Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

20 June 2024 : Animal Research  

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

Shiqin Xie1BCDEF, Leyao Fang1BCF, Na Deng1BCD, Junxi Shen1BC, Zhoujin Tan1AG*, Xinxin Peng2AF

DOI: 10.12659/MSM.944185

Med Sci Monit 2024; 30:e944185

Abstract

0:00

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-1β (IL-1β), and transforming growth factor-β1 (TGF-β1) 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-1β and TNF. The experimental results demonstrated that SSP decoction significantly improved the general behavioral profiles of the mice, and also reduced TMAO, NLRP3, IL-1β, and TGF-β1 levels (P<0.05). Correlation analysis revealed significant positive correlations between TMAO concentrations and NLRP3, IL-1β and TGF-β1 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-1β, and TGF-β1 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.

Keywords: inflammation, Sishen Wan, trimethyloxamine

Add Comment 0 Comments

Editorial

01 July 2024 : Editorial  

Editorial: The Global Threats of Increasing Antimicrobial Resistance Require New Approaches to Drug Development, Including Molecular Antimicrobial Adjuvants

Dinah V. Parums

DOI: 10.12659/MSM.945583

Med Sci Monit 2024; 30:e945583

0:00

In Press

Clinical Research  

Prognostic Impact of Tumor-Infiltrating Immune Cells on Efficacy of Neoadjuvant Chemotherapy in Patients wi...

Med Sci Monit In Press; DOI: 10.12659/MSM.943170  

Clinical Research  

Impact of Denture Use on Oral Health-Related Quality of Life in Yemeni Patients: A Cross-Sectional Analysis

Med Sci Monit In Press; DOI: 10.12659/MSM.944682  

Clinical Research  

Minimally Invasive versus Traditional Surgery: Efficacy of PELD and PLIF in Treating Pyogenic Spondylodiscitis

Med Sci Monit In Press; DOI: 10.12659/MSM.943176  

Clinical Research  

Frontal Plane Body Posture as a Predictor of Musculoskeletal Injuries in Amateur Athletes: A Comprehensive ...

Med Sci Monit In Press; DOI: 10.12659/MSM.944810  

Most Viewed Current Articles

17 Jan 2024 : Review article   3,861,054

Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron Variant

DOI :10.12659/MSM.942799

Med Sci Monit 2024; 30:e942799

0:00

14 Dec 2022 : Clinical Research   1,585,498

Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase Levels

DOI :10.12659/MSM.937990

Med Sci Monit 2022; 28:e937990

0:00

16 May 2023 : Clinical Research   690,905

Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...

DOI :10.12659/MSM.940387

Med Sci Monit 2023; 29:e940387

0:00

01 Jan 2022 : Editorial   50,731

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...

DOI :10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

0:00

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750