Diltiazem mitigates acute liver injury by targeting NFκB-TXNIP/NLRP3 axis in Rats: New insights beyond calcium channel blockade.

Acute liver injury is characterized by the rapid onset of inflammation in the liver, which in turn plays a role in the development of hypertension. Additionally, hypertension increases susceptibility to liver diseases associated with inflammatory states. Recently, the antihypertensive drug diltiazem has demonstrated anti-inflammatory properties and has been shown to inhibit the expression of the thioredoxin-interacting protein (TXNIP), an upstream regulator of the NOD-like receptor pyrin-3 (NLRP3) inflammasome pathway.

Vildagliptin, a DPP-4 inhibitor, attenuates carbon tetrachloride-induced liver fibrosis by targeting ERK1/2, p38α, and NF-κB signaling.

Mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-ĸB signaling have been recognized for their causal connection with liver fibrosis. Hence, it is encouraging to discover drugs that can modify the interactions between these signaling cascades. It has been suggested that glucagon-like peptide-1 receptors (GLP-1Rs) might have a role in the observed hepatoprotection of dipeptidyl peptidase-4 inhibitors other than vildagliptin (VLD).

Celastrol augments sensitivity of NLRP3 to CP-456773 by modulating HSP-90 and inducing autophagy in dextran sodium sulphate-induced colitis in rats.

NLRP3, one of the HSP-90 clients, has been defined as a critical component of IBD. In a rat model of DSS-induced colitis, we investigated the anti-inflammatory potential of the combined therapy with CP-456773 (CP), an NLRP3 inhibitor, and celastrol (CSR), an NF-κB inhibitor. Our results revealed that the CSR/CP combined therapy (CCCT) attenuated colon shortening, DAI and MDI in addition to improvement of the colonic histological picture.

Novel complementary antitumour effects of celastrol and metformin by targeting IκBκB, apoptosis and NLRP3 inflammasome activation in diethylnitrosamine-induced murine hepatocarcinogenesis.

One promising strategy for minimizing chemotherapeutic resistance in hepatocellular carcinoma (HCC) is the use of effective chemosensitizers. We studied the complementary multi-targeted molecular mechanisms of metformin and celastrol in mice with diethylnitrosamine-induced HCC to investigate whether metformin could augment the sensitivity of HCC tissue to the effect of celastrol. Simultaneous administration of celastrol (2 mg/kg) and metformin (200 mg/kg) improved liver function, enhanced the histological picture and prolonged survival.