Evidence map›Paper›PMID 42560608›Full record

ArticleDigestive diseases and sciences2026

Saikosaponin D Improves Diarrhea-Predominant Irritable Bowel Syndrome by Regulating the Brain-Gut Axis: Based on Changes in the Gut HMGB1-TLR4/NF-κB Pathway and Hypothalamic HPA Axis.

Guilin Dong, Ao Li, Haizhou Zeng, Xinran Li, Yanli Xiong, Xiaoqing Xu, Jingjing Li, Yunxia Kuang, Chunli Lu, Guoqiang Qian

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Article in Digestive diseases and sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

10 authors.

Guilin DongSchool of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
Ao LiSchool of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
Haizhou ZengSchool of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
Xinran LiSchool of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
Yanli XiongSchool of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
Xiaoqing XuSchool of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
Jingjing LiLaboratory of Oncology and Immunology, School of Basic Medical Sciences, Guangdong Provincial Experimental Teaching Demonstration Center for TCM Clinical Skills, Guangdong Pharmaceutical University, 280 Huandong Road, University Town, Guangzhou, 510006, China.
Yunxia KuangLaboratory of Oncology and Immunology, School of Basic Medical Sciences, Guangdong Provincial Experimental Teaching Demonstration Center for TCM Clinical Skills, Guangdong Pharmaceutical University, 280 Huandong Road, University Town, Guangzhou, 510006, China.
Chunli LuInstitute of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China.ORCID http://orcid.org/0000-0003-2939-1327
Guoqiang QianSchool of Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China. tgqqian@gdpu.edu.cn.ORCID http://orcid.org/0000-0003-3036-1512

Funding

Correlation study on the mechanism of iron deposition and ferroptosis initiation in brain tissue induced by inflammatory bowel disease SGYY2024A010Study on the mechanism of Sini San improving IBS-D through Nesfatin-1-mediated HMGB1/TLR4/NF-κB signaling pathway based on the theory of liver depression and spleen deficiency 2024ZDZX2075
6 · The paper itself

Abstract

backgroundDiarrhea-predominant irritable bowel syndrome (IBS-D) is characterized by diarrhea and is often accompanied by depression, abdominal symptoms, and emotional comorbidities. Preclinical and clinical studies have shown that dysfunction of the brain-gut axis is a key pathogenic factor in IBS-D, yet the specific mechanisms remain unclear. Saikosaponin D (SSD), a major bioactive component of Bupleurum chinense DC., exhibits anti-inflammatory, antidepressant, and antitumor activities, with multi-target and multi-pathway interactions.

methodsAcetic acid and restraint stress induced an IBS-D mouse model. SSD (purity ≥ 98%, Macklin Inc.) was administered orally at low, medium, and high doses (5, 10, 20 mg/kg). Visceral sensitivity, inflammatory status, intestinal barrier function, HPA axis activity, and gut microbiota composition were systematically evaluated using behavioral tests, Western blot, qRT-PCR, and 16S rRNA sequencing.

resultsSSD significantly alleviated visceral hypersensitivity and depression-like behavior, inhibited the peripheral HMGB1-TLR4/NF-κB inflammatory pathway, and restored intestinal barrier integrity. SSD also downregulated hypothalamic Nesfatin-1/CRH/p-CREB expression, suppressed hyperactivation of the stress-related HPA neuroendocrine axis, and reshaped the gut microbial community structure (β-diversity). Network pharmacology analysis suggested that SSD targets were significantly enriched in brain-gut axis-related pathways.

conclusionThe present results indicate that SSD could ameliorate IBS-D by synergistically regulating peripheral inflammation, central stress, and intestinal microbes via the brain-gut-microbiota axis, providing experimental evidence for its potential application in TCM-based treatment.

Indexed as

Brain-Gut AxisDiarrheaHMGB1 ProteinHypothalamo-Hypophyseal SystemIrritable Bowel SyndromeOleanolic AcidPituitary-Adrenal SystemSaponinsAcetic AcidAnimalsDisease Models, AnimalGastrointestinal MicrobiomeIntestinal Barrier FunctionMaleMiceNF-kappa BAcetic AcidHMGB1 ProteinHMGB1 protein, mouseNF-kappa BOleanolic Acidsaikosaponin DSaponinsTlr4 protein, mouseToll-Like Receptor 4Brain–gut axisDepressionDiarrhea-predominant irritable bowel syndrome (IBS-D)Gut microbiotaInflammationSaikosaponin D

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.