Jul 2026· Journal of Ethnopharmacology· pp.
122163
· 0 citations· 80 references
Medicine
TL;DR
S. macrosperma ameliorates 5-FU-induced diarrhea, and the mechanism potentially involves the PI3K-AKT pathway, which provides a scientific basis for clinical application and offer potential chemical markers for future quality control studies of this species.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE
5-Fluorouracil (5-FU)-induced diarrhea severely impacts chemotherapy outcomes. Swertia macrosperma (C. B. Clarke) C. B. Clarke in Hook. f. is traditionally used for diarrhea, yet its efficacy and mechanism remain unclear.
Aim
OF THE STUDY
This study first investigated the anti-diarrheal potential of 70% ethanol extract from S. macrosperma (SME).
Materials And Methods
In a 5-FU-induced mouse model, SME was evaluated for its effects on diarrhea severity, weight loss, intestinal histopathology, oxidative stress (MDA, SOD, GSH), inflammation (TNF-α, IL-6, COX-2, iNOS), and tight junction proteins (Claudin-1, Occludin). Phytochemical investigation (including isolation, structural elucidation, and UPLC-MS quantification), IEC-6 cell-based mechanistic studies, network pharmacology, and Western blot analysis (for PI3K-AKT pathway) were performed.
Results
SME significantly alleviated weight loss, diarrhea severity, and intestinal histopathological damage. It inhibited oxidative stress and inflammation while upregulating tight junction proteins, thereby protecting intestinal barrier integrity. Phytochemical investigation yielded 57 compounds, including three new isolates (swemacronosides A-C) and 37 first-time reports for this species. UPLC-MS quantification identified compounds 7, 8, and 23 as the predominant constituents. Mechanistic studies indicated that SME ameliorated diarrhea symptoms in mice via the PI3K-AKT signaling pathway. Western blot confirmed that compounds 7 and 23 significantly restored the 5-FU-induced downregulation of PI3K expression and the p-AKT/AKT ratio.
Conclusion
S. macrosperma ameliorates 5-FU-induced diarrhea, and the mechanism potentially involves the PI3K-AKT pathway. However, under the present experimental conditions, it did not significantly reverse 5-FU-induced thymic and splenic atrophy. These findings provide a scientific basis for clinical application and offer potential chemical markers for future quality control studies of S. macrosperma.
The crude ethanolic extract of O. tenuiflorum demonstrated consistent, multi-target bioactivity, combining antioxidant, anti-inflammatory, and cytotoxic effects, supporting its potential as a chemopreventive and therapeutic agent against CRC.
Aishwarya H. K., S. Harishkumar, Pruthvi Gowda et al.· Frontiers in Oncology· 0 citations
Results suggest SYH mitigates ALI by inhibiting the pro-inflammatory TLR4/MYD88/NF-κB pathway and activating the antioxidant Keap-1/Nrf2/HO-1/NQO1 pathway.
Zhongde Xie, Xiaoyuan Peng, Xuelian Dai et al.· Natural Product Research· 0 citations
ETHNOPHARMACOLOGICAL RELEVANCE
Astragalus membranaceus var. mongholicus (Bunge) P.K.Hsiao (AM), a classic Qi-tonifying herb, has been widely used for treating a range of inflammatory diseases. Nevertheless, the protective effects of AM against irinotecan-induced gut toxicity (IGT) remains insufficiently characterized, while the active pharmacological fractions and the underlying anti-IGT mechanisms have not been fully elucidated.
AIMS
This study aimed to investigate the ameliorative effects of the water extract of AM and its fractions on IGT in mice, as well as to identify the most potent anti-IGT fraction and to reveal the underlying anti-IGT mechanisms.
METHODS
The water extract of AM (WEA) was administered to an IGT murine model. Therapeutic efficacy was assessed using the Disease Activity Index (DAI), while histopathology was evaluated via H&E and PAS staining. Intestinal barrier integrity was examined by measuring ZO-1, Occludin, and Muc2 expression using RT-qPCR, immunofluorescence, and immunohistochemistry. Colonic pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) were quantified by ELISA. Following confirmation of efficacy, four fractions were isolated and compared. The most effective fraction, Astragalus membranaceus polysaccharides (APS), was further investigated using 16S rRNA sequencing, microbial metabolomics, transcriptomic, and Western blot.
RESULTS
APS significantly improved body weight loss and reduced DAI in IGT mice. H&E staining showed that APS ameliorated structural damage and inflammatory infiltration in colonic tissues. PAS staining revealed a notable increase in goblet cell numbers following APS treatment. RT-PCR and immunohistochemical staining confirmed that APS enhanced the expression of intestinal barrier markers (ZO-1, Occludin, Muc2) and promoted crypt proliferation (Ki67) in colonic tissue. Consequently, APS markedly reduced the levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in colonic tissues from IGT mice. 16S rRNA sequencing showed that APS regulated gut microbiota composition, thereby increasing the beneficial metabolites (e.g. butyrate acid) in colonic lumen. It was also found that APS significantly reduced the abundance of gmβ-GUS-producing bacteria, which in turn, decreasing gmβ-GUS enzymatic activity and the intestinal exposure levels of the toxic metabolite SN-38. Finally, transcriptomic analysis of colonic tissues revealed that APS suppressed the MAPK signaling pathway (MEK, ERK, P38, JNK) and down-regulated apoptosis-related genes (Bax, Bcl-2) in IGT mice.
CONCLUSION
Our findings suggest that APS, the key active fraction of AM against IGT, mitigate IGT by modulating microbiota-metabolite-MAPK axis, offering novel mechanistic insight for the ethnopharmacological use of AM to mitigate chemotherapy-induced intestinal toxicity.
Bolin Wu, Chenyang Zhou, Chuting Xu et al.· Journal of Ethnopharmacology· 0 citations
Introduction Cimicifuga foetida L. is widely applied in the clinical treatment of ulcerative colitis (UC); however, its active components and mechanisms have not been deeply investigated. The objective of this study is to investigate the potential bioactive constituents of C. foetida L. for the treatment of UC, and elucidate its therapeutic mechanism. Methods The crude polysaccharide of C. foetida L. was extracted by hot water and purified by DEAE Sepharose™ Fast Flow column to obtain, and named SM05. The structure was determined by HPLC, FT-IR and SEM. The effect of polysaccharide (SM05) on the mouse UC model and its mechanism of action were investigated using a dextran sodium sulfate (DSS)-induced UC model. Changes in body weight, disease activity index, colon length, organ index, histopathological injury, cytokine expression and intestinal tight junction proteins were measured to evaluate the effect of SM05 on UC. IHC, RT-qPCR, and 16s rDNA sequencing were performed to elucidate the underlying mechanism. Results SM05 is mainly composed of mannose, glucose, galactose, and arabinose. SM05 exerts antioxidant effects by activating the Nrf2/Keap1 pathway, thereby inhibiting the NLRP3-induced pyroptosis pathway. This reduces abnormal intestinal cell death and the secretion of inflammatory cytokines, thus protecting the intestinal barrier and suppressing further inflammation. Additionally, SM05 modulates the gut microbiota structure in mice with ulcerative colitis by reducing pathogenic bacteria (e.g., Bacteroides and Desulfovibrio) that damage the intestinal barrier and increasing the abundance of beneficial bacteria (e.g., Akkermansia and Saccharibacteria), thereby alleviating the progression of ulcerative colitis. Discussion In the preliminary biological assessment, the polysaccharide subfraction SM05 alleviated the symptoms of UC induced by DSS. This effect may be related to the activation of the Nrf2/Keap1 pathway, the inhibition of pyroptosis, and the regulation of the intestinal microbiota.
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C. nutans demonstrates significant medicinal potential, and future research priorities should include bioactivity-guided isolation of novel metabolites, validated in vivo mechanistic studies, pharmacokinetic and metabolomic profiling, and the implementation of standardized Phase I/II clinical trials and veterinary evaluations to support its further development and application.
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