The beneficial role of Naringin- a citrus bioflavonoid, against oxidative stress-induced neurobehavioral disorders and cognitive dysfunction in rodents: A systematic review and meta-analysis.

OBJECTIVES: Naringin is a bioflavonoid, very abundantly found in citrus species. In literature, naringin has been scientifically well documented for its beneficial effects in various neurological disorders. In this systematic review and meta-analysis, we have made an attempt to correlate the protective role of naringin against oxidative stress-induced neurological disorders in rodents. METHODS: The systematic search was performed using electronic databases; the search was mainly focused on the role of naringin in oxidative stress-induced neuropathological conditions in rodents. While, the meta-analysis was performed on the effect of naringin on oxidative stress markers [superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), reduced glutathione (GSH), lipid peroxidation (LPO)], nitrite, mitochondrial complexes (I to IV) and enzymes (acetylcholinesterase, Na+-K+-ATPase, Ca2+-ATPase, and Mg2+-ATPase) in the rodent brain. The data was analyzed using Review Manager Software. THE RESULTS: Based on the inclusion and exclusion criteria, twenty studies were selected. The meta-analysis revealed that, naringin could significantly inhibit various physical and chemical stimuli- induced neurological perturbances in the rodent brain, mediated through oxidative stress. Further, naringin also significantly restored the levels of all the oxidative stress markers (oxidative, nitrosative, enzymes, and mitochondrial complexes) in different parts of the rodent brain. SUMMARY: This systematic review and meta-analysis supports the available scientific evidence on the beneficial role of naringin in the management of various neurological ailments. However, further studies involving human subjects is recommended to establish the safety and therapeutic efficacy in humans.

Alleviation of transient global ischemia/reperfusion-induced brain injury in rats with 1,2,3,4,6-penta-O-galloyl-ß-d-glucopyranose isolated from Mangifera indica.

Present study was undertaken to evaluate the protective effect of 1,2,3,4,6-penta-O-galloyl-ß-d-glucopyranose (PGG) against transient global ischemia/reperfusion (I/R)-induced brain injury in rats. Sixty minutes of global ischemia, followed by 24h of reperfusion caused significant alterations in cognition and memory (p<0.01), significant deterioration of motor coordination, grip strength, and limb tone (P<0.01) associated with neurological deficit. In addition, significant decrease in catalase (P<0.01), and superoxide dismutase (SOD) (P<0.01) activities, increase in lipid peroxidation (P<0.01), depletion of reduced glutathione (GSH) (P<0.01), and increase in brain volume (P<0.01) was observed. Additionally, I/R insult has aggravated the cerebral infarct formation (P<0.01), and the histopathology of brain showed congestion of blood vessels, edema of brain parenchyma, leukocyte infiltration as signs of neuroinflammation, and necrosis of brain tissue. Interestingly, pre-treatment with quercetin (20mg/kg, i.p.), and PGG (5 and 10mg/kg, i.p.) for 7 days showed significant, and dose dependent protection against I/R-induced brain injury by alleviating all the behavioral, neurological, morphological, and histological changes induced by I/R. Besides, PGG is a well-known antioxidant, and its protective effect against I/R-induced brain injury is thought to be due to its potent antioxidant property.

Anticonvulsant activity of 1,2,3,4,6-penta-O-galloyl-ß-D-glucopyranose isolated from leaves of Mangifera indica.

The present study was aimed to evaluate the anticonvulsant activity of 1,2,3,4,6-penta-O-galloyl-ß-D-glucopyranose (PGG) isolated from methanolic leaf extracts of Mangifera indica in mice. Anticonvulsant activity of PGG was evaluated against pentylenetetrazole (PTZ)-induced and maximal electroshock (MES)-induced convulsions in mice. Additionally, locomotor activity and GABA levels in the brain were estimated to explore the possible CNS-depressant activity and mechanism behind the anticonvulsant activity, respectively. In these studies, PGG (2.5, 5, and 10 mg/kg, intraperitoneal (i.p.)) showed significant and dose-dependent inhibition of PTZ and MES-induced convulsions. Furthermore, PGG administration showed significant decrease in the locomotor activity as an indication of its CNS-depressant property; also, PGG has significantly increased the GABA levels in the cerebellum and whole brain other than the cerebellum. In conclusion, PGG isolated from M. indica showed potent anticonvulsant activity, and possible mechanism may be due to enhanced GABA levels in the brain.

Hesperidin ameliorates immobilization-stress-induced behavioral and biochemical alterations and mitochondrial dysfunction in mice by modulating nitrergic pathway.

The present study was aimed to evaluate the protective effect of hesperidin against immobilization-stress-induced alterations in biochemical, behavioral, and mitochondrial functions in mice. In many instances neuroscientists have reported that acute immobilization stress for 6 h resulted in anxiety and impaired locomotor activity due to excess oxidative-nitrergic stress, depletion of antioxidant defense mechanisms, and mitochondrial dysfunction in animals. In the present study, 6 h of acute immobilization stress had significantly altered the behavioral (anxiety and memory) and biochemical parameters coupled with mitochondrial dysfunction in Swiss albino mice. Fourteen days of pretreatment with Hesperidin (50 and 100 mg/kg, p.o.) significantly and dose-dependently inhibited the behavioral and biochemical alterations and mitochondrial dysfunction caused by acute immobilization stress. Furthermore, pre-treatment of l-arginine (50 mg/kg, i.p.), a nitric oxide precursor, reversed the protective effect of Hesperidin (50 and 100 mg/kg) (P < 0.05). In contrast, pretreatment of l-NAME (5 mg/kg, i.p.), a nitric oxide synthase inhibitor, potentiated the protective effect of Hesperidin (P < 0.05). These results suggest the possible involvement of nitrergic pathway in the protective effect Hesperidin against immobilization-stress-induced behavioral, biochemical, and mitochondrial dysfunction in mice.