Gene ontology enrichment analysis of PPAR-γ modulators from Cassia glauca in diabetes mellitus.

BACKGROUND: PPAR-γ has an integrative role in the management of insulin resistance; ligands of this receptor have emerged as potent insulin sensitizers and may modulate proteins involved in the pathogenesis of diabetes mellitus. Hence the present study is aimed to identify PPAR-γ modulators from the plant Cassia glauca and predict the ontology enrichment analysis utilizing various in-silico tools. METHODS: ChEBI database was used to mine the phytoconstituents present in the plant C. glauca, SwissTargetPrediction database was used to identify the targets, and scrutinizing of phytoconstituents modulating PPAR-γ was performed. Autodock4.0 was used to dock phytoconstituent ligands with the target PPAR-γ. Multiple open-source databases and in-silico tools were utilized to predict the drug-likeness characters and predict side effects of the phytoconstituents modulating PPAR-γ and STRING database was used to construct a network between the modulated genes. RESULTS: Twenty-four phytoconstituents were identified from the plant Cassia glauca from which four were found to modulate PPAR-γ, sennoside was predicted to have the greatest drug-likeness score and a significantly less side effect whereas diphenyl sulfone was predicted to show hepatotoxicity with the greatest pharmacological activity of 0.815. [epicatechin-(4beta- > 8)]5-epicatechin showed the lowest binding affinity with target PPAR-γ i.e. -8.6 kcal/mol and possessing a positive drug-likeness score with no side effect data. CONCLUSION: Bioctives were found free from probable side effects leaving out diphenyl sulfone having a prediction of hepatotoxicity, the anti-diabetic property of the plant may be due to the presence of [epicatechin-(4beta- > 8)]5-epicatechin which needs further validation by in-vitro and in-vivo protocols.

Gene set enrichment analysis of α-amylase and α-glucosidase inhibitors of Cassia glauca.

BACKGROUND: The present study aimed to evaluate in vitro α-amylase and α-glucosidase inhibitory activity of various extracts of Cassia glauca, predict the binding affinity of multiple phytoconstituents with both enzymes via in silico molecular docking and identify the probably modulated pathways by the lead hit. METHODS: Different extracts of Cassia glauca i.e. acetone, ethanol, and aqueous extracts were evaluated for α-amylase and α-glucosidase inhibitory activity using in vitro method in which starch and 4-Nitrophenyl ß-D-glucopyranoside were used as substrate respectively. Similarly, the docking study was performed using autodock4 to predict the binding affinity of phytoconstituents with α-amylase and α-glucosidase. After docking, ten different poses were obtained for the ligand molecule. Among them, the pose of ligand molecule with the lowest binding energy was visualized in Discovery Studio 2019. RESULTS AND CONCLUSION: Among the multiple extracts, the aqueous extract showed the highest α-amylase (IC50:652.10 ± 20.09) and α-glucosidase (IC50:482.46 ± 8.70) inhibitory activity. Similarly, cassiaoccidentalin B was predicted to have the highest binding affinity with both enzymes. The potency of aqueous extract to inhibit α-amylase and α-glucosidase could be due to multiple water-soluble compounds like saponins, flavonoids, and glycosides.

Induction of apoptosis in A431 skin cancer cells by Cissus quadrangularis Linn stem extract by altering Bax-Bcl-2 ratio, release of cytochrome c from mitochondria and PARP cleavage.

Skin is generally damaged through genetic and environmental factors such as smoking, exposure to xenobiotics, heat, hormonal changes, and ultraviolet light. These factors can cause skin diseases. Cissus quadrangularis Linn. (CQ) has been used in folk medicine for the treatment of skin diseases since ancient times. Taking in to consideration the medicinal properties exhibited by this genus, it was decided to investigate the anti-cancer activity of CQ. Extracts obtained from CQ and their phenolic contents were subjected to in vitro evaluation of anticancer activity by using A431 (skin epidermoid carcinoma, human) cell line. The A431 cells were treated with different extracts of CQ in a dose dependent manner. Out of five extracts, the acetone extract demonstrated significant anti-cancer activity in the A431 cell line. Hexane, chloroform, ethyl acetate and methanol extracts also exhibited cytotoxicity but to a comparatively lesser extent than the acetone extract. The GI(50) value of the acetone extract was found to be 8 µg mL(-1), whereas GI(50) value of purified fraction of acetone extract, termed as AFCQ (active acetone fraction of CQ) with respect to A431 cells, was found to be 4.8 µg mL(-1). Furthermore, the mechanism of anticancer activity exhibited by AFCQ was investigated by comparing its effect with the standard anticancer drug Doxorubicin (DOX) by evaluating the status of apoptotic markers after treatment of A431 cells with AFCQ and DOX. Bax-Bcl-2 ratio along with the release of cytochrome c from mitochondria to cytoplasm, which is a hallmark of apoptosis, was also evaluated. Cleavage of PARP revealed that AFCQ induces apoptosis in A431 cells with reference to DOX.

Evaluation of Cissus quadrangularis extracts as an inhibitor of COX, 5-LOX, and proinflammatory mediators.

ETHNOPHARMACOLOGICAL RELEVANCE: Cissus quadrangularis is an ancient medicinal plant. It is an active ingredient of one Ayurvedic formula called "Laksha Gogglu". Its stem is used in food preparation in India. Traditionally it is used to treat various diseases like asthma, indigestion, ear diseases, irregular menstruation, skin diseases, piles, fractured bones, etc. AIM OF THE STUDY: This study aimed to evaluate the ability of the plant extracts to inhibit cycloxygenase (COX-1), cycloxygenase (COX-2), and 5-lipoxygenase (5-LOX) enzyme activity. Western blot analysis was also carried out in the quest to determine the effect of active acetone fraction of Cissus quadrangularis (AFCQ) on proinflammatory mediators as acetone extract is found to be the most effective in this study. MATERIALS AND METHODS: The differential extract of the stem were tested for enzyme inhibition of COX and 5-LOX using spectroscopic and polarigraphic method. Effective acetone extract was partially purified by silica column, one of the active fraction showed dual inhibition against COX and 5-LOX. Western blotting shows downregulation of proinflammatory mediators as well as upregulation of phase-II enzymes. RESULTS: AFCQ extract showed COX and 5-LOX inhibition with IC(50) values of 7 µg/ml, 0.4 µg/ml, and 20 µg/ml for COX-1, COX-2 and 5-LOX respectively. It also showed anti-inflammatory activity on RAW 264.7 cell line with IC(50) value 65 µg/ml. In addition to this it is showing inhibition of proinflammatory mediators like iNOS and TNFα, along with translocation of Nrf-2 and upregulation of HO-1. CONCLUSION: AFCQ is a COX and 5-LOX inhibitor isolated from the stems of Cissus quadrangularis. It is also effectively downregulate the iNOS, TNFα, and upregulation of HO-1.

Antihyperlipidemic activity of Salacia chinensis root extracts in triton-induced and atherogenic diet-induced hyperlipidemic rats.

OBJECTIVES: The aim of this study has been to investigate the possible antihyperlipidemic effect of Salacia chinensis root extract in triton (400mg/kg b.w.)-induced and atherogenic diet-induced hyperlipidemic rats. MATERIALS AND METHODS: Petroleum ether (60-80°C), chloroform, ethanol and aqueous extracts of Salacia chinensis roots were evaluated for antihyperlipidemic activity in triton- and atherogenic diet-induced hyperlipidemic rats. A comparison was also made between the action of Salacia chinensis root extract and a known antihyperlipidemic drug simvastatin (10 mg/kg body wt.). The results of the study were expressed as mean± S.E. and data was analyzed by using one way analysis of variance test (ANOVA) followed by Dunnett's t-test for multiple comparisons. Values with P < 0.05 were considered as significant. RESULTS: Oral administration of 500 mg/kg body wt. of the chloroform extract and alcoholic extract of Salacia chinensis root exhibited a significant reduction (P<0.01) in serum lipid parameters like total cholesterol, triglycerides, low density lipoprotein (LDL), very low density lipopreotein (VLDL) and increase in high density lipoprotein (HDL) in hyperlipidemic rats of both models as compared to hyperlipidemic control statistically. These extracts were found to possess better antihyperlipidemic potential as compared to pet ether and aqueous extract. CONCLUSIONS: Our results demonstrated that chloroform and alcoholic extract of Salacia chinensis roots possessed significant antihyperlipidemic activity and hence it could be a potential herbal medicine as adjuvant with existing therapy for the treatment of hyperlipidemia.

Antidiabetic activity of Crateva nurvala stem bark extracts in alloxan-induced diabetic rats.

OBJECTIVES: The aim of this study was to investigate the antidiabetic activity of Crateva nurvala stem bark (family: Capparidaceae) extracts in alloxan-induced diabetic albino rats. A comparison was made between the action of different extracts of C. nurvala and a known antidiabetic drug glibenclamide (600 µg/kg b. wt.). An oral glucose tolerance test (OGTT) was also performed in diabetic rats. MATERIALS AND METHODS: The petroleum ether, chloroform, alcohol, and aqueous extracts of C. nurvala stem bark were obtained by simple maceration method and were subjected to standardization by following pharmacognostical and phytochemical screening methods. Dose selection was made on the basis of acute oral toxicity study (50-5000 mg/kg b. wt.) as per Organization for Economic Co-operation and Development (OECD) guidelines. RESULTS AND CONCLUSIONS: C. nurvala petroleum ether extract (CNPEE) and ethanolic extract (CNEE) showed significant (P< 0.001) antidiabetic activities. In alloxan-induced model, blood glucose level of these extracts on seventh day of study were CNPEE (126.33±13.703 mg/dl) and CNEE (126.66±13.012 mg/dl) when compared with diabetic control (413.50±4.752 mg/dl) and chloroform extract (320.83±13.516 mg/dl). In OGGT model (glucose loaded rats), CNPEE showed a glucose level of 178.83±3.070 mg/dl after 30 min and 131.66±2.486 mg/dl after 90 min, whereas CNEE showed 173.66±4.224 mg/dl after 30 min and 115.50±3.394 mg/dl after 90 min. These extracts also prevented body weight loss in diabetic rats. The drug has the potential to act as an antidiabetic drug.

Antidiabetic activity of Pongamia pinnata leaf extracts in alloxan-induced diabetic rats.

The antidiabetic activity of Pongamia pinnata ( Family: Leguminosae) leaf extracts was investigated in alloxan-induced diabetic albino rats. A comparison was made between the action of different extracts of P. pinnata and a known antidiabetic drug glibenclamide (600 µg/kg b. wt.). An oral glucose tolerance test (OGTT) was also performed in experimental diabetic rats. The petroleum ether, chloroform, alcohol and aqueous extracts of P. pinnata were obtained by simple maceration method and were subjected to standardization using pharmacognostical and phytochemical screening methods. Dose selection was made on the basis of acute oral toxicity study (50-5000 mg/kg b. w.) as per OECD guidelines. P. pinnata ethanolic extract (PPEE) and aqueous extract (PPAE) showed significant (P < 0.001) antidiabetic activity. In alloxan-induced model, blood glucose levels of these extracts on 7th day of the study were 155.83 ± 11.211mg/dl (PPEE) and 132.00 ± 4.955mg/dl (PPAE) in comparison of diabetic control (413.50 ± 4.752mg/dl) and chloroform extract (210.83 ± 14.912mg/dl). In glucose loaded rats, PPEE exhibited glucose level of 164.50 ± 6.350mg/dl after 30 min and 156.50 ± 4.089mg/dl after 90 min, whereas the levels in PPAE treated animals were 176 ± 3.724mg/dl after 30 min and 110.33 ± 6.687mg/dl after 90 min. These extracts also prevented body weight loss in diabetic rats. The drug has the potential to act as an antidiabetic drug.

A Study of hepatoprotective activity of Hedyotis corymbosa. Linn, in albino rats.

Hedyotis corymbosa Linn is spreading, suffruticose annual, belongs to family Rubiaceae frequently met with in field through out India, usually during rainy season. This plant is used for their medicinal properties as a folk medicine to treat jaundice, mouth wash in toothache. Hence the present study was aimed to investigate the hepatoprotective activity of ethanolic extract of Hedyotis corymbosa which was separated in to different fractions against carbon tetrachloride intoxification. The results indicate that, Intoxification with CCl(4) increase the levels of SGOT and SGPT. The elevated levels of SGOT and SGPTwere significantly decreased by ether and butanol fractions at P<0.001 and butanone and ethanol at p<0.05, where as petroleum ether and ethyl acetate did not shown any significant reduction in the level of SGOT and SGPT.

Development and evaluation of hepatoprotective polyherbal formulation containing some indigenous medicinal plants.

The present study explores the hepatoprotective activity of various extracts of Ferula asafoetida, Momordica charantia Linn and Nardostachys jatamansi against experimental hepatotoxicity. Polyherbal suspensions were formulated using extracts showing significant activity and evaluated for both physicochemical and hepatoprotective activity in comparison with LIV-52 as standard. Petroleum ether (60-80 degrees ), chloroform, benzene, ethanol and aqueous extracts of Ferula asafetida, Momordica charantia Linn and Nardostachys jatamansi were evaluated for hepatoprotective activity against carbon tetrachloride-induced liver toxicity in Wistar rats. Polyherbal suspensions were prepared by the trituration method using a suspending agent and other excipients. Formulation F3 has shown significant hepatoprotective effect by reducing the elevated serum enzyme levels such as glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and alkaline phosphatase. These biochemical observations were supplemented by histopathological examination of liver sections. Various parameters evaluated for all formulations were within the official specifications. Experimental data suggested that treatment with formulation F3 enhances the recovery from carbon tetra chloride-induced hepatotoxicity. From these results it may be concluded that the F3 formulation (containing chloroform, petroleum ether and aqueous extracts of Ferula asafetida, petroleum ether and ethanol extracts of Momordica charantia Linn. and petroleum ether and ethanol extracts of Nardostachys jatamansi) demonstrated significant hepatoprotective activity, that might be due to combined effect of all these extracts.

Effect of substrate feeding on production of fructosyltransferase by Penicillium purpurogenum

Penicillium purpurogenum was found to produce both extracellular and intracellular fructosyltransferase. The organism could also produce sucrose hydrolytic enzyme. Sucrose was found to be the best carbon source for fructosyltransferase production. Maximum intracellular and extracellular fructosyltransferase production was observed after 3rd and 4th day of cultivation, respectively. The enzyme activity was optimum at temperature of 55°C and pH 5.5. The addition of amino acids, like leucine induced slightly the extracellular fructosyltransferase production, where as histidine and leucine had little inductive effect on intracellular fructosyltransferase production. Enhanced production of fructosyltransferase by Penicillium purpurogenum was observed when sucrose content was restored by additional sucrose feeding to the cultivation medium during production period.

Penicillium purpurogenum foi identificado como produtor extracellular e intracelular de frutosiltransferase. O microrganismo também é capaz de produzir uma enzima hidrolítica de sacarose. Sacarose foi identificada como a melhor fonte de carbono para a produção de frutosiltransferase. A produção máxima de frutosiltransferase extracelular e intracelular foi observada após o 3° e 4° dia de cultivo, respectivamente. Atividade ótima da enzima foi observada na temperatura de 55° C e pH 5,5. A adição de amino ácidos, como leucina, induziu ligeiro aumento na produção extracelular de frutosiltransferase, enquanto que histidina e leucina induziram um pequeno aumento na produção da frutosiltransferase intracelular. Observou-se aumento na produção de frutosiltransferase por Penicillium purpurogenum quando a quantidade de sacarose era restaurada por adição do carboidrato ao meio de cultura durante o período de produção.

Control and prevention of rat fever (Leptospirosis) outbreak in six villages of Raichur district, Karnataka.

The study describes an attempt to record leptospirosis in Raichur taluk/district, in Karnataka, by serological test such as microscopic test and IgM by ELISA. A house to house survey was done in six villages of Krishna river basin. Cases were interviewed regarding chief complaints like, fever, headache and oliguria, age, sex and treatment given with diclofenac, doxycycline, tetracycline and vitamin B complex. A total of 1516 cases were treated. The age of the patients ranged between 10 and 71 years. Most of them were agricultural workers. Out of 15 blood samples 12 samples sent to DHO Office, 3 were negative for leptospirosis, the density of rats were increased in all villages, the mode of transmission was food and water contamination, duration of incubation period was 5 to 10 days. Health education, for the community was undertaken to take measures against rats. Causative agent may be Leptospirosis interrogans, 3 cases were referred to Civil Hospital, Raichur and Navodaya Medical College, Raichur. Community participation was excellent. This study showed the presence of leptospirosis among the community of 6 villages, the disease is posing health hazards for agricultural workers in Raichur taluka villages.

Biodegradable microparticulate system of captopril.

Albumin microparticles have found many applications in diagnosis and treatment in recent years and more than 100 diagnostic agents and drugs have been incorporated into albumin microparticles. In the present study, bovine serum albumin (BSA) based microparticles bearing captopril were prepared by an emulsification-heat stabilization technique. Four batches of microparticles with varying ratio of drug and polymer were prepared. The prepared microparticles were studied for drug loading, particle size distribution, in vitro release characteristics, in vivo tissue distribution study and stability studies. The microparticles had mean diameter between 2 and 11 microm of which more than 70% were below 5 microm and incorporation efficiency of 41-63% was obtained. In vitro release profile for formulations containing captopril-loaded albumin microparticles with heat stabilizing technique shows slow controlled release up to 24 h. The in vivo result of drug-loaded microparticles showed preferential drug targeting to liver followed by lungs, kidneys and spleen. Stability studies showed that maximum drug content and closest in vitro release to initial data were found in the formulation stored at 4 degrees C. In the present study, captopril-loaded BSA microparticles were prepared and targeted to various organs to a satisfactory level and were found to be stable at 4 degrees C.

Production of a-Glucosidase by Penicillium purpurogenum

Verificou-se que Penicillium purpurogenum foi capaz de produzir a-glucosidase intracelular, com atividade máxima sobre a sacarose. Vários parâmetros culturais para producão da enzima foram otimizados. Verificou-se que a producão máxima da enzima ocorria após 96 h de cultivo a 30º;C. A adicão dos amino-ácidos histidina e cisteína induziram a síntese da enzima até certo ponto. A temperatura e pH ótimos para atividade da enzima foram 50º;C e 5,5, respectivamente. A a-glucosidase de Penicillium purpurogenum foi estável em pH 2,0, o que torna a enzima ideal para uso na indústria de sucos de frutas e vinhos.

Ethno - veterinary Plants of Nadurbar district of Maharashtra, India.

A survey of medicinal plants of Nandurbar district of Maharashtra, India in regard to their veterinary uses, has been done. While collecting the data, special emphasis is given to the foot and Mouth disease, Haemorrhagic Septicaemia, Maggotted Wounds, Retention of Placcenta, Timpany and Worms, which are the most common animal ailment in the district. After short listing, about 29 plant species are found to be in regular use by various tribal veterinary doctors in the district.