The inhibitory effects of Qingchang Wenzhong granule on the interactive network of inflammation, oxidative stress, and apoptosis in rats with dextran sulfate sodium‐induced colitis

Abstract

Background: Ulcerative colitis (UC) is a kind of complex immune disease, the pathogenesis of which remains elusive. Destruction of the intestinal barrier, extreme inflammation, oxidative stress, and apoptosis might play key roles in the development of UC. In previous studies, we observed that Qingchang Wenzhong granule (QCWZG) had the exact effect on the remission of UC in the clinic; however, the underlying mechanism has not been identified. This study aimed to reveal the effects of QCWZG on the intestinal physical barrier and the interactive network of inflammation, oxidative stress, and apoptosis in rats with dextran sulfate sodium (DSS)induced colitis.Methods: Sixty rats were randomly divided into six groups: blank group, model group, high/mild/low-dose QCWZG groups, and mesalazine group. The rats in the experimental group drank 4% DSS for 7 days and 1% DSS for the subsequent 7 days. Different medications or distilled water was supplied by intragastric administration for 7 days. The levels of colitis and indices related to inflammation, oxidative stress, and apoptosis were assessed.Results: Compared with the model group, the QCWZG group (P < 0.05) demonstrated attenuated disease activity index, colonic mucosa disease index, histological lesions, and colonic weights; lower levels of inflammatory substances, such as interleukin (IL)-1α, IL-6, tumor necrosis factor-α, and myeloperoxidase; lower levels of malondialdehyde; and increased levels of superoxide dismutase and glutathione peroxidase. The QCWZG group also demonstrated elevated expression of Bcl-2 and occluding but downregulated db expression of Bax and caspase 3 in the colon. Conclusion: QCWZG could relieve rats with DSS-induced colitis from UC symptoms by improving the intestinal physical barrier, which resists the interactive network of inflammation, oxidative stress, apoptosis, and their overactivated interactions.

Network Pharmacology-based Strategy for Studying the Mechanism of Gegen Qinlian Decoction for the Treatment of Acute Colitis

“…The HIF-1 signaling pathway is derived from KEGG database, as shown in Figure 11, It is found that the expression of HIF-1α is regulated by PI3K-Akt signaling pathway, which is consistent with the literatures [50 , 51]. PI3K-AKT signaling pathway can regulate a wide range of cellular, is involved in the regulation and release of multiple pro-in ammatory cytokines, and these pro-in ammatory cytokines play an important role in the development of AC [43]. So we speculated that the active components of GQD may achieve the therapeutic effect on AC by regulating HIF-1 signaling pathway and PI3K-Akt signaling pathway.…”

Targeting IL‐10, ZO‐1 gene expression and IL‐6/STAT‐3 trans‐signaling by a combination of atorvastatin and mesalazine to enhance anti‐inflammatory effects and attenuates progression of oxazolone‐induced colitis

“…The combination of mesalazine and atorvastatin induced a more significant suppression of MPO activity compared with single therapy. Furthermore, the mesalazine‐treated group significantly decreased the expression of caspase‐3 in colonic tissue and these investigations are parallel with other studies [63,64]. The anti‐inflammatory and anti‐apoptotic effects of mesalazine may be attributed to a PPAR‐gamma‐dependent mechanism and inhibition of inflammatory mediators [55].…”

Gut Microbiota-Mediated NLRP12 Expression Drives the Attenuation of Dextran Sulphate Sodium-Induced Ulcerative Colitis by Qingchang Wenzhong Decoction

“…We found QCWZD can alleviate inflammatory reaction and improve the intestinal barrier function in DSS-induced UC rats by downregulating the IP10/CXCR3 axis [8] and upregulating the MSP/RON pathway [7]. Furthermore, we also found that QCWZD could resist the interactive network of inflammation, oxidative stress, apoptosis, and their overactivated interactions [29]. Recently we found that there was a significant difference in the composition and abundance of gut microbiota between UC patients and healthy people [9].…”