Unveiling the therapeutic potential of exogenous β-hydroxybutyrate for chronic colitis in rats: novel insights on autophagy, apoptosis, and pyroptosis

Ulcerative colitis (UC) is a chronic relapsing inflammatory disease of the colorectal area that demonstrates a dramatically increasing incidence worldwide. This study provides novel insights into the capacity of the exogenous β-hydroxybutyrate and ketogenic diet (KD) consumption to alleviate dextran sodium sulfate (DSS)-induced UC in rats. Remarkably, both interventions attenuated disease activity and colon weight-to-length ratio, and improved macro and microstructures of the damaged colon. Importantly, both β-hydroxybutyrate and KD curbed the DSS-induced aberrant NLRP3 inflammasome activation as observed in mRNA and protein expression analysis. Additionally, inhibition of the NLRP3/NGSDMD-mediated pyroptosis was detected in response to both regimens. In parallel, these modalities attenuated caspase-1 and its associated consequences of IL-1β and IL-18 overproduction. They also mitigated apoptosis as indicated by the inactivation of caspase-3. The anti-inflammatory effects of BHB and KD were confirmed by the reported decline in the levels of inflammatory markers including MPO, NFκB, IL-6, and TNF-α. Moreover, these interventions exhibited antioxidative properties by reducing ROS production and improving antioxidative enzymes. Their effectiveness in mitigating UC was also evident in the renovation of normal intestinal epithelial barrier function, as shown by correcting the discrepancies in the levels of tight junction proteins ZO-1, OCLN, and CLDN5. Furthermore, their effects on the intestinal microbiota homeostasis were investigated. In terms of autophagy, exogenous β-hydroxybutyrate upregulated BECN-1 and downregulated p62, which may account for its superiority over KD in attenuating colonic damage. In conclusion, this study provides experimental evidence supporting the potential therapeutic use of β-hydroxybutyrate or β-hydroxybutyrate-boosting regimens in UC

EFFECT OF BLACK CUMIN (NIGELLA SATIVA) POWDER ON SERUM LIPID PROFILE, MALONDIALDHYDES, NITRITES, sICAM-1 AND sVCAM-1 IN EXPERIMENTALLY INDUCED ATHEROSCLEROSIS

Objective: Black cumin (Nigella Sativa), have been used for nutritional and medicinal purposes in many countries. This work was done to study the effect of black cumin powder during and after induction of atherosclerosis in cholesterol-enriched diet fed rabbits.Methods: Thirty male New Zealand White rabbits, (4-5 months old, average body weight  1.5 kg) were used. Rabbits were divided into five groups:  negative control group, positive control group (fed atherogenic diet for 20 weeks); prophylactically treated group (each rabbit in this group fed atherogenic diet and given black cumin powder 150 mg/kg body weight /day by gavage for 20 weeks to show the possible protective effect of black cumin on atherosclerotic process); positive control group for development of atherosclerosis (fed atherogenic diet for 12 weeks); and Atherosclerotic treated group (each rabbit in this group fed atherogenic diet for 12 weeks and after the development of atherosclerosis received black cumin powder 150 mg/kg body weight /day by gavage to show the effect of black cumin on the progression of atherosclerosis).Results: Administration of black cumin during the development of atherosclerosis produced significant inhibition of aortic atherosclerotic changes. Also, administration of black cumin during or after the development of atherosclerosis produced significant decrease (P < 0.05) in total-cholesterol (TC), LDL-cholesterol, Triglycerides (TG), Malondialdhydes (MDA), sICAM-1 and sVCAM-1 while HDL-cholesterol and nitrite was significantly increased.Conclusion: Black cumin has anti-atherosclerotic effects which may be exerted by inhibiting the release of free radicals, hypocholesterolemic effect and through their effect on adhesion molecules.Â