National Academy of Agricultural Sciences (NAAS)
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PRINT ISSN : 2319-7692
Online ISSN : 2319-7706 Issues : 12 per year Publisher : Excellent Publishers Email : editorijcmas@gmail.com submit@ijcmas.com Editor-in-chief: Dr.M.Prakash Index Copernicus ICV 2018: 95.39 NAAS RATING 2020: 5.38 |
Berberine (BBR), a naturally occurring isoquinoline alkaloid found in several medicinal plants, has diverse pharmacological properties. Growing scientific evidence suggests that in addition to antioxidant and anti-inflammatory properties, BBR possesses broad antiviral potential. This review summarizes experimental and computational studies investigating the antiviral activity of BBR against a range of DNA and RNA viruses. Experimental studies have reported activity against hepatitis B virus, hepatitis C virus, human adenovirus, respiratory syncytial virus, influenza A virus, dengue virus, Zika virus, chikungunya virus, enterovirus 71, coxsackievirus B3 and human immunodeficiency virus. The reported antiviral actions involve interference with viral entry and replication, modulation of host signaling pathways, regulation of oxidative stress and suppression of excessive inflammatory responses. Computational studies further suggest possible interactions of BBR with several viral and host targets, including viral proteases, polymerases, envelope glycoproteins and host proteins involved in infection. However, in-silico predictions require appropriate in-vitro and in-vivo validation before their biological significance can be established. Translation of these findings into therapeutic application is further limited by the poor oral bioavailability of BBR, which is associated with poor solubility, limited intestinal permeability and extensive metabolism. Although newer formulations and nanocarrier-based delivery approaches may help address some of these limitations, further pharmacokinetic, toxicological, preclinical and clinical investigations are required. Overall, BBR represents a promising natural compound for further antiviral drug development.
Alorabi, M., Cavalu, S., Al-Kuraishy, H.M., Al-Gareeb, A.I., Mostafa-Hedeab, G., Negm, W.A., Youssef, A., El-Kadem, A.H., Saad, H.M. and Batiha, G.E.S. (2022) ‘Pentoxifylline and BBR mitigate diclofenac-induced acute kidney injury in male rats via modulation of inflammation and oxidative stress’, Inflammopharmacology, 30(6), pp. 2315–2330. doi: 10.1007/s10787-022-01060-5
Ansari, H.K., Alisha, Baig, M.S., Reza, A., Prakash, P., Ansari, M.A. and Krishnan, A. (2026) ‘Identification and validation of natural dengue virus NS1 inhibitors with promising antiviral potential’, Molecular Diversity, 30(4), pp. 5527–5543. doi: 10.1007/s11030-025-11447-5
Asadi-Samani, M., Altememy, D., Jasim, A.Z., Saffari-Chaleshtori, J. and Moradi, M.T. (2023) ‘Evaluation of BBR inhibitory effects on influenza neuraminidase enzyme: a molecular dynamics study’, Journal of Herbmed Pharmacology, 12(4), pp. 453–458. doi: 10.34172/jhp.2023.42334
Babalghith, A.O., Al-Kuraishy, H.M., Al-Gareeb, A.I., De Waard, M., Al-Hamash, S.M., Jean-Marc, S., Negm, W.A. and Batiha, G.E. (2022) ‘The role of BBR in COVID-19: potential adjunct therapy’, Inflammopharmacology, 30(6), pp. 2003–2016. doi: 10.1007/s10787-022-01080-1
Bhargava, U., Shah, A., Garg, S.P., Khan, S.A., Kumar, S., Rawat, D.S. and Coumar, M.S. (2011) ‘Synthesis of 9-substituted derivatives of BBR as anti-HIV agents’, European Journal of Medicinal Chemistry, 46(3), pp. 912–920. doi: 10.1016/j.ejmech.2011.01.002
Cao, J., Zhang, H., Zhang, J., Wang, J., Li, C., Ma, J., Ye, Z., Zheng, Y., Liu, H., Xiao, G., Dai, W. and Zhang, L. (2025) ‘Screening of botanical drugs reveals the potential anti-human adenovirus activity of BBR’, Antiviral Research, 237, p. 106105. doi: 10.1016/j.antiviral.2025.106105
Chen, F., Yang, Z., Liu, Y., Li, L., Liang, W., Wang, X., Zhou, W., Yang, Y. and Hu, R.M. (2008) ‘BBR inhibits the expression of TNFα, MCP1, and IL-6 in AcLDL-stimulated macrophages through PPARγ pathway’, Endocrine, 33(3), pp. 331–337. doi: 10.1007/s12020-008-9089-3
Cicero, A.F. and Tartagni, E. (2012) ‘Antidiabetic properties of BBR: from cellular pharmacology to clinical effects’, Hospital Practice, 40(2), pp. 56–63. doi: 10.3810/hp.2012.04.970
Cui, G., Wang, H., Yang, C., Zhou, X., Wang, J., Wang, T. and Ma, T. (2022) ‘BBR prevents lethal EV71 neurological infection in newborn mice’, Frontiers in Pharmacology, 13, p. 1027566. doi: 10.3389/fphar.2022.1027566
Cui, Y., Zhou, Q., Jin, M., Jiang, S., Shang, P., Dong, X., & Li, L. (2024). Research progress on pharmacological effects and bioavailability of BBR. Naunyn-Schmiedeberg's archives of pharmacology, 397(11), 8485–8514. https://doi.org/10.1007/s00210-024-03199-0
Dai, Q., He, X., Yu, H. et al., (2021) ‘BBR impairs coxsackievirus B3-induced myocarditis through the inhibition of virus replication and host pro-inflammatory response’, Journal of Medical Virology, 93, pp. 3581–3589. doi: 10.1002/jmv.26747
Enkhtaivan, G., Muthuraman, P., Kim, D.H. and Mistry, B. (2017) ‘Discovery of BBR based derivatives as anti-influenza agent through blocking of neuraminidase’, Bioorganic & Medicinal Chemistry, 25(20), pp. 5185–5193. doi: 10.1016/j.bmc.2017.07.006
Hung, T.C., Jassey, A., Liu, C.H., Lin, C.J., Lin, C.C., Wong, S.H., Wang, J.Y., Yen, M.H. and Lin, L.T. (2019) ‘BBR inhibits hepatitis C virus entry by targeting the viral E2 glycoprotein’, Phytomedicine, 53, pp. 62–69. doi: 10.1016/j.phymed.2018.09.008
Ivanovska, N., Philipov, S., Hristova, M. and Radicheva, L. (2006) ‘Influence of BBR on xanthine oxidase activity and reactive oxygen species production in endothelial cells’, International Immunopharmacology, 6(11), pp. 1683–1691. doi: 10.1016/j.intimp.2006.06.012
Jawed Khan, M., Hafeez, A. and Aftab Siddiqui, M., 2023. Nanocarrier based delivery of BBR: a critical review on pharmaceutical and preclinical characteristics of the bioactive. Current pharmaceutical biotechnology, 24(11), pp.1449-1464. https://doi.org/10.2174/1389201024666230112141330
Jiao, Y. and Yang, R. (2025) ‘BBR alleviates respiratory syncytial virus (RSV)-induced pediatric bronchiolitis and fibrosis via suppressing the HMGB1/TLR4/NF-κB pathway’, Microbiology Spectrum, 13(8), p. e0090025. doi: 10.1128/spectrum.00900-25
Khoshandam, A., Imenshahidi, M. and Hosseinzadeh, H., 2022. Pharmacokinetic of BBR, the main constituent of Berberis vulgaris L.: A comprehensive review. Phytotherapy Research, 36(11), pp.4063-4079.
Kong, W., Wei, J., Abidi, P., Lin, M., Inaba, S., Li, C., Wang, Y., Wang, Z., Si, S., Pan, H. and Wang, S. (2004) ‘BBR is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins’, Nature Medicine, 10(12), pp. 1344–1351. doi: 10.1038/nm1135
Kumar, M. et al., (2021) ‘Molecular docking studies and biological evaluation of BBR-benzothiazole derivatives as an anti-influenza agent via blocking of neuraminidase’, International Journal of Molecular Sciences, 22(5), p. 2368. doi: 10.3390/ijms22052368
Li, H., Wang, P., Wang, S. and Yang, J. (2014a) ‘BBR prevents the progression of left ventricular hypertrophy caused by pressure overload in rats through inhibition of inflammatory signalling’, Journal of Cardiovascular Pharmacology, 63(4), pp. 341–349. doi: 10.1097/FJC.0000000000000055
Li, X., Li, Y., Zhang, X. and Yuan, Y. (2014b) ‘Inhibitory effects of BBR on CD4+ T cell proliferation and differentiation into Th1 and Th17 cells’, International Immunopharmacology, 22(2), pp. 421–429. doi: 10.1016/j.intimp.2014.07.014
Ma, X., Egawa, T., Kimura, H. and Hayashi, T. (2010) ‘BBR treats obesity by modulating central and peripheral AMPK pathways and serotonin neurotransmission’, American Journal of Physiology-Endocrinology and Metabolism, 298(5), pp. E912–E923. doi: 10.1152/ajpendo.00756.2009
Mi, Y., Sun, X., Luan, H., Liu, Y. and Wang, Z. (2019) ‘BBR improves peripheral glucose uptake by increasing the expression of glucose transporter 4 (GLUT-4)’, Phytomedicine, 58, p. 152865. doi: 10.1016/j.phymed.2019.152865
Mukhtar, M., Khan, H.A., Ibisanmi, T.A., Faleti, A.I. and Zaidi, N.S.S. (2024) ‘Computational exploration of Berberis lycium Royle: a hidden treasure trove for antiviral development’, Bioinformatics and Biology Insights, 18. doi: 10.1177/11779322241264144
Narkhede, R.R., Pise, A.V., Cheke, R.S. and Shinde, S.D. (2020) ‘Recognition of natural products as potential inhibitors of COVID-19 main protease (Mpro): in-silico evidences’, Natural Products and Bioprospecting, 10(5), pp. 297–306. doi: 10.1007/s13659-020-00253-1
Neag, M.A., Mocan, A., Echeverría, J., Pop, R.M., Bocsan, C.I., Crişan, G. and Buzoianu, A.D. (2018) ‘BBR: botanical occurrence, traditional uses, extraction methods, and relevance in cardiovascular, metabolic, hepatic, and renal disorders’, Frontiers in Pharmacology, 9, p. 557. doi: 10.3389/fphar.2018.00557
Oner, E. et al., (2023) ‘Investigation of BBR and its derivatives in SARS-CoV-2 main protease structure by molecular docking, PROTOX-II and ADMET methods: in machine learning and in silico study’, Journal of Biomolecular Structure and Dynamics, 41(19), pp. 9366–9381. doi: 10.1080/07391102.2022.2142848
Pammi, S.S.S., Suresh, B. and Giri, A. (2023) ‘Antioxidant potential of medicinal plants’, Journal of Crop Science and Biotechnology, 26, pp. 13–26. doi: 10.1007/s12892-022-00159-z
Pei, Y., Wang, J., Liu, H. and Zhang, J. (2019) ‘BBR dampens ox-LDL-induced monocyte adhesion to endothelial cells by inhibiting ICAM-1 and VCAM-1 expression’, Vascular Pharmacology, 116, pp. 34–41. doi: 10.1016/j.vph.2019.02.003
Ratanakomol, T., Roytrakul, S., Wikan, N. and Smith, D.R. (2021) ‘BBR inhibits dengue virus through dual mechanisms’, Molecules, 26(18), p. 5501. doi: 10.3390/molecules26185501
Sahoo, M., Jena, L., Daf, S. and Kumar, S. (2016) ‘Virtual screening for potential inhibitors of NS3 protein of Zika virus’, Genomics & Informatics, 14(3), pp. 104–111. doi: 10.5808/GI.2016.14.3.104
Shao, J., Zeng, D., Tian, S., Liu, G. and Fu, J. (2020) ‘Identification of the natural product BBR as an antiviral drug’, AMB Express, 10, p. 164. doi: 10.1186/s13568-020-01088-2
Shen, M. and Xia, J. (2026) ‘Screening of key host targets and mechanistic assessment of BBR modulation of host responses to respiratory syncytial virus’, Journal of International Medical Research, 54(7). doi: 10.1177/03000605261470649
Sun, H., Wang, N., Chang, M., Zhang, F. and Zhang, K. (2016) ‘BBR reduces body weight by upregulating brain GLP-1, neuropeptide Y, and orexin-A’, Neuroscience Letters, 612, pp. 132–138. doi: 10.1016/j.neulet.2015.12.012
Vargas-Echeverría, C. et al., (2025) ‘Structure-based identification of natural inhibitors targeting the Gc glycoprotein of Oropouche virus: an in silico approach’, International Journal of Molecular Sciences, 26(21), p. 10541. doi: 10.3390/ijms262110541
Varghese, F.S., Thaa, B., Amrun, S.N., Cowling, B.J. and Mirazimi, A. (2020) ‘Antiviral activity of BBR’, Phytomedicine, 70, p. 153204. doi: 10.1016/j.phymed.2020.153204
Wang, Z.Z. et al., (2021) ‘A small molecule compound BBR as an orally active therapeutic candidate against COVID-19 and SARS: a computational and mechanistic study’, The FASEB Journal, 35(4), p. e21360. doi: 10.1096/fj.202001792R
Warowicka, A., Nawrot, R. and Goździcka-Józefiak, A. (2020) ‘Antiviral activity of BBR’, Archives of Virology, 165, pp. 1935–1945. doi: 10.1007/s00705-020-04706-3
Xu, Y., Shen, J., Cao, B. and Zhang, Y. (2021) ‘BBR activates the AMPK/SIRT1 axis to regulate mitochondrial proton outflow and thermogenesis via uncoupling protein 2 (UCP2)’, Phytotherapy Research, 35(8), pp. 4390–4401. doi: 10.1002/ptr.7118
Xu, Z., Feng, W., Shen, Q., Yu, N., Yu, K., Wang, S., Chen, Z., Shioda, S. and Guo, Y. (2017) ‘RhizomaCoptidis and BBR as a natural drug to combat aging and aging-related diseases via anti-oxidation and AMPK activation’, Aging and Disease, 8(6), pp. 760–777. doi: 10.14336/AD.2016.0620
Yamashita, A., Kasai, H., Maekawa, S., Tanaka, T., Akaike, Y., Ryo, A., Enomoto, N. and Moriishi, K. (2024) ‘BBR promotes K48-linked polyubiquitination of HNF4α, leading to the inhibition of HBV replication’, Antiviral Research, 232, p. 106027. doi: 10.1016/j.antiviral.2024.106027
Zha, W., Liang, G., Xiao, J., Studer, E.J., Hylemon, P.B., Pandak, W.M., Wang, G., Li, X. and Zhou, H. (2010) ‘BBR inhibits HIV protease inhibitor-induced inflammatory response by modulating ER stress signalling pathways in murine macrophages’, PLoS ONE, 5(2), p. e9069. doi: 10.1371/journal.pone.0009069
Zhao, M., Deng, D., Liu, H., Guo, R., Wu, J., Hao, Y. and Yang, M. (2025) ‘BBR suppresses influenza A virus-triggered pyroptosis in macrophages via intervening in the mtROS-MAVS-NLRP3 inflammasome pathway’, Viruses, 17(4), p. 539. doi: 10.3390/v17040539
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