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Targeting the Gut-Kidney Axis in Diarrhea with Kidney-Yang Deficiency Syndrome: The Role of Sishen Pills in Regulating TMAO-Mediated Inflammatory Response.

التفاصيل البيبلوغرافية
العنوان: Targeting the Gut-Kidney Axis in Diarrhea with Kidney-Yang Deficiency Syndrome: The Role of Sishen Pills in Regulating TMAO-Mediated Inflammatory Response.
المؤلفون: Xie S; Hunan University of Chinese Medicine, Changsha, Hunan, China (mainland)., Fang L; Hunan University of Chinese Medicine, Changsha, Hunan, China (mainland)., Deng N; Hunan University of Chinese Medicine, Changsha, Hunan, China (mainland)., Shen J; Hunan University of Chinese Medicine, Changsha, Hunan, China (mainland)., Tan Z; Hunan University of Chinese Medicine, Changsha, Hunan, China (mainland)., Peng X; The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China (mainland).
المصدر: Medical science monitor : international medical journal of experimental and clinical research [Med Sci Monit] 2024 Jun 20; Vol. 30, pp. e944185. Date of Electronic Publication: 2024 Jun 20.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: International Scientific Information, Inc Country of Publication: United States NLM ID: 9609063 Publication Model: Electronic Cited Medium: Internet ISSN: 1643-3750 (Electronic) Linking ISSN: 12341010 NLM ISO Abbreviation: Med Sci Monit Subsets: MEDLINE
أسماء مطبوعة: Publication: 2014- : Smithtown, NY : International Scientific Information, Inc.
Original Publication: Warsaw, Poland : Medical Science International
مواضيع طبية MeSH: Yang Deficiency*/metabolism , Yang Deficiency*/drug therapy , Gastrointestinal Microbiome*/drug effects , Diarrhea*/drug therapy , Diarrhea*/microbiology , Diarrhea*/metabolism , Methylamines*/metabolism , Drugs, Chinese Herbal*/pharmacology , Drugs, Chinese Herbal*/therapeutic use , Kidney*/metabolism , Kidney*/drug effects , Kidney*/pathology , Inflammation*/metabolism , Inflammation*/drug therapy, Animals ; Mice ; Male ; Disease Models, Animal ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Interleukin-1beta/metabolism ; RNA, Ribosomal, 16S/genetics ; Mice, Inbred C57BL ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/drug effects
مستخلص: BACKGROUND Sishen Pills (SSPs) are commonly used to treat diarrhea with kidney-yang deficiency syndrome. Trimethylamine-N-oxide (TMAO) is produced through the metabolism of gut microbiota and can participate in diarrhea in kidney-yang deficiency syndrome by mediating the "gut-kidney axis" to transmit inflammatory factors. This study combined network pharmacology with animal experiments to explore whether SSPs can treat diarrhea with kidney-yang deficiency syndrome by affecting the interaction between TMAO and gut microbiota. MATERIAL AND METHODS A mouse model of diarrhea with kidney-yang deficiency syndrome was constructed by using adenine and Folium sennae decoction, and SSP decoction was used for treatment. This study utilized network pharmacology to predict the potential mechanisms of SSPs in treating diarrhea with kidney-yang deficiency syndrome. 16S rRNA high-throughput sequencing was used to analyze gut mucosal microbial characteristics. ELISA was used to measure TMAO, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), interleukin-1ß (IL-1ß), and transforming growth factor-ß1 (TGF-ß1) levels. We performed Masson and immunohistochemical (Occludin, ZO-1) staining of kidney and small intestinal tissues. The fluorescein diacetate (FDA) hydrolysis spectrophotometric method was used to assess the microbial activity in contents of the small intestine. RESULTS Network pharmacology analysis revealed that SSPs can modulate 108 target points involved in the development of diarrhea, including IL-1ß and TNF. The experimental results demonstrated that SSP decoction significantly improved the general behavioral profiles of the mice, and also reduced TMAO, NLRP3, IL-1ß, and TGF-ß1 levels (P<0.05). Correlation analysis revealed significant positive correlations between TMAO concentrations and NLRP3, IL-1ß and TGF-ß1 levels (P<0.05). Pathological analysis revealed improvements in renal fibrosis and increased expression of the Occludin and ZO-1 proteins in intestinal tissue. In the SSP group, there was a significant increase in microbial activity (P<0.001). According to the sequencing results, the characteristic bacteria of the SSP and NR groups included Succinatimonas hippei, uncultured Solirubrobacter sp., and Clostridium tyrobutyricum. Furthermore, TMAO, NLRP3, IL-1ß, and TGF-ß1 were significantly positively correlated (P<0.05) with Succinatimonas hippei and Clostridium tyrobutyricum. By modulating Firmicutes, Succinatimonas hippei, and Clostridium tyrobutyricum, SSP decoction lowers TMAO levels to alleviate diarrhea with kidney-yang deficiency syndrome. CONCLUSIONS TMAO likely plays a significant role in the "gut-kidney axis" of diarrhea with kidney-yang deficiency syndrome. By adjusting gut microbiota to reduce the inflammatory response that is transmitted through the "gut-kidney axis" as a result of elevated TMAO levels, SSP decoction can alleviate diarrhea with kidney-yang deficiency syndrome.
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المشرفين على المادة: FLD0K1SJ1A (trimethyloxamine)
0 (Methylamines)
0 (Drugs, Chinese Herbal)
0 (NLR Family, Pyrin Domain-Containing 3 Protein)
0 (Interleukin-1beta)
0 (RNA, Ribosomal, 16S)
تواريخ الأحداث: Date Created: 20240620 Date Completed: 20240620 Latest Revision: 20240808
رمز التحديث: 20240808
DOI: 10.12659/MSM.944185
PMID: 38898640
قاعدة البيانات: MEDLINE
الوصف
تدمد:1643-3750
DOI:10.12659/MSM.944185