Neuroprotective effects of quercetin produced by an endophytic fungus Nigrospora oryzae isolated from Tinospora cordifolia.

AIMS: Alzheimer's disease is considered one of the most prevalent neurodegenerative disorders and dementia is the core symptom of this disease. This study was aimed to test the bioactive compounds produced by endophytic fungus for the inhibition of acetylcholinesterase (AChE) activity and to identify the compound responsible for this activity. METHODS AND RESULTS: Endophytic fungi were isolated from the medicinal plant Tinospora cordifolia and screened for AChE inhibition and antioxidant activity. The extract of one of the isolates Nigrospora oryzae (GL15) showed maximum AChE inhibition as well as antioxidant activity. The compound responsible for AChE inhibition (fraction 3) was identified as quercetin based on UV, FTIR spectra, HPLC and ESI-MS analyses. Furthermore, the identification of quercetin in the extract of fraction 3 was confirmed by 1 H NMR analysis. This extract showed anti-dementia-like activity in scopolamine (SCO) model. The minimal effective dose of the extract of fraction 3 modulated the SCO-provoked cognitive deficits such as impairments in spatial recognition memory and latency period in Y-maze test and passive avoidance test, respectively. The SCO-induced modulation in cholinergic pathway was ameliorated by the extract of N. oryzae in hippocampus, resulting in decrease in AChE activity and restoration of cytoarchitecture of hippocampus. CONCLUSIONS: The bioactive compound quercetin produced by N. oryzae may cure the learning and memory shortfalls via AChE-mediated mechanism in experimental mice. SIGNIFICANCE AND IMPACT OF THE STUDY: The endophytic fungus N. oryzae serves as a potential source for the bioactive compound quercetin, which plays an important role in the management of Alzheimer's disease.

Gastroprotective activity of polyphenolic-rich extract of Potentilla mooniana.

CONTEXT: Potentilla mooniana Wight. (Rosaceae) is a plant found in the Himalayan region where the root is traditionally used to treat stomach problems including gastric-ulcer. OBJECTIVE: To scientifically validate the gastro-protective effect and derive the possible mechanistic activity of the ethanol root extract from P. mooniana (EPM). MATERIALS AND METHODS: The gastroprotective effect of EPM (100-400 mg/kg, p.o.) was evaluated on both the physical (Pyloric ligation, PL; Cold restrain stress, CRS) and chemical (absolute ethanol, EtOH; aspirin, ASP) ulcerogens induced ulceration in rats. The mechanistic activity of EPM was tested on various gastric-ulcer parameters, namely gastric pH, volume, acid-pepsin output, DNA content, histamine level, H(+)K(+)-ATPase activity, mucus content, microvascular permeability, antioxidant markers, and gastric-histopathological study. RESULTS: EPM significantly reduces the ulcer score against all the four tested gastric-ulcer models. In the PL model, EPM showed significant reduction (p < 0.05) in acid-pepsin output and cell shedding; however, no significant effect was observed on gastric volume, cell proliferation, stomach glandular weight, and histamine levels. EPM (400 mg/kg, p.o.) when compared with ulcer control showed significant increase in gastric pH by 41.6% and decrease in H(+)K(+)-ATPase activity by 47.73%. In addition, EPM showed significant increase in mucus content by 58.60% and a decrease in the microvascular permeability of Evans Blue by 85.00%, justifying its protective effects. Furthermore, EPM also showed significant antioxidant activity and histopathologically possessed excellent cytoprotective effect. CONCLUSION: The gastro-protective effect of EPM is attributed mainly to the defensive mechanism owing to the presence of a good quantity of polyphenolic components.

Prosopis cineraria: a potential nootropic agent.

CONTEXT: Prosopis cineraria (L.) Druce (Leguminosae), a plant of the Thar Desert of India and Pakistan is used traditionally by local people for the treatment of memory disorders and to arrest wandering of the mind. OBJECTIVE: The study includes scientific validation of P. cineraria for nootropic activity. To elucidate the possible mechanism, the anticholinesterase activity was also investigated in different parts of the brain. MATERIALS AND METHODS: Methanol extract of P. cineraria stem bark (200, 400 and 600 mg/kg body weight p.o.) was administered once in a day for 7 days to rats and these rats were then subjected to Morris water-maze (MWM) test for spatial reference memory (SRM) and spatial working memory (SWM) versions of memory testing. The inhibitory effect of the extract on acetylcholinesterase (AChE) in discrete rat brain regions (prefrontal cortex [PFC], hippocampus [HIP] and amygdala [AMY]) was also investigated using acetyl thiocholine iodide and dithiobisnitrobenzoic acid reagent. RESULTS AND DISCUSSION: The oral administrations of methanol extract of P. cineraria in all doses tested, significantly (p < 0.05) improved both spatial reference and working memories in the MWM test in terms of decrease in escape latency during SRM and increase in time spent in the target quadrant during SWM probe trial. A ceiling effect was observed at 400 mg/kg. Pre-treatment for 7 days significantly inhibited the activity of AChE in the HIP, PFC and AMY. CONCLUSION: The extract exerted significant nootropic activity in the MWM test which may be attributed to the inhibition of brain AChE.

Inhibitory effect of two Indian medicinal plants on aldose reductase of rat lens in vitro.

OBJECTIVE: To assesse the inhibitory effect of alcoholic extract of two Indian medicinal plants namely Ceasalpinia digyna Rottler and, Alangium lamarckii Thwaits on aldose reductase (AR) of rat lens. METHODS: Rats lens were enucleated through posterior approach and their homogenate was prepared and centrifuged to obtain a clear supernatant for the determination of AR activity and protein content. RESULTS: The alcoholic extract of Ceasalpinia digyna and Alangium lamarckii had a potent inhibitory effect on the lens AR enzyme. The IC(50) values of alcoholic extract of the selected plants were calculated and were (46.29±11.17) and (106.00±5.11) µg/mL, respectively. Quercetin was used as a positive control and its IC(50) value was (2.95±1.53) µg/mL. CONCLUSIONS: Thus, it is concluded that alcoholic extracts of the selected plant exhibit significant inhibitory effects on AR in the rat lens in vitro.

Non-steroidal anti-inflammatory drug sodium salicylate, but not diclofenac or celecoxib, protects against 1-methyl-4-phenyl pyridinium-induced dopaminergic neurotoxicity in rats.

We evaluated the hydroxyl radical (*OH) scavenging action of nonsteroidal anti-inflammatory drugs (NSAIDs), sodium salicylate (SA), diclofenac and celecoxib in Fenton's reaction and their neuroprotective effects in 1-methyl-4-phenylpyridinium (MPP(+))-induced striatal dopamine (DA) depletion in rats. Salicylate hydroxylation procedure employing HPLC-electrochemistry was used to assay formation of *OH in Fenton's reaction in test tubes. While SA dose- and time-dependently hydroxylated itself and inactivated *OH, celecoxib (up to 10 mM) showed no effect on *OH formation and diclofenac caused a reduction in *OH generation only at high doses (100 microM-10 mM). Administration of the non-selective cyclooxygenase (COX) inhibitor, SA (50, 100 mg/kg, i.p.) significantly attenuated striatal DA depletion caused by intrastriatal infusion of MPP(+) (100 nmol in 4 microl). Treatment with another nonselective, reversible COX inhibitor, diclofenac (5, 10 mg/kg) did not protect against MPP(+)-induced DA depletion. The selective COX-2 inhibitor, celecoxib (2.5-50 mg/kg) treatment exacerbated MPP(+)-induced decrease in DA. Failure of celecoxib or diclofenac to render protection in animals against MPP(+)-induced DA depletion indicates absence of prostaglandin involvement in MPP(+) action. These results also suggest that the neuroprotective ability of SA is independent of prostaglandin mediation. A relationship between inactivation of *OH by SA and its ability to protect DA depletion in the striatum caused by MPP(+) indicates a direct involvement of *OH in the action of this neurotoxin. The present study establishes potent neuroprotective activity of SA and suggests the use of aspirin in adjuvant therapy in Parkinson's disease.

Oral sildenafil (Viagra) in male erectile dysfunction: use, efficacy and safety profile in an unselected cohort presenting to a British district general hospital.

INTRODUCTION: Sildenafil (Viagra) is one of the drugs used in the first line therapy of male erectile dysfunction (MED). We have recorded outcomes, adverse events and acceptability of Sildenafil (Viagra) therapy in an unselected group of men presenting with ED to a British district general hospital. METHODS: In this prospective observational study, 147 men with ED were seen since Oct 1999. Study patients were reviewed at 4, 12 and 52 weeks. All the patients filled the International Index of Erectile Function (IIEF) questionnaire and were asked about their willingness to pay (WTP) for treatment. RESULTS: All suitable men accepted Viagra as first line therapy. 91% of our patients found sildenafil treatment successful. 80% of these patients were willing to continue with sildenafil therapy. Side effect profile of sildenafil was different in this study with much higher incidence of headache, dyspepsia, flushing and abnormal vision. 92% of men with ED expect to be treated by the NHS. Of those men eligible for treatment in the NHS, 30% qualify under the clinical categories and 18% under the 'distress' category. Only 55% of those with cardiovascular risk factors qualify for NHS treatment. CONCLUSIONS: Sildenafil is widely accepted as first line therapy among British men with ED and has a success rate of 91%. Nearly half of men with ED qualify for NHS treatment. Nearly half of those with vascular risk factors do not qualify for NHS treatment. Most men with ED could possibly be managed in primary care.