Study on the Material Basis and Mechanism of Action of Different Parts of Honey Bran Cimicifuga Rhizoma in the Treatment of IBS-D

Abstract

Background of the study: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common disease of the brain–gut axis with clinical manifestations such as abdominal pain and abdominal leakage. It is usually accompanied by anxiety and depression, which severely affects the activities of daily living of patients. After Cimicifuga Rhizoma (CR) is processed through the honey bran, the effect of replenishing qi to increase yang is enhanced, and it is often used to treat abdominal pain, diarrhea, and other gastrointestinal discomforts. Honey Bran CR (HBCR) is clinically available for the treatment of IBS-D, but there is a lack of research on its material basis and mechanism of action, among other aspects.

Aim of the study: This study aimed to investigate the material basis of HBCR for replenishing qi to increase yang and predict its mechanism of action in treating IBS-D. Materials and Methods: First, the chemical constituents of different fractionated extracts of HBCR were identified by UPLC-Q-TOF-MS/MS, and the ingredient library was established. Second, the therapeutic effects of different parts on IBS-D model rats were compared. Third, the spectrum–effect relationship between the chemical components and pharmacodynamic indexes of HBCR was established by gray correlation analysis. Network pharmacology and molecular docking techniques were utilized to validate the effectiveness of the effector components. Finally, the action mechanism of HBCR for IBS-D was further analyzed by serum metabolomics.

Results: A total of 61 chemical constituents were identified by UPLC-Q-TOF-MS/MS. They included 40 for the petroleum ether group, 48 for the dichloromethane group, 26 for the ethyl acetate group, 37 for the N-butanol group, and 19 for the water group. The results of AWR experiments showed that the IBS-D rat model was successfully constructed. The NGF and TRPV1 immunohistochemical sections; TNF-α, VIP, and 5-HT expressions in the colon; and SP, BDNF, and 5-HT expressions in the hypothalamus showed that different extracted parts of HBCR had curative effects on IBS-D model rats, and the treatment effect of the ethyl acetate group was the best. So the different extracted parts of HBCR could inhibit the release of TRPV1 and SP mediators by downregulating the expressions of BDNF and NGF. It could also affect the production of 5-HT to alleviate the development of visceral hypersensitivity and inhibit the production of inflammatory factors such as TNF-α and the downregulation of gastrointestinal motility by VIP to treat IBS-D. Six potential effective components were screened using the spectrum–effect relationship: fukiic acid (Peak 1), cimicifugic acid C (Peak 26), piscidic acid (Peak 3), cimicifugic acid B (Peak 30), cimicifugic acid A (Peak 29), and cimicifugic acid D (Peak 25). The results of network pharmacology and molecular docking showed that the effective components played a role in replenishing qi to increase yang through multiple targets and pathways. Metabolomics studies have revealed that different fractionated extracts of HBCR can regulate unsaturated fatty acid biosynthesis metabolism, arachidonic acid metabolism, pyruvic acid metabolism, and other pathways to play a therapeutic role in the treatment of IBS-D.

Conclusion: In this study, we developed a library of chemical constituents of different extracted parts of HBCR for the first time, and the effective components for replenishing qi to increase yang were screened using the spectrum–effect relationship. This study preliminarily elucidated the action mechanism of different extracted parts of HBCR for the treatment of IBS-D. This laid a foundation for the study of the pharmacokinetics and quality standards of HBCR and provided a scientific basis for its clinical application.