.-F., Lin J.-J. Mechanisms of suppression of inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells by andrographolide. Br. J. Pharmacol. 2000;129:1553–1560. doi: 10.1038/sj.bjp.0703191.
    1. Panossian A., Hambardzumyan M., Hovhanissyan A., Wikman G. The Adaptogens Rhodiola and Schizandra Modify the Response to Immobilization Stress in Rabbits by Suppressing the Increase of Phosphorylated Stress-activated Protein Kinase, Nitric Oxide and Cortisol. Drug Target. Insights. 2007;2 doi: 10.1177/117739280700200011.
    1. Dai Y., Chen S.-R., 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:S17–S29. doi: 10.1080/10408398.2018.1501657.
    1. Fei X.J., Zhu L.L., Xia L.M., Peng W.B., Wang Q. Acanthopanax senticosus attenuates inflammation in lipopolysaccharide-induced acute lung injury by inhibiting the NF-κB pathway. Genet. Mol. Res. 2014;13:10537–10544. doi: 10.4238/2014.December.12.16.
    1. Han J., Liu L., Yu N., Chen J., Liu B., Yang D., Shen G. Polysaccharides from Acanthopanax senticosus enhances intestinal integrity through inhibiting TLR4/NF-κB signaling pathways in lipopolysaccharide-challenged mice. Anim. Sci. J. 2016;87:1011–1018. doi: 10.1111/asj.12528.
    1. Kim J.-A., Kim D.-K., Jin T., Kang O.-H., Choi Y.-A., Choi S.-C., Kim T.-H., Nah Y.-H., Choi S.-J., Kim Y.-H., et al. Acanthoic acid inhibits IL-8 production via MAPKs and NF-κB in a TNF-α-stimulated human intestinal epithelial cell line. Clin. Chim. Acta. 2004;342:193–202. doi: 10.1016/j.cccn.2004.01.004.
    1. Lin Q.-Y., Jin L.-J., Cao Z.-H., Li H.-Q., Xu Y.-P. Protective effect of Acanthopanax senticosus extract against endotoxic shock in mice. J. Ethnopharmacol. 2008;118:495–502. doi: 10.1016/j.jep.2008.05.018.
    1. Lin Q.-Y., Jin L.-J., Cao Z.-H., Xu Y.-P. Inhibition of inducible nitric oxide synthase by Acanthopanax senticosus extract in RAW264.7 macrophages. J. Ethnopharmacol. 2008;118:231–236. doi: 10.1016/j.jep.2008.04.003.
    1. Kim H.S., Park S.Y., Kim E.K., Ryu E.Y., Kim Y.H., Park G., Lee S.J. Acanthopanax senticosus has a heme oxygenase-1 signaling-dependent effect on Porphyromonas gingivalis lipopolysaccharide-stimulated macrophages. J. Ethnopharmacol. 2012;142:819–828. doi: 10.1016/j.jep.2012.06.006.
    1. Wang X., Zhuang X., Wei R., Wang C., Xue X., Mao L. Protective effects of Acanthopanax vs. Ulinastatin against severe acute pancreatitis-induced brain injury in rats. Int. Immunopharmacol. 2015;24:285–298. doi: 10.1016/j.intimp.2014.12.020.
    1. Yamazaki T., Shimosaka S., Sasaki H., Matsumura T., Tukiyama T., Tokiwa T. (+)-Syringaresinol-di-O-β-d-glucoside, a phenolic compound from Acanthopanax senticosus Harms, suppresses proinflammatory mediators in SW982 human synovial sarcoma cells by inhibiting activating protein-1 and/or nuclear factor-κB activities. Toxicol. Vitr. 2007;21:1530–1537. doi: 10.1016/j.tiv.2007.04.016.
    1. Zhang A., Liu Z., Sheng L., Wu H. Protective effects of syringin against lipopolysaccharide-induced acute lung injury in mice. J. Surg. Res. 2017;209:252–257. doi: 10.1016/j.jss.2016.10.027.
    1. Kang B., Kim C.Y., Hwang J., Sun S., Yang H., Suh H.J., Choi H.-S. Red ginseng extract regulates differentiation of monocytes to macrophage and inflammatory signalings in human monocytes. Food Sci. Biotechnol. 2019;28:1819–1828. doi: 10.1007/s10068-019-00611-x.
    1. Oh G.S., Pae H.O., Choi B.M., Seo E.A., Kim D.H., Shin M.K., Kim J.D., Kim J.B., Chung H.T. 20(S)-Protopanaxatriol, one of ginsenoside metabolites, inhibits inducible nitric oxide synthase and cyclooxygenase-2 expressions through inactivation of nuclear factor-κB in RAW 264.7 macrophages stimulated with lipopolysaccharide. Cancer Lett. 2004;205:23–29. doi: 10.1016/j.canlet.2003.09.037.
    1. Surh Y.-J., Lee J.-Y., Choi K.-J., Ko S.-R. Effects of Selected Ginsenosides on Phorbol Ester-Induced Expression of Cyclooxygenase-2 and Activation of NF-κB and ERK1/2 in Mouse Skin. Ann. N. Y. Acad. Sci. 2002;973:396–401. doi: 10.1111/j.1749-6632.2002.tb04672.x.
    1. Surh Y.J., Na H.K., Lee J.Y., Keum Y.S. Molecular mechanisms underlying anti-tumor promoting activities of heat-processed Panax ginseng C.A. Meyer. J. Korean Med. Sci. 2001;16:S38–S41. doi: 10.3346/jkms.2001.16.S.S38.
    1. Keum Y.-S., Han S.S., Chun K.-S., Park K.-K., Park J.-H., Lee S.K., Surh Y.-J. Inhibitory effects of the ginsenoside Rg3 on phorbol ester-induced cyclooxygenase-2 expression, NF-κB activation and tumor promotion. Mutat. Res. Fundam. Mol. Mech. Mutagenesis. 2003;523–524:75–85. doi: 10.1016/S0027-5107(02)00323-8.
    1. Borgonetti V., Governa P., Biagi M., Dalia P., Corsi L. Rhodiola rosea L. modulates inflammatory processes in a CRH-activated BV2 cell model. Phytomedicine. 2020;68:153143. doi: 10.1016/j.phymed.2019.153143.
    1. Hu R., Wang M.-Q., Ni S.-H., Wang M., Liu L.-Y., You H.-Y., Wu X.-H., Wang Y.-J., Lu L., Wei L.-B. Salidroside ameliorates endothelial inflammation and oxidative stress by regulating the AMPK/NF-κB/NLRP3 signaling pathway in AGEs-induced HUVECs. Eur. J. Pharmacol. 2020;867:172797. doi: 10.1016/j.ejphar.2019.172797.
    1. Li J.-S., Fan L.-Y., Yuan M.-D., Xing M.-Y. Salidroside Inhibits Lipopolysaccharide-ethanol-induced Activation of Proinflammatory Macrophages via Notch Signaling Pathway. Curr. Med. Sci. 2019;39:526–533. doi: 10.1007/s11596-019-2069-4.
    1. Tang H., Gao L., Mao J., He H., Liu J., Cai X., Lin H., Wu T. Salidroside protects against bleomycin-induced pulmonary fibrosis: Activation of Nrf2-antioxidant signaling, and inhibition of NF-κB and TGF-β1/Smad-2/-3 pathways. Cell Stress Chaperones. 2016;21:239–249. doi: 10.1007/s12192-015-0654-4.
    1. Xin X., Yao D., Zhang K., Han S., Liu D., Wang H., Liu X., Li G., Huang J., Wang J. Protective effects of Rosavin on bleomycin-induced pulmonary fibrosis via suppressing fibrotic and inflammatory signaling pathways in mice. Biomed. Pharmacother. 2019;115:108870. doi: 10.1016/j.biopha.2019.108870.
    1. Xu F., Xu J., Xiong X., Deng Y. Salidroside inhibits MAPK, NF-κB, and STAT3 pathways in psoriasis-associated oxidative stress via SIRT1 activation. Redox Rep. 2019;24:70–74. doi: 10.1080/13510002.2019.1658377.
    1. Zhang P., Li Y., Guo R., Zang W. Salidroside Protects Against Advanced Glycation End Products-Induced Vascular Endothelial Dysfunction. Med. Sci. Monit. 2018;24:2420–2428. doi: 10.12659/MSM.906064.
    1. Zhang X., Lai W., Ying X., Xu L., Chu K., Brown J., Chen L., Hong G. Salidroside Reduces Inflammation and Brain Injury After Permanent Middle Cerebral Artery Occlusion in Rats by Regulating PI3K/PKB/Nrf2/NFκB Signaling Rather than Complement C3 Activity. Inflammation. 2019;42:1830–1842. doi: 10.1007/s10753-019-01045-7.
    1. Ci X., Ren R., Xu K., Li H., Yu Q., Song Y., Wang D., Li R., Deng X. Schisantherin A Exhibits Anti-inflammatory Properties by Down-Regulating NF-κB and MAPK Signaling Pathways in Lipopolysaccharide-Treated RAW 264.7 Cells. Inflammation. 2010;33:126–136. doi: 10.1007/s10753-009-9166-7.
    1. Kwon D.H., Cha H.-J., Choi E.O., Leem S.-H., Kim G.-Y., Moon S.-K., Chang Y.-C., Yun S.-J., Hwang H.J., Kim B.W., et al. Schisandrin A suppresses lipopolysaccharide-induced inflammation and oxidative stress in RAW 264.7 macrophages by suppressing the NF-κB, MAPKs and PI3K/Akt pathways and activating Nrf2/HO-1 signaling. Int. J. Mol. Med. 2018;41:264–274. doi: 10.3892/ijmm.2017.3209.
    1. Luo G., Cheng B.C.-Y., Zhao H., Fu X.-Q., Xie R., Zhang S.-F., Pan S.-Y., Zhang Y. Schisandra Chinensis Lignans Suppresses the Production of Inflammatory Mediators Regulated by NF-κB, AP-1, and IRF3 in Lipopolysaccharide-Stimulated RAW264.7 Cells. Molecules. 2018;23:3319. doi: 10.3390/molecules23123319.
    1. Ran J., Ma C., Xu K., Xu L., He Y., Moqbel S.A.A., Hu P., Jiang L., Chen W., Bao J., et al. Schisandrin B ameliorated chondrocytes inflammation and osteoarthritis via suppression of NF-κB and MAPK signal pathways. Drug Des. Devel. Ther. 2018;12:1195–1204. doi: 10.2147/DDDT.S162014.
    1. Song F.-J., Zeng K.-W., Chen J.-F., Li Y., Song X.-M., Tu P.-F., Wang X.-M. Extract of Fructus Schisandrae chinensis Inhibits Neuroinflammation Mediator Production from Microglia via NF-κ B and MAPK Pathways. Chin. J. Integr. Med. 2019;25:131–138. doi: 10.1007/s11655-018-3001-7.
    1. Heyninck K., Lahtela-Kakkonen M., Van der Veken P., Haegeman G., Vanden Berghe W. Withaferin A inhibits NF-kappaB activation by targeting cysteine 179 in IKKβ. Biochem. Pharmacol. 2014;91:501–509. doi: 10.1016/j.bcp.2014.08.004.
    1. Mulabagal V., Subbaraju G.V., Rao C.V., Sivaramakrishna C., DeWitt D.L., Holmes D., Sung B., Aggarwal B.B., Tsay H.-S., Nair M.G. Withanolide sulfoxide from Aswagandha roots inhibits nuclear transcription factor-kappa-B, cyclooxygenase and tumor cell proliferation. Phytother. Res. 2009;23:987–992. doi: 10.1002/ptr.2736.
    1. Oh J.H., Kwon T.K. Withaferin A inhibits tumor necrosis factor-α-induced expression of cell adhesion molecules by inactivation of Akt and NF-κB in human pulmonary epithelial cells. Int. Immunopharmacol. 2009;9:614–619. doi: 10.1016/j.intimp.2009.02.002.
    1. Singh D., Aggarwal A., Maurya R., Naik S. Withania somnifera inhibits NF-κB and AP-1 transcription factors in human peripheral blood and synovial fluid mononuclear cells. Phytother. Res. 2007;21:905–913. doi: 10.1002/ptr.2180.
    1. Moniruzzaman M., Ghosal I., Das D., Chakraborty S.B. Melatonin ameliorates H2O2-induced oxidative stress through modulation of Erk/Akt/NFkB pathway. Biol. Res. 2018;51 doi: 10.1186/s40659-018-0168-5.
    1. Adeoye B.O., Asenuga E.R., Oyagbemi A.A., Omobowale T.O., Adedapo A.A. The Protective Effect of the Ethanol Leaf Extract of Andrographis Paniculata on Cisplatin-Induced Acute Kidney Injury in Rats Through nrf2/KIM-1 Signalling Pathway. Drug Res. 2018;68:23–32. doi: 10.1055/s-0043-118179.
    1. Lee J.-C., Tseng C.-K., Young K.-C., Sun H.-Y., Wang S.-W., Chen W.-C., Lin C.-K., Wu Y.-H. 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;171:237–252. doi: 10.1111/bph.12440.
    1. Lin H.-C., Su S.-L., Lu C.-Y., Lin A.-H., Lin W.-C., Liu C.-S., Yang Y.-C., Wang H.-M., Lii C.-K., Chen H.-W. Andrographolide inhibits hypoxia-induced HIF-1α-driven endothelin 1 secretion by activating Nrf2/HO-1 and promoting the expression of prolyl hydroxylases 2/3 in human endothelial cells. Environ. Toxicol. 2017;32:918–930. doi: 10.1002/tox.22293.
    1. Lu C.-Y., Yang Y.-C., Li C.-C., Liu K.-L., Lii C.-K., Chen H.-W. Andrographolide inhibits TNFα-induced ICAM-1 expression via suppression of NADPH oxidase activation and induction of HO-1 and GCLM expression through the PI3K/Akt/Nrf2 and PI3K/Akt/AP-1 pathways in human endothelial cells. Biochem. Pharmacol. 2014;91:40–50. doi: 10.1016/j.bcp.2014.06.024.
    1. Mussard E., Cesaro A., Lespessailles E., Legrain B., Berteina-Raboin S., Toumi H. Andrographolide, a Natural Antioxidant: An Update. Antioxidants. 2019;8:571. doi: 10.3390/antiox8120571.
    1. Pan C.-W., Yang S.-X., Pan Z.-Z., Zheng B., Wang J.-Z., Lu G.-R., Xue Z.-X., Xu C.-L. Andrographolide ameliorates d-galactosamine/lipopolysaccharide-induced acute liver injury by activating Nrf2 signaling pathway. Oncotarget. 2017;8:41202–41210. doi: 10.18632/oncotarget.17149.
    1. Seo J.Y., Pyo E., An J.-P., Kim J., Sung S.H., Oh W.K. Andrographolide Activates Keap1/Nrf2/ARE/HO-1 Pathway in HT22 Cells and Suppresses Microglial Activation by Aβ42 through Nrf2-Related Inflammatory Response. Mediat. Inflamm. 2017;2017:5906189. doi: 10.1155/2017/5906189.
    1. Tan W.S.D., Liao W., Zhou S., Wong W.S.F. Is there a future for andrographolide to be an anti-inflammatory drug? Deciphering its major mechanisms of action. Biochem. Pharmacol. 2017;139:71–81. doi: 10.1016/j.bcp.2017.03.024.
    1. Wong S.Y., Tan M.G.K., Wong P.T.H., Herr D.R., Lai M.K.P. Andrographolide induces Nrf2 and heme oxygenase 1 in astrocytes by activating p38 MAPK and ERK. J. Neuroinflammation. 2016;13:251. doi: 10.1186/s12974-016-0723-3.
    1. Wang X., Hai C.X., Liang X., Yu S.X., Zhang W., Li Y.L. The protective effects of Acanthopanax senticosus Harms aqueous extracts against oxidative stress: Role of Nrf2 and antioxidant enzymes. J. Ethnopharmacol. 2010;127:424–432. doi: 10.1016/j.jep.2009.10.022.
    1. Chu S.F., Zhang Z., Zhou X., He W.B., Chen C., Luo P., Liu D.D., Ai Q.D., Gong H.F., Wang Z.Z., et al. Ginsenoside Rg1 protects against ischemic/reperfusion-induced neuronal injury through miR-144/Nrf2/ARE pathway. Acta Pharmacol. Sin. 2019;40:13–25. doi: 10.1038/s41401-018-0154-z.
    1. Li J.-P., Gao Y., Chu S.-F., Zhang Z., Xia C.-Y., Mou Z., Song X.-Y., He W.-B., Guo X.-F., Chen N.-H. Nrf2 pathway activation contributes to anti-fibrosis effects of ginsenoside Rg1 in a rat model of alcohol- and CCl4-induced hepatic fibrosis. Acta Pharmacol. Sin. 2014;35:1031–1044. doi: 10.1038/aps.2014.41.
    1. Saw C.L.L., Yang A.Y., Cheng D.C., Boyanapalli S.S.S., Su Z.-Y., Khor T.O., Gao S., Wang J., Jiang Z.-H., Kong A.-N.T. Pharmacodynamics of Ginsenosides: Antioxidant Activities, Activation of Nrf2, and Potential Synergistic Effects of Combinations. Chem. Res. Toxicol. 2012;25:1574–1580. doi: 10.1021/tx2005025.
    1. Shaukat A., Yang C., Yang Y., Guo Y.-F., Jiang K., Guo S., Liu J., Zhang T., Zhao G., Ma X., et al. Ginsenoside Rb 1: A novel therapeutic agent in Staphylococcus aureus-induced Acute Lung Injury with special reference to Oxidative stress and Apoptosis. Microb. Pathog. 2020;143:104109. doi: 10.1016/j.micpath.2020.104109.
    1. Han J., Xiao Q., Lin Y.-H., Zheng Z.-Z., He Z.-D., Hu J., Chen L.-D. Neuroprotective effects of salidroside on focal cerebral ischemia/reperfusion injury involve the nuclear erythroid 2-related factor 2 pathway. Neural Regen Res. 2015;10:1989–1996. doi: 10.4103/1673-5374.172317.
    1. Li R., Wang S., Li T., Wu L., Fang Y., Feng Y., Zhang L., Chen J., Wang X. Salidroside Protects Dopaminergic Neurons by Preserving Complex I Activity via DJ-1/Nrf2-Mediated Antioxidant Pathway. Parkinsons Dis. 2019;2019:6073496. doi: 10.1155/2019/6073496.
    1. Zhu Y., Zhang Y.-J., Liu W.-W., Shi A.-W., Gu N. Salidroside Suppresses HUVECs Cell Injury Induced by Oxidative Stress through Activating the Nrf2 Signaling Pathway. Molecules. 2016;21:1033. doi: 10.3390/molecules21081033.
    1. Gao J., Yu Z., Jing S., Jiang W., Liu C., Yu C., Sun J., Wang C., Chen J., Li H. Protective effect of Anwulignan against D-galactose-induced hepatic injury through activating p38 MAPK-Nrf2-HO-1 pathway in mice. Clin. Interv. Aging. 2018;13:1859–1869. doi: 10.2147/CIA.S173838.
    1. Shen Z., Geng Q., Huang H., Yao H., Du T., Chen L., Wu Z., Miao X., Shi P. Antioxidative and Cardioprotective Effects of Schisandra chinensis Bee Pollen Extract on Isoprenaline-Induced Myocardial Infarction in Rats. Molecules. 2019;24:1090. doi: 10.3390/molecules24061090.
    1. Zhang X., Jing S., Lin H., Sun W., Jiang W., Yu C., Sun J., Wang C., Chen J., Li H. Anti-fatigue effect of anwulignan via the NRF2 and PGC-1α signaling pathway in mice. Food Funct. 2019;10:7755–7766. doi: 10.1039/C9FO01182J.
    1. Heyninck K., Sabbe L., Chirumamilla C.S., Szarc vel Szic K., Vander Veken P., Lemmens K.J.A., Lahtela-Kakkonen M., Naulaerts S., Op de Beeck K., Laukens K., et al. Withaferin A induces heme oxygenase (HO-1) expression in endothelial cells via activation of the Keap1/Nrf2 pathway. Biochem. Pharmacol. 2016;109:48–61. doi: 10.1016/j.bcp.2016.03.026.
    1. Palliyaguru D.L., Chartoumpekis D.V., Wakabayashi N., Skoko J.J., Yagishita Y., Singh S.V., Kensler T.W. Withaferin A induces Nrf2-dependent protection against liver injury: Role of Keap1-independent mechanisms. Free Radic. Biol. Med. 2016;101:116–128. doi: 10.1016/j.freeradbiomed.2016.10.003.
    1. Reuland D.J., Khademi S., Castle C.J., Irwin D.C., McCord J.M., Miller B.F., Hamilton K.L. Upregulation of phase II enzymes through phytochemical activation of Nrf2 protects cardiomyocytes against oxidant stress. Free Radic. Biol. Med. 2013;56:102–111. doi: 10.1016/j.freeradbiomed.2012.11.016.
    1. Shin E.-J., Chung Y.H., Le H.-L.T., Jeong J.H., Dang D.-K., Nam Y., Wie M.B., Nah S.-Y., Nabeshima Y.-I., Nabeshima T., et al. Melatonin Attenuates Memory Impairment Induced by Klotho Gene Deficiency Via Interactive Signaling Between MT2 Receptor, ERK, and Nrf2-Related Antioxidant Potential. Int. J. Neuropsychopharmacol. 2015;18 doi: 10.1093/ijnp/pyu105.
    1. Carota G., Raffaele M., Sorrenti V., Salerno L., Pittalà V., Intagliata S. Ginseng and heme oxygenase-1: The link between an old herb and a new protective system. Fitoterapia. 2019;139:104370. doi: 10.1016/j.fitote.2019.104370.
    1. Asea A., Kaur P., Panossian A., Wikman K.G. Evaluation of molecular chaperons Hsp72 and neuropeptide Y as characteristic markers of adaptogenic activity of plant extracts. Phytomedicine. 2013;20:1323–1329. doi: 10.1016/j.phymed.2013.07.001.
    1. Panossian A., Wikman G., Kaur P., Asea A. Adaptogens exert a stress-protective effect by modulation of expression of molecular chaperones. Phytomedicine. 2009;16:617–622. doi: 10.1016/j.phymed.2008.12.003.
    1. Panossian A., Wikman G., Kaur P., Asea A. Adaptogens Stimulate Neuropeptide Y and Hsp72 Expression and Release in Neuroglia Cells. Front. Neurosci. 2012;6:6. doi: 10.3389/fnins.2012.00006.
    1. Carrillo-Vico A., Lardone P.J., Álvarez-Sánchez N., Rodríguez-Rodríguez A., Guerrero J.M. Melatonin: Buffering the immune system. Int. J. Mol. Sci. 2013;14:8638–8683. doi: 10.3390/ijms14048638.
    1. He B., Zhao Y., Xu L., Gao L., Su Y., Lin N., Pu J. The nuclear melatonin receptor RORα is a novel endogenous defender against myocardial ischemia/reperfusion injury. J. Pineal Res. 2016;60:313–326. doi: 10.1111/jpi.12312.
    1. Thakur A., Dey A., Chatterjee S., Kumar V. Reverse Ayurvedic Pharmacology of Ashwagandha as an Adaptogenic Anti-Diabetic Plant: A Pilot Study. Curr. Tradit. Med. 2015;1:51–61. doi: 10.2174/2215083801999150527115205.
    1. Thakur A.K., Chatterjee S.S., Kumar V. Adaptogenic potential of andrographolide: An active principle of the king of bitters (Andrographis paniculata) J. Tradit. Complementary Med. 2015;5:42–50. doi: 10.1016/j.jtcme.2014.10.002.
    1. Kaur P., Makanjuola V.O., Arora R., Singh B., Arora S. Immunopotentiating significance of conventionally used plant adaptogens as modulators in biochemical and molecular signalling pathways in cell mediated processes. Biomed. Pharmacother. 2017;95:1815–1829. doi: 10.1016/j.biopha.2017.09.081.
    1. EMA . Final Assessment Report on Glycyrrhiza Glabra L. and/or Glycyrrhiza Inflata Bat. and/or Glycyrrhiza Uralensis Fisch., Radix. Committee on Herbal Medicinal Products (HMPC). European Medicines Agency; Amsterdam, The Netherlands: 2013.
    1. EMA . Final Assessment Report on Panax Ginseng C.A. Meyer, Radix. Committee on Herbal Medicinal Products (HMPC). European Medicines Agency; Amsterdam, The Netherlands: 2014.
    1. EMA . Final Assessment Report on Rhodiola Rosea. Committee on Herbal Medicinal Products (HMPC). European Medicines Agency; Amsterdam, The Netherlands: 2012.
    1. Hancke J.L., Burgos R.A., Ahumada F. Schisandra chinensis (Turcz.) Baill. Fitoterapia. 1999;70:451–471. doi: 10.1016/S0367-326X(99)00102-1.
    1. Nowak A., Zakłos-Szyda M., Błasiak J., Nowak A., Zhang Z., Zhang B. Potential of Schisandra chinensis (Turcz.) Baill. in Human Health and Nutrition: A Review of Current Knowledge and Therapeutic Perspectives. Nutrients. 2019;11:333. doi: 10.3390/nu11020333.
    1. Panossian A., Wikman G. Pharmacology of Schisandra chinensis Bail.: An overview of Russian research and uses in medicine. J. Ethnopharmacol. 2008;118:183–212. doi: 10.1016/j.jep.2008.04.020.
    1. Szopa A. Current knowledge of Schisandra chinensis (Turcz.) Baill. (Chinese magnolia vine) as a medicinal plant species: A review on the bioactive components, pharmacological properties, analytical and biotechnological studies. Phytochem. Rev. 2017;16:195–218. doi: 10.1007/s11101-016-9470-4.
    1. Dar N.J., Hamid A., Ahmad M. Pharmacologic overview of Withania somnifera, the Indian Ginseng. Cell. Mol. Life Sci. 2015;72:4445–4460. doi: 10.1007/s00018-015-2012-1.
    1. Kalra R., Kaushik N. Withania somnifera (Linn.) Dunal: A review of chemical and pharmacological diversity. Phytochem. Rev. 2017;16:953–987. doi: 10.1007/s11101-017-9504-6.
    1. Tripathi N., Shrivastava D., Ahmad Mir B., Kumar S., Govil S., Vahedi M., Bisen P.S. Metabolomic and biotechnological approaches to determine therapeutic potential of Withania somnifera (L.) Dunal: A review. Phytomedicine. 2018;50:127–136. doi: 10.1016/j.phymed.2017.08.020.
    1. Reyes B.A.S., Bautista N.D., Tanquilut N.C., Anunciado R.V., Leung A.B., Sanchez G.C., Magtoto R.L., Castronuevo P., Tsukamura H., Maeda K.I. Anti-diabetic potentials of Momordica charantia and Andrographis paniculata and their effects on estrous cyclicity of alloxan-induced diabetic rats. J. Ethnopharmacol. 2006;105:196–200. doi: 10.1016/j.jep.2005.10.018.
    1. Subramanian R., Asmawi M.Z. Inhibition of α-Glucosidase by Andrographis paniculata. Ethanol Extract in Rats. Pharm. Biol. 2006;44:600–606. doi: 10.1080/13880200600896892.
    1. Zhang X., Tan B.K.-H. Anti-diabetic property of ethanolic extract of Andrographis paniculata in streptozotocin-diabetic rats. Acta Pharmacol. Sin. 2000;21:1157–1164.
    1. Zhang X.F., Tan B.K.H. Antihyperglycaemic and anti-oxidant properties of andrographis paniculata in normal and diabetic rats. Clin. Exp. Pharmacol. Physiol. 2000;27:358–363. doi: 10.1046/j.1440-1681.2000.03253.x.
    1. EMA . Final Assessment Report on Eleutherococcus Senticosus (Rupr. et Maxim.) Maxim., Radix. Committee on Herbal Medicinal Products (HMPC). European Medicines Agency; Amsterdam, The Netherlands: 2014.
    1. Akowuah G., Zhari I., Mariam A., Yam M. Absorption of andrographolides from Andrographis paniculata and its effect on CCl4-induced oxidative stress in rats. Food Chem. Toxicol. 2009;47:2321–2326. doi: 10.1016/j.fct.2009.06.022.
    1. Lin F.L., Wu S.J., Lee S.C., Ng L.T. Antioxidant, antioedema and analgesic activities of Andrographis paniculata extracts and their active constituent andrographolide. Phytother. Res. 2009;23:958–964. doi: 10.1002/ptr.2701.
    1. Verma N., Vinayak M. Antioxidant action of Andrographis paniculata on lymphoma. Mol. Biol. Rep. 2008;35:535–540. doi: 10.1007/s11033-007-9119-x.
    1. Sheeja K., Kuttan G. Protective Effect of Andrographis paniculata and Andrographolide on Cyclophosphamide-Induced Urothelial Toxicity. Integr. Cancer Ther. 2006;5:244–251. doi: 10.1177/1534735406291984.
    1. Saranya P., Geetha A., Selvamathy S.N. A biochemical study on the gastroprotective effect of andrographolide in rats induced with gastric ulcer. Indian J. Pharm. Sci. 2011;73:550. doi: 10.4103/0250-474X.99012.
    1. Wasman S.Q., Mahmood A.A., Chua L.S., Alshawsh M.A., Hamdan S. Antioxidant and gastroprotective activities of Andrographis paniculata (Hempedu Bumi) in Sprague Dawley rats. Indian J. Exp. Biol. 2011;49:767–772.
    1. Chander R., Srivastava V., Tandon And J.S., Kapoor N.K. Antihepatotoxic Activity of Diterpenes of Andrographis Paniculata (Kal-Megh) Against Plasmodium Berghei-Induced Hepatic Damage in Mastomys Natalensis. Int. J. Pharmacogn. 1995;33:135–138. doi: 10.3109/13880209509055213.
    1. Koh P.H., Mokhtar R.A.M., Iqbal M. Andrographis paniculata ameliorates carbon tetrachloride (CCl4)-dependent hepatic damage and toxicity: Diminution of oxidative stress. Redox Rep. 2011;16:134–143. doi: 10.1179/1351000211Y.0000000003.
    1. Nagalekshmi R., Menon A., Chandrasekharan D.K., Nair C.K.K. Hepatoprotective activity of Andrographis Paniculata and Swertia Chirayita. Food Chem. Toxicol. 2011;49:3367–3373. doi: 10.1016/j.fct.2011.09.026.
    1. Pramyothin P., Udomuksorn W., Poungshompoo S., Chaichantipyuth C. Hepatoprotective effect of Andrographis paniculata and its constituent, andrographolide, on ethanol hepatotoxicity in rats. Asia Pac. J. Pharmacol. 1994;9:73–78.
    1. Wang D., Zhao H. Prevention of atherosclerotic arterial stenosis and restenosis after angioplasty with Andrographis paniculata nees and fish oil. Experimental studies of effects and mechanisms. Chin. Med. J. 1994;107:464–470.
    1. Zhang C.Y., Tan B.K.H. Mechanisms of cardiovascular activity of Andrographis paniculata in the anaesthetized rat. J. Ethnopharmacol. 1997;56:97–101. doi: 10.1016/S0378-8741(97)01509-2.
    1. Sheeja K., Guruvayoorappan C., Kuttan G. Antiangiogenic activity of Andrographis paniculata extract and andrographolide. Int. Immunopharmacol. 2007;7:211–221. doi: 10.1016/j.intimp.2006.10.002.
    1. Sheeja K., Kuttan G. Modulation of Natural Killer Cell Activity, Antibody-Dependent Cellular Cytotoxicity, and Antibody-Dependent Complement-Mediated Cytotoxicity by Andrographolide in Normal and Ehrlich Ascites Carcinoma-Bearing Mice. Integr. Cancer Ther. 2007;6:66–73. doi: 10.1177/1534735406298975.
    1. Sheeja K., Kuttan G. Activation of Cytotoxic T Lymphocyte Responses and Attenuation of Tumor Growth in vivo by Andrographis paniculata Extract and Andrographolide. Immunopharmacol. Immunotoxicol. 2007;29:81–93. doi: 10.1080/08923970701282726.
    1. Mandal S.C., Dhara A.K., Maiti B.C. Studies on psychopharmacological activity ofAndrographis paniculata extract. Phytother. Res. 2001;15:253–256. doi: 10.1002/ptr.704.
    1. Thakur A.K., Soni U.K., Rai G., Chatterjee S.S., Kumar V. Protective Effects of Andrographis paniculata Extract and Pure Andrographolide Against Chronic Stress-Triggered Pathologies in Rats. Cell. Mol. Neurobiol. 2014;34:1111–1121. doi: 10.1007/s10571-014-0086-1.
    1. Zhang J.-J., Gao T.-T., Wang Y., Wang J.-L., Guan W., Wang Y.-J., Wang C.-N., Liu J.-F., Jiang B. Andrographolide Exerts Significant Antidepressant-Like Effects Involving the Hippocampal BDNF System in Mice. Int. J. Neuropsychopharmacol. 2019;22:585–600. doi: 10.1093/ijnp/pyz032.
    1. Amsterdam J.D., Panossian A.G. Rhodiola rosea L. as a putative botanical antidepressant. Phytomedicine. 2016;23:770–783. doi: 10.1016/j.phymed.2016.02.009.
    1. Darbinyan V., Aslanyan G., Amroyan E., Gabrielyan E., Malmström C., Panossian A. Clinical trial of Rhodiola rosea L. extract SHR-5 in the treatment of mild to moderate depression. Nord. J. Psychiatry. 2007;61:343–348. doi: 10.1080/08039480701643290.
    1. Hu X.-Y., Wu R.-H., Logue M., Blondel C., Lai L.Y.W., Stuart B., Flower A., Fei Y.-T., Moore M., Shepherd J., 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:e0181780. doi: 10.1371/journal.pone.0181780.
    1. Hancke J., Burgos R., Caceres D., Wikman G. A double-blind study with a new monodrug Kan Jang: Decrease of symptoms and improvement in the recovery from common colds. Phytother. Res. 1995;9:559–562. doi: 10.1002/ptr.2650090804.
    1. Caceres D., Hancke J., Burgos R., Sandberg F., Wikman G. Use of visual analogue scale measurements (VAS) to asses the effectiveness of standardized Andrographis paniculata extract SHA-10 in reducing the symptoms of common cold. A randomized double blind-placebo study. Phytomedicine. 1999;6:217–223. doi: 10.1016/S0944-7113(99)80012-9.
    1. Melchior J., Palm S., Wikman G. Controlled clinical study of standardized Andrographis paniculata extract in common cold—A pilot trial. Phytomedicine. 1997;3:315–318. doi: 10.1016/S0944-7113(97)80002-5.
    1. Saxena R.C., Singh R., Kumar P., Yadav S.C., Negi M.P.S., Saxena V.S., Joshua A.J., Vijayabalaji V., Goudar K.S., Venkateshwarlu K., et al. A randomized double blind placebo controlled clinical evaluation of extract of Andrographis paniculata (KalmCold™) in patients with uncomplicated upper respiratory tract infection. Phytomedicine. 2010;17:178–185. doi: 10.1016/j.phymed.2009.12.001.
    1. Gagarin I.A. Adaptation and Adaptogens, Proceedings of the 2nd Symposium, May 1975. Academy of Science of the USSR Far East Science Centre; Vladivostok, USSR: 1977. Eleutherococcus in the Prophylaxis of the disease incidence in the Arctic; p. 128.
    1. Galanova L.K. Adaptation and Adaptogens, Proceedings of the 2nd Symposium. Academy of Science of the USSR Far East Science Centre; Vladivostok, USSR: 1977. Eleutherococcus in preventive maintenance of a flu and relapses of hypertonic illness; pp. 126–127.
    1. Schezin A.K., Zinkovich V.I., Matsuk V.S. Tentative data on the mass Eleutherococcus prophylaxis of influenza at the main assembly line and metallurgic plant of the Volga Automobile Plant; Proceedings of 2nd All-Union Conference on Human Adaptation to Different Conditions; Novosibirsk, USSR. 1977. pp. 44–46.
    1. Shadrin A.S., Kustikova Y.G., Belogolovkina N.A. New Data on Eleutherococcus Proceedings of the II International Symposium on Eleutherococcus, Moscow, USSR, 1984. Far East Academy of Sciences of the USSR; Vladivostok, USSR: 1986. Estimation of prophylactic and immunostimulating effects of Eleutherococcus and Schizandra chinensis preparations; pp. 213–215.
    1. Barkan A., Gaĭduchenia L., Makarenko I. Effect of Eleutherococcus on respiratory viral infectious morbidity in children in organized collectives. Pediatria. 1980:65–66.
    1. Sheparev A.A.Z., Kozlenko I.Y. New Data on Eleutherococcus Proceedings of the II International Symposium on Eleutherococcus, Moscow, USSR, 1984. Far East Academy of Sciences of the USSR; Vladivostok, USSR: 1986. Effect of preventive administration of Eleutherococcus extract on health of children under school age; pp. 201–203.
    1. Kwon Y.J., Son D.H., Chung T.H., Lee Y.J. A Review of the Pharmacological Efficacy and Safety of Licorice Root from Corroborative Clinical Trial Findings. J. Med. Food. 2020;23:12–20. doi: 10.1089/jmf.2019.4459.
    1. Scaglione F., Cattaneo G., Alessandria M., Cogo R. Efficacy and safety of the standardised Ginseng extract G115 for potentiating vaccination against the influenza syndrome and protection against the common cold [corrected] Drugs Exp. Clin. Res. 1996;22:65–72.
    1. Scaglione F., Weiser K., Alessandria M. Effects of the Standardised Ginseng Extract G115® in Patients with Chronic Bronchitis. Clin. Drug Investig. 2001;21:41–45. doi: 10.2165/00044011-200121010-00006.
    1. Lee C.S., Lee J.H., Oh M., Choi K.-M., Jeong M.R., Park J.D., Kwon D.Y., Ha K.C., Park E.O., Lee N., et al. Preventive Effect of Korean Red Ginseng for Acute Respiratory Illness: A Randomized and Double-Blind Clinical Trial. J. Korean Med. Sci. 2012;27:1472–1478. doi: 10.3346/jkms.2012.27.12.1472.
    1. Chuang M.-L., Wu T.-C., Wang Y.-T., Wang Y.-C., Tsao T.C.Y., Wei J.C.-C., Chen C.-Y., Lin I.F. Adjunctive Treatment with Rhodiola Crenulata in Patients with Chronic Obstructive Pulmonary Disease—A Randomized Placebo Controlled Double Blind Clinical Trial. PLoS ONE. 2015;10:e0128142. doi: 10.1371/journal.pone.0128142.
    1. Zhang S., Gao W., Xu K., Guo Y., Lin S., Xue X., Lu G., Li N., Liu H., Liu W. Early use of Chinese drug rhodiola compound for patients with post-trauma and inflammation in prevention of ALI/ARDS. Zhonghua Wai Ke Za Zhi. 1999;37:238–240.
    1. Lu W.S.Z., Cao X.W.S.F. Early use of Chinese drug rhodiola compound for patients with thoracic operation inprevention of ALI. Med. J. Natl. Defending Forces Northwest China. 2004;2
    1. Ahmed M., Henson D.A., Sanderson M.C., Nieman D.C., Zubeldia J.M., Shanely R.A. Rhodiola rosea exerts antiviral activity in athletes following a competitive marathon race. Front. Nutr. 2015;2:24. doi: 10.3389/fnut.2015.00024.
    1. Yu L., Qin Y., Wang Q., Zhang L., Liu Y., Wang T., Huang L., Wu L., Xiong H. The efficacy and safety of Chinese herbal medicine, Rhodiola formulation in treating ischemic heart disease: A systematic review and meta-analysis of randomized controlled trials. Complementary Ther. Med. 2014;22:814–825. doi: 10.1016/j.ctim.2014.05.001.
    1. Lebedev A.A. The effect of Schisandra seed tincture on morbidity rate among workers of Chirick shoe factory during the 1969 influenza epidemic. In: Brekhman I.I., Fruentov N.K., editors. Medicinal Products of the Far East. Far East Branch of the USSR Academy of Science, Khabarovsk Medical Institute; Khabarovsk, USSR: 1970. pp. 115–119.
    1. Lebedev A.A. Schizandra seed tincture and dibazole as means of non-specific prophylaxis of acute respiratory infections during the peak of influenza at the beginning of 1969. Med. Zhurnal Uzb. 1971;6:70–72.
    1. Pavlushchenko E.V. Pneumonia in aged and old people in conditions of the monsoon climate of the southern Primorskij region. In: Bulanov A.E., Dardimov I.V., Li S.E., editors. New Data on Eleutherococcus and Other Adaptogens. Far East Branch of the USSR Academy of Science, Institute of Marine Biology; Vladivostok, USSR: 1981. pp. 119–122.
    1. Tandon N., Yadav S.S. Safety and clinical effectiveness of Withania Somnifera (Linn.) Dunal root in human ailments. J. Ethnopharmacol. 2020;255:112768. doi: 10.1016/j.jep.2020.112768.
    1. Sandhu J.S., Shah B., Shenoy S., Chauhan S., Lavekar G.S., Padhi M.M. Effects of Withania somnifera (Ashwagandha) and Terminalia arjuna (Arjuna) on physical performance and cardiorespiratory endurance in healthy young adults. Int. J. Ayurveda Res. 2010;1:144–149. doi: 10.4103/0974-7788.72485.
    1. Caceres D., Hancke J., Burgos R., Wikman G. Prevention of common colds with Andrographis paniculata dried extract. A pilot double blind trial. Phytomedicine. 1997;4:101–104. doi: 10.1016/S0944-7113(97)80051-7.
    1. Gabrielian E.S., Shukarian A.K., Goukasova G.I., Chandanian G.L., Panossian A.G., Wikman G., Wagner H. A double blind, placebo-controlled study of Andrographis paniculata fixed combination Kan Jang in the treatment of acute upper respiratory tract infections including sinusitis. Phytomedicine. 2002;9:589–597. doi: 10.1078/094471102321616391.
    1. Kulichenko L.L., Kireyeva L.V., Malyshkina E.N., Wikman G. A Randomized, Controlled Study of Kan Jang versus Amantadine in the Treatment of Influenza in Volgograd. J. Herb. Pharmacother. 2003;3:77–93. doi: 10.1080/J157v03n01_04.
    1. Melchior J., Spasov A.A., Ostrovskij O.V., Bulanov A.E., Wikman G. Double-blind, placebo-controlled pilot and Phase III study of activity of standardized Andrographis paniculata Herba Nees extract fixed combination (Kan jang) in the treatment of uncomplicated upper-respiratory tract infection. Phytomedicine. 2000;7:341–350. doi: 10.1016/S0944-7113(00)80053-7.
    1. Spasov A.A., Ostrovskij O.V., Chernikov M.V., Wikman G. Comparative controlled study of Andrographis paniculata fixed combination, Kan Jang® and an Echinacea preparation as adjuvant, in the treatment of uncomplicated respiratory disease in children. Phytother. Res. 2004;18:47–53. doi: 10.1002/ptr.1359.
    1. Anon . Periodic Safety Update Report for Kan Jang. Swedish Herbal Institute; Gothenburg, Sweden: 2010. Period Covered by this Report: From 23 November 2006 to 22 November 2009.
    1. Cook D.N., Kang H.S., Jetten A.M. Retinoic Acid-Related Orphan Receptors (RORs): Regulatory Functions in Immunity, Development, Circadian Rhythm, and Metabolism. Nucl. Recept. Res. 2015;2:101185. doi: 10.11131/2015/101185.
    1. Jetten A.M. Retinoid-Related Orphan Receptors (RORs): Critical Roles in Development, Immunity, Circadian Rhythm, and Cellular Metabolism. Nucl. Recept. Signal. 2009;7:nrs.07003. doi: 10.1621/nrs.07003.
    1. Kojetin D.J., Burris T.P. REV-ERB and ROR nuclear receptors as drug targets. Nat. Rev. Drug Discov. 2014;13:197–216. doi: 10.1038/nrd4100.
    1. Pandi-Perumal S.R., BaHammam A.S., Brown G.M., Spence D.W., Bharti V.K., Kaur C., Hardeland R., Cardinali D.P. Melatonin Antioxidative Defense: Therapeutical Implications for Aging and Neurodegenerative Processes. Neurotox. Res. 2013;23:267–300. doi: 10.1007/s12640-012-9337-4.
    1. Tarocco A., Caroccia N., Morciano G., Wieckowski M.R., Ancora G., Garani G., Pinton P. Melatonin as a master regulator of cell death and inflammation: Molecular mechanisms and clinical implications for newborn care. Cell Death Dis. 2019;10:317. doi: 10.1038/s41419-019-1556-7.
    1. Arushanian E., Beĭer E. Pineal hormone melatonin is an universal adaptogenic agent. Uspekhi Fiziol. Nauk. 2012;43:82.
    1. Maestroni G.J.M. Melatonin and the Immune System Therapeutic Potential in Cancer, Viral Diseases, and Immunodeficiency States. In: Bartsch C., Bartsch H., Blask D.E., Cardinali D.P., Hrushesky W.J.M., Mecke D., editors. The Pineal Gland and Cancer: Neuroimmunoendocrine Mechanisms in Malignancy. Springer; Berlin/Heidelberg, Germany: 2001. pp. 384–394.
    1. Arnao M.B., Hernández-Ruiz J. Melatonin and its relationship to plant hormones. Ann. Bot. 2018;121:195–207. doi: 10.1093/aob/mcx114.
    1. Fan J., Xie Y., Zhang Z., Chen L. Melatonin: A Multifunctional Factor in Plants. Int. J. Mol. Sci. 2018;19:1528. doi: 10.3390/ijms19051528.
    1. Hardeland R. Aging, Melatonin, and the Pro- and Anti-Inflammatory Networks. Int. J. Mol. Sci. 2019;20:1223. doi: 10.3390/ijms20051223.
    1. Nawaz M.A., Huang Y., Bie Z., Ahmed W., Reiter R.J., Niu M., Hameed S. Melatonin: Current Status and Future Perspectives in Plant Science. Front. Plant. Sci. 2016;6:1230. doi: 10.3389/fpls.2015.01230.
    1. Karasek M. Melatonin, human aging, and age-related diseases. Exp. Gerontol. 2004;39:1723–1729. doi: 10.1016/j.exger.2004.04.012.
    1. Arnao M.B., Hernández-Ruiz J. The physiological function of melatonin in plants. Plant. Signal. Behav. 2006;1:89–95. doi: 10.4161/psb.1.3.2640.
    1. Chen G., Huo Y., Tan D.-X., Liang Z., Zhang W., Zhang Y. Melatonin in Chinese medicinal herbs. Life Sci. 2003;73:19–26. doi: 10.1016/S0024-3205(03)00252-2.
    1. Arnao M.B., Hernández-Ruiz J. The potential of phytomelatonin as a nutraceutical. Molecules. 2018;23:238. doi: 10.3390/molecules23010238.
    1. Manchester L.C., Tan D.-X., Reiter R.J., Park W., Monis K., Qi W. High levels of melatonin in the seeds of edible plants: Possible function in germ tissue protection. Life Sci. 2000;67:3023–3029. doi: 10.1016/S0024-3205(00)00896-1.
    1. Pérez-Llamas F., Hernández-Ruiz J., Cuesta A., Zamora S., Arnao M.B. Development of a Phytomelatonin-Rich Extract from Cultured Plants with Excellent Biochemical and Functional Properties as an Alternative to Synthetic Melatonin. Antioxidants. 2020;9:158. doi: 10.3390/antiox9020158.
    1. Andersen L.P., Werner M.U., Rosenkilde M.M., Harpsøe N.G., Fuglsang H., Rosenberg J., Gögenur I. Pharmacokinetics of oral and intravenous melatonin in healthy volunteers. BMC Pharmacol. Toxicol. 2016;17:1–5. doi: 10.1186/s40360-016-0052-2.
    1. Zhou Y., Hou Y., Shen J., Huang Y., Martin W., Cheng F. Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discov. 2020;6:14. doi: 10.1038/s41421-020-0153-3.
    1. Anderson G., Reiter R.J. Melatonin: Roles in influenza, Covid-19, and other viral infections. Rev. Med. Virol. 2020;30:e2109. doi: 10.1002/rmv.2109.
    1. Shneider A., Kudriavtsev A., Vakhrusheva A. Can melatonin reduce the severity of COVID-19 pandemic? Int. Rev. Immunol. 2020;39:153–162. doi: 10.1080/08830185.2020.1756284.
    1. Zhang R., Wang X., Ni L., Di X., Ma B., Niu S., Liu C., Reiter R.J. COVID-19: Melatonin as a potential adjuvant treatment. Life Sci. 2020;250:117583. doi: 10.1016/j.lfs.2020.117583.
    1. Huang S.-H., Liao C.-L., Chen S.-J., Shi L.-G., Lin L., Chen Y.-W., Cheng C.-P., Sytwu H.-K., Shang S.-T., Lin G.-J. Melatonin possesses an anti-influenza potential through its immune modulatory effect. J. Funct. Foods. 2019;58:189–198. doi: 10.1016/j.jff.2019.04.062.
    1. Huang S.-H., Cao X.-J., Liu W., Shi X.-Y., Wei W. Inhibitory effect of melatonin on lung oxidative stress induced by respiratory syncytial virus infection in mice. J. Pineal Res. 2010;48:109–116. doi: 10.1111/j.1600-079X.2009.00733.x.
    1. Silvestri M., Rossi G.A. Melatonin: Its possible role in the management of viral infections-a brief review. Ital. J. Pediatrics. 2013;39:61. doi: 10.1186/1824-7288-39-61.
    1. Ben-Nathan D., Maestroni G., Lustig S., Conti A. Protective effects of melatonin in mice infected with encephalitis viruses. Arch. Virol. 1995;140:223–230. doi: 10.1007/BF01309858.
    1. Bonilla E., Rodón C., Valero N., Pons H., Chacín-Bonilla L., Tamayo J.G., Rodríguez Z., Medina-Leendertz S., Añez F. Melatonin prolongs survival of immunodepressed mice infected with the Venezuelan equine encephalomyelitis virus. Trans. R. Soc. Trop. Med. Hyg. 2001;95:207–210. doi: 10.1016/S0035-9203(01)90170-1.
    1. Bonilla E., Valero N., Chacín-Bonilla L., Medina-Leendertz S. Melatonin and viral infections. J. Pineal Res. 2004;36:73–79. doi: 10.1046/j.1600-079X.2003.00105.x.
    1. Bonilla E., Valero-Fuenmayor N., Pons H., Chacin-Bonilla L. Melatonin protects mice infected with Venezuelan equine encephalomyelitis virus. Cell. Mol. Life Sci. CMLS. 1997;53:430–434. doi: 10.1007/s000180050051.
    1. Nejati Moharrami N., Bjørkøy Tande E., Ryan L., Espevik T., Boyartchuk V. RORα controls inflammatory state of human macrophages. PLoS ONE. 2018;13:e0207374. doi: 10.1371/journal.pone.0207374.
    1. Delerive P., Monté D., Dubois G., Trottein F., Fruchart-Najib J., Mariani J., Fruchart J.-C., Staels B. The orphan nuclear receptor RORα is a negative regulator of the inflammatory response. EMBO Rep. 2001;2:42–48. doi: 10.1093/embo-reports/kve007.
    1. Gold M.J., Antignano F., Halim T.Y.F., Hirota J.A., Blanchet M.-R., Zaph C., Takei F., McNagny K.M. Group 2 innate lymphoid cells facilitate sensitization to local, but not systemic, TH2-inducing allergen exposures. J. Allergy Clin. Immunol. 2014;133:1142–1148.e1145. doi: 10.1016/j.jaci.2014.02.033.
    1. Halim Timotheus Y.F., MacLaren A., Romanish Mark T., Gold Matthew J., McNagny Kelly M., Takei F. Retinoic-Acid-Receptor-Related Orphan Nuclear Receptor Alpha Is Required for Natural Helper Cell Development and Allergic Inflammation. Immunity. 2012;37:463–474. doi: 10.1016/j.immuni.2012.06.012.
    1. Lo B.C., Gold M.J., Hughes M.R., Antignano F., Valdez Y., Zaph C., Harder K.W., McNagny K.M. The orphan nuclear receptor ROR alpha and group 3 innate lymphoid cells drive fibrosis in a mouse model of Crohn’s disease. Sci. Immunol. 2016;1:eaaf8864. doi: 10.1126/sciimmunol.aaf8864.
    1. Friesenhagen J., Viemann D., Börgeling Y., Schmolke M., Spiekermann C., Kirschnek S., Ludwig S., Roth J. Highly Pathogenic Influenza Viruses Inhibit Inflammatory Response in Monocytes via Activation of Rar-Related Orphan Receptor RORa. J. Innate Immun. 2013;5:505–518. doi: 10.1159/000346706.
    1. Yanuck S.F.P., Messier H.J., Fitzgerald K.N. Evidence Supporting a Phased Immuno-physiological Approach to COVID-19 from Prevention through Recovery. Integr. Med. 2020;19:8–35.
    1. Narimanian M., Badalyan M., Panosyan V., Gabrielyan E., Panossian A., Wikman G., Wagner H. Impact of Chisan® (ADAPT-232) on the quality-of-life and its efficacy as an adjuvant in the treatment of acute non-specific pneumonia. Phytomedicine. 2005;12:723–729. doi: 10.1016/j.phymed.2004.11.004.

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