Journal of ethnopharmacology · 2025
Comparative efficacy and mechanism of Moringa oleifera leaves as a substitute for Rhei Radix et Rhizoma in Houpo Sanwu Decoction: A transcriptomic analysis of constipation alleviation via the PI3K-Akt pathway.
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Wang Zhihao, Yue Xingnan, Feng Shuyi, Li Jiaqi, Wang Shuo, Lan Xuemei, Li Caifeng, Wang Lan, Li Zhiyong, Yang Bin
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Moringa oleifera leaves (MOLs), a safe and medicinal herb, are recognized for their Pancha (na) karma (purgative) effect in Ayurvedic medicine. As a promising alternative in traditional Chinese medicine, MOL is of considerable interest as a potential substitute for Rhei Radix et Rhizoma (RRR), a traditional laxative not recommended for long-term use due to the side effects associated with anthraquinones.
AIM OF THE STUDY: This study aimed to evaluate the efficacy and underlying mechanisms of replacing RRR with MOL in the classical formula Houpo Sanwu Decoction (HSD) for treating constipation induced by a low-fiber diet in mice.
MATERIALS AND METHODS: The laxative effects of RRR, MOL, HSD, and a modified formulation replacing RRR with MOL (HMO) were assessed in a mouse model of constipation. Fecal parameters, gastrointestinal hormone levels, histopathological changes, and gene expression profiles were examined. RNA sequencing, gene set enrichment analysis (GSEA), and RT-qPCR validation were conducted to explore the molecular mechanisms involved.
RESULTS: RRR significantly increased fecal water content in constipated mice, while MOL enhanced intestinal motility. Both HSD and HMO provided dual benefits by increasing fecal water content and promoting intestinal movement. ELISA results showed that MOL increased levels of motilin (MTL), vasoactive intestinal peptide (VIP), and somatostatin (SS), whereas RRR elevated gastrin (GAS) and SS. HSD raised levels of neuropeptide Y (NPY), SS, VIP, and MTL, while HMO enhanced MTL and SS but reduced NPY. Histological and immunohistochemical analyses revealed that RRR, MOL, HSD, and HMO all contributed to repairing the intestinal mucosa and decreasing aquaporin-3 expression. Transcriptomic analysis and GSEA identified complex laxative mechanisms for each treatment. The phosphoinositide 3-kinase/protein kinase B (PI3K-Akt) and calcium signaling pathways were commonly involved in the effects of both RRR and MOL. Notably, the PI3K-Akt pathway was also shared by the formulations HSD and HMO. However, the direction and intensity of PI3K-Akt pathway regulation varied among RRR, MOL, HSD, and HMO.
CONCLUSIONS: MOL has the potential to replace RRR as an effective laxative component in HSD, with HMO maintaining or even enhancing the therapeutic efficacy of the original formula. Moreover, the PI3K-Akt signaling pathway, shared by both RRR and MOL, was consistently activated in their respective formulations, HSD and HMO.
AIM OF THE STUDY: This study aimed to evaluate the efficacy and underlying mechanisms of replacing RRR with MOL in the classical formula Houpo Sanwu Decoction (HSD) for treating constipation induced by a low-fiber diet in mice.
MATERIALS AND METHODS: The laxative effects of RRR, MOL, HSD, and a modified formulation replacing RRR with MOL (HMO) were assessed in a mouse model of constipation. Fecal parameters, gastrointestinal hormone levels, histopathological changes, and gene expression profiles were examined. RNA sequencing, gene set enrichment analysis (GSEA), and RT-qPCR validation were conducted to explore the molecular mechanisms involved.
RESULTS: RRR significantly increased fecal water content in constipated mice, while MOL enhanced intestinal motility. Both HSD and HMO provided dual benefits by increasing fecal water content and promoting intestinal movement. ELISA results showed that MOL increased levels of motilin (MTL), vasoactive intestinal peptide (VIP), and somatostatin (SS), whereas RRR elevated gastrin (GAS) and SS. HSD raised levels of neuropeptide Y (NPY), SS, VIP, and MTL, while HMO enhanced MTL and SS but reduced NPY. Histological and immunohistochemical analyses revealed that RRR, MOL, HSD, and HMO all contributed to repairing the intestinal mucosa and decreasing aquaporin-3 expression. Transcriptomic analysis and GSEA identified complex laxative mechanisms for each treatment. The phosphoinositide 3-kinase/protein kinase B (PI3K-Akt) and calcium signaling pathways were commonly involved in the effects of both RRR and MOL. Notably, the PI3K-Akt pathway was also shared by the formulations HSD and HMO. However, the direction and intensity of PI3K-Akt pathway regulation varied among RRR, MOL, HSD, and HMO.
CONCLUSIONS: MOL has the potential to replace RRR as an effective laxative component in HSD, with HMO maintaining or even enhancing the therapeutic efficacy of the original formula. Moreover, the PI3K-Akt signaling pathway, shared by both RRR and MOL, was consistently activated in their respective formulations, HSD and HMO.