Abstract:

Acute gouty arthritis (AGA) is marked by a swift inflammatory response triggered by the accumulation of monosodium urate (MSU) crystals around the joints, often linked to hyperuricemia (HUA). Traditional approaches in AGA management usually prove inadequate, prompting a recent focus on the potential of herbal medicines (HMs) for AGA treatment. This review aims to outline the pharmacological mechanisms of HMs in treating AGA, exploring their active components, extracts, and prescriptions, and discussing relevant molecular targets extensively. Scientific publications on anti-AGA HMs were gathered from diverse journals and databases like PubMed, Elsevier, and Google Scholar. The review identified numerous therapeutic targets for AGA treated by HMs through in vitro and in vivo studies. HMs and their active ingredients were found to alleviate AGA symptoms by influencing various immune cell targets. The study revealed that HMs have multiple therapeutic targets that effectively address AGA symptoms through in vitro and in vivo studies. The review systematically categorized the anti-AGA properties of HMs, highlighting phenolic, flavonoid, terpenoid, and alkaloid compounds as key ingredients for AGA improvement. HMs and their active ingredients are shown to enhance efficacy by interacting with multiple targets, with NLRP3 being a primary therapeutic focus. Further research is needed to fully understand how HMs alleviate AGA due to the complex nature of HMs.

References:

[1].   Tausche, A.-K., Jansen, T. L., Schröder, H.-E., Bornstein, SR, Aringer, M, Müller-Ladner, U. 2009. Gout—current diagnosis and treatment. Deutsches Ärzteblatt International 106:549.

[2].   Choi, H. K., McCormick, N., Yokose, C., 2022. Excess comorbidities in gout: the causal paradigm and pleiotropic approaches to care. Nature Reviews Rheumatology 18:97-111.

[3].   Liu, W., Peng, J., Wu, Y., Ye, Z., Zong, Z., et al. 2023. Immune and inflammatory mechanisms and therapeutic targets of gout: An update. International immunopharmacology 121:110466.

[4].   Zhao, J., Wei, K., Jiang, P., Chang, C., Xu, L., et al. 2022. Inflammatory response to regulated cell death in gout and its functional implications. Frontiers in immunology 13:888306.

[5].   Zhao, L., Ye, W., Zhu, Y., Chen, F., Wang, Q., et al. 2022. Distinct macrophage polarization in acute and chronic gout. Laboratory Investigation 102:1054-63

[6].   Keller, S. F., Mandell, B. F., 2021. Management and cure of gouty arthritis. Medical Clinics 105:297-310.

[7].   Wang, S., Liu, W., Wei, B., Wang, A., Wang, Y., et al. 2024. Traditional Herbal Medicine: Therapeutic Potential in Acute Gouty Arthritis. Journal of Ethnopharmacology:118182.

[8].   Tai, F. W. D., McAlindon, M. E., 2021. Non-steroidal anti-inflammatory drugs and the gastrointestinal tract. Clinical Medicine 21:131-4.

[9].   Sun, X., Yang, L., Sun, H., Sun, Y., Wei, S., et al. 2023. TCM and related active compounds in the treatment of gout: the regulation of signaling pathway and urate transporter. Frontiers in Pharmacology 14:1275974.

[10].  Liu, L., Zhu, L., Liu, M., Zhao, L., Yu, Y., et al. 2022. Recent insights into the role of macrophages in acute gout. Frontiers in immunology 13:955806.

[11].  Liu‐Bryan, R., Scott, P., Sydlaske, A., Rose, DM, Terkeltaub, R. 2005. Innate immunity conferred by Toll‐like receptors 2 and 4 and myeloid differentiation factor 88 expression is pivotal to monosodium urate monohydrate crystal–induced inflammation. Arthritis & Rheumatism 52:2936-46.

[12].  Cobo, I., Murillo-Saich, J, Alishala, M, Guma, M. 2023. Epigenetic and Metabolic Regulation of Macrophages during Gout. Gout, Urate, and Crystal Deposition Disease 1:137-51.

[13].  Liu, C., Zhou, M., Jiang, W., Ye., S., Tian, S., et al. 2022. GPR105-targeted therapy promotes gout resolution as a switch between NETosis and apoptosis of neutrophils. Frontiers in Immunology 13:870183.

[14].  Li, C., Wu, C., Li, F., Xu, W., Zhang, X., et al. 2024. Targeting Neutrophil Extracellular Traps in Gouty Arthritis: Insights into Pathogenesis and Therapeutic Potential. Journal of Inflammation Research:1735-63.

[15].  Liu, L., Shan, L., Wang, H., Schauer, C., Schoen, J., et al. 2023. Neutrophil Extracellular Trap–Borne Elastase Prevents Inflammatory Relapse in Intercritical Gout. Arthritis & Rheumatology 75:1039-47.

[16].  Di, H., Han, X., Yin, Y., Zhang, Y., Zeng, X., 2024. Role of Chemotaxis of Vδ2 T Cells to the Synovium in the Pathogenesis of Acute Gouty Arthritis. Journal of Inflammation Research:721-36.

[17].  Wang, B., Chen, S., Qian, H., Zheng, Q., Chen, R., et al. 2020. Role of T cells in the pathogenesis and treatment of gout. International immunopharmacology 88:106877.

[18].  Zhao, J., Liu, H., Hong, Z., Luo, W., Mu, W., et al. 2023. Tanshinone I specifically suppresses NLRP3 inflammasome activation by disrupting the association of NLRP3 and ASC. Molecular Medicine 29:84.

[19].  Campbell, K. S., Hasegawa, J., 2013. Natural killer cell biology: an update and future directions. Journal of Allergy and Clinical Immunology 132:536-44.

[20].  O’Brien, K. L., Finlay, D. K., 2019. Immunometabolism and natural killer cell responses. Nature Reviews Immunology 19:282-90.

[21].  Li, D., Yuan, S., Deng, Y., Wang, X., Wu, S., et al. 2023. The dysregulation of immune cells induced by uric acid: mechanisms of inflammation associated with hyperuricemia and its complications. Frontiers in Immunology 14:1282890.

[22].  Wei, L., Yuanhao, W., Bin, X., Yue, J., Shumin, Z., et al. 2021. Effect of integrated Traditional Chinese and Western Medicine on gout. Journal of Traditional Chinese Medicine 41.

[23].  Zhou, Q., Sun, H.-j., Liu, S.-m., 2023. Effects of total saponins from Dioscorea nipponica makino on monosodium urate-induced M1-polarized macrophages through arachidonic acid signaling pathway: an in vitro study. Chinese journal of integrative medicine 29:44-51.

[24].  Meng, Q., Meng, W., Bian, H., Zheng, F., Gu, H., et al. 2021. Total glucosides of paeony protects THP-1 macrophages against monosodium urate-induced inflammation via MALAT1/miR-876-5p/NLRP3 signaling cascade in gouty arthritis. Biomedicine & Pharmacotherapy 138:111413.

[25].  Lin, X., Shao, T., Huang, L., Wen, X., Wang, M., et al. 2020. Simiao decoction alleviates gouty arthritis by modulating proinflammatory cytokines and the gut ecosystem. Frontiers in Pharmacology 11:955.

[26].  Bai, J., Zhang, Y., Tang, C., Hou, Y., Ai, X., et al. 2021. Gallic acid: Pharmacological activities and molecular mechanisms involved in inflammation-related diseases. Biomedicine & pharmacotherapy 133:110985.

[27].  Ren, G., Sun, A., Deng, C., Zhang, J., Wu, X., et al. 2015. The anti-inflammatory effect and potential mechanism of cardamonin in DSS-induced colitis. American Journal of Physiology-Gastrointestinal and Liver Physiology 309:G517-G27.

[28].  Wang, X., Chi, J., Dong, B., Xu, L., Zhou, Y., et al. 2021. MiR‐223‐3p and miR‐22‐3p inhibit monosodium urate‐induced gouty inflammation by targeting NLRP3. International journal of rheumatic diseases 24:599-607.

[29].  Gong, Z., Wang, Y., Li, L., Li, X., Qiu, B., Hu, Y., 2023. Cardamonin alleviates chondrocytes inflammation and cartilage degradation of osteoarthritis by inhibiting ferroptosis via p53 pathway. Food and Chemical Toxicology 174:113644.

[30].  Lin, X., Wang, H., An, X., Zhang, J., Kuang, J., et al. 2021. Baeckein E suppressed NLRP3 inflammasome activation through inhibiting both the priming and assembly procedure: Implications for gout therapy. Phytomedicine 84:153521.

[31].  Wang, L., Zhu, L., Duan, C., Li, L., Chen, G., 2020. Total saponin of Dioscorea collettii attenuates MSU crystal‑induced inflammation via inhibiting the activation of the NALP3 inflammasome and caspase‑1 in THP‑1 macrophages. Molecular medicine reports 21:2466-74.

[32].  Dinesh, P., Rasool, M., 2017. Berberine, an isoquinoline alkaloid suppresses TXNIP mediated NLRP3 inflammasome activation in MSU crystal stimulated RAW 264.7 macrophages through the upregulation of Nrf2 transcription factor and alleviates MSU crystal induced inflammation in rats. International immunopharmacology 44:26-37.

[33].  Xu, L., Liu, X., Zhang, Y., Jia, T., Li, L., et al. 2022. Tanshinone IIA improves acute gouty arthritis in rats through regulating neutrophil activation and the NLRP3 inflammasome. Disease markers 2022:5851412.

[34].  He, M., Hu, C., Chen, M., Gao, Q., Li, L., Tian W., 2022. Effects of Gentiopicroside on activation of NLRP3 inflammasome in acute gouty arthritis mice induced by MSU. Journal of natural medicines:1-10

[34]. Cao, Y., 2021. Icariin alleviates MSU‐induced rat GA models through NF‐κB/NALP3 pathway. Cell biochemistry and function 39:357-66.