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<p>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.</p> Graphical abstract <p></p> <p>Functional importance of iridoid glycosides: evidence-based study. The graphic connects chemistry with biology by dividing it into two conceptual tiers. The structural tier features a triptych of core carbon skeletons that define three major classes of iridoid metabolites: iridoid glycosides, secoiridoids, and simple iridoids. This tier emphasizes the subtle scaffold variations that underpin divergent pharmacological profiles. The functional tier includes three infographic panels that illustrate hallmark biological mechanisms validated for each sub-class. The graphic breaks down the mechanisms of iridoid glycosides into Mutagenic Activity and Neuroprotection, Immunogenic Activity, and Anti-inflammatory Activity. The structural tier highlights the synthesis of TrkA/NGF dimer receptors, enhancing neuronal differentiation and rescue. The immunogenic tier highlights the split mitochondrion/nucleus schematic, contrasting unchallenged vs. trained immunity and the anti-inflammatory activity of simple iridoids. The graphic visually co-locates structural class over signature pharmacology, conveying the central theme that even modest architectural tweaks in iridoids create distinct, therapeutically exploitable bio-mechanisms.</p>

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Deciphering the iridoids' boundaries: from soil ecology to anti-inflammatory medicines

  • 期刊论文

  • 发表日期：

    2025年8月12日

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  • M. V. N. L. Chaitanya,
  • Hemanth Kumar Manikyam,
  • Neerugatti Dora Babu,
  • Sachin Kumar Singh,
  • Avijit Mazumder,
  • Sanjesh Kumar,
  • Ramanjireddy Tatiparthi,
  • T. Prabha,
  • Sakshi Sharma

摘要

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.

Graphical abstract

Functional importance of iridoid glycosides: evidence-based study. The graphic connects chemistry with biology by dividing it into two conceptual tiers. The structural tier features a triptych of core carbon skeletons that define three major classes of iridoid metabolites: iridoid glycosides, secoiridoids, and simple iridoids. This tier emphasizes the subtle scaffold variations that underpin divergent pharmacological profiles. The functional tier includes three infographic panels that illustrate hallmark biological mechanisms validated for each sub-class. The graphic breaks down the mechanisms of iridoid glycosides into Mutagenic Activity and Neuroprotection, Immunogenic Activity, and Anti-inflammatory Activity. The structural tier highlights the synthesis of TrkA/NGF dimer receptors, enhancing neuronal differentiation and rescue. The immunogenic tier highlights the split mitochondrion/nucleus schematic, contrasting unchallenged vs. trained immunity and the anti-inflammatory activity of simple iridoids. The graphic visually co-locates structural class over signature pharmacology, conveying the central theme that even modest architectural tweaks in iridoids create distinct, therapeutically exploitable bio-mechanisms.