Anti-inflammatory effects of Brucea javanica oil emulsion by suppressing NF-κB activation on dextran sulfate sodium-induced ulcerative colitis in mice.

Brucea javanica is an important traditional medicinal herb used for the treatment of dysentery, malaria, inflammation and cancer in southeast Asia for many years. However, the anti-inflammatory mechanism of Brucea javanica in the treatment of dysentery (also known as ulcerative colitis, UC) has not been fully illuminated. Brucea javanica oil emulsion (BJOE) is the major active and most common application form of Brucea javanica oil (BJO), which has a variety of pharmacological activities. The aim of this study was to investigate the potential anti-inflammatory effect of BJOE and possible mechanism of action on dextran sulfate sodium (DSS)-induced UC in mice. The components of BJOE were determined by gas chromatography-mass spectrometry (GC-MS). Balb/C mice with dextran sulfate sodium (DSS, 30mg/mL) induced colitis were treated with BJOE (0.5, 1 and 2g/kg) and two positive drugs (sulfasalazine, SASP, 200mg/kg; and azathioprine, AZA, 13mg/kg) once daily by gavage for 7 days. Mice in normal control group and DSS group were orally given the same volume of distilled water and soybean lecithin suspension (0.15g/kg) respectively. The effects of BJOE on DSS-induced UC were assessed by determination of body weight loss, disease activity index (DAI), colon length, histological analysis, as well as levels of pro-inflammatory cytokines. The mRNA expression of MPO, iNOS and COX-2 in colon tissues was detected by qRT-PCR. In addition, NF-κB p65, p-p65 and IκB-α, p-IκBα protein expression levels in colon tissues were investigated using Western blotting. The major components of BJOE were found to be oleic acid (62.68%) and linoleic acid (19.53%) as detected by GC-MS. Our results indicated that BJOE, SASP and AZA showed beneficial effect on DSS-induced colitis in mice, and significantly reduced the body weight loss and DAI, restored the colon length, repaired colonic pathological variations, decreased histological scores, and decreased the levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-17 and IFN-γ) as compared with the DSS group. In addition, the mRNA expression of MPO, iNOS and COX-2 induced by DSS treatment was remarkably inhibited by BJOE, SASP or AZA treatments. Furthermore, when compared with DSS-treated mice, the activation of NF-κB was significantly inhibited by AZA and BJOE treatment. Our study shows that BJOE possessed appreciable anti-inflammatory effect against murine experimental UC induced by DSS. The protective mechanism of BJOE may involve inhibition of NF-κB signal transduction pathways and subsequent down-regulation of inflammatory mediators. These findings suggest that BJOE might be an efficacious and promising therapeutic approach for the treatment of UC. Our investigation might also provide experimental evidence for the traditional application of Brucea javanica in the treatment of dysentery and might add new dimension to the clinical indications for BJOE.

Huang YF ，Zhou JT ，Qu C ，Dou YX ，Huang QH ，Lin ZX ，Xian YF ，Xie JH ，Xie YL ，Lai XP ，Su ZR ... -  《-》

Therapeutic effect of Brucea javanica oil emulsion on experimental Crohn's disease in rats: Involvement of TLR4/ NF-κB signaling pathway.

Brucea javanica is an important Chinese folk medicine traditionally used for the treatment of dysentery (also known as inflammatory bowel diseases). Brucea javanica oil emulsion (BJOE), the most common preparation of Brucea javanica, has a variety of pharmacological activities. In this follow-up investigation, we endeavored to illuminate the potential benefit of BJOE on 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced Crohn's disease (CD) in rats and decipher the mechanism of action. The result illustrated that BJOE treatment significantly reduced the body weight loss, disease activity index and macroscopic scores, ameliorated shortening of colon length, arrested colonic histopathological deteriorations, lowered the histological scores in parallel to the model group. Furthermore, BJOE also decreased the levels of MPO and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-17, IL-23 and IFN-γ), and increased the levels of anti-inflammatory cytokines (IL-4, IL-10 and TGF-β) as compared with the model group. In addition, the elevated mRNA expression of MMP-1, MMP-3 and RAGE induced by TNBS was remarkably inhibited by BJOE, SASP or AZA treatments, while the mRNA expression of PPAR-γ was significantly enhanced. Furthermore, the activation of TLR4/NF-κB signaling pathway was significantly inhibited by AZA and BJOE treatment when compared with that of TNBS-treated rats. Our study suggested that BJOE exerted superior therapeutic effect to SASP and AZA in treating TNBS-induced colitis in rats. The protective effect of BJOE may involve the inhibition of the TLR4/NF-κB-mediated inflammatory responses. These results indicated that BJOE held promising potential to be further developed into a novel candidate for the treatment of CD.

Huang YF ，Li QP ，Dou YX ，Wang TT ，Qu C ，Liang JL ，Lin ZX ，Huang XQ ，Su ZR ，Chen JN ，Xie YL ... -  《-》

Brusatol-Enriched Brucea javanica Oil Ameliorated Dextran Sulfate Sodium-Induced Colitis in Mice: Involvement of NF-κB and RhoA/ROCK Signaling Pathways.

Brucea javanica oil (BJO) is beneficial for the treatment of ulcerative colitis (UC), and that quassinoids in particular brusatol are bioactive components. However, it is still uncertain whether or not other components in BJO, such as oleic acid and fatty acids, have an anti-UC effect. The present study is aimed at comparing the anti-UC effects between brusatol-enriched BJO (BE-BJO) and brusatol-free BJO (BF-BJO) and at exploring the effects and mechanisms of BE-BJO on colon inflammation and intestinal epithelial barrier function. Balb/C mice received 3% (wt/vol) DSS for one week to establish the UC model. Different doses of BE-BJO, BF-BJO, or BJO were treated. The result illustrated that BE-BJO alleviated DSS-induced loss of body weight, an increase of disease activity index (DAI), and a shortening of colon, whereas BF-BJO did not have these protective effects. BE-BJO treatment improved the morphology of colon tissue, inhibited the production and release of TNF-α, IFN-γ, IL-6, and IL-1β in the colon tissue, and reversed the decreased expressions of ZO-1, occludin, claudin-1, and E-cadherin induced by DSS but augmented claudin-2 expression. Mechanistically, BE-BJO repressed phosphorylation of NF-κB subunit p65, suppressed RhoA activation, downregulated ROCK, and prevented phosphorylation of myosin light chain (MLC) in DSS-treated mice, indicating that the protective effect of BE-BJO is attributed to suppression of NF-κB and RhoA/ROCK signaling pathways. These findings confirm that brusatol is an active component from BJO in the treatment of UC.

Zheng X ，Mai L ，Wang T ，Xu Y ，Su Z ，Chen J ，Zeng H ，Xie Y ... -  《-》

Intestinal anti-inflammatory effects of fuzi-ganjiang herb pair against DSS-induced ulcerative colitis in mice.

Fuzi and ganjiang are widely used as traditional Chinese medicines (TCM) in China, Korea, Japan, and many other southeast Asian countries for treating ulcerative colitis (UC), emesis and heart failure for more than 1800 years. However, the underlying mechanism of fuzi, ganjiang and fuzi-ganjiang herb pair is still unclear. In our study, we explored the therapeutic effects of fuzi, ganjiang and fuzi-ganjiang herb pair against dextran sulfate sodium (DSS)-induced UC in mice model, along with the relevant mechanism. The contents of each marker compound in fuzi decoction (FD), ganjiang decoction (GD) and fuzi-ganjiang decoction (FGD) were determined using LC-MS/MS. During the experiment, bodyweight changes in each group were monitored every 5 days. On the day of sacrifice, colonic length, disease activity index (DAI) and spleen weight were also evaluated and histopathological examination was performed through hematoxylin & eosin (H&E) staining. The levels of myeloperoxidase (MPO) and inflammatory cytokines in colon tissues were determined by enzyme-linked immunosorbent assay (ELISA), and then the relative mRNA productions of inflammatory mediators, such as MPO, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 were measured by real-time polymerase chain reaction (PCR). Involvement of MAPK, STAT3 and NF-κB signaling pathways in the pathogenesis of UC was determined in each group using Western Blot (WB) analysis. Compared with fuzi and ganjiang single decoction, the content of the alkaloids derived from fuzi (especially the diester alkaloid with strong toxicity, hypaconitine) in fuzi-ganjiang herb pair decoction was reduced. Additionally, the 6-gingerol, which was not found in ganjiang single decoction, was retained in fuzi-ganjiang herb pair decoction. FD, GD, and FGD significantly restored the bodyweight reduction, colon shortening, DAI elevation, splenomegaly and histological score in DSS-induced UC mice. Furthermore, except for the failure of low dosage of ganjiang decoction (GD-L) on IL-17A, all FD, GD and FGD significantly inhibited the production of MPO and inflammatory cytokines, such as IFN-γ, TNF-α, IL-1β, IL-6, IL-10 and IL-17A, and suppressed the relative expression of inflammatory mediators, such as MPO, iNOS and COX-2 mRNA in colon tissues of DSS-induced mice. According to WB analysis, fuzi, ganjiang and fuzi-ganjiang combination inhibited the activation of MAPK, NF-κB and STAT3 signaling pathways. Our study demonstrated that fuzi, ganjiang and fuzi-ganjiang combination possess prominent anti-inflammatory activities against DSS-induced UC mice; the involved mechanism may be related to inhibition the activation of MAPK, NF-κB, and STAT3 signaling pathways.

Huang C ，Dong J ，Jin X ，Ma H ，Zhang D ，Wang F ，Cheng L ，Feng Y ，Xiong X ，Jiang J ，Hu L ，Lei M ，Wu B ，Zhang G ... -  《-》

Therapeutic effect of a hydroxynaphthoquinone fraction on dextran sulfate sodium-induced ulcerative colitis.

Zhang ZL ，Fan HY ，Yang MY ，Zhang ZK ，Liu K ... -  《-》