Molecular Mechanisms of Natural Saponins in Treating Acute Lung Injury: Systemic Regulatory Roles Involving Multiple Cell Types and Signaling Pathways
Abstract
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening conditions characterized by severe pulmonary dysfunction, with persistently high global incidence and mortality. Although glucocorticoids, the standard pharmacotherapy for ALI/ARDS, have been reported to reduce short-term mortality and improve outcomes, their clinical benefit is limited by dose- and duration-dependent adverse effects, thereby driving the exploration of complementary or alternative approaches. Natural saponins, a structurally diverse group of glycosides widely distributed in medicinal plants, have gained considerable interest owing to their multitarget anti-inflammatory, antioxidant, and antiapoptotic activities demonstrated in various in vitro and in vivo ALI models. Here, we systematically review the protective mechanisms of natural saponins from the perspectives of cellular regulation and signaling pathways, highlighting their modulatory effects on macrophages, neutrophils, and other effector cells, as well as their actions through key pathways related to inflammation, oxidative stress, and apoptosis. We further discuss current strategies to overcome the major translational barriers of saponins, particularly structural modifications and formulation approaches aimed at improving oral bioavailability and reducing hemolytic activity. This review consolidates the pharmacological basis for saponin-based ALI therapy and provides a forward-looking perspective on addressing their limitations to facilitate clinical translation.
Related
- Deciphering the molecular regulatory mechanisms of seed oil in soybean for higher-oil breeding
- Crosstalk between PI3K/AKT signaling and epigenetic regulation in hepatocellular carcinoma: molecular mechanisms and therapeutic opportunities
- VEGF Signaling and Targeted Therapies in Cancer: Molecular Mechanisms, Clinical Applications, Resistance, and Cardiorenal Toxicities
- β-Ionone for Cancer Therapy: Molecular Mechanisms, Apoptotic Signaling, Preclinical Evidence, and Translational Perspectives
- Molecular Mechanisms and Signaling Pathways Underlying the Synergistic Effect of Metformin and Paclitaxel in Preclinical Cancer Models: A Systematic Review.
BibTeX
@article{mei2026molecular,
title = {{Molecular Mechanisms of Natural Saponins in Treating Acute Lung Injury: Systemic Regulatory Roles Involving Multiple Cell Types and Signaling Pathways}},
author = {Zicheng Mei and Yuji Pan and Changshun Chen and Huijun Guo and Chao Zhong and Yanyun Fang and Yanfei Xie and Jun Yu and Wenli Lyu},
journal = {Biological and Pharmaceutical Bulletin},
year = {2026},
month = sep,
doi = {10.1248/bpb.b26-00161},
url = {https://www.jstage.jst.go.jp/article/bpb/49/9/49_b26-00161/_article},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Molecular Mechanisms of Natural Saponins in Treating Acute Lung Injury: Systemic Regulatory Roles Involving Multiple Cell Types and Signaling Pathways
AU - Zicheng Mei
AU - Yuji Pan
AU - Changshun Chen
AU - Huijun Guo
AU - Chao Zhong
AU - Yanyun Fang
AU - Yanfei Xie
AU - Jun Yu
AU - Wenli Lyu
PY - 2026
DA - 2026/09/01
JO - Biological and Pharmaceutical Bulletin
DO - 10.1248/bpb.b26-00161
UR - https://www.jstage.jst.go.jp/article/bpb/49/9/49_b26-00161/_article
AB - Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening conditions characterized by severe pulmonary dysfunction, with persistently high global incidence and mortality. Although glucocorticoids, the standard pharmacotherapy for ALI/ARDS, have been reported to reduce short-term mortality and improve outcomes, their clinical benefit is limited by dose- and duration-dependent adverse effects, thereby driving the exploration of complementary or alternative approaches. Natural saponins, a structurally diverse group of glycosides widely distributed in medicinal plants, have gained considerable interest owing to their multitarget anti-inflammatory, antioxidant, and antiapoptotic activities demonstrated in various in vitro and in vivo ALI models. Here, we systematically review the protective mechanisms of natural saponins from the perspectives of cellular regulation and signaling pathways, highlighting their modulatory effects on macrophages, neutrophils, and other effector cells, as well as their actions through key pathways related to inflammation, oxidative stress, and apoptosis. We further discuss current strategies to overcome the major translational barriers of saponins, particularly structural modifications and formulation approaches aimed at improving oral bioavailability and reducing hemolytic activity. This review consolidates the pharmacological basis for saponin-based ALI therapy and provides a forward-looking perspective on addressing their limitations to facilitate clinical translation.
SN - 1347-5215
SN - 0918-6158
ER -