Pulsatilla decoction alleviates colitis by enhancing autophagy and regulating PI3K‑Akt‑mTORC1 signaling pathway

Mao

et al. 2023

Preprint

Objective A case-control study was carried out to research the effects of Baitouweng decoction combined with drugs and endoscopy on clinical symptoms, immune level, and long-term prognosis of patients with ulcerative colitis (UC). Methods From March 2019 to March 2022, 100 patients with UC cured were arbitrarily divided into control and study groups in our hospital. The former group was cured with general treatment according to diagnosis and treatment and Mesalamine Rectal Enema at the same time. The effective rate was calculated. The syndrome scores, immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM) levels, enteroscopy score, and colon pathology score were compared before and after treatment. Results There was a 96.00% resultful rate in the study group, while the resultful rate in the control group was 76.00%. The study group achieved a higher resultful rate (P < 0.05). After 3 months of treatment, the total score of abdominal pain, diarrhea, abdominal distension, acute weight, purulent and bloody stool, fatigue, addiction, and TCM syndrome decreased noticeably. The research group's TCM syndrome scores were considerably lower (P < 0.05). The score of colonoscopy and colon pathology in the study group was lower (P < 0.05). And the levels of IgA, IgM, and IgG in the study group were lower (P < 0.05). In the control group, intestinal obstruction occurred in 4 cases, rectal canceration in 6 cases, and colonic polyp in 2 cases. The total incidence of complications was 24.00%. There was 1 case of intestinal obstruction, 2 cases of rectal canceration, and 1 case of colonic polyp with a total of 8.00% complications. Complication rates in the study group were noticeably lower (P < 0.05). Conclusion Baitouweng decoction combined with medicine and endoscopy has a noticeable clinical effect on patients with UC, which can not only effectively enhance the clinical symptoms and intestinal mucosa and histopathology of patients with UC, but also noticeably strengthen the recovery of immune function of patients with UC.

Section: Discussionmentioning

confidence: 75%

A cohort study on the effects of Baitouweng decoction combined with drugs and endoscopy on clinical symptoms, immune level, and long- term prognosis in patients with ulcerative colitis

Mao

et al. 2023

Preprint

“…Esculin extracted from C. fraxini was found to alleviate inflammation via the pathways of PPARγ/NF-кB and AKT/GSK3β/NF-κB ( Tian et al, 2019 ; Xu et al, 2021 ), with coptisine from C. chinensis regulating the PI3K/AKT pathway ( Wu et al, 2019 ). Moreover, PD was recently shown to alleviate colitis by enhancing autophagy and regulating the PI3K-AKT-mTORC1 pathway ( Wang et al, 2022 ). However, most of these studies focused on the anti-inflammatory effects of PD, suggesting the need to further study its antifibrotic mechanism.…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology-Based Strategy to Identify the Pharmacological Mechanisms of Pulsatilla Decoction against Crohn’s Disease

et al. 2022

Purpose: To explore pharmacological mechanisms of Pulsatilla decoction (PD) against Crohn’s disease (CD) via network pharmacology analysis followed by experimental validation.Methods: Public databases were searched to identify bioactive compounds and related targets of PD as well as related genes in patients with CD. Analyses using the drug–compound–target–disease network, the protein–protein interaction (PPI) network, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict the core targets and pathways of PD against CD. Colon tissue resected from patients with CD and tissue samples from a mouse model of CD fibrosis treated with PD were assessed to verify the major targets of PD in CD predicted by network pharmacologic analysis.Results: A search of the targets of bioactive compounds in PD and targets in CD identified 134 intersection targets. The target HSP90AA1, which was common to the drug–compound–target–disease and PPI networks, was used to simulate molecular docking with the corresponding bioactive compound. GO and KEGG enrichment analyses showed that multiple targets in the antifibrotic pathway were enriched and could be experimentally validated in CD patients and in a mouse model of CD fibrosis. Assays of colon tissues from CD patients showed that intestinal fibrosis was greater in stenoses than in nonstenoses, with upregulation of p-AKT, AKT, p-mTOR, mTOR, p-ERK1/2, ERK1/2, p-PKC, and PKC targets. Treatment of CD fibrosis mice with PD reduced the degree of fibrosis, with downregulation of the p-AKT, AKT, p-mTOR, mTOR, p-ERK1/2, ERK1/2, and PKC targets.Conclusion: Network pharmacology analysis was able to predict bioactive compounds in PD and their potential targets in CD. Several of these targets were validated experimentally, providing insight into the pharmacological mechanisms underlying the biological activities of PD in patients with CD.

“…Regarding the intracellular pathways, although the Niu et al study did not examine the related pathways activated by PD, the suppressive effect of PD on various pro-inflammatory cytokines might indicate its potential effect on the NF-κB pathway. Moreover, a study by Wang et al [ 84 ] disclosed that PD might also regulate the PI3K-AKT-mTORC1 signaling pathway in alleviating colitis. In addition, Li et al [ 85 ] observed that PD could regulate the GPR43-NLRP3 pathway in the treatment of UC.…”

Section: Traditional Medicine and Their Derivatives Act On Scfas To A...mentioning

confidence: 99%

Short Chain Fatty Acids: Essential Weapons of Traditional Medicine in Treating Inflammatory Bowel Disease

Yao,

Liu,

et al. 2024

Molecules

Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal inflammatory disease, mainly including Crohn’s disease (CD) and ulcerative colitis (UC). In recent years, the incidence and prevalence of IBD have been on the rise worldwide and have become a significant concern of health and a huge economic burden on patients. The occurrence and development of IBD involve a variety of pathogenic factors. The changes in short-chain fatty acids (SCFAs) are considered to be an important pathogenic mechanism of this disease. SCFAs are important metabolites in the intestinal microbial environment, which are closely involved in regulating immune, anti-tumor, and anti-inflammatory activities. Changes in metabolite levels can reflect the homeostasis of the intestinal microflora. Recent studies have shown that SCFAs provide energy for host cells and intestinal microflora, shape the intestinal environment, and regulate the immune system, thereby regulating intestinal physiology. SCFAs can effectively reduce the incidence of enteritis, cardiovascular disease, colon cancer, obesity, and diabetes, and also play an important role in maintaining the balance of energy metabolism (mainly glucose metabolism) and improving insulin tolerance. In recent years, many studies have shown that numerous decoctions and natural compounds of traditional Chinese medicine have shown promising therapeutic activities in multiple animal models of colitis and thus attracted increasing attention from scientists in the study of IBD treatment. Some of these traditional Chinese medicines or compounds can effectively alleviate colonic inflammation and clinical symptoms by regulating the generation of SCFAs. This study reviews the effects of various traditional Chinese medicines or bioactive substances on the production of SCFAs and their potential impacts on the severity of colonic inflammation. On this basis, we discussed the mechanism of SCFAs in regulating IBD-associated inflammation, as well as the related regulatory factors and signaling pathways. In addition, we provide our understanding of the limitations of current research and the prospects for future studies on the development of new IBD therapies by targeting SCFAs. This review may widen our understanding of the effect of traditional medicine from the view of SCFAs and their role in alleviating IBD animal models, thus contributing to the studies of IBD researchers.