A flavonoid-rich fraction of Monolluma quadrangula inhibits xanthine oxidase and ameliorates potassium oxonate-induced hyperuricemia in rats.

Hyperuricemia represents a risk factor for the progression of chronic kidney disease. Oxidative stress and inflammation are implicated in the mechanisms underlying hyperuricemia-mediated kidney injury. Monolluma quadrangula possesses several beneficial effects; however, its effect on hyperuricemia has not been investigated. This study evaluated the renoprotective and xanthine oxidase (XO) inhibitory activity of M. quadrangula in hyperuricemic rats. Phytochemical investigation revealed the presence of six known flavonoid isolated for the first time from this species. The rats received M. quadrangula extract (MQE) and potassium oxonate (PO) for 7 days. In vitro assays showed the radical scavenging and XO inhibitory activities of MQE, and in silico molecular docking revealed the inhibitory activity of the isolated flavonoids towards XO. Hyperuricemic rats showed elevated serum uric acid, creatinine, urea, and XO activity, and renal pro-inflammatory cytokines, MDA and NO, and decreased GSH, SOD, and catalase. MQE ameliorated serum uric acid, urea, creatinine, and XO activity, and renal pro-inflammatory cytokines. In addition, MQE attenuated renal oxidative stress, enhanced antioxidants, downregulated URAT-1, and GLUT-9 and upregulated OAT-1 in PO-induced rats. In conclusion, M. quadrangula attenuated hyperuricemia and kidney impairment by suppressing XO activity, oxidative stress and inflammation, and modulating urate transporters.

Pimpinella anisum extract attenuates spontaneous and agonist-induced uterine contraction in term-pregnant rats.

ETHNOPHARMACOLOGY RELEVANCE: Pimpinella anisum is a well-known traditional medicinal herb which has been used in folk medicine as an antiulcer, anticancer, antibacterial and as a muscle relaxant. AIM OF THE STUDY: This study was performed to explore the modulatory effects of Pimpinella anisum on term-pregnant rat uterine contractility and to investigate its possible underlying mechanisms. MATERIAL AND METHODS: Intact uterine strips without endometrial layer were isolated from female term-pregnant Wistar rats (22 days of gestation) and mounted in a tissue bath apparatus for in vitro isometric force recording. The effects of different concentrations of Pimpinella anisum extract (PAE) (1, 3, 5, and 7 mg/mL) were examined on uterine contractions generated spontaneously or induced with oxytocin (5 nmol/L), Bay K8644 (1 µmol/L), and carbachol (10 µmol/L). In some experiments, PAE was applied on depolarized myometrium in the presence of high-KCl solution (60 mmol/L). The effect on Ca2+ release was also examined. RESULTS: Application of PAE significantly reduced uterine contractions generated spontaneously or induced with oxytocin, Bay K8644, and carbachol in a concentration-dependent manner (n = 7; P < 0.01). In depolarized myometrium, PAE significantly reduced the tonic force induced by high-KCl solution (n = 7; P < 0.01). PAE prevented oxytocin-induced transient contraction in the entire absence of external calcium (n = 7; P < 0.01). CONCLUSION: The present findings demonstrate the potentials of PAE to relax pregnant uterine contractions possibly by blocking Ca2+ entry via L-type calcium channels and inhibiting Ca2+ release from the internal store. The tocolytic effects of PAE may be a potential adjuvant against strong premature uterine contractions which threaten early pregnancy although clinical studies are required.

Olea europaea leaf extract up-regulates Nrf2/ARE/HO-1 signaling and attenuates cyclophosphamide-induced oxidative stress, inflammation and apoptosis in rat kidney.

Olive leaf extract (OLE) has potential health benefits and protects against cytotoxicity in different organs. However, nothing has yet been reported on its potential to prevent cyclophosphamide (CP)-induced nephrotoxicity. This study investigated the possible protective effect of OLE on CP-induced kidney injury in rats, focusing on oxidative stress, inflammation, apoptosis and Nrf2/ARE/HO-1 signaling. Rats received 100 or 200 mg/kg body weight OLE for 15 days and a single injection of 150 mg/kg CP at day 16. CP induced kidney injury evidenced by the significantly increased serum creatinine and urea, and histopathological alterations, including glomerular atrophy, interstitial hemorrhage, dilated urinary space and necrosis. CP-induced rats exhibited increased kidney lipid peroxidation, protein carbonyl, nitric oxide (NO) and pro-inflammatory cytokines, and up-regulated NF-κB, Bax, cytochrome c and caspase-3. OLE ameliorated kidney function markers and prevented CP-induced tissue damage. In addition, OLE significantly prevented oxidative stress, inflammation and apoptosis by enhancing the antioxidant defenses and Bcl-2 expression, and suppressing the pro-inflammatory and pro-apoptotic markers NF-κB, Bax, cytochrome c and caspase-3. OLE up-regulated Nrf2, HO-1 and NQO-1 expression in the kidney of CP-induced rats. In conclusion, OLE has a substantial protective role against CP-induced nephrotoxicity in rats by up-regulating the Nrf2/ARE/HO-1 signaling, enhancing the antioxidant activity and attenuating inflammation and apoptosis.