caryophyllene and Ischemia

Hepatic ischemia-reperfusion (H I/R) injury is a frequent clinical event during which the leading contributing players are inflammation and oxidative stress responses. β-caryophyllene (BCP), a natural bicyclic sesquiterpene, is an essential oil component of different plant species and edibles. This study aims to identify whether BCP pretreatment could avert H I/R injury with inspections of the underlying mechanisms.. Animals were devised into five groups; Sham and BCP + Sham; the animals were administered saline or BCP (200 mg/kg, orally) respectively; H I/R group, the animals were administered saline orally for 14 days before induction of H I/R; BCP100 and BCP200, the animals were administered BCP (100 and 200 mg/kg, respectively) for 14 days, followed by induction of H I/R.. H I/R showed markedly increased ALT, AST, MDA, and lowered antioxidant enzyme activities, while the Nrf2/HO1/NQO1 pathway components were significantly augmented. The TLR4/NF-κB/NLRP3 elements were deterred, and subsequently, escalations in the inflammatory mediators (IL-1β, IL-6, and TNF-α), adhesion molecule ICAM-1, neutrophils infiltration (MPO), and apoptotic markers were observed. Pretreatment with BCP amplified the antioxidant enzyme activities and Keap1/Nrf2/HO1/NQO1 pathway components. BCP pretreatment lowered TLR4/NF-κB/NLRP3 pathway elements, which mitigated inflammatory mediators, ICAM-1, MPO, and apoptotic markers.. The protective effect of BCP against hepatic I/R induced injury might be accomplished via mitigation of oxidative stress by regulating the Keap1/Nrf2/HO1/NQO1 pathway and inhibition of the inflammatory process via manipulating the TLR4/ NF-κB/ NLRP3, reflected by inflammatory markers, neutrophils recruitment, and adhesion molecules reduction. BCP might be a potential therapeutic agent for alleviating hepatic I/R-induced injury.

Topics: Animals; Antioxidants; Inflammation Mediators; Intercellular Adhesion Molecule-1; Ischemia; Kelch-Like ECH-Associated Protein 1; NF-E2-Related Factor 2; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Reperfusion; Reperfusion Injury; Signal Transduction; Toll-Like Receptor 4

Current treatments for stroke, which account for 6.5 million global deaths annually, remain insufficient for treatment of disability and mortality. One targetable hallmark of stroke is the inflammatory response following infarct, which leads to significant damage post-infarct. Cannabinoids and their endogenous targets within the CNS have emerged as potential treatments for neuroinflammatory indications. We and others have previously shown that synthetic agonists of the cannabinoid CB2 receptor reduce infarct size and microglial activation in rodent models of stroke. The non-cannabinoid receptor mediated effects of the phytocannabinoid cannabidiol (CBD) have also shown effectiveness in these models. The present aim was to determine the single and combined effects of the cannabis-derived sesquiterpene and putative CB2 receptor agonist β-caryophyllene (BCP) and CBD on permanent ischemia without reperfusion using a mouse model of photothrombosis. Because BCP and CBD likely work through different sites of action but share common mechanisms of action, we sought to determine whether combinations of BCP and CBD were more potent than either compound alone. Therefore we determined the effect of BCP (3-30 mg/kg IP) and CBD (3-30 mg/kg IP), given alone or in combination (30:3, 30:10, and 30:30 BCP:CBD), on infarct size, microglial activation, and motor performance.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Cannabidiol; Disease Models, Animal; Drug Therapy, Combination; Ischemia; Male; Mice, Inbred C57BL; Microglia; Polycyclic Sesquiterpenes