Interleukin-6 (IL-6), a pleiotropic cytokine, plays a pivotal role in the pathophysiology of various diseases including diabetes, atherosclerosis, Alzheimer's disease, multiple myeloma, rheumatoid arthritis, and prostate cancer. The signaling pathways associated with IL-6 offer promising targets for therapeutic interventions in inflammatory diseases and IL-6-dependent tumors. Although certain anti-IL-6 monoclonal antibodies are currently employed clinically, their usage is hampered by drawbacks such as high cost and potential immunogenicity, limiting their application. Thus, the imperative arises to develop novel small non-peptide molecules acting as IL-6 inhibitors. Various natural products derived from diverse sources have been investigated for their potential to inhibit IL-6 activity. Nevertheless, these natural products remain inadequately explored in terms of their structure-activity relationships. In response, our review aims to provide syntheses and structure activity perspective of natural IL-6 inhibitors. The comprehensive amalgamation of information presented in this review holds the potential to serve as a foundation for forthcoming research endeavors by medicinal chemists, facilitating the design of innovative IL-6 inhibitors to address the complexities of inflammatory diseases.

中文翻译：

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天然产物作为炎症性疾病 IL-6 抑制剂：合成和 SAR 观点

白细胞介素-6 (IL-6) 是一种多效细胞因子，在糖尿病、动脉粥样硬化、阿尔茨海默氏病、多发性骨髓瘤、类风湿性关节炎和前列腺癌等多种疾病的病理生理学中发挥着关键作用。与 IL-6 相关的信号通路为炎症性疾病和 IL-6 依赖性肿瘤的治疗干预提供了有前景的靶点。尽管某些抗IL-6单克隆抗体目前已应用于临床，但其使用受到成本高和潜在免疫原性等缺点的限制，限制了其应用。因此，开发充当 IL-6 抑制剂的新型非肽小分子势在必行。人们已经研究了不同来源的各种天然产物抑制 IL-6 活性的潜力。然而，这些天然产物在其结构-活性关系方面仍未得到充分探索。为此，我们的综述旨在提供天然 IL-6 抑制剂的合成和结构活性观点。本综述中提供的信息的全面整合有可能成为药物化学家未来研究工作的基础，促进创新 IL-6 抑制剂的设计，以解决炎症性疾病的复杂性。