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Evaluation of traditionally used royal jelly (RJ) for the management of hepato-renal damage and gastrointestinal ulcerations caused by diclofenac. Methods: Forty adult male Wistar rats were allocated into four groups. Rats of the 1 st group received only saline and served as normal group. The remaining 3 groups received diclofenac (50 mg/kg/day, I.P.) for 7 days. Group 2 served as diclofenac-control group. Groups 3 and 4 received RJ (150 and 300 mg/kg/day, P.O.) respectively for 30 days. Twenty-four hours after the last treatment, blood samples were collected, rats were sacrificed, and livers, kidneys, stomachs & intestines were harvested. Stomachs and intestines were tested for ulcer counts. Serum levels of AST, ALT, creatinine and urea were investigated. Hepatic, renal, gastric and intestinal tissue contents of myeloperoxidase (MPO) and prostaglandin-E2 (PGE2) were measured. Histopathological examinations were also performed followed by immunohistochemical determination of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression. Results: Diclofenac administration caused significant deterioration of all the above mentioned parameters. RJ improved hepatic and renal functions. Gastric and intestinal ulcer counts were significantly ameliorated. Hepatic, renal, gastric and intestinal tissue PGE-2 contents and COX-2 expression were significantly elevated. RJ also significantly reduced MPO content and iNOS expression as compared to diclofenac-control group. Improvements of the histopathological pictures of hepatic, renal, gastric and intestinal tissues were also apparent. Conclusion:The study demonstrates promising protective effects of RJ against diclofenac-induced hepato-renal damage and gastrointestinal ulceration in rats.

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Stroke is the leading cause of death worldwide. Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of anti-diabetic drugs for treatment of type-2 diabetes mellitus. The aim of this study is to evaluate the possible neuroprotective effect of a dipeptidyl peptidase-4 inhibitor, vildagliptin, independent of its anti-diabetic properties in non-diabetic rats subjected to cerebral ischemia. Anesthetized Wistar rats were subjected to either left middle cerebral artery occlusion (MCAO) or sham operation followed by reperfusion after 30 min of MCAO. The other three groups were orally administered vildagliptin at 3 dose levels (2.5, 5, 10 mg/kg) for 3 successive weeks before subjected to left focal cerebral ischemia/reperfusion and till the end of the study. Neurological deficit scores and motor activity were assessed 24 h following reperfusion. Forty-eight hours following reperfusion, rats were euthanized and their left brain hemispheres were harvested and used in biochemical, histopathological, and immunohistochemical investigations. Vildagliptin pretreatment improved neurological deficit score, locomotor activity, and motor coordination in MCAO rats. Moreover, vildagliptin reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), phosphotylinosital 3 kinase (PI3K), phosphoryated of protein kinase B (p-AKT), and mechanistic target of rapamycin (mTOR) brain contents in addition to reducing protein expression of caspase-3. Also, vildagliptin showed a dose-dependent attenuation in neuronal cell loss and histopathological alterations in MCAO rats. This study proves that vildagliptin exerted a neuroprotective effect in a dose-dependent manner as shown in the attenuation of the infarct area, neuronal cell loss, and histopathological damage in MCAO rats, which may be mediated by attenuating neuronal and motor deficits, its antioxidant property, activation of the PI3K/AKT/mTOR pathway, and its anti-apoptotic effect.

This study aimed to investigate the anti-depressant effect of hesperidin (Hsp) in streptozotocin (STZ)-induced diabetic rats. Additionally, the effect of Hsp on hyperglycaemia, oxidative stress, inflammation, brain-derived neurotrophic factor (BDNF), and brain monoamines in diabetic rats was also assessed. The Wistar rats in the experimental groups were rendered hyperglycaemic with a single dose of STZ (52.5 mg·(kg body mass)(-1), by intraperitoneal injection). The normal group received the vehicle only. Hyperglycaemic rats were treated with Hsp (25.0, 50.0, or 100.0 mg·(kg body mass)(-1)·day(-1), per oral) and fluoxetine (Flu) (5.0 mg·(kg body mass)(-1)·day(-1), per oral) 48 h after the STZ injection, for 21 consecutive days. The normal and STZ control groups received the vehicle (distilled water). Behavioral and biochemical parameters were then assessed. When Hsp was administered to the STZ-treated rats, this reversed the STZ-induced increase in immobility duration in the forced swimming test (FST) and attenuated hyperglycaemia, decreased malondialdehyde (MDA), increased reduced glutathione (GSH) decreased interleukin-6 (IL-6), and increased BDNF levels in the brain. Treatment with Hsp attenuated STZ-induced neurochemical alterations, as indicated by increased levels of monoamines in the brain, namely, norepinephrine (NE), dopamine (DA), and serotonin (5-hydroxytryptamine; 5-HT). All of these effects of Hsp were similar to those observed with the established anti-depressant Flu. This study shows that Hsp exerted anti-depressant effect in diabetic rats, which may have been partly mediated by its amelioration of hyperglycaemia as well as its anti-oxidant and anti-inflammatory activities, the enhancement of neurogenesis, and changes in the levels of monoamines in the brain.