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REVIEW article
Front. Pharmacol.
Sec. Inflammation Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1584035
Natural Saponins and Macrophage Polarization: Mechanistic Insights and Therapeutic Perspectives in Disease Management
Provisionally accepted- 1 The First People’s Hospital of Shuangliu District, Chengdu, Chengdu, Sichuan Province, China
- 2 Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
- 3 Chengdu First People's Hospital, Chengdu, Sichuan Province, China
Macrophage polarization plays a pivotal role in immune homeostasis and disease progression across inflammatory, neoplastic, and metabolic disorders. Saponins, which are natural compounds with steroidal/triterpenoid structures, demonstrate therapeutic potential through immunomodulatory, anti-inflammatory, and anti-tumor activities. This study aims to highlight the potential of key saponins—such as ginsenosides, astragaloside IV, dioscin, platycodin D, pulsatilla saponins, and panax notoginseng saponins—in modulating macrophage polarization and enhancing conventional therapies, particularly in oncology. We conducted structured searches in PubMed, Google Scholar, and SciFinder (2013-2024) using controlled vocabulary, including "saponins," "macrophage polarization," and "therapeutic effects." Our findings demonstrate that saponins significantly modulate immune responses and improve treatment efficacy. However, clinical translation is hindered by challenges such as poor bioavailability and safety concerns, which limit systemic exposure and therapeutic utility. To overcome these barriers, innovative delivery strategies, including nanoemulsions and engineered exosomes, are essential for enhancing pharmacokinetics and therapeutic index. Future research should prioritize elucidating the molecular mechanisms underlying saponin-mediated macrophage polarization, identifying novel therapeutic targets, and optimizing drug formulations. Addressing these challenges will enable the restoration of immune balance and more effective management of diverse diseases.
Keywords: Saponin, Macrophage polarization, Molecular mechanism, Pharmacokinetics, Bioavailability, Natural products 5-LOX, 5-lipoxygenase, A3, Anemoside A3, AGEs, Advanced glycation end products, ALK5, activin receptor-like kinase 5, ALT, alanine aminotransferase, ARG1, arginase-1, AsC, Araloside C, ASD, Akebia saponin D
Received: 26 Feb 2025; Accepted: 24 Mar 2025.
Copyright: © 2025 Xiong, Wang, Song, Lan, Li and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Fang Wang, Chengdu First People's Hospital, Chengdu, Sichuan Province, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.