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
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Huangqin Decoction Attenuates DSS-Induced Mucosal Damage and Promotes Epithelial Repair via Inhibiting TNF-α-Induced NF-κB Activation.
To investigate the protective effect of Chinese herbal formula Huangqin Decoction (HQD) on ulcerative colitis mouse model induced by dextran sulphate sodium (DSS) and human intestinal epithelial cell injury induced by tumour necrosis factor-α (TNF-α).
In vivo, 30 male C57BL/6 mice were divided into 5 groups using a random number table (n=6 per group), including control, DSS, 5-aminosalicylic acid (5-ASA), HQD low- (HQD-L) and high-dose (HQD-H) groups. The colitis mouse model was established by 3% (w/v) DSS water for 5 days. Meanwhile, mice in the HQD-L, HQD-H and 5-ASA groups were administrated with 100, 200 mg/kg HQD or 100 mg/kg 5-ASA, respectively, once daily by gavage. After 9 days of administration, the body weight, disease activity index (DAI) score and colon length of mice were measured, the pathological changes of colons were analyzed by hematoxylin-eosin staining (HE) staining, and the levels of serum interleukin (IL)-6, IL-1β and TNF-α were measured by enzyme linked immunosorbent assay. In vitro, the human colon epithelial normal cells (FHC cells) were exposed to HQD (0.6 mg/mL) for 12 h and then treated with TNF-α (10 ng/mL) for 24 h. The tight junction (TJ) protein expression levels of Claudin-4 and Occludin, and the protein phosphorylation levels of p65 and inhibitor of nuclear factor kappaB (NF-κB)-α (IκBα) were measured by Western blot.
In vivo, compared with the DSS group, HQD-H treatment attenuated the weight loss and reduced DAI score of mice on the 8th day (P<0.05). Moreover, HQD-H treatment ameliorated the colon shortening in the DSS-induced colitis mice (P<0.05). HE staining showed HQD attenuated the pathological changes of colitis mice, and the histological scores of HQD-H and 5-ASA groups were significantly decreased compared with the DSS group (P<0.05). Meanwhile, HQD-H and 5-ASA significantly decreased the serum IL-1β, IL-6 and TNF-α levels of mice (P<0.05). In vitro experiments showed that HQD up-regulated Occludin and Claudin-4 protein expressions and inhibited p-p65 and p-IκBα levels in FHC cells compared with the TNF-α group (P<0.05).
HQD significantly relieved the symptoms in DSS-induced colitis mice by inhibiting pro-inflammatory cytokines expression and maintained the homeostasis of TJ protein in FHC cells by suppressing TNF-α-induced NF-κB activation.
Gu LM
，Li H
，Xia JQ
，Pan CY
，Gu C
，Tian YZ
... -
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Banxia xiexin decoction protects against dextran sulfate sodium-induced chronic ulcerative colitis in mice.
Banxia Xiexin decoction (BXD), one of a traditional Chinese medicine chronicled in Shang Han Lun, is commonly used to treat gastroenteritis, ulcerative colitis and diarrhea. In our study, we used current biomedical approaches to investigate the therapeutic efficacy of BXD and possible protective mechanism involved in inhibiting dextran sulfate sodium (DSS)-induced chronic ulcerative colitis model.
Chronic DSS colitis was induced in C57BL/6 male mice by three cycles of 5 days of 2% DSS in drinking water, alternating with 5 days of normal water, totaling 30 days. In BXD group, the mice were administered at a dose of 8.7g/kg BXD for 5 days before and during DSS treatment via oral gavage per day. Mice in vehicle group and DSS group were given orally the same volume of drinking water, instead. Body weight, stool characters and hematochezia were observed everyday. The colorectal tissues were used to detect levels of TNF-α, IL-4, IL-10, IL-1β, IL-17, IL-23 and MPO by ELISA or qRT-PCR. The expression of COX-2, 8-Oxoguanine and Nrf2 were examined by IHC, and p-p65 was examined by western blotting. ThOD and the content of MDA were measured according to kits respectively.
BXD significantly protected against DSS-induced chronic ulcerative colitis by amelioration of body weight loss, DAI and histology score. The level of TNF-α, IL-1β, IL-17, IL-23, COX-2 and p-p65 were decreased significantly, while the level of IL-10 improved with the treatment of BXD. MDA, MPO and 8-Oxoguanine were decreased, meanwhile SOD activity and Nrf2 expression were elevated significantly by BXD.
BXD possesses the potential of anti-inflammation and anti-oxidation to treat colitis. The protective mechanism of BXD may involve in inhibition of NF-κBp65 activation and increasement of Nrf2 expression in colorectums of mice.
Chen G
，Yang Y
，Liu M
，Teng Z
，Ye J
，Xu Y
，Cai X
，Cheng X
，Yang J
，Hu C
，Wang M
，Cao P
... -
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