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.

Anti-inflammatory and antiarthritic activity of anthraquinone derivatives in rodents.

Aloe emodin is isolated compound of aloe vera which is used traditionally as an anti-inflammatory agent. In vitro pharmacokinetic data suggest that glucuronosyl or sulfated forms of aloe emodin may provide some limitations in its absorption capacity. Aloe emodin was reported to have in vitro anti-inflammatory activity due to inhibition of inducible nitric oxide (iNO) and prostaglandin E2, via its action on murine macrophages. However, present work evidenced that molecular docking of aloe emodin modulates the anti-inflammatory activity, as well as expression of COX-2 (cyclooxygenase-2) in rodent. The AEC (4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracene-2 carboxylic acid) was synthesized using aloe emodin as starting material. The study was planned for evaluation of possible anti-inflammatory and antiarthritic activity in carrageenan rat induced paw oedema and complete Freund's adjuvant induced arthritis in rats. The AE (aloe emodin) and AEC significantly (P < 0.001) reduced carrageenan induced paw edema at 50 and 75 mg/kg. Complete Freund's adjuvant induced arthritis model showed significant (P < 0.001) decrease in injected and noninjected paw volume, arthritic score. AE and AEC showed significant effect on various biochemical, antioxidant, and hematological parameters. Diclofenac sodium 10 mg/kg showed significant (P < 0.001) inhibition in inflammation and arthritis.

Silymarin improves the behavioural, biochemical and histoarchitecture alterations in focal ischemic rats: a comparative evaluation with piracetam and protocatachuic acid.

Comparative neuroprotective potential of silymarin, piracetam and protocatechuic acid ethyl ester (PCA) was evaluated in focal ischemic rats. Various pharmacological, biochemical (lipid peroxidation, reduced glutathione, catalase, nitrite content, brain water content) and behavioural (memory impairment, motor control, neurological score) including infarct size and histopathological alterations were evaluated. Silymarin (200mg/kg) and PCA treatment significantly improved behavioural, biochemical and histopathological changes, and reduced water content and infarct size. However, piracetam only improved behavioural and histopathological changes, reduced water content and infarct size. The findings indicate that silymarin exhibits neuroprotective activity better than PCA and piracetam in focal ischemia/reperfusion reflected by its better restoration of behavioural and antioxidant profile.

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.

Anti-inflammatory and analgesic activity of protocatechuic acid in rats and mice.

Anti-inflammatory and analgesic activity of protocatechuic acid (PCA), a natural product, was evaluated in different rat models (viz., carrageenan-induced paw oedema, cotton pellet-induced granuloma and Freund's adjuvant arthritis) of inflammation and chemical and heat induced mouse models of pain. Treatment with PCA inhibited significantly different biological parameters like hind paw oedema, granuloma exudates formation and arthritis index in carrageenan oedema, cotton pellet granuloma and Freund's adjuvant arthritis, respectively. The biochemical changes viz., glutathione, superoxide dismutase, catalase, lipid peroxidation and NO in oedematous or in liver tissues and serum alanine aminotransferase and lactic dehydrogenase occurred during different types of inflammation were either significantly restored or inhibited with PCA pretreatment. Present experimental findings demonstrate promising anti-inflammatory and analgesic activity of PCA which is comparable with that of standard drugs used.

DPP IV inhibitors: successes, failures and future prospects.

The dipeptidyl peptidase IV (DPP IV) enzyme is a novel target for the treatment of type 2 diabetes. Several DPP IV inhibitors are in the clinical development, since they are safe and tolerable with no increased risk of adverse events compared to placebo and have a low risk of hypoglycemia. They are flourishing as monotherapy and also in combination with commonly prescribed antidiabetic agents and are appropriate for once-daily oral dosing. However, further studies are needed to validate both long-term ß-cell preservation and the role of these agents in the management of diabetes. The present review gives an inside out of the DPP IV inhibitors for its success, failure and future prospects in the treatment of diabetes and associated complication.

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.