Anchang Yuyang Decoction inhibits experimental colitis-related carcinogenesis by regulating PPAR signaling pathway and affecting metabolic homeostasis of host and microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammatory bowel disease (IBD) presents a risk of carcinogenesis, which escalates with the duration of IBD. Persistent histological inflammation is considered to be the driving factor of colitis carcinogenesis. Effective control of inflammation is helpful to prevent and treat colitis-related colorectal cancer (CAC). Anchang Yuyang Decoction (AYD), a traditional Chinese medicine (TCM) formula, is originated from the ancient prescription of TCM for treating colitis and colorectal cancer. AYD has demonstrated efficacy in treating IBD and potential anti-carcinogenic properties. AIM OF THE STUDY: This research aims to assess the therapeutic efficacy of AYD in ameliorating experimental colitis-related carcinogenesis induced by AOM/DSS. It further seeks to elucidate its potential mechanisms by integrating multiple omics sequencing approaches. MATERIALS AND METHODS: A rat model for colitis-related carcinogenesis was developed using azoxymethane (AOM)/dextran sulfate sodium (DSS). UPLC-MS identified AYD's chemical constituents. Rats were administered varying doses of AYD (18.37, 9.19 and 4.59 g/kg) orally for 53 days, with mesalazine as a positive control. The study evaluated anti-carcinogenic effects by examining adenoma number, adenoma load, abnormal crypt foci (ACF), histopathological damage, and tumor-related protein expression. Anti-inflammatory and reparative effects were assessed through body weight, disease activity index (DAI), colon length, spleen index, inflammatory cytokine levels, and tight junction protein expression. The effects on intestinal microbiota and host metabolism were explored through 16S rRNA sequencing, targeted short-chain fatty acid (SCFA) metabonomics, and non-targeted colon metabolomics. Potential AYD targets were identified through transcriptomic sequencing and validated by qRT-PCR and western blotting. RESULTS: AYD significantly reduced adenoma number, adenoma load, neoplasm-associated lesions, ACF, and tumor-related protein expression (e.g., p53, PCNA) in AOM/DSS-induced rats, thus impeding colitis-related carcinogenesis progression. AYD also alleviated histopathological damage and inflammation, promoting intestinal mucosal barrier repair. Furthermore, AYD modulated intestinal flora structure, enhanced SCFA production, and regulated colon metabolites. Transcriptomic sequencing revealed a significant impact on the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Subsequent qRT-PCR and western blotting experiments indicated AYD's influence in up-regulating PPAR-γ and down-regulating PPAR-α, PPAR-ß/δ, and related proteins (thrombomodulin [Thbd], fatty acid binding protein 5 [Fabp5], stearoyl-CoA desaturase 2 [Scd2], phospholipid transfer protein [Pltp]). CONCLUSIONS: This study demonstrates AYD's ability to inhibit experimental colitis-related carcinogenesis induced by AOM/DSS. Its mechanism likely involves modulation of the PPAR signaling pathway, impacting intestinal microbiota and host metabolic equilibrium.

Atractylodes macrocephala-Paeonia lactiflora Class Formula for the Treatment of Irritable Bowel Syndrome: A Systematic Review With Meta-Analysis and Trial Sequential Analysis.

Previous meta-analyses suggested that Chinese herbal medicine (CHM) is effective for irritable bowel syndrome (IBS). Formulas with Atractylodes macrocephala and Paeonia lactiflora as the core pairs have been widely used by traditional Chinese medicine (TCM) practitioners for the treatment of IBS. We aimed to examine the efficacy and safety of the Atractylodes macrocephala-Paeonia lactiflora class formula (A-P CHM) for IBS through a meta-analysis and trial-sequential analysis (TSA). The protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42023439087. We searched seven databases for data up to May 23, 2023. The primary outcome was global IBS symptom relief. The secondary outcomes included the IBS severity scoring system (IBS-SSS) score and treatment-related adverse events. The relative ratio (RR) (dichotomous variables), the standardized mean difference (SMD) (continuous variables), the number needed to treat (NNT), the number needed to harm (NNH), and the required information size (RIS) were calculated. Twenty-four eligible articles with 3,768 participants were included. Thirteen trials were at low risk of bias (RoB). Compared with placebo or Western medication, A-P CHM was associated with a significantly higher proportion of relief of global IBS symptoms. The TSA analysis verified the primary outcome. For the secondary outcome, the A-P CHM IBS-SSS score was lower than Western medication or placebo at the end of the treatment, which was further confirmed by the TSA analysis. We asserted that A-P CHM might be a potential candidate for patients with IBS, especially for IBS-D. It may provide a theoretical basis for future optimization of irritable bowel syndrome with diarrhea (IBS-D) herbal formulas. The overall certainty of the evidence was not high; more tightly designed randomized controlled trials (RCTs) are required in the future.

[Clinical effects of acupoint catgut embedding with quadruple therapy on Hp (+) chronic atro-phic gastritis of spleen and stomach deficiency syndrome].

OBJECTIVE: To evaluate the clinical effects of acupoint catgut embedding combined with quadruple therapy on Helicobacter pylori (Hp)-positive (+) chronic atrophic gastritis (CAG) of spleen and stomach deficiency syndrome and explore the underlying mechanism. METHODS: Hp (+) CAG patients with spleen and stomach deficiency syndrome were randomly divi-ded into a control group (n=68) and a treatment group (n=71). In addition to the routine quadruple therapy for two weeks, the patients in the control group received oral Weifuchun Tablets (4 tablets once, tid.), and those in the treatment group underwent acupoint catgut embedding at Pishu (BL20), Weishu (BL21), Zhongwan (CV12), and Zusanli (ST36), once a week. The two groups were treated for three months in total. The scores of traditional Chinese medicine (TCM) symptoms and signs, clinical efficacies, quality of life scale scores (PRO scores and HAMA scores), endoscopic and histopathologic scores, Hp eradication rates detected by 13C breath test, and the recurrence rates after six months of the two group were compared. The changes in serum gastrin 17 (G-17), pepsinogen Ⅰ (PGⅠ) and pepsinogen Ⅱ (PGⅡ) were detected by ELISA, and PGⅠ/PGⅡ was calculated. RESULTS: There was no significant difference in the eradication rate of Hp between the two groups after treatment (P>0.05), but the recurrence rate after six months in the treatment group was lower than that of the control group (P<0.05). After treatment, the scores of TCM symptoms and signs, endoscopic and histopathologic scores, PRO scores, and HAMA scores were decreased in both groups (P<0.01), while serum levels of G-17, PG Ⅰ, PG Ⅱ, and PG Ⅰ/PG Ⅱ were increased (P<0.05, P<0.01). The treatment group was superior to the control group in alleviating stomach discomfort by pressing or warmth, decreasing the total score of TCM symptoms and signs, relieving anorexia, mottled gastric mucosa, mucosal ulcer, chronic inflammation, and activity, improving anxiety, and regulating G-17 (P<0.05, P<0.01). The effective rates of the treatment group and the control group were 40.85% (29/71) and 23.53% (16/68)，the treatment group was higher than the control group (P<0.05). CONCLUSION: Acupoint catgut embedding combined with quadruple therapy in the treatment of Hp (+) CAG of spleen and stomach deficiency syndrome is significant in clinical efficacy and low in recurrence rate, which is presumedly achieved by repairing gastric mucosa and sensitizing the secretion of G-17 and pepsinogen.