We have studied the effects of various angiotensin-converting enzyme (ACE) inhibitors on intraocular pressure (IOP) of rabbits with experimentally induced ocular hypertension and their mechanism of action. Acute ocular hypertension was induced by infusion of 5% glucose (15 ml/kg) through marginal ear vein, whereas chronic glaucoma was induced by injection of alpha-chymotrypsin into the posterior chamber of the eye. IOP was measured by tonometer. All ACE inhibitors were instilled topically in the eye in a sterile solution. The effect of ACE inhibitors also was studied on serum cholinesterase (true and pseudo) and the enzyme ACE in vitro. Enalaprilat, ramiprilat, and fosinopril produced a time-dependent decrease of IOP in both acute and chronic models of ocular hypertension in rabbits. The decrease in IOP was observed for >4 h, and the extent of decrease was comparable to that with both pilocarpine and betaxolol. Prodrugs enalapril and ramipril failed to produced any change in IOP. Losartan also produced a significant decrease in IOP in the chronic model of ocular hypertension in rabbits. All the three ACE inhibitors were found to inhibit ACE activity in aqueous humor. The enzyme cholinesterase was found to be inhibited by enalaprilat, ramiprilat, and fosinopril. However, atropine did not alter the IOP-lowering effect of enalaprilat in rabbits. Indomethacin pretreatment produced slight but significant inhibition of the IOP-lowering effect of enalaprilat in rabbits. Our data suggest that ACE inhibitors enalaprilat, ramiprilat, and fosinopril produce a significant ocular hypotensive effect in acute and chronic models of ocular hypertension in rabbits. Inhibition of ACE in aqueous humor, and in ocular tissues, resulting in reduced angiotensin II formation, could be one of the major mechanisms responsible for the IOP reduction by ACE inhibitors in rabbits.

The clinical management of PCOS is multifaceted but often unsatisfactory. The aim of the current study is to evaluate the effect of Vitex negundo L. in the letrozole-induced polycystic ovarian syndrome. Female Sprague-Dawley rats were divided into six groups, each containing 6 animals. Group I (Control) daily received 1% carboxymethylcellulose (CMC) suspension as a vehicle control. Letrozole (1 mg/kg) was administered per orally (p.o) for a period of 21 days for the induction of PCOS in Group II to VI. PCOS induced animals were treated with aqueous (Group III - 200 mg/kg and IV- 400 mg/kg) and hydroalcoholic extract (Group V- 200 mg/kg and VI- 400 mg/kg) of Vitex negundo up to 66 days using 0.5% w/v CMC as the vehicle. Body weight and estrous cycle phase were measured every day. Blood samples were collected on 0, 21 and 66 days for the measurement of fasting blood glucose, lipid profile, LH, FSH and hormonal level. Oral glucose tolerance test was performed to study insulin resistance effect. Toxicity markers; SGOT, SGPT, and creatinine also measured at the end of the study. The administration of Letrozole led to an abnormality in serum sex steroid profile, lipid profile, glucose and estrous cycle. It was able to successfully exert its protective effect by restoring parameters to the normal level and disappearance of cysts in ovaries. This can be attributed to phyto-components present in the extract. The aqueous and hydro-alcoholic extracts of seeds of Vitex negundo showed significant amelioration of Letrozole induced PCOS.

Objective:The present study was undertaken to explore the effect of piperine in obesity-induced dyslipidemia.Materials and Methods:Male Sprague Dawley rats were fed high-fat diet (HFD) for the first eight weeks, to develop obesity-induced dyslipidemia. Later on piperine (40 mg / kg) and sibutramine (5 mg / kg) were administered for three weeks along with the continuation of HFD to two separate groups, which served as the test and standard groups, respectively. Body weight, food intake, serum triglyceride, total cholesterol, LDL, VLDL, and HDL were measured at the end of the fourth, eighth (before treatment), and eleventh (after treatment) week, while the fat mass was measured at the end of the eleventh week in the normal, HFD-control, test, and standard groups.Results:Supplementing piperine with HFD significantly reduced not only body weight, triglyceride, total cholesterol, LDL, VLDL, and fat mass, but also increased the HDL levels, with no change in food intake.Conclusion:The above results suggest that piperine possesses potential fat reducing and lipid lowering effects, without any change in food appetite, at a small dose of 40 mg / kg. The mechanism of action for such an activity needs to be determined. However, looking to structural similarity with the presently known Melanocortin-4 (MC-4) agonists, involvement of MC-4 receptors in its activity can be guessed.

Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism, oligo-anovulation, polycystic ovaries and metabolic syndrome. Many researchers reported that PCOS often starts with menarche in adolescents. Presently available animal model focuses on ovarian but not metabolic features of PCOS. Therefore, we hypothesized that high-fat diet feeding to pre-pubertal female rats results in both reproductive and metabolic features of PCOS. Pre-pubertal female rats were divided into two groups: group I received normal pellet diet and group II received high-fat diet (HFD). In the letrozole study, adult female rats were divided into two groups: group I received 1% carboxy methyl cellulose and group II received 1 mg/kg letrozole orally. Oral glucose tolerance test, lipid profile, fasting glucose, insulin, estrus cycle, hormonal profile, ovary weight, luteinizing hormone (LH) receptor and follicle-stimulating hormone receptor expression were measured. Polycystic ovarian morphology was assessed through histopathological changes of ovary. Feeding of HFD gradually increase glucose intolerance and fasting insulin levels. Triglyceride level was higher in HFD study while total cholesterol level was higher in the letrozole study. Alteration in testosterone and estrogen levels was observed in both studies. LH receptor expression was upregulated only in HFD study. Histopathological changes like increase cystic follicle, diminished granulosa cell layer and thickened theca cell layer were observed in letrozole as well as HFD study. High-fat diet initiated at pre-puberty age in rats produces both metabolic disturbances and ovarian changes similar to that observed clinically in PCOS patients. Letrozole on the other hand induces change in ovarian structure and function.