The pharmacological evidence of the chang-yan-ning formula in the treatment of colitis

Abstract

Ulcerative colitis (UC) is a subtype of inflammatory bowel disease (IBD) and occurs mainly in the colon. The etiology of UC is rather complex and involves various pathological factors, including genetic susceptibility, dietary intakes, environment, and microbiota. In China, the Chang-Yan-Ning (CYN) formula has been utilized in the clinic to treat gastrointestinal disorders, but its pharmacological evidence remains elusive. The investigation was designed to explore the molecular and cellular mechanisms of CYN. Liquid Chromatography with tandem mass spectrometry (LC/MS) was performed to identify the key components in the formula; Network pharmacology analysis was executed to predict the potential targets of CYN; An experimental murine colitis model was established by utilizing 2% dextran sodium sulfate (DSS), and CYN was administered for 14 days. The pharmacological mechanism of the CYN formula was corroborated by in-vivo and in-vitro experiments, and high throughput techniques including metabolomics and 16S rRNA sequencing. Results: LC/MS identified the active components in the formula, and network pharmacology analysis predicted 37 hub genes that were involved in tumor necrosis factor (TNF), interleukin (IL)-17, hypoxia-inducible factor (HIF) signaling pathways. As evidenced by in-vivo experiments, DSS administration shortened the length of the colon and led to weight loss, with a compromised structure of epithelium, and the CYN formula reversed these pathological symptoms. Moreover, CYN suppressed the levels of pro-inflammatory cytokines, including IL-4, IL-1b, and TNFαin the serum, inhibited the protein abundance of IL17 and HIF-1αand increased PPARγ and CCL2 in the colon, and facilitated the alternative activation of peritoneal macrophages. While peritoneal macrophages of colitis mice enhanced reactive oxygen species (ROS) production in murine intestinal organoids, the ROS level remained stable co-cultured with the macrophages of CYN-treated mice. Furthermore, the decreased microbiota richness and diversity and the prevalence of pathogenic taxa in colitis mice were rescued after the CYN treatment. The altered metabolic profile during colitis was also restored after the therapy. We posit that the CYN therapy attenuates the development and progression of colitis by maintaining the homeostasis of immune responses and microbiota.

Efficacy and safety of Changyanning tablets in the treatment of diarrhea-predominant irritable bowel syndrome and its effect on gut microbiota：Study protocol for a multicenter, randomized, double-blind, placebo-controlled trial

“…Essential oil from Liquidambar formosana leaves has certain anti-in ammatory activity, which can ameliorates in ammatory response in lipopolysaccharideactivated mouse macrophages [31] .The remarkable clinical e cacy of CYN tablets may come from the comprehensive effect of multi-components and multi-targets of different herbs. Identi cation and analysis using liquid chromatography-tandem mass spectrometry (LC-MS) revealed that the main active components of CYN (a TCM formula) include quercetin, gallic acid, catechol, luteolin, kaempferol, etc., which possess various biological activities such as anti-in ammatory, visceral pain relief, antioxidant, alleviation of visceral hypersensitivity, and modulation of gut microbiota [32][33][34][35][36] .…”

Efficacy and safety of Chinese patent medicine combined with 5-aminosalicylic acid for patients with ulcerative colitis: A network meta-analysis of randomized controlled trials

“…Liquid chromatography coupled with tandem mass spectrometry analysis revealed that the primary constituents of CYN are gallic acid, methyl gallate, catechol, asperulosidic acid, kaempferol, and quercetin [ 89 ]. Animal studies showed that CYN reduces the levels of pro-inflammatory cytokines in the serum of a murine colitis model, downregulating IL-17 and HIF-1α and upregulating PPARγ and CCL2 in the colon, facilitating the alternative activation of peritoneal macrophages [ 90 ]. Additionally, CYN treatment has been shown to enhance the diversity and richness of the intestinal microbiota in UC mice, while restoring the metabolic profile during colitis [ 91 ].…”

Exploration of the in vitro Antiviral Effects and the Active Components of Changyanning Tablets Against Enterovirus 71

“…Clinically, CYN tablets have been proven effective for the treatment of diarrhea, acute gastroenteritis, and ulcerative colitis. [14][15][16] When we screened the anti-EV71 medicines, we found by chance that the aqueous solution of CYN tablets has in vitro anti-EV71 effects. The 2020 edition of the Chinese Pharmacopoeia records that CYN tablets have the effects of clearing heat and relieving dampness, which is consistent with the therapeutic principle of HFMD.…”