Alcoholic liver disease (ALD) refers to hepatic ailments induced by excessive alcohol intake. The pathogenesis of ALD comprises a complex interplay between various mechanistic pathways, among which inflammation and oxidative stress are key players. Boswellic acids (BAs), found in Boswellia serrata, have shown hepatoprotective effects owing to their antioxidant and anti-inflammatory activities, nevertheless, their therapeutic potential against ALD has not been previously investigated. Hence, this study was performed to depict the possible protective effect of BAs and detect their underlying mechanism of action in an experimentally-induced ALD mouse model. Male BALB/c mice were equally categorized into six groups: control, BAs-treated, ALD, and ALD that received BAs at three-dose levels (125, 250, and 500 mg/kg) by oral gavage for 14 days. Results showed that the high dose of BAs had the most protective impact against ALD according to histopathology examination, blood alcohol concentration (BAC), and liver function enzymes. Mechanistic investigations revealed that BAs (500 mg/kg) caused a significant decrease in cytochrome P450 2E1(CYP2E1), nicotine adenine dinucleotide phosphate oxidase (NOX) 1/2/4, p38 mitogen-activated protein kinase (MAPK), and sterol regulatory element-binding protein-1c (SREBP-1c) levels, and the expression of miR-155, yet increased peroxisome proliferator-activated receptor alpha (PPARα) levels. This led to an improvement in lipid profile and reduced hepatic inflammation, oxidative stress, and apoptosis indices. In summary, our study concludes that BAs can protect against ethanol-induced hepatic injury, via modulating NOX/p38 MAPK/PPARα pathways and miR-155 expression.

In the present study, we investigated the potential beneficial impact of the addition of antioxidant supplements to diclofenac regimen in a model of carrageenan-induced paw. Rats were treated daily with antioxidants, that is, a-lipoic acid (50 mg/kg), selenium (2.5 mg/kg), vitamin C (1 g/kg), vitamin E (300 mg/kg), or zinc (25 mg/kg) on seven successive days and then received a single treatment with diclofenac or saline before carrageenan was injected to induce paw inflammation. The results indicated that these combinations did not significantly affect the percentage inhibition of paw edema caused by diclofenac alone; however, some combination treatments ameliorated signs of concomitant oxidative stress (such as alterations in plasma malondialdehyde (MDA) levels, hemolysate reduced glutathione levels, and erythrocytic superoxide dismutase enzyme activities) imparted by diclofenac alone. In some cases, few tested antioxidants in combination with diclofenac resulted in increased plasma levels of interleukin- (IL-) 6 and C-reactive protein (CRP). In conclusion, the results of these studies suggested to us that the added presence of natural antioxidants could be beneficial as standard anti-inflammatory therapeutics for a patient under diclofenac treatment, albeit that these effects do not appear to significantly build upon those that could be obtained from this common anti-inflammatory agentper se.

Objectives: Toll-like receptor-4 (TLR-4) activation plays a major role in triggering oxidative stress (OS) and inflammation implicated in the pathogenesis of ulcerative colitis (UC). Due to sophorolipids (SLs) antioxidant and anti-inflammatory properties, they are interestingly becoming more valued for their potential effectiveness in treating a variety of diseases. This study was designed to explore the effect of SLs produced by microbial conversion of Moringa oleifera oil cake using isolated yeast Yarrowia lipolytica against UC induced by acetic acid (AA) in rats. Methods: The produced SLs were identified by FTIR, 1H NMR and LC-MS/MS spectra, and administered orally for 7 days (200 mg/kg/day) before AA (2 ml, 4% v/v) to induce UC intrarectally on day eight. Biochemically, the levels of TLR-4, c-Jun N-terminal kinase (JNK), nuclear factor kappa B-p65 (NFκB-p65), interleukin-1beta (IL-1β), malondialdehyd, glutathione, Bax/Bcl2 ratio and the immunohistochemical evaluation of inducible nitric oxide synthase and caspase-3 were assayed. Key findings: SLs significantly reduced OS, inflammatory and apoptotic markers in AA-treated rats, almost like the reference sulfasalazine. Conclusions: This study provided a novel impact for SLs produced by microbial conversion of M. oleifera oil cake against AA-induced UC in rats through hampering the TLR-4/p-JNK/NFκB-p65 signalling pathway.