Neeraj S. Vyawahare

Diabetes-induced erectile dysfunction: epidemiology, pathophysiology and management

Erectile dysfunction (ED) is defined as the inability of the male to attain and maintain erection of penis sufficient to permit satisfactory sexual intercourse. Prevalence of impotence in diabetic men is ≥50%. The pathophysiology of diabetes-induced erectile dysfunction (DIED) is multifactorial and no single etiology is at the forefront. The proposed mechanisms of erectile dysfunction in diabetic patients includes elevated advanced glycation end-products, increased levels of oxygen free radicals, impaired nitric oxide synthesis, increased endothelin B receptor binding sites and up-regulated RhoA/Rho-kinase pathway, neuropathic damage and impaired cyclic guanosine monophosphate (cGMP)-dependent protein kinase-1. The treatment of DIED is multimodal. Treatment of the underlying hyperglycemia and comorbidities is of utmost importance to prevent or halt the progression of disease. Oral medications are considered as the first line therapy for management of DIED. If oral agents cannot be used or have insufficient efficacy despite appropriate dosing and education, second-line treatments should be addressed. When there is lack of efficacy or when there is dissatisfaction with other modalities, penile prostheses are often the best alternative for ED and are considered as the third line therapy for DIED. Future strategies in the evolution of the treatment of DIED are aimed at correcting or treating the underlying mechanisms of DIED.

Potential analgesic, anti-inflammatory and antioxidant activities of hydroalcoholic extract of Areca catechu L. nut

The hydroalcoholic extract of Areca catechu L. (ANE) nut was screened for its analgesic, anti-inflammatory and in vitro antioxidant potential. Three doses of ANE (250, 500 and 1000 mg/kg orally) were tested for analgesic and anti-inflammatory activities. Evaluation of analgesic activity of ANE was performed using hot plate and formalin test in mice. ANE showed maximum increase in hot plate reaction time (56.27%, p<0.01), while reduced the duration of licking/biting behaviors in first (39.45%, p<0.05) and second (92.71%, p<0.01) phases of the formalin test indicating significant analgesic activity. ANE reduced the paw edema considerably (86.79% inhibition after 24h, p<0.01) in dose-dependent manner compared to carrageenan-induced rat. In addition, in vitro antioxidant activity of ANE was investigated by total phenolic content (TPC) and hydrogen peroxide assay. The IC(50) observed in hydrogen peroxide assay was 83.14 μg/ml and TPC 120.56±21.09 mg QE/g. Altogether, these results suggest that the hydroalcoholic extract of Areca catechu could be considered as a potential analgesic, anti-inflammatory and antioxidant agent.

Evaluation of anti-migraine potential of Areca catechu to prevent nitroglycerin-induced delayed inflammation in rat meninges: Possible involvement of NOS inhibition

ETHNOPHARMACOLOGICAL RELEVANCE Areca catechu nut extract is a popular folk remedy for the treatment of migraine in Kerala and Tamil Nadu states of India. AIM OF THE STUDY In order to prove the claimed utilization of plant, the effect of hydroalcoholic extract of Areca catechu nut (ANE) was investigated in nitroglycerine induced inflammation in rat meninges. In these models infusion of nitric oxide donor glyceryl trinitrate (GTN) produces augmented plasma protein extravasation (PPE) in dura mater, provides an important substrate for the development of migraine in rats. MATERIALS AND METHODS The effect on plasma protein extravasation was assessed in both the models of intravenous and topical GTN application following oral administration of ANE (250 mg/kg and 500 mg/kg) in both curative and preventive treatment and compared with that of control positive. The l-NAME (15 mg/kg, i.v.) was used as reference standard. Plasma protein extravasation was measured using fluorescein as marker and was measured using a Perkin-Elmer LS-30 luminescence spectrometer. RESULTS Expression of iNOS in the spleen after intravenous injection produced PPE into the dura mater in control positive group was significantly (P<0.01) reduced to 1.553±0.02499 and 1.398±0.01887 by preventive treatment with ANE at the dose of 250 and 500 mg/kg, orally, respectively. The extravasation produced by topical GTN due to expression of iNOS in dural macrophages was also reduced to 1.555±0.03384 and 1.425±0.01204 by preventive treatment with ANE at the dose of 250 and 500 mg/kg, orally, respectively. While ANE do not showed any significant results in curative treatment in both the models of i.v. and topical GTN application. CONCLUSION These findings collectively indicate that the extract exhibited significant inhibition of iNOS, which may be the probable mechanism for its anti-migraine activity, providing evidence, at least in part, for its folkloric use.

Hygrophila spinosa: A comprehensive review.

Hygrophila spinosa T Ander, belonging to the family Acanthaceae, is a promising medicinal plant with great economic potential. The medicinal value of H. spinosa has been appreciated in the ancient medical literature. The plant contains terpenoids, alkaloids, flavonoids, and is traditionally known as an aphrodisiac, renal tonic, and for its health-promoting properties. The plant is cultivated throughout India. However, systematic information on the different aspects of this species is not available. In this review, an attempt has been made to present this information.

Effect of Hygrophila spinosa in ethylene glycol induced nephrolithiasis in rats.

Objective: Hygrophila spinosa (Acanthaceae) is traditionally used to treat urinary calculi. The present study aimed to evaluate the antiurolithiatic activity of methanolic extract of Hygrophila spinosa (Acanthaceae) in ethylene glycol induced nephrolithiasic rats. Materials and Methods: Methanolic extract of Hygrophila spinosa (HSME) (250 and 500 mg/ kg body weight) was administered orally to male Wistar albino rats. Ethylene glycol (EG) was used to induce nephrolithiasis. The parameters studied included water intake, urinary volume, urinary pH, urinary and kidney oxalate and calcium, urinary magnesium and serum uric acid. Results: Ethylene glycol feeding resulted in hyperoxaluria as well as increased renal excretion of calcium and serum uric acid along with decreased excretion of urinary magnesium. Treatment with HSME significantly reduced the elevated urinary oxalate, urinary calcium and serum uric acid with increase in reduced urinary magnesium. Ethylene glycol feeding also resulted in increased levels of calcium and oxalate in kidney which was decreased after the treatment with HSME. The increased deposition of stone forming constituents in the kidneys of ethylene glycol treated rats was significantly lowered by treatment with HSME. Conclusion: The results indicate that the aerial parts of Hygrophila spinosa are endowed with antiurolithiatic activity, thereby justifying its traditional claim.

Effect of novel synthetic evodiamine analogue on sexual behavior in male rats

AbstractCurrently phosphodiestrase5 (PDE5) inhibitors are the first-line treatment for erectile dysfunction. Drugs such as sildenafil and tadalafil are available as PDE5 inhibitors which are potent and reversible but lack selectivity with side effects such as headache, facial flushing, dyspepsia, and visual disturbances. We herein report for the first time novel condensed thienopyrimidines as evodiamine analogue and their effect on sexual behavior in male rats hitherto unreported. Novel synthetic evodiamine significantly showed improvement in male rat copulatory behavior. The test compound MKAC9 could be of promising importance in the treatment of sexual disorders like desire disorder or erectile dysfunction. FigureEvodiamine analogue on sexual behavior in male rats

H. Spinosa T. Anders ameliorates diabetic neuropathy in Wistar albino rats.

Diabetic neuropathic pain, an important microvascular complication in diabetes, is recognised as one of the most difficult types of pain to treat. The development of tolerance, inadequate relief, and potential toxicity of classical antinociceptives warrant the investigation of the newer agents to relieve this pain. Reactive oxygen/nitrogen species, increased oxidative stress, cytokines, and apoptosis are implicated in the pathogenesis of diabetic neuropathy. The aim of the present study was to explore the effect of methanolic extract of aerial parts of H. spinosa (HSME) on alloxan induced diabetic neuropathy in Wistar rats. Diabetic rats developed neuropathy after the third week of diabetes induction. Chronic treatment with HSME (250, 500, and 750 mg/kg body weight; p.o.) for 6 weeks starting from the 3rd week of alloxan injection showed significant increase in the pain threshold levels as compared to diabetic rats. HSME treated diabetic animals showed significant decrease in blood glucose level and increase in body weight as compared to diabetic control animals. The changes in lipid peroxidation status and antioxidant enzymes levels observed in sciatic nerve of diabetic rats were significantly restored by HSME treatment. Thus, the results suggest therapeutic potential of H. spinosa in treatment of diabetic neuropathy.

Protective effect of Hygrophila spinosa against cisplatin induced nephrotoxicity in rats

Objective: To evaluate the nephroprotective effect of methanolic extract of Hygrophila spinosa (HSME) (Acanthaceae) in (CP)-induced acute renal failure in rats. Materials and Methods: HSME (250 mg/kg and 500 mg/kg body weight), were administered orally to male wistar albino rats.CP was used to induce acute renal failure. The parameters studied included blood urea and serum creatinine and malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and GSH peroxidase activities. Histopathological examination was also carried out. Results: The results revealed that HSME pretreatment signiûcantly reduced blood urea and serum creatinine levels elevated by CP administration. Furthermore, HSME signiûcantly attenuated CP-induced increase in MDA and decrease in reduced GSH, and CAT and SOD and GSH peroxidase activities in renal cortical homogenates. Additionally, histopathological examination showed that HSME markedly ameliorated CP-induced renal tubular necrosis. Conclusion: The results indicate that the aerial parts of H. spinosa are endowed with nephroprotective activity.

Neuroprotective and antioxidant role of Phoenix dactylifera in permanent bilateral common carotid occlusion in rats

Abstract Objective To investigate neuroprotective and antioxidant effect of Phoenix dactylifera (P. dactylifera) (PD) fruits. Methods Methanolic extract of P. dactylifera fruits (MEPD) at doses of 30, 100 and 300 mg/kg was studied against permanent BCCAO (long-term hypoperfusion) in rats. Chronic occlusion of bilateral common carotid arteries (BCCA) caused significant elevation in malondialdehyde levels due to increased lipid peroxidation as well as decrease in levels of other biochemical enzymes i.e. glutathione, glutathione peroxidase, glutathione reductase, glutathione-S-transferse, catalase and superoxide dismutase. Results Post occlusion treatment for 15 d with 100 and 300 mg/kg doses of MEPD significantly reduced the enhanced malondialdehyde levels and reversed the alterations in the declined levels of antioxidant enzymes in brain homogenates of hypoperfused rats. Long-term cerebral hypoperfusion in rats caused a propensity towards anxiety and restlessness (open field paradigm) accompanied by deficits of spatial learning and memory (Morris water maze testing). Additionally, histopathological observations in hypoperfused brains revealed reactive changes like shrinkage and necrosis of neurons. 100 and 300 mg/kg doses of MEPD significantly alleviated these alterations. Conclusions These results confirmed the protective role of P. dactylifera in ischemia hypoperfusion and thereby its beneficial role in cerebrovascular insufficiency states and related complications.

Anti-migraine effect of Areca Catechu L. nut extract in bradykinin-induced plasma protein extravasation and vocalization in rats

ETHNOPHARMACOLOGICAL RELEVANCE Areca catechu Linn. (Arecaceae) nut is a popular folk remedy for the treatment of migraine in Kerala and Tamil Nadu states of India. AIM OF THE STUDY This study was designed to investigate the effect of hydroalcoholic extract of A. catechu L. nut (ANE) treatment on migraine pain in rat models to strengthen its use as an anti-migraine therapy. MATERIALS AND METHODS Bradykinin (0.1 μmol/kg) injection in to left femoral vein of rat produced PPE which was measured with luminescence spectrometer. Vocalizations were produced in rats with 10 μg of bradykinin infusion into common carotid artery. Phonogram was recorded before, during and for 5min after bradykinin injection and sumatriptan was used as a standard anti-migraine drug. In both models, the ANE was orally administered at doses of 250 and 500 mg/kg, 60 min before bradykinin infusion. RESULTS The PPE was reduced in both ANE treated groups of rats. The percent fluorescein was significantly increased in positive control group (97.00±1.7%; p<0.0001) compared to negative control (63.87±1.2%). With ANE treatments (250 and 500 mg/kg) PPE was significantly decreased to 88.88±1.4% (p<0.01) and 83.55±0.1% (p<0.0001) compared to positive control group, respectively. On the other hand in the model of vocalization, with 250 and 500 mg/kg ANE treatment, vocalization was significantly reduced to 33.33% and 16.66%, respectively, compared to saline treated rats. The reduction in vocalization is comparable to the reference drug sumatriptan. CONCLUSION The findings provide the strong evidence for anti-migraine potential of ANE in rat models of migraine. In summary, therapeutic intervention with ANE treatment could be a promising strategy for prevention of migraine.