Chaitanya M V N L, Manikyam Hemanth Kumar, Babu Neerugatti Dora, Singh Sachin Kumar, Mazumder Avijit, Kumar Sanjesh, Tatiparthi Ramanjireddy, Prabha T, Sharma Sakshi
School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, 144411, India.
Department of Pharmaceutical Sciences, Chalapathi Institute of Pharmaceutical Sciences, Chalapathi Nagar (Affiliated to Acharya Nagarjuna University), Guntur, 522001, Andhra Pradesh, India.
Inflammopharmacology. 2025 Aug 12. doi: 10.1007/s10787-025-01893-w.
Iridoid glycosides (IGs) are monoterpenoids that protect against stress and modulate the immune system. A comprehensive analysis of preclinical and clinical data on IGs' adaptogenic and immunogenic properties, molecular processes, and knowledge gaps was conducted. The study found that oral catalpol, aucubin, geniposide, harpagoside, loganin, and globularifolin can reduce stress and depression by diminishing anhedonia, enhancing corticosterone, BDNF, and decreasing COX 2 levels. IGs also enhance cognition and mitochondrial integrity in diabetes encephalopathy and renal oxidative models by preserving redox equilibrium. Aucubin inhibits LPS-induced lung damage by activating Nrf2/HO-1 via AMPK and suppressing NF-κB and pro-inflammatory cytokines. Geniposide inhibits NF-κB/IκB activation in rats, resulting in anti-inflammatory and immuno-resolving effects on adjuvant arthritis symptoms. Harpagoside and harpagide from Harpagophytum procumbens inhibit LPS or TNF-α-induced cytokine surges and osteoclastogenesis via modulating Syk/NF-κB/RANK. Finally, globularifolin is immunomodulating and cytoprotective, lowering inflammatory markers and boosting THP-1 cell survival. It is recommended that well-designed and adequately powered clinical trials be conducted on people to test the efficacy of IG'S in reducing stress and modulating immune responses. Up order to find new immunogenic and adoptogenic therapeutic leads, this review aims to fill up the gaps between iridoid glycosides and the functional processes by which they work.
环烯醚萜苷(IGs)是一类单萜类化合物,具有抗应激和调节免疫系统的作用。本研究对IGs的适应原性和免疫原性特性、分子过程及知识空白的临床前和临床数据进行了全面分析。研究发现,口服梓醇、桃叶珊瑚苷、栀子苷、哈巴苷、马钱苷和球花甙可通过减轻快感缺失、提高皮质酮、脑源性神经营养因子(BDNF)水平以及降低环氧化酶2(COX 2)水平来减轻应激和抑郁。在糖尿病脑病和肾脏氧化模型中,IGs还通过维持氧化还原平衡来增强认知能力和线粒体完整性。桃叶珊瑚苷通过激活AMPK途径的Nrf2/HO-1并抑制NF-κB和促炎细胞因子,从而抑制脂多糖(LPS)诱导的肺损伤。栀子苷抑制大鼠体内NF-κB/IκB的激活,对佐剂性关节炎症状产生抗炎和免疫调节作用。南非钩麻中的哈巴苷和哈巴吉通过调节Syk/NF-κB/RANK抑制LPS或肿瘤坏死因子-α(TNF-α)诱导的细胞因子激增和破骨细胞生成。最后,球花甙具有免疫调节和细胞保护作用,可降低炎症标志物水平并提高THP-1细胞存活率。建议针对人群开展设计良好且样本量充足的临床试验,以测试IGs在减轻应激和调节免疫反应方面的疗效。为了找到新的免疫原性和适应原性治疗线索,本综述旨在填补环烯醚萜苷与其作用的功能过程之间的空白。