piplartine and Reperfusion-Injury

Piperlongumine (PL), an alkaloid from the Piper longum plant, is acknowledged for various biological properties. The study aimed to explore the protective effect of PL on ischemia reperfusion injury (I/R) in rat kidney.. 24 adult male Sprague-Dawley rats (200 to 250 mg) were randomly allocated to four groups (n = 6/group): Group I: sham control, Group II: (I/R) renal ischemia/reperfusion kidney renal blocked for 1hour using clamps, followed by 2hr reperfusion. Group III: PL (25 μg/kg) + I/R group and Group IV: PL (50 μg/kg) + I/R group. Rat kidneys were exposed to 60 min of two-sided deep ischemia followed by 120 min of reperfusion. PL (25 and 50 μg/kg bw) was administered intraperitoneally half an hour before the ischemia. Creatinine, urea, and few renal markers activity in serum were assessed. Oxidative stress and inflammatory markers were also evaluated. In addition, the expressions of COX-2 and eNOS in animal kidneys were tested by western blotting.. Pre-treatment with PL in ischemia‑reperfused rats significantly reduced the pathological damage in the kidney and declined the levels of serum creatinine and other renal parameters. PL treatment diminished the serum levels of TNF-α, IL-6, and IL-1β, as well as messenger RNA expressions. Important biological defence parameters such as superoxide dismutase and glutathione levels were upregulated while malondialdehyde levels were down-regulated in PL ischemia rats.. PL exhibits a protective effect against inflammation and oxidation in ischemia reperfusion animals (Fig. 5, Ref. 32).

Topics: Animals; Apoptosis; Creatinine; Inflammation; Ischemia; Kidney; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reperfusion Injury

The supplementation of exogenous antioxidants to scavenge excessive reactive oxygen species (ROS) is an effective treatment for cerebral ischemia-reperfusion injury (CIRI) in stroke. Piperlongumine (PL), a natural alkaloid, has a great potential as a neuroprotective agent, but it also has obvious toxicity. Moreover, its neuroprotective effects remain to be improved. In this study, we designed a series of novel PL analogs by hybridizing the screened low-toxicity diketene skeleton with antioxidant effect and the 3,4,5-trimethoxyphenyl group, which may increase the antioxidant activity of PL. The intermediate was synthesized by a novel green synthesis method, and 34 compounds were obtained. The compounds without obvious cytotoxicity have remarkable antioxidant effects, especially compared with diketene skeletons and PL. The cytoprotection of the active compound decreased significantly by reduction of the carbon-carbon double bonds of the Michael acceptor in the diketene skeleton. More importantly, further study revealed that compound

Topics: Animals; Antioxidants; Astrocytes; Brain Ischemia; Cell Survival; Dioxolanes; Drug Design; Green Chemistry Technology; Male; Oxidative Stress; PC12 Cells; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Reperfusion Injury