Blood pressure-lowering and cardiovascular effects of plumbagin in rats: An insight into the underlying mechanisms.

Background: Plumbagin, a natural phenolic compound is investigated for response against blood pressure and vascular reactivity. Methodology: Blood pressure lowering effects were observed by in-vivo invasive evaluation in normotensive rats, and in-vitro experimentation to measure changes of tension in isolated rat aorta and contractility in atria. Results: The percentage decrease in mean arterial pressure (MAP) observed with plumbagin intravenously at doses of 0.1, 0.5, 1, 5, 10 â€‹µg/kg in normotensive rats was 7.16 â€‹± â€‹2.35, 15.5 â€‹± â€‹5.62, 19.5 â€‹± â€‹5.27, 26 â€‹± â€‹6.67, 34.33 â€‹± â€‹8.80, respectively. Plumbagin exerted vasorelaxant effects in rat aorta, unaffected by the removal of vascular endothelium, and L-NAME and methylene blue pretreatment. Plumbagin completely inhibited phenylephrine (1 â€‹µM) and High K+ (80 â€‹mM) induced contractions. Similar to a Ca+2 channel antagonist, plumbagin caused a rightward shift in the Ca+2 concentration-response-curves (CRCs), resembling nifedipine. Pre-incubation with plumbagin, significantly suppressed contractions induced by phenylephrine in Ca+2-free medium via disrupting Ca+2 release from intracellular stores. No change in vasorelaxant response was observed with the addition of potassium channel blockers, TEA and BaCl2. In rat atrial strips, plumbagin exerted significant negative inotropic and chronotropic effects. No significant change was observed with atropine and atenolol pretreatment, so the effect appeared independent of muscarinic and beta-adrenergic receptors. Conclusion: This study suggests the blood pressure lowering effects of plumbagin. That could be contributed by a decrease in vascular resistance via calcium antagonism, interferences in calcium efflux, and depressive effects on the rate and force of cardiac contraction. Further studies would be necessary to probe deeper into the underlying mechanisms.

Pharmacological evaluation of cardioprotective potential of Berberis orthobotrys Bien.ex Aitch.

The resurgence of scrutiny in plant-based medicine is mainly due to the current widespread belief that "green medicine" is safe and more dependable than the expensive synthetic drugs. The current study was focused to evaluate the anti-myocardial ischemic potential of Berberis orthobotrys Bien ex Aitch against chemically induced myocardial ischemia in animal models. Myocardial ischemia was instigated in Sprague Dawley rats of either sex (250-450g) by administration of Isoproterenol (ISO) and doxorubicin (DOX) at doses of 25mg/kg b.w and 15mg/kg b.w. respectively. The protective effect of the plant extract was explored by pretreating a group of animals with aqueous methanolic extract of Berberis orthobotrys roots at a dose of 50mg/kg b.w. (orally) for 10 days in ISO-ischemic model while for doxorubicin ischemic model; the study was conducted for 14 days. The findings of the study revealed that serum levels of cardiac marker enzymes were significantly increased (p<0.0001) followed by the administration of Isoproterenol and doxorubicin whereas the pretreatment with aqueous methanolic plant extract had significantly (p<0.0001) prevented the rise in the same, as compared to both intoxicated groups. The statistical analysis of the study led to the conclusion that Berberis orthobotrys possesses cardio protective potential against chemically induced myocardial ischemia.

Cardioprotective potential of Thymus linearis Benth.

In developing countries, myocardial ischemia and the resulting impairments in heart function are the leading cause of illness and mortality. Thymus linearis Benth has been used as an antibiotic, antioxidant, and antihypertensive agent for centuries. The goal of this investigation was to see if Thymus linearis could protect isoproterenol and doxorubicin-induced myocardial ischemia in vivo at doses of 25 mg/kg s.c. and 15 mg/kg i.p., respectively. The level of cardiac enzymes (CK-MB, LDH, and AST) in the serum isolated from the experimental animal's blood was used to determine myocardial ischemia. The anti-ischemic potential was assessed by comparing the levels of the aforementioned cardiac biomarkers in the intoxicated and treated animal groups. The study found substantial increase (p0.0001) in the serum levels of CK-MB, LDH, AST when compared to intoxicated groups, while pretreatment of animals with crude extract of Thymus linearis significantly reduced the rise in serum cardiac indicators. The findings of the study indicated that the aqueous methanolic Thymus linearis crude extract has cardioprotective potential against Isoproterenol and Doxorubicin-induced cardiac necrosis in rats.

Appraisal of hypotensive effect of natural monoterpene: Bornyl acetate and in-silico molecular docking analysis.

The modern trend of research is highly focused on finding new bioactive molecules from medicinal plants. As a functional bicyclic monoterpene, Bornyl acetate (BA) has displayed antioxidant and anti-inflammatory properties in different types of cells and tissues. The purpose of this research was to evaluate the probable hypotensive effect of BA, an underlying mechanism(s) backboned by in-silico studies. Mean arterial pressure and heart rate were recorded via invasive blood pressure measuring technique in normotensive Sprague-Dawley rats following the administration of BA (1-80mg/kg). Docking studies were carried out with various targets involved in the pathophysiology of hypertension.RO5 and ADMET properties were also evaluated. In the current study dose-dependent reduction in systolic, diastolic and mean arterial pressure was observed. Pretreatment with atropine and captopril significantly (p<0.001) reduced the hypotensive effect produced by BA. On the other hand docking studies showed pronounced interactions with M2 mAch receptor in an agonistic way and ACE protein in an antagonistic way. BA justified all cut-off limits of RO5 and had an acceptable predicted computational toxicity profile. Results postulate that dose-dependent hypotensive effect of BA is mediated through the muscarinic pathway and ACE inhibitory activity corresponding well with findings of in-silico studies.

Phytochemical analysis and hypotensive potential of Teucrium stocksianum Boiss.

Teucrium stocksianum Boiss. is an aromatic perennial herb. It has long been used traditionally in the treatment of hypertension in northern areas of Pakistan. The aim of this study was to evaluate its folkloric claim as hypotensive plant, phytochemical analysis and to predict potential phytoconstituent through in-silico studies. Hypotensive effect was investigated in anesthetized normotensive Sprague-Dawley rats. Recording of chronotropic and inotropic effect of plant extract in isolated right atria was done using tissue organ bath technique. Further, phytochemical characterization was performed through LC-MS. Whereas docking studies were carried out against M2 mAchR and Ca2+ Channel receptor. Dose dependent reduction in systolic, diastolic, mean arterial pressure and heart rate was observed. Pretreatment with atropine and amlodipine significantly (p<0.001) reduced the hypotensive and negative chronotropic and inotropic effect. Phytochemical studies revealed the presence of twenty active compounds including Luteolin, Sarmentosin epoxide and Quinic acid. Docking studies showed pronounced interactions of majority of these phytochemicals with M2 mAch receptor in agonistic way and Ca2+ Channel receptor in antagonistic way. Results speculate that dose dependent hypotensive and bradycardia effect of Teucrium stocksianum are mediated through muscarinic pathway and Ca2+antagonism and is also well predicted by in-silico studies.

ANTI-INFLAMMATORY, ANALGESIC AND ANTIPYRETIC ACTIVITIES OF THE AQUEOUS METHANOLIC EXTRACT OF BERBERIS CALLIOBOTRYS IN ALBINO MICE.

The aqueous methanolic extract of stem part of Berberis calliobotiys (AMEBC) was evaluated for anti-inflammatory, analgesic and antipyretic activities in albino mice. Anti-inflammatory activity was evaluated by using carrageenan and albumin induced paw edema, while the analgesic effect was assessed by using formalin-induced paw licking and acetic acid induced abdominal writhing in mice. The brewer's yeast-induced pyrexia model was used for antipyretic investigation. Ibuprofen (40 mg/kg) was used as a standard drug in all the three models. The aqueous methanolic extract at both (250 mg/kg and 500 mg/kg) doses, showed highly significant (p < 0.001) reduction in paw edema induced by carrageenan and albumin. Moreover, the aqueous methanolic extract also highly significantly (p < 0.001) reduced (87%) the formalin-induced paw licking at 500 mg/kg. The highly significant (p < 0.001) reductions (24.48% and 37.9%) was also observed in the number of writhings. Furthermore, aqueous methanolic extract also demonstrated significant (p < 0.001) antipyretic activity against yeast induced pyrexia. The maximum effect was observed in all the three parameters at 500 mg/kg dose. The results suggest a potential benefit of the aqueous methanolic extract of Berbeis calliobotrys in treating conditions associated with inflammation, pain and fever.

PHYTOCHEMICAL ANALYSIS AND CARDIOTONIC ACTIVITY OF METHANOLIC EXTRACT OF RANUNCULUS MURICATUS LINN. IN ISOLATED RABBIT HEART.

Ranunculus muricatus Linn. (RML) have been traditionally used for the treatment of various cardiovascular disorders. The aim of present study was to evaluate their cardiovascular effects in isolated perfused rabbit heart. The methanolic extract of RML was prepared by cold maceration process. The methanolic extract of RML (1 ng to 10 mg) was used to determine the percentage change in force of contraction (FC), heart rate (HR) and perfusion pressure (PP) by using Langendorff's Perfused Heart Apparatus. The PP, FC and HR of isolated rabbit heart were measured by power lab data acquisition system. Moreover, phytochemical analysis and acute toxicity study were also performed. The methanolic extract at the doses from I ng to 10 mg exhibited a significant increase in perfusion pressure and force of contraction. Moreover, the crude extract of RML revealed a significant increase in heart rate at doses from 1 ng to µg. The maximum rise in all the thee parameters was observed at 1 µg and 1 ng, respectively In another study, the melhanoliC extract was tested in the presence of propranolol and verapamil on isolated perfused rabbit heart. The study shown that the increase in HR and FC produced by the plant extracts was significantly reduced in the presence of propranolol whereas PP remained significantly raised even in the presence of propranolol. However, in the presence of verapamil, this increased PP was significantly reversed to a decrease while a significant positive inotropic and chronotropic effects were observed. It is concluded that the cardiotonic activity of methanolic extract of RML might be due certain cardio active chemical compounds. Further studies are needed to isolate these pharmacologically active phytochemical constituents and elucidate their exact mechanism of action.

EVALUATION OF ANTI-DIABETIC EFFECTS OF POLY-HERBAL PRODUCT "DIABETIC BAL" IN ALLOXAN-INDUCED DIABETIC RABBITS.

The current study was conducted to evaluate the anti-diabetic effect of polyherbal product "diabetic bal" in normal and alloxan induced diabetic rabbits. Glibenclamide was used as standard drug. Diabetes was induced by single i.v. injection of 150 mg/kg b.w. of alloxan monohydrate in rabbits. "Diabetic bal" (250 and 500 mg/kg) significantly decreased the blood glucose level both in normal and diabetic rabbits in dose dependent manner. In oral glucose tolerance test, "Diabetic bal" demonstrated a significant inhibitory effect on rise of blood glucose level compared to control. "Diabetic bal" showed synergistic anti-hyperglycemic effect with dif- ferent units of insulin in diabetic rabbits. The "diabetic bal" decreased the glucose level and prevented the weight loss of diabetic rabbits as compared to control for an extended period of one month. It caused a significant increase (p < 0.001) in the insulin level of treated diabetic rabbits in 30 days study. In addition AST, ALT, ALP, cholesterol, LDLs, VLDLs and triglyceride level were significantly reduced whereas HDLs level was sig- nificantly elevated in diabetic rabbits with 500 mg/kg dose. The herbal product did not cause any significant change in CBC as compared to normal control in diabetic rabbits for one month. It is conceivable; therefore, that "diabetic bal" is effective in diabetes and its associated complications which support its use in folklore.

Urinary tract infections associated with multidrug resistant enteric bacilli: characterization and genetical studies.

Urinary tract infections (UTIs) are among the most commonly prevalent infections in clinical practice. Escherichia coli is the causative agent in about 85% of community-acquired UTIs, followed by Klebsiella that accounts for 6 to 17% of such infections. Present study is based on the isolation-identification and antibiotic resistance pattern of about 60 indigenous bacterial isolates from UTI patients. Prevalence rates were consistent with those from major recent studies reported in the literature, i.e. 73% isolates were identified as E. coli, 16% as K. pneumoniae and 11% as Proteus sp. Bases of identification included morpho-cultural and biochemical characteristics. To assess the breadth of multidrug resistance among these isolates, culture medium incorporation method was employed using ampicillin, fosfomycin, chloramphenicol, tetracycline, and three aminoglycosides (kanamycin, gentamicin, and streptomycin). Of these isolates, 30% offered multidrug resistance to three or more agents. Among multidrug resistant isolates, 100% were resistant to ampicillin, 47% to streptomycin, 41% to chloramphenicol, gentamicin and tetracycline, 35% offered resistance to kanamycin while only 6% showed resistance to fosfomycin. After curing treatment with acridine orange, some of the isolates lost their resistance, thereby indicating the extrachromosomal location of the resistance determinants. Plasmid DNA (bearing multidrug resistant genes) was isolated from the uncured cells, and was stably transformed into the competent cured recipient cells.