New Thiazole Acetic Acid Derivatives: A Study to Screen Cardiovascular Activity Using Isolated Rat Hearts and Blood Vessels.

Cardiovascular diseases are one of the major causes of mortalities worldwide. In the present research, new synthetic derivatives of thiazole were studied using isolated hearts and blood vessels of rats. The heart and thoracic aorta were tested with six new synthesized thiazole acetic acid derivatives (SMVA-10, SMVA-35, SMVA-40, SMVA-41, SMVA-42 and SMVA-60), and the data obtained were statistically analyzed and compared. Isolated rat hearts were used to record the changes in developed tension and heart rate, while thoracic aortas were used to measure the contractile response, before and after treatments. Analysis of the results indicated a significant (p < 0.01) increase in developed tension with the addition of SMVA-35, SMVA-40, SMVA-41 and SMVA-42, which was augmented in the presence of adrenaline without affecting the heart rate. On the other hand, acetylcholine significantly decreased the developed tension, which was significantly reversed (p < 0.01) in the presence of compounds (SMVA-35 and SMVA-60). However, in the presence of SMVA-35 and SMVA-40, acetylcholine-induced bradycardia was significantly (p < 0.01) reduced. Furthermore, only SMVA-42 induced a dose-dependent contractile response in the isolated blood vessel, which was abolished in the presence of prazosin. Therefore, it can be concluded that some of the new synthesized thiazole derivatives exhibited promising results by raising the developed tension without changing the heart rate or blood vessel function, which could be helpful in failing heart conditions. However, more research is required to fully comprehend the function, mechanism and effectiveness of the compounds.

Erectogenic and Aphrodisiac Property of Moringa oleifera: Involvement of Soluble Epoxide Hydrolase Enzyme.

Soluble epoxide hydrolase (sEH) inhibitors have been reported to improve penile erection; therefore, sEH could be useful for management of erectile dysfunction. Methanolic and aqueous extracts of 30 Indian medicinal plants were screened for their sEH inhibition potential. Fifteen extracts showed >50% inhibition when screened at 50 µg/mL in sEH inhibition assay. Methanolic extract of Moringa oleifera Lam. (Moringaceae) seeds (MEMO) was most potent with IC50 1.7 ± 0.1 µg/mL and was selected for in vitro studies on isolated rat corpus cavernosum smooth muscle and in vivo sexual behaviour studies on healthy and diabetic rats. Rats were divided into five groups, each containing six animals and treated orally with either water, vehicle (1% Tween-20), MEMO (45 and 90 mg/kg/day for 21 days), and standard drug, sildenafil (5 mg/kg/day for 7 days). An equal number of female rats were used, and the effect of MEMO and sildenafil was compared with that of vehicle. MEMO significantly relaxed isolated rat corpus cavernosum smooth muscle at 0.1-100 µg/mL in vitro and significantly increased (p < 0.05) sexual activity, intracavernous pressure/mean arterial pressure in normal and diabetic rats. The increase in erectile function of rats by MEMO could be because of its sEH inhibitory activity. Copyright © 2016 John Wiley & Sons, Ltd.

Preclinical Studies to Evaluate the Gut Stimulatory Activity of Aloe Musabbar.

Background: Constipation is a common functional gastrointestinal disorder. Medicines derived from nature are routinely used to treat it. The present study evaluates the gut stimulatory activity of Aloe musabbar (processed powder of Aloe vera) using in vitro and in vivo models for gut stimulatory activity. Materials and Methods: In vitro tests were conducted on isolated rat colon, guinea pig ileum, and rabbit jejunum, while in vivo study was performed using mice intestinal transit time. Aloe musabbar (A. musabbar) was tested at doses 0.2-200 mg/mL (in-vitro study) and 86.6 mg/kg (in vivo study). In vitro studies were done in the presence and absence of atropine sulphate (1 ng/ml). The results were statistically analyzed, and p < 0.05 was considered to indicate the significance. Results: A. musabbar exhibited dose-dependent increase in the smooth muscle contraction of isolated gut tissues. Presence of atropine minimized the contractile responses and shifted the dose-response curves towards the right-hand side. The intestinal transit time in mice was observed to be increased significantly (p < 0.01) in A. musabbar-treated animals, when compared with normal animals. Conclusion: A mild smooth muscle contraction induced by A. musabbar suggests that it can stimulate intestinal bowel movement without causing spasms. The diminished responses in the presence of atropine indicated that the gut stimulatory activity could be mediated partially through parasympathetic innervations. More studies are needed to determine the precise mechanism of action including the specific active ingredient responsible for the gut stimulatory activity.

Pharmacodynamic and Pharmacokinetic Interactions of Propranolol with Garlic (Allium sativum) in Rats.

Garlic preparations and propranolol (PRO) are agents recognized as cardioprotective and potent antihypertensive agents when they are used individually. However, there is no report available to explain the role of combined therapy during simultaneous hypertension and myocardial damage in rats. We aimed to determine the pharmacokinetic and pharmacodynamic interaction of PRO with garlic homogenate (GH), in rats. The influence of garlic on pharmacokinetics of PRO was determined by HPLC method; while pharmacodynamic interaction was studied in animals with hypertension (10% fructose) and myocardial damage (isoproterenol, 175 mg kg(-1), s.c. 2 days). PRO was given orally at 10 mg kg(-1) for 1 week, whereas, GH was administered at three different doses of 125, 250 and 500 mg kg(-1), p.o. in their respective groups during fourth to sixth week of high fructose (HF) period, once daily. Systolic blood pressure (SBP), heart rate, cholesterol, triglycerides, glucose, creatine phosphokinase-MB, lactate dehydrogenase, superoxide dismutase and catalase were measured and histopathological studies were carried out. The bioavailability and half life of PRO were significantly enhanced by 2- and 3-fold, respectively, in animals pretreated with garlic (250 mg kg(-1)). Administration of PRO and low to moderate doses of GH (125, 250 mg kg(-1)), either alone or together showed fall in fluid intake and body weight. The combined therapy of GH 250 mg kg(-1) and PRO was found to be most effective in reducing SBP, cholesterol, triglycerides and glucose. These observations suggest that careful addition of garlic in moderate doses in PRO regimen might result in beneficial effect during treatment of hypertensive animals with myocardial damage.

Pharmacodynamic interaction of captopril with garlic in isoproterenol-induced myocardial damage in rat.

It is known that various preparations of garlic and angiotensin-converting enzyme (ACE) inhibitor such as captopril (CAP) have beneficial effects on the left ventricular function and cardiovascular events after myocardial infarction (MI) when used individually. There is no reported interaction between garlic homogenate (GH) and CAP during and after acute MI. Thus the purpose of the current study was to evaluate the possible pharmacodynamic interaction of GH with CAP on isoproterenol (ISO)-induced myocardial damage in rat. Female Wistar albino rats were treated with GH at three different doses of 125; 250 and 500 mg/kg orally for 30 days and CAP (30 mg/kg, p.o.) was incorporated in the interactive groups during the last seven days of GH treatment. Myocardial damage was induced by administration of ISO (150 mg/kg, s.c.) for two consecutive days. Biochemical parameters were studied in serum and heart tissue homogenate of all animals. The GH 250 mg/kg was found to dislodge the effect of ISO on superoxide dismutase and catalase and retained the activities of LDH and CK-MB. Incorporation of CAP during GH treatment provided further protection to myocardium from injury. However, higher dose of GH alone or with CAP failed to prevent damaging effect of ISO. Histopathological determinations confirmed biochemical findings. Thus it is concluded that the combination needs to be used carefully when garlic is consumed at high doses.

Pharmacodynamic interaction of garlic with propranolol in ischemia-reperfusion induced myocardial damage.

The present study was undertaken to explore the interaction of garlic homogenate (GH) with propranolol (PRO) on ischemia-reperfusion injury (IRI) in isolated rat heart preparation. Albino rats were treated with GH at three different doses of 125 mg/kg, (GH-125), 250 mg/kg (GH-250) and 500 mg/kg (GH-500) for 30 days orally. The hearts were excised and mounted on modified Langendorff setup and subjected to 15 min global no flow ischemia and reperfused for 15 min. Pretreatment of animals with PRO, GH-125 and GH-250 (either alone or in combination) provided significant protection to myocardium from IRI damage as indicated by significant decrease in LDH and CK-MB activities in perfusate and an increase in activities of these enzymes in heart tissue homogenate. Similarly, the recovery (%) in developed tension and heart rate were significantly more in treated groups during post-ischemia when compared to control. Moreover, GH-250 either alone or with PRO showed significant increase in activities of antioxidant enzymes such as superoxide dismutase and catalase during IRI damage. However, GH-500 failed to show cardioprotective effect when given alone or along with PRO. These biochemical findings were supported by changes in histopathological studies.

Effect of conventional antihypertensive drugs on hypolipidemic action of garlic in rats.

The present study was undertaken to determine the possible alteration in hypolipidemic actions of garlic homogenate (GH) in presence of conventional antihypertensive drugs, propranolol (PRO), hydrochlorothiazide (HYD) and captopril (CAP). Albino rats fed with normal fat diet (NFD) or high fat diet (HFD) were treated with GH at three different doses (125, 250 and 500 mg/kg) orally for 30 days or in combination with PRO (10 mg/kg, po), HYD (10 mg/kg, po) and CAP (30 mg/kg, po) during last 7 days of GH treatment. After the treatment, total cholesterol (TC), LDL-cholesterol, triglyceride (TG) and HDL-cholesterol were measured in serum and antiatherogenic index was calculated. The result showed that moderate and high doses of GH possessed potential antiatherosclerotic property that was significantly attenuated by PRO and HYD. However, GH antihyperlipidemic activity was augmented by CAP. It was concluded that administration of PRO and HYD decrease the hypolipidemic effect of GH and administration of GH along with CAP augmented the hypolipidemic effect of GH in rats.

Pharmacodynamic interaction of garlic with hydrochlorothiazide in rats.

The purpose of current study was to evaluate the influence of hydrochlorothiazide (HCTZ) on protective effects of garlic homogenate (GH) in rats subjected to myocardial damage induced by ischemia-reperfusion (IRI) and isoproterenol (ISO). Female Wistar albino rats were treated with GH at three different doses of 125; 250 and 500 mg/kg orally for 30 days and HCTZ (10 mg/kg, p.o.) was incorporated in the interactive groups during the last seven days of GH treatment. At the end of treatment, animals were subjected to IRI or ISO induced myocardial damage in their respective models. The GH 250 mg/kg was found to dislodge the effect of ISO and IRI on superoxide dismutase & catalase and retained the activities of LDH and CK-MB. Adding HCTZ improved biochemical, antioxidant and histological status of myocardium during myocardial damage. Since no toxic effects were observed, HCTZ may safely be used to improve GH therapy.

Antioxidant Potential and Ability of Phloroglucinol to Decrease Formation of Advanced Glycation End Products Increase Efficacy of Sildenafil in Diabetes-Induced Sexual Dysfunction of Rats.

INTRODUCTION: Diabetes-induced sexual dysfunction is associated with an increase in oxidative stress. Scavengers of reactive oxygen species (ROS) have been shown to reduce oxidative stress and aid in the management of sexual dysfunction in diabetes. AIM: The aim of the study was to test the hypothesis that antioxidant, which scavenge ROS and reduce formation of advanced glycation end products (AGEs), can potentiate efficacy of phosphodiesterase type 5 inhibitors in diabetes-induced sexual dysfunction that is associated with oxidative stress. MATERIALS AND METHODS: Effect of phloroglucinol and sildenafil on serum glucose level, sexual function, penile smooth muscle : collagen ratio, and phenylephrine precontracted corpus cavernosum smooth muscle (CCSM) was studied. The ability of phloroglucinol to reduce the formation of AGEs and its ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) was also evaluated. MAIN OUTCOME MEASURES: Antioxidant potential of phloroglucinol was studied in addition to its effect on diabetes-induced sexual dysfunction in presence and absence of sildenafil. RESULTS: Phloroglucinol (50 mg/kg, p.o.) significantly decreased serum glucose level and increased sexual function in streptozotocin-induced diabetic rats when compared with diabetic control rats. Sildenafil (5 mg/kg, p.o.) had no effect on glycemia but significantly increased sexual function of diabetic rats. Coadministration of phloroglucinol increased the efficacy of sildenafil by improving sexual function. Treatment of diabetic rats with phloroglucinol + sildenafil maintained smooth muscle : collagen levels similar to that of normal rat penile tissue. Phloroglucinol decreased formation of AGEs and significantly scavenged DPPH radical activity in vitro. Sildenafil relaxed isolated CCSM of normal rat and diabetic rat significantly, but phloroglucinol did not show any significant effect. Phloroglucinol also inhibited human CYP3A4 enzyme activity in vitro. CONCLUSION: Phloroglucinol coadministration increases efficacy of sildenafil in diabetes-induced sexual dysfunction. However, further studies are required to ascertain the benefits of phloroglucinol owing to its undesirable CYP3A4 inhibition activity.

IM-133N - A Useful Herbal Combination for Eradicating Disease-triggering Pathogens in Mice via Immunotherapeutic Mechanisms.

OBJECTIVES: The present study was undertaken to evaluate the immunomodulatory (IM) activity of IM-133N, a herbal combination in various immunotherapeutic experimental models. METHODS: The IM activity of IM-133N was evaluated against three experimental models namely, effect of IM- 133N against Escherichia coli (E. coli)-induced abdominal sepsis in mice, and carbon clearance test was performed in Wistar albino rats to evaluated the phagocytic potential of IM-133N, in addition IM-133N was evaluated for its immunoglobulin enhancing potential in rats, where the immunoglobulin levels were measured by zinc sulphate turbity (ZST) test. Further, IM-133N was subjected for detailed liquid chromatography-mass spectrometry (LC-MS)/MS analysis to identify the probable active constituents present in it. RESULTS: The findings of the present study has demonstrated very promising IM property of IM-133N in all the experimental models. Briefly, pretreatment with IM-133N at 125, 250, 500 and 1,000 mg/kg, p.o. doses had protected the mice against E. coli-induced abdominal sepsis and mortality, further the effect of IM- 133N was found to be significant and dose-dependent. In support of this, in another study administration of IM-133N showed a significant and dose-dependent increase in serum immunoglobulin levels, estimated by ZST test. In line with the above findings, in the carbon clearance test the low doses (125 and 250 mg/ kg, p.o.) of IM-133N increased the rate of carbon clearance, whereas the higher doses (500 and 1,000 mg/kg, p.o.) did not sustain the response, and saturation effect was considered as one of the possible reason for futility of higher doses for IM-133N. In addition, A detailed LC-MS/MS analysis of IM-133N showed 17 bioactive phytochemical constituents: namely, apigenin, chaulmoogric acid, mesquitol, quercetin, symphoxanthone, salireposide, ß-sitosterol, nonaeicosanol, ß-amyrin, betulic acid, oleanolic acid, symplososide, symponoside, symploveroside, symplocomoside, symconoside A and locoracemoside B. CONCLUSION: These findings suggest that IM-133N possesses significant IM activity and, hence, could be useful for eradicating opportunistic disease-triggering pathogens via immunotherapeutic mechanisms. The findings also suggest IM-133N may also useful in other immunity disorders.

Efficacy of ellagic acid and sildenafil in diabetes-induced sexual dysfunction.

BACKGROUND: Diabetes induced sexual dysfunction is a leading cause of male sexual disorder and an early indicator of cardiovascular complication. Reactive oxygen species generated in body during diabetes is a main causative factor for erectile dysfunction, a sexual dysfunction. Adjuvant antioxidant therapy along with phosphodiesterases type 5 enzyme inhibitor (PDE5i) is more effective than PDE5i alone. OBJECTIVE: The aim of the study was to investigate efficacy of ellagic acid a known antioxidant and sildenafil in diabetes induced erectile dysfunction. MATERIALS AND METHODS: Type 1 diabetes was induced in male rats and rats were treated with ellagic acid (50 mg/kg, p.o.) and a combination of ellagic acid (50 mg/kg, p.o.) and sildenafil (5 mg/kg, p.o.), a PDE5i for 28 days. Sexual function was observed in diabetic rat and compared with those of treatment group and normal rats. Effect of ellagic acid was studied on advanced glycation end products (AGE) and isolated rat corpus cavernosum in vitro. RESULTS: Sexual function of diabetic rats was found to be reduced and ellegic acid treatment could preserve sexual function of diabetic rats to some extent. Ellagic acid + sildenafil treatment was more efficient in management of diabetes induced sexual dysfunction. Ellagic acid inhibited (AGE) in vitro implying its role in reducing oxidative stress in diabetes. The polyphenol could not increase sexual function in normal rats and relax isolated rat corpus cavernosum smooth muscle significantly. CONCLUSION: The study proves usefulness of adjuvant antioxidant therapy in the management of erectile dysfunction in diabetes.

The critical steps for successful research: The research proposal and scientific writing: (A report on the pre-conference workshop held in conjunction with the 64(th) annual conference of the Indian Pharmaceutical Congress-2012).

An interactive workshop on 'The Critical Steps for Successful Research: The Research Proposal and Scientific Writing' was conducted in conjunction with the 64(th) Annual Conference of the Indian Pharmaceutical Congress-2012 at Chennai, India. In essence, research is performed to enlighten our understanding of a contemporary issue relevant to the needs of society. To accomplish this, a researcher begins search for a novel topic based on purpose, creativity, critical thinking, and logic. This leads to the fundamental pieces of the research endeavor: Question, objective, hypothesis, experimental tools to test the hypothesis, methodology, and data analysis. When correctly performed, research should produce new knowledge. The four cornerstones of good research are the well-formulated protocol or proposal that is well executed, analyzed, discussed and concluded. This recent workshop educated researchers in the critical steps involved in the development of a scientific idea to its successful execution and eventual publication.

Modulation of haemodynamics, endogeneous antioxidant enzymes, and pathophysiological changes by selective inhibition of angiotensin II type 1 receptors in pressureoverload rats.

BACKGROUND: Constriction of the thoracic or abdominal aorta provides an experimental model of pressure-overload cardiac hypertrophy. Blockade of AT1 receptors is beneficial in preventing target-organ damage in hypertension. OBJECTIVE: To examine the effect of angiotensin II receptor antagonists on blood pressure, endogenous antioxidant enzyme and histopathological changes in pressure-overload rats. METHODS: Pressure overload was produced by abdominal aortic banding (AAB) using a blunt 22-guage needle in male rats as a model of cardiac hypertrophy. After surgery, the AAB-induced hypertension (AABIH) rats were treated with losartan 40 mg/kg/day, candesartan 10 mg/kg/day, irbesartan 10 mg/kg/day per os for 16 weeks. At 16 weeks of surgery, the rats were observed for general characteristics and mortality, and we determined non-invasive blood pressure (NIBP), endogenous antioxidant enzyme catalase and superoxide dismutase (SOD) activities, and histology of the target organs. RESULTS: In the AABIH group, significant increase in systolic blood pressure was observed from weeks 3 to 16 compared with the control group, along with reduced serum catalase and SOD activities. The treated groups showed significant reduction in systolic BP and increase in serum SOD and catalase activities. The histological changes induced in the target organs, namely heart, liver, kidneys and thoracic aorta in the AABIH rats were attenuated in the treated rats. CONCLUSION: Blockade of the AT1 receptor caused an improvement in the myocardial antioxidant reserve and decreased oxidative stress in the hypertensive rats, which was evidenced by the protection observed in the treatment groups.

Efficacy of Cinnamomum cassia Blume. in age induced sexual dysfunction of rats.

OBJECTIVE: Cinnamomum cassia has been suggested in Ayurveda for the management of sexual dysfunction. This research work was conducted to shed some light on the mechanism of action of the extract, and evaluate the efficacy of its methanol extract in age induced sexual dysfunction in male Wistar rats. Secondary objective of the project was to study the effect of treatment on sperm parameters and smooth muscle:collagen level in rat penile tissue. METHODS: Young and aged male rats were treated with methanol extract of Cinnamomum cassia at a dose of 100 mg/kg and sexual behavior was observed on 28th day in presence of female rats in estrous phase. Sildenafil was used as standard medicine. Effect of treatment was studied on epididymal sperm parameters, and Massons trichrome staining of rat penile tissues was performed to know the level of smooth muscle:collagen. RESULTS: The treatment significantly increased sexual function in aged rats that had decreased in comparison to young rats, but did not have any significant effect on sperm count, live and defective sperm percentage. However, treatment induced an increase in smooth muscle level and a decrease in collagen level in the aged rat penile tissue in comparison to that of age matched control. CONCLUSION: Based on our studies, we found that Cinnamomum cassia extract was effective in management of sexual dysfunction in aged rats and hence we propose a possible mechanism of action for Cinnamomum cassia which could be responsible for restoring sexual activity in aged rat.

Erectogenic and Aphrodisiac Effects of Butea frondosa Koenig ex Roxb. in Rats: Involvement of Enzyme Inhibition.

Butea frondosa Koenig ex Roxb. (BF) is traditionally used to manage male sexual disorders including erectile dysfunction (ED). Methanol extract of BF (bark) inhibited Rho-kinase 2 (ROCK-II) enzyme activity in vitro with an IC50 of 20.29 ± 1.83 µ g/mL. The relaxant effect of methanol extract of BF (MEBF) was studied on phenylephrine precontracted corpus cavernosum smooth muscle (CCSM) isolated from young rats. The effect of MEBF treatment on sexual behaviour of both young (5 month) and aged (24 month) rats was also studied in addition to the influence on smooth muscle, collagen (collagen-I and -III) level in penis, and sperm characteristics of young and aged rats. MEBF relaxed CCSM up to 21.77 ± 2.57% and increased sexual behavior of young and aged rats. This increase in sexual function could be attributed to ROCK-II inhibition and increase in ratio of smooth muscle to collagen level in rat penile tissue. Increased sperm production and decreased defective sperms in young and aged rats corroborate the usefulness of Butea frondosa in male infertility in addition to ED.

Screening for Rho-kinase 2 inhibitory potential of Indian medicinal plants used in management of erectile dysfunction.

THE AIM OF THE STUDY: Activation of Rho-kinase 2 (ROCK-II) results in contraction of corpus cavernosum smooth muscle and ROCK-II inhibitors relax corpus cavernosum in vitro and in vivo hence, plant extracts capable of inhibiting ROCK-II enzyme may be useful in management of erectile dysfunction (ED). The aim of the study was to screen selected Indian medicinal plants, having similar ethnopharmacological use for ROCK-II inhibition. MATERIALS AND METHODS: Some Indian medicinal plants reported as aphrodisiacs in Ayurveda and modern scientific literature were collected, authenticated and extracted. Direct methanol and successive aqueous extracts of these plants were screened for ROCK-II inhibitory activity using HTRF(®)KinEASE™ STK S2 Kit (Cisbio Bioassays). Relaxant effect of potent extract was recorded on isolated rat corpus cavernosum. RESULTS: Methanolic and successive aqueous extracts of 30 plants were screened for ROCK-II inhibition and 15 herbal extracts showed inhibition ranging between 50 and 88% at 50 µg/mL. While IC(50) of Y-27632, a standard ROCK-II inhibitor, was found to be 163.8 ± 1.2 nM. The Methanolic extract of Terminalia chebula (METC) with IC(50) value of 6.09 ± 0.17 µg/mL was found to be most potent and relaxed isolated rat corpus cavernosum significantly (p<0.01). Chebulagic and chebulinic acid of METC were found to inhibit ROCK-II and might be responsible for the inhibitory potential of the extract. The traditional use of plants like Butea frondosa, Syzygium aromaticum, Butea superba, Chlorophytum borivilianum and Mucuna pruriens, as aphrodisiacs and for male sexual disorder (MSD) might be in part due to the ROCK II inhibitory potential of these plants. CONCLUSION: Some of the Indian medicinal plants have ROCK-II inhibitory potential and those deserve further investigation.

The potential benefits of a garlic and hydrochlorothiazide combination as antihypertensive and cardioprotective in rats.

The purpose of the present study was to investigate the protective effects of combined therapy of garlic homogenate and hydrochlorothiazide (HCTZ) in animals with hypertension and myocardial damage. Three weeks of high fructose (10% w/v) in fluid to albino rats resulted in hypertension. They were subsequently administered garlic (125, 250 and 500 mg/kg, 3 weeks in separate groups) and HCTZ (10 mg/kg, 6th week) once daily in their respective groups. At the end of 6 weeks, myocardial damage was induced by subcutaneous administration of isoproterenol (175 mg/kg) for 2 consecutive days. The results showed that garlic and HCTZ increase the lactate dehydrogenase, creatinine phosphokinase, superoxide dismutase and catalase activities in heart homogenate when used concurrently or separately. Further, restoration of normal values in fluid/food intake, body weight, systolic blood pressure, cholesterol, triglycerides, glucose and histopathological scores were observed in all treated groups. Furthermore, histological disturbances and hypertension were significantly ameliorated in treated animals. Moreover, moderate dose of garlic was more effective than low dose, while a high dose of garlic was least effective in correcting electrocardiographic changes. Thus it is concluded that garlic in moderate dose (250 mg/kg) with added HCTZ possesses synergistic cardioprotective and antihypertensive properties against fructose- and isoproterenol-induced toxicities.

Modulation of hemodynamics, endogenous antioxidant enzymes, and pathophysiological changes by Angiotensin-converting enzyme inhibitors in pressure-overload rats.

INTRODUCTION: We sought to assess the role of angiotensin-converting enzyme (ACE) inhibitors on systolic blood pressure (BP), endogenous antioxidant enzymes and histopathological changes in pressure-overload rats. METHODS: Pressure overload was produced in male rats by abdominal aortic banding (AAB) using a blunt 22-gauge needle, as a model of cardiac hypertrophy. After surgery, AAB-induced hypertensive (AABIH) groups were treated with captopril 4 mg and ramipril 10 mg/kg per day p.o. for 16 weeks. At 16 weeks, rats were observed for general characteristics and mortality, non-invasive blood pressure (NIBP) and endogenous antioxidant enzyme catalase and superoxide dismutase (SOD) activity and histological evaluation of target organs. RESULTS: In the AABIH group a significant increase in systolic BP was observed in week 3 (149.3 ± 0.821) and persisted until week 16, along with lower levels of serum catalase (144.7 ± 2.204) and SOD (12.92 ± 0.4601) activity compared to the control group. Captopril and ramipril treated groups showed a significantly smaller increase in systolic BP (25.47 ± 3.685, 20.21 ± 3.306) and greater serum SOD (27.33 ± 2.338, 28.95 ± 1.143) and catalase (181.7 ± 8.407, 187.9 ± 8.497) activity, respectively, than the hypertensive rats. The histological changes induced in target organs (heart, liver, kidneys and thoracic aorta) in AABIH rats were attenuated in treated rats. CONCLUSIONS: ACE-inhibition causes an improvement in myocardial antioxidant reserve, reduces oxidative stress, and prevents pathophysiological alterations, while showing a trend for potential target organ protection in hypertensive rats.

Potential of Crocus sativus (saffron) and its constituent, crocin, as hypolipidemic and antioxidant in rats.

The aim of the present study was to evaluate the hypolipidemic and antioxidant potential of saffron and its active constituent, crocin, in hyperlipidemic rats. The animals fed either with normal fat diet or high fat diet were administered orally saffron (25, 50, and 100 mg/kg) or crocin (4.84, 9.69, and 19.38 mg/kg) in their respective groups for five consecutive days. Biochemical estimations of triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), alkaline phosphatase (ALP), aspartate transaminase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA), glutathione peroxidase enzyme activity (GSHPx), total glutathione (GSH), and oxidized glutathione (GSSG) in serum and superoxide dismutase (SOD), catalase (CAT), thiobarbituric acid reactive species (TBARS), ferric reducing/antioxidant power (FRAP), and total sulfhydryl (SH) groups in liver tissue homogenate were carried out. Both saffron and crocin were effective in decreasing the elevated levels of TG, TC, ALP, AST, ALT, MDA, GSHPx, GSH, and GSSG in serum and increasing SOD, CAT, FRAP, and SH values in liver tissue with reduction in TBARS. The saffron was found to be superior to crocin indicating the involvement of other potential constituents of saffron apart from crocin for its synergistic behavior of quenching the free radicals and ameliorating the damages of hyperlipidemia.

The potential for interaction of hydrochlorothiazide with garlic in rats.

The present study was undertaken to determine the pharmacokinetic and pharmacodynamic interaction of hydrochlorothiazide (HCTZ) with garlic homogenate (GH), in rats. The influence of garlic on pharmacokinetics of HCTZ was studied by HPLC method, while pharmacodynamic interaction was studied using diuretic activity, ECG and BP changes and isoproterenol (ISO) induced myocardial injury. HCTZ was given orally at 10mg/kg and GH was administered at three different doses of 125, 250 and 500 mg/kg, p.o. The CK-MB, LDH, SOD, catalase and histopathological studies were carried out. The administration of HCTZ in GH pretreated rats found to decrease the QRS duration, RR interval, QT segment, systolic blood pressure, heart rate, serum potassium level, serum LDH and serum CK-MB activities significantly. The diuretic effect of HCTZ was significantly increased in presence of GH; however, kaliuresis was significantly reduced in presence of GH 250 mg/kg. Histopathological studies of heart tissue reveal the protective effect of GH 250 mg/kg in presence or absence of HCTZ during ISO stress to myocardium. The pharmacokinetic studies show that GH increases the bioavailability and half-life, along with decrease in clearance and elimination rate of HCTZ when administered orally. It was concluded that careful addition of garlic in moderate doses might result in beneficial effect during treatment of hypertension in patients with myocardial stress as garlic causes substantial fall in excretion of potassium when compared to HCTZ alone treatment in rats. This could be important in reducing the dose of HCTZ to achieve enhanced therapeutic effect with minimal adverse effect.