Integrated Serum Pharmacochemistry, 16S RDNA Sequencing, and Metabolomics to Reveal the Material Basis and Mechanism of Shouhui Tongbian Capsule Against Diphenoxylate-induced Slow Transit Constipation in Rats

Overview

Journal Chin Med

Publisher Biomed Central

Specialty Biomedical Engineering

Date 2024 Oct 11

PMID 39394615

Authors

Jiaying Yang

He Xiao

Jingchun Yao

Pin Zhang

Bojiao Yi

Zhengyu Fang

Na Guo

Yongxia Guan

Guimin Zhang

Affiliations

Soon will be listed here.

Abstract

Background: Slow transit constipation (STC) is highly prevalent and has rising incidence. Shouhui Tongbian capsule (SHTB) is a traditional Chinese Medicine formula with extensive and highly efficacious usage in STC treatment, however, its mechanism of action, especially the regulation of microbiome and lipid metabolites, remains unclear.

Methods: After quality control of SHTB using LC‒MS to obtain its material basis, we tried to elucidate the cohesive modulatory network of SHTB against STC using hyphenated methods from microbiomics, lipidomics, mass spectrometry imaging (MSI) and molecular methods.

Results: SHTB could repair intestinal barrier damage, reduce systemic inflammation and increase intestinal motility in a diphenoxylate-induced STC rat model. Based on 16S rDNA sequencing results, SHTB rehabilitated the abnormal changes in Alloprevotella, Coprococcus, Marvinbryantia, etc., which were associated with STC symptoms. Meanwhile, microbial functional prediction showed that lipid metabolism was improved with SHTB administration. The differential lipids, including fatty acids, lysophosphatidylcholine, phosphatidylcholine, sphingomyelin triglyceride and ceramide, that are closely related to STC disease and SHTB efficacy. Furthermore, SHTB significantly reversed the abnormal expression of these key target enzymes in colon samples, including CTP-phosphocholine cytidylyltransferase, CTP-phosphoethanolamine cytidylyltransferase, phosphatidic acid phosphatase, acid sphingomyelinase etc. CONCLUSIONS: Combined analysis demonstrated that SHTB reducing lipid accumulation and recovery of intestinal microbial homeostasis was the critical mechanism by which SHTB treats STC.

References

Bosques-Padilla F, Vazquez-Elizondo G, Gonzalez-Santiago O, Del Follo-Martinez L, Gonzalez O, Gonzalez-Gonzalez J . Hypertriglyceridemia-induced pancreatitis and risk of persistent systemic inflammatory response syndrome. Am J Med Sci. 2014; 349(3):206-11. DOI: 10.1097/MAJ.0000000000000392. View

Yang Z, Ye S, Xu Z, Su H, Tian X, Han B . Dietary synbiotic ameliorates constipation through the modulation of gut microbiota and its metabolic function. Food Res Int. 2021; 147:110569. DOI: 10.1016/j.foodres.2021.110569. View

Yang J, Wang M, Yang D, Yan H, Wang Z, Yan D . Integrated lipids biomarker of the prediabetes and type 2 diabetes mellitus Chinese patients. Front Endocrinol (Lausanne). 2023; 13:1065665. PMC: 9897314. DOI: 10.3389/fendo.2022.1065665. View

Strati F, Cavalieri D, Albanese D, De Felice C, Donati C, Hayek J . New evidences on the altered gut microbiota in autism spectrum disorders. Microbiome. 2017; 5(1):24. PMC: 5320696. DOI: 10.1186/s40168-017-0242-1. View

Suares N, Ford A . Prevalence of, and risk factors for, chronic idiopathic constipation in the community: systematic review and meta-analysis. Am J Gastroenterol. 2011; 106(9):1582-91. DOI: 10.1038/ajg.2011.164. View

Fagundes D, Gonzalo S, Arruebo M, Plaza M, Murillo M . Melatonin and Trolox ameliorate duodenal LPS-induced disturbances and oxidative stress. Dig Liver Dis. 2009; 42(1):40-4. DOI: 10.1016/j.dld.2009.04.014. View

Morrison D, Preston T . Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes. 2016; 7(3):189-200. PMC: 4939913. DOI: 10.1080/19490976.2015.1134082. View

Stevens B, Goel R, Seungbum K, Richards E, Holbert R, Pepine C . Increased human intestinal barrier permeability plasma biomarkers zonulin and FABP2 correlated with plasma LPS and altered gut microbiome in anxiety or depression. Gut. 2017; 67(8):1555-1557. PMC: 5851874. DOI: 10.1136/gutjnl-2017-314759. View

Asp L, Kartberg F, Fernandez-Rodriguez J, Smedh M, Elsner M, Laporte F . Early stages of Golgi vesicle and tubule formation require diacylglycerol. Mol Biol Cell. 2008; 20(3):780-90. PMC: 2633395. DOI: 10.1091/mbc.e08-03-0256. View

10.

Kennedy E, Weiss S . The function of cytidine coenzymes in the biosynthesis of phospholipides. J Biol Chem. 1956; 222(1):193-214. View

11.

Sun L, Jiang H, Liu B, Li W, DU A, Luo X . Effects of rhein on intestinal transmission, colonic electromyography and expression of aquaporin-3 by colonic epithelium cells in constipated mice. Int J Clin Exp Pathol. 2020; 11(2):614-623. PMC: 6958053. View

12.

Qiao J, Huang F, Naikawadi R, Kim K, Said T, Lum H . Lysophosphatidylcholine impairs endothelial barrier function through the G protein-coupled receptor GPR4. Am J Physiol Lung Cell Mol Physiol. 2006; 291(1):L91-101. DOI: 10.1152/ajplung.00508.2005. View

13.

Rumsey R, Squires P, Read N . In vitro effects of sennoside on contractile activity and fluid flow in the perfused large intestine of the rat. Pharmacology. 1993; 47 Suppl 1:32-9. DOI: 10.1159/000139840. View

14.

Malik E, Muller C . Anthraquinones As Pharmacological Tools and Drugs. Med Res Rev. 2016; 36(4):705-48. DOI: 10.1002/med.21391. View

15.

Cui Y, Chen L, Huang T, Ying J, Li J . The pharmacology, toxicology and therapeutic potential of anthraquinone derivative emodin. Chin J Nat Med. 2020; 18(6):425-435. DOI: 10.1016/S1875-5364(20)30050-9. View

16.

Forootan M, Bagheri N, Darvishi M . Chronic constipation: A review of literature. Medicine (Baltimore). 2018; 97(20):e10631. PMC: 5976340. DOI: 10.1097/MD.0000000000010631. View

17.

Zeyue Y, Liyu H, Zongyuan L, Jianhui S, Hongying C, Hairu H . Correlation between slow transit constipation and spleen deficiency, and gut microbiota: a pilot study. J Tradit Chin Med. 2022; 42(3):353-363. PMC: 9924678. DOI: 10.19852/j.cnki.jtcm.20220408.002. View

18.

Yu C, Xiong Y, Chen D, Li Y, Xu B, Lin Y . Ameliorative effects of atractylodin on intestinal inflammation and co-occurring dysmotility in both constipation and diarrhea prominent rats. Korean J Physiol Pharmacol. 2017; 21(1):1-9. PMC: 5214900. DOI: 10.4196/kjpp.2017.21.1.1. View

19.

Lin P, Welch E, Gao X, Malik A, Ye R . Lysophosphatidylcholine modulates neutrophil oxidant production through elevation of cyclic AMP. J Immunol. 2005; 174(5):2981-9. DOI: 10.4049/jimmunol.174.5.2981. View

20.

Zhang C, Liu C, Qu Y, Cao Y, Liu R, Sun Y . LC-MS-Based Qualitative Analysis and Pharmacokinetic Integration Network Pharmacology Strategy Reveals the Mechanism of H.W.Li Treatment of Pneumonia. ACS Omega. 2021; 6(6):4495-4505. PMC: 7893793. DOI: 10.1021/acsomega.0c06201. View