Huangkui Lianchang Decoction Ameliorates DSS-Induced Ulcerative Colitis in Mice by Inhibiting the NF-kappaB Signaling Pathway

Abstract

Background. The nuclear factor kappa beta (NF-κB) signaling pathway plays an important role in ulcerative colitis (UC). Huangkui Lianchang decoction (HLD) is an effective traditional Chinese medicinal compound used in the treatment of UC. HLD has good effects in the clinic, but the mechanism by which HLD acts is unclear. This study aims to reveal the exact molecular mechanism of HLD in the treatment of UC. Methods. Mouse ulcerative colitis was induced by dextran sulfate sodium (DSS) and treated with HLD. Intestinal damage was assessed by disease activity index (DAI), colon macroscopic lesion scores, and histological scores. Interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β were detected in colon tissue using ELISA. Myeloperoxidase (MPO) and superoxide dismutase (SOD) activities in the colonic mucosa were measured. The levels of IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in the colon were determined by real-time quantitative polymerase chain reaction (qPCR). The expression of NF-κB, IκBα, and p-IκBα in the colon was measured by Western blot. Results. After treatment with HLD, the DAI scores, macroscopic lesion scores, and histological scores decreased, and the levels of inflammatory cytokines related to the NF-κB signaling pathway, such as IL-6, TNF-α, and IL-1β, as well as those of iNOS and COX-2, were reduced; at the same time, colonic pathological damage was alleviated, and the MPO and SOD activities decreased. Western blot confirmed that HLD can inhibit the NF-κB signaling pathway in DSS-induced ulcerative colitis. Conclusion. HLD can alleviate the inflammation caused by ulcerative colitis. In particular, high doses of HLD can significantly alleviate intestinal inflammation and have comparable efficacy to Mesalazine. We propose that the anti-inflammatory activity of HLD on DSS-induced colitis in mice may involve the inhibition of the NF-κB pathway.

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“…Upregulation of NF-κB is closely related to the occurrence of Alzheimer’s disease, and inhibition of NF-κB might be a therapeutic method to treat Alzheimer’s disease 37. It has been indicated that proinflammatory cytokines, such as TNF-α, IL-1β, IL-6 and MCP-1, play an important role in the NF-κB signaling pathway 38. NF-κB could activate the proinflammatory cytokines TNF-α, IL-1β, IL-6 and MCP-1 in cells, which could induce inflammation response 38.…”

Targeting NF-κB pathway for treating ulcerative colitis: comprehensive regulatory characteristics of Chinese medicines

“…Huangkui Lianchang decoction (HLD) is a Chinese medicinal cocktail used to treat UC. Study indicates that HLD (9.425, 18.85, 37.70 g/kg) treatment alleviates colonic pathological damage in DSS-induced UC mice, and decreases IL-6, TNF-α, and IL-1β levels via the inhibition of the NF-κB pathway [150].…”

“…Decrease the NF-B levels [150] Bawei Xilei powder UC patients Decrease the expression of NF-κBp65 [151] medicine and formulae, and detoxificating and purgative medicine exert distinguished actions, which embodies enhancing the activity of IκBα to decrease phosphorylated p65 or inhibiting the degradation of IκBα binding to p65. Apart from affecting IκBα, some Chinese medicines and their active compounds are able to regulate the activity of NF-κB by affecting AKT, TLR4/ MyD88, PPARγ/SIRT1, p-IKKβ/IKKβ, p38MAPK/ERK/ JNK, TLR5/MyD88, p-STAT3.…”

“…Decrease the IκBα and p-IκBα levels [150] Warming yang and drying dampness category Modified ZenWu decoction…”

Network Pharmacology-Based Investigation into the Mechanisms of Quyushengxin Formula for the Treatment of Ulcerative Colitis

“…To date, an increasing number of traditional Chinese herbal compounds are successfully used for treating UC with less side effects, such as Gegen Qinlian decoction [10], Jianpi Qingchang decoction [11,12], Zhikang capsule [13], Huangkui Lianchang decoction [14], and Qingchang Wenzhong decoction [15,16]. Quyushengxin formula is mainly composed of four herbs, Panax ginseng C.A.…”