Meselhy Ragab

In the present work, antioxidant activity, total phenolics (TP), and total flavonoids (TF) contents of aqueous and methanol extracts of celery were determined, in addition to untargeted metabolites profiling its methanol celery root extract (MCRE) via UPLC-MS. Although MCRE exhibited the lowest TPC and TFC levels, it presented the most potential hydroxyl radical quenching effect using electron paramagnetic resonance spin trapping technique. Treatment of Acetaminophen-induced hepatotoxicity (AAH) rats with MCRE lowered serum levels of AST, ALT, ALP, TNF-α, and IL-1β significantly. Additionally, MCRE significantly increased total antioxidant capacity (TAC) and glutathione (GSH) levels relative to AAH rats. Strikingly, Kaplan-Meier survival analysis of all groups revealed a 100% prevention of acetaminophen-induced mortality of rats by MCRE pretreatment (100 mg/kg/day). MCRE prevented AAH-associated severe weight loss and elicited normal behavior in the rescued rats. Our results suggest that pretreatment with MCRE can mitigate against overdosed acetaminophen-induced acute liver failure and warrant further investigations on the potential of postinjury intervention. PRACTICAL APPLICATIONS: Acetaminophen-induced hepatotoxicity (AAH) accounts for alerting numbers of overdose-related acute liver failure and liver transplant cases with increased morbidity and mortality rates. Currently proposed mechanisms implicate mitochondria-mediated oxidative stress and inflammation in the pathogenesis of AAH, which underline current interventions employing antioxidants to combat liver damage by over-dosed acetaminophen. The present work uncovers potent protective effects of some celery extracts (and their fractions) against acetaminophen-induced oxidative stress and inflammation. Treatment of rats with fatal liver injury with methanol extract of celery root significantly reduced secretion of liver enzymes and markedly decreased inflammatory as well as oxidative stress markers in these animals. This, in turn, rescued challenged rats exposed to fatal doses of acetaminophen completely, which establishes methanol extracts of celery roots as effective therapeutic intervention against AAH. The antioxidant capacity of the extracts was determined using EPR technique, and the secondary metabolites related to antioxidant activity were characterized via UPLC-MS.

Three new compounds; epi-mukulin, (Z)-Δ(1,2) dehydroguggulsterone and Δ(6,7)dehydro-20-hydroxygugglsterone were isolated from the n-hexane-soluble fraction (HSF) of the methanol extract of guggul, the oleogum resin of Commiphora wightii together with six known compounds: diasesartemin, (+)-epi-magnolin, (+)-diayangambin, gugglsterol I, (E)-guggulsterone and (Z)-guggulsterone. Their structures were elucidated on the basis of different spectroscopic data. α-Glucosidase inhibitory effects of HSF and the isolated compounds were evaluated calorimetrically. The HSF showed significant α-glucosidase inhibitory effect [IC(50) value of 140 µg mL(-1) (p < 0.05)]. Under the assay conditions, diasesartemin (IC(50) = 60.6 ± 0.01 µM) was found to be more potent than the positive control, acarbose (IC(50) = 92.94 ± 0.01 µM); a known α-glucosidase inhibitor (p < 0.05). The IC(50) values of epi-mukulin and (Z)-guggulsterone were found to be 159.33 and 132.14 µM, respectively. Other compounds showed weak α-glucosidase inhibitory effects, <30% inhibition of the enzyme activity at 0.1 mg mL(-1).