Search

Background: Lavandula stoechas is the main member of Labiatae (Lamiaceae) family. People use this medicinal plant in the treatment of several diseases around the world. The purpose of this work was to evaluate the cytotoxic effect of different fractions like ethanol, ethyl acetate and n-hexane from methanol extract of Lavandula stoechas aerial parts on HepG2 cell line and analysis of chemical composition of the most active fraction of the Lavandula stoechas aerial parts. Methods: Methanolic extract was prepared by cold maceration. Fractions from extract were prepared in solvents of increasing polarity i.e. n-hexane, ethyl acetate and ethanol. In order to evaluate the cytotoxic effect of Lavandula stoechas, MTT assay method was used. For this purpose, HepG2 cells line were treated with the above mentioned Lavandula stoechas aerial parts fractions with different concentrations 10, 25, 50, 100, 250, 500 and 1000 μg/ml. The cells without treatment were served as a control. Results: The result of this study showed that ethanolic fraction showed major reduction in % cell survival compared to other fractions. These results showed that Lavandula stoechas Ethanolic fraction was highly inhibitory. Further, phyto chemical analysis of ethanolic fraction was carried out using GC-MS technique and the reports showed Lupeol, Phytol, α-Cadinol, Lup-20(29)-en-3-one, hydrocoumarin, Lup-20(29)-en-3-one. Other compounds included fatty acids and their esters. Some of these compounds are being first time reported here from this plant. Conclusion: MTT assay showed morphological changes, which clearly support Lavandula stoecha ethanolic fraction possesses anticancer effect which may be due to the presence of phytosterols.

Acute and subacute toxicity screening of novel entrants in the stream of polyherbal formulations opens new doors towards the scientific approach of establishing them in the clinical market. Toxicity profiling asserts the humongous pharmacological potential that the natural herbs hold and establishes their safety profile. To exemplify this statement, this study further deals with acute and subacute toxicity studies of an olive oil-based polyherbal combination (PHC). This combination has been developed with the view that it proves to be clinically effective in diabetic cardiomyopathy and neuropathy. However, until now, the acute and subacute toxicity studies have been done on the developed PHC, and experimentally effective dose combinations have been identified. The follow-up part of this research includes the screening of the PHC against specific in vivo screening models in its initial stages. This research paper strictly summarises the acute and subacute profile of the salubrious polyherbal combination. Three herbs with strong literature background were selected: Tinospora cordifolia, Withania somnifera and Boerrhavia diffusa; and their crude extracts were prepared. The reported ED50 values of each of these plants were selected and mixed in 5 different combinations and subjected to Acute Toxicity studies. It was followed by the 28-days subacute toxicity screening of 9 different combinations that were elucidated from the acute toxicity study results. The findings were supported with recovery group studies to conform to any late toxicity symptoms of the polyherbal combination. The findings of this study helped in reaching some pathbreaking conclusions on the polyherbal combination designed.

Obesity is an alarming sign and considered as a threat word wide. Since it not only hurt the human body but plays as a basis for other serious diseases like cardiovascular and many more. The 50% hydro-ethanolic extract of Dalbergia latifolia bark (D. latifolia) (DLBE; %yield = 16.34) and methanolic extract (4.32%) of D. latifolia were made. The DLBE was used for the acute oral toxicity and anti-obesity activity in the rodent. However, methanolic extract was used for characterization by high-performance thin layer chromatography (HPTLC) method. During acute toxicity study, it was shown that certainly there was no mortality or morbidity observed up to the maximum dose of 2000 mg/kg after administration of DLBE. The ultimate body weight, food intake, liver weight, total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), triglycerides (TG), aspartate aminotransferase (AST), alanine transaminase (ALT), serum creatinine and blood urea nitrogen (BUN) of rats treated with DLBE at a dose of 200 and 400 mg/kg respectively was considerably diminished to p 0.05) effects on above parameters. The histopathological findings of the study from the cross section of liver and kidney show normal architecture in the cells treated with DLBE at a dose of 200 and 400 mg/kg respectively. Thus we can conclude that the bark extract of D. latifolia can be used for the treatment of obesity and a novel approach for further investigations of its pathology.

In spite of high toxicological risk Aconitum napellus (ACON) is tremendously used for the treatment of rheumatoid and joint pain. The acute toxicity study was assessed for cow milk treated (CMT), g...

Onosma echioides is a perennial herb widely used for the treatment of various ailments such as sciatica, gout, and rheumatism. This study focused on toxicological assessment of bark extract of O. e...

The present study was designed to explore the neuroprotective properties of Aconitum napellus (Ranunculaceae). The plant detoxification was done using either water, or cow or goat milk as per the Ayurvedic shodhana method. The evaluation of the neuroprotective role of A. napellus was performed on diabetic neuropathy induced by streptozotocin in Sprague Dawley (SD) rats. Body mass, blood sugar level, oral glucose tolerance test, hyperalgesia, cold allodynia, motor co-ordination test, and locomotor activity, oxidative biomarkers (TBARS, reduced glutathione, catalase and superoxide dismutase) and sciatic nerve histomorphology were assessed. The in vitro studies were done on human neuroblastoma cell line SHSY-5Y and used an MTT assay to assess the antiproliferative activity of different extracts. Results suggest that the goat milk treated chloroform extract has less percentage of aconitine. After administration of the detoxified chloroform extract to the diabetic animals, there was a significant improvement in the myelination and degenerative changes of the nerve fibers along with behavioral changes (p &lt, 0.05 as compared with diabetic control group). The findings of the in vitro research show an effective neuroprotective role of A. napellus. This suggests that A. napellus should be further investigated for its effect in diabetic pathology.

India has got rich cultural inheritage in the forms of Ayurveda texts which are a rich and ample source of herbs, shrubs, trees and affluent in medicinally active phytoconstituents. Aconitum napellus is used for the cure of many ailments including rheumatoid arthritis, sciatica and gout. The present work attempts to evaluate the physicochemical and preliminary phytochemical studies on the tubers of Aconitum napellus along with its antidiabetic activity. The herbal standardization was carried out on the basis of organoleptic properties, physical characteristics and physicochemical properties. The body weight of ACON-I (1.25 mg/kg) and ACON-II (2.5 mg/kg) was recorded as 190.40 and 209.40 g, respectively, compared with 163.00 g in diabetic rats at day 28. The body weight of ACON-I and ACON-II was significantly increased compared with diabetic rats (p

India has got rich cultural inheritage in the forms of Ayurveda texts which are a rich and ample source of herbs, shrubs, trees and affluent in medicinally active phytoconstituents. Aconitum napellus is used for the cure of many ailments including rheumatoid arthritis, sciatica and gout. The present work attempts to evaluate the physicochemical and preliminary phytochemical studies on the tubers of Aconitum napellus along with its antidiabetic activity. The herbal standardization was carried out on the basis of organoleptic properties, physical characteristics and physicochemical properties. The body weight of ACON-I (1.25 mg/kg) and ACON-II (2.5 mg/kg) was recorded as 190.40 and 209.40 g, respectively, compared with 163.00 g in diabetic rats at day 28. The body weight of ACON-I and ACON-II was significantly increased compared with diabetic rats (p

Background The fruit Terminalia belerica is a rich source of vitamins, acids, and nutraceuticals which have free radical scavenging activity. Thus, the ethanolic extract of fruit and its isolated compound (Tb-01) were intended to estimate antiplatelet and antioxidant activities. Methods The ethanolic extract was submitted to Si-gel CC and the compound was isolated. The compound Tb-01 was characterized as benzoyl- β -D-(4′→10″ geranilanoxy)-pyranosides on the basis of spectral data [ultra violet (UV), infrared (IR), 1 H nuclear magnetic resonance (NMR), 13 C NMR, and Mass Spectroscopy] and chemical analyses. The ethanolic extract and Tb-01 at different concentrations were in vitro screened for antiplatelet and antioxidant activity. The antiplatelet activity was carried out by using platelet rich plasma prepared by centrifugation of rabbit whole blood (containing 0.9% sodium citrate as anticoagulant) and antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl, reducing power, and nitric oxide anion scavenging activity models. Results The compound Tb-01 was an amorphous brownish powder, yield 0.64% (w/w), melting point 105–110°C, Retardation factor/Retention Value (R f value) at 0.42 in methanol:chloroform (20:80) solvent system, UV absorption maxima at 243nm, and molecular peak [M + H] + at 394.15 m/z. It was observed that the ethanolic extract and Tb-01 at different concentrations showed significant antiplatelet and antioxidant activity. The antioxidant activity, like scavenging of 1,1-diphenyl-2-picrylhydrazyl radicals, nitric oxide radical, and reductive power were found to be concentration-dependent and increased when increasing amounts of sample were used. Conclusion Mass spectra and 1 H NMR confirmed the isolated compound structure which was supported by 13 C NMR and IR spectra. Tb-01could be promising for future applications in the treatment of blood clots, pulmonary embolism, and other related diseases.

In the present study, triterpenoidal glycoside was isolated from ethanolic extract of aerial part of the plant Nepeta hindostana. The ethanolic extract was subjected to Si-gel CC and compound was isolated. The isolated compound Napedinolside has been characterized as 1β,11α,30-trihydroxy-lup-20(29)ene-(3 → 1′)-β-D-pyranoside on the basis of spectroscopic (UV, IR, 1 H, 13 C NMR and MS) methods. The ethanolic and aqueous extract at different concentrations were screened for antiplatelet activity using platelet rich plasma (PRP) prepared by centrifugation of rabbit whole blood (containing 0.9 % sodium citrate as anticoagulant) at 1500 rpm for 15 mins. The Np-01 was identified as triterpenoidal glycoside which was amorphous brownish white powder; yield 0.64 % (w/w); mp 125–127. N. hindostana showed very excellent antiplatelet activity in both aqueous and alcoholic extracts. The minimum concentration showed antiplatelet activity was 0.5 μg/ml. These findings demonstrate that ethanolic and aqueous extract of the selected plant material at different concentrations showed significant antiplatelet activity. The triterpenoidal glycoside from aerial parts of N. hindostana could hold promise for future application in the treatment of blood clot and pulmonary embolism related diseases.

Introduction Triphala is widely prescribed herbal drug in the Indian traditional system of medicine. It is rich in antioxidants and possesses diverse beneficial properties. It is used to treat many diseases such as anemia, jaundice, constipation, asthma, fever, chronic ulcer and various gastrointestinal disorders. The aim of this study was to investigate the ulcer ameliorative effect of hydro-alcoholic extract of Triphala in indomethacin-induced gastric ulcer in Wistar rats. Methods Gastric ulcer was induced by indomethacin (10 mg/kg b wt, po) in Wistar rats. Triphala extract (1000 mg/kg b wt, po) or vehicle (1 ml/kg/day po of 1% CMC) was given to the rats for 15 days by oral gavage ( n = 6). The ulcer ameliorative effect of Triphala extract was compared with standard drug ranitidine (50 mg/kg b wt, po for 15 days). The ulcer index was calculated. Gastric histopathology and biochemical parameters like mucus, lipid peroxide, glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) were determined. Results Treatment with Triphala extract significantly decreased the levels of ulcer index and lipid peroxide in the treated rats. The extract also significantly elevated the levels of mucus, GSH, CAT and SOD. These findings matched the results of histopathological studies. Conclusion Triphala extract possesses an ulcer ameliorative effect in gastric ulcer through strengthening the gastric mucosa, restoring the free radical scavenging enzymes and reducing the lipid peroxide production.

A series of N-(2-(benzoyl/4-chlorobenzoyl)-benzofuran- 3-yl)-2-(substituted)-acetamide derivatives (4a-l, 5a-l) was synthesized in good yield. All synthesized compounds were in agreement with elemental and spectral data. The anticonvulsant activity of all synthesized compounds was assessed against the maximal electroshock induced seizures (MES) model in mice. Neurotoxicity was evaluated using the rotarod method. The majority of compounds exhibited anticonvulsant activity at a dose of 30 mg kg-1 body mass during 0.5-4 h, indicating their ability to prevent seizure spread at low doses. Relative to phenytoin, [N-(2-(4-chlorobenzoyl)benzofuran-3-yl)-2-(cyclohexyl( methyl) amino)-acetamide] (5i) and [N-(2-(4-chlorobenzoyl)benzofuran-3-yl)-2-(4-methylpiperidin-1- yl)-acetamide] (5c) demonstrated comparable relative anticonvulsant potency of 0.74 and 0.72, respectively, whereas [(N-(2-(4-chlorobenzoyl)benzofuran-3-yl)-2-(4-(furan-2-carbonyl)-piperazin-1-yl)-acetamide] (5f) exhibited the lowest relative potency of 0.16. The ALD50 of tested compounds ranged from 1.604 to 1.675 mmol kg-1 body mass. The ED50 of synthesized compounds ranged from 0.055 to 0.259 mmol kg-1 (~23.4 to 127.6 mg kg-1) body mass. The pharmacophore mapping of the examined compounds on standard drugs (phenobarbital, phenytoin, ralitolin and carbamazepine) strongly suggests that these compounds may exert their anticonvulsant activity via the same established mechanism as that of known drugs.

HPLC validated hexane bark extract of Onosma echioides L. root (OE) was evaluated for cure of human diabetic neuropathy in human neuroblastoma cell line. HPLC analysis was performed. Human neuroblastoma cells were grouped into control, normal glucose, high glucose (HG) and HG plus different concentrations of OE extract (10, 25 and 50 μg/mL). MTT, DCFH-DA staining and nuclear condensation assays were performed on neuroblastoma cells to evaluate antiproliferative activity, ROS activity level and apoptotic effect of OE. HPLC analysis revealed the existence of maximum yield of shikonin in n-hexane extract of OE. Exposure with different concentrations of OE effectively decreased ROS level and apoptosis of cells and as a result improved the viability of cells in a dose dependent manner in response to HG-induced oxidative stress. Thus, OE possesses the property to cure human diabetic neuropathy and further can be clinically tested for its use in diabetic neuropathy.

Onosma echioides Linn (Boraginaceae) is the most frequently used curative herb widely used for kidney obstruction, sciatic pain, and gout. The present study was designed to investigate the therapeutic effects of n-hexane bark extract of O. echioides (OE) L. root in vivo against Streptozotocin-induced diabetic neuropathy in SD rats. For in vivo activity, the experiment was categorized into five different groups (n = 5). Group-I was considered as nondiabetic/normal control (NC) treated with 0.5% carboxymethyl cellulose (CMC), Group II as diabetic control, Group-III, IV, and V served as diabetic treated with OE 50, OE 100, and pregabalin at a dose of 50, 100, and 10 mg/kg body weight, orally, respectively. Body weight, blood glucose, oral glucose tolerance test, behavioral studies (motor coordination test, thermal hyperalgesia, cold allodynia, locomotor activity, oxidative biomarkers (thio barbituric acid reactive substances [TBARS], superoxide dismutase [SOD], glutathione [GSH], and catalase), and histopathology of the sciatic nerve were performed. Treatment with OE showed a dose-dependent increase in neuroprotective activity by improving the myelination and decreasing the axonal swelling of nerve fibers. The verdicts of behavioral activities showed a remarkable effect on animals after the treatment of extract and standard drug pregabalin. In conclusion, our findings supported the traditional application of OE and explored its importance in the management of diabetic neuropathy. Additional clinical experiments may provide novel therapeutic drugs for diabetes and its complications.

Interruption of blood supply to the heart results in acute myocardial infarction (AMI), and further damages the heart muscles. Available drugs for the treatment MI have one or other side effects, and there is a need for development of better alternative drugs from herbal sources. Here, we evaluated cardioprotective effect of Cyperus rotundus on isoprenaline- induced myocardial infarction. Thirty five Wistar rats, aged 60-100 days with body wt. 150-200 g, pretreated with ethanolic extract of Cyperus rotundus L. (@ 250 and 500 mg/kg body wt.) orally before induction of myocardial necrosis by administrating isoprenaline (85 mg/kg, s.c.) on 19th and 20th day of the pretreatment period. The treated rats were examined for gross functioning of heart, heart weight/body wt. Ratio, and also observed histopathologically. Further, activities of various cardiac enzymes such as aspartate transaminase, alanine transaminase, creatinine kinase-myoglobulin, lactate dehydrogenase, and the gold marker troponin-I were also determined. The levels altered by isoproterenol were found to be restored significantly by the test extracts especially at higher dose. Biochemical observations viz., serum ALT (P0.0001), AST (P0.0001), creatine kinase-myoglobulin (CK-MB) (P0.0001), LDH (P0.0001) demonstrated significant cardioprotective activity of the ethanolic extract of C. rotundus (500 mg/kg body wt.), against isoprenaline induced myocardial infarction. These results were also substantiated by physical parameters and histopathological observations. All these results were comparable with that of two standard drugs metoprolol (10 mg/kg/day), ramipril (3 mg/kg/day) as well as polyherbal formulation Abana (50 mg/kg/day).

Prostate cancer is the second most common malignancy in the human reproductive system. Eupalitin is one of the O-methylated flavonol-exhibited enhanced cancer chemopreventive agents. The current study highlights the structural determination of eupalitin and aims to explore the antitumor activity of eupalitin in human prostate cancer cell (PC3) and its underlying mechanism. Eupalitin structure was determined by using FTIR, (1)H NMR, and (13)C NMR. PC3 cells were treated with increasing concentrations of eupalitin, followed by analysis of the cell viability with an MTT assay. The results demonstrated that eupalitin markedly inhibited the proliferation of PC3 cells in a concentration-dependent manner. The results from fluorescent microscopic analysis of nuclear condensation and intracellular ROS generation determined that eupalitin significantly induced ROS level lead to nuclear apoptosis. Cell cycle analysis revealed that eupalitin-induced cell cycle progression as a percentage of cells in G0/G1 phase decreased whereas S phase increased. Caspase-3 immunofluorescence analysis confirms the efficacy of eupalitin-inducing apoptotic pathway and cell death. Thus, our study is helpful in understanding the mechanism underlying these effects in prostate cancer and it may provide novel molecular targets for prostate cancer therapy.

The aim of this study is to explore the effect of Tinospora cordifolia (Guduchi) on cardiotoxicity in streptozotocin induced diabetic rats. All animals were divided into 8 groups of 5 animals each, fed with High fat diet (HFD) except the ones in Sham, NPD and NPD-C-I groups. Food and water intake were monitored daily at the same time during the experimental period. The Food Efficiency Ratio (FER) was calculated during the experiment period. All the animals were pretreated as per the treatment protocol. Streptozotocin; STZ (50mg/ Kg) was administered subcutaneously to induce the diabetes which was confirmed in all the administered groups by testing blood glucose level after 48 hours. Cardiotoxicity was induced by administering isoprenaline (85mg/Kg). Troponin was checked after 4-5 hours of second isoprenaline injection to confirm cardiac damage. At the end of the study the animals were weighed and then sacrificed with high dose of Diethyl ether. Blood samples were collected from retro-orbital plexus and were used for biochemical estimations. The hearts were excised immediately and were weighed. Photomicrographs were taken for gross examination rest of the hearts were kept in 10% Formalin solution for histopathological studies. Pretreatment with Tinospora cordifolia (200 mg/kg ) showed very significant improvement against Streptozotocin induced diabetes (p< 0.01) as blood glucose level were found to be decreased when compared to the untreated D-HFD group. The Food efficiency ratio (FER) was found to be significantly increased when compared to D-HFD (p

Piperaquine-dihydroartemisinin combination is the latest addition to the repertoire of ACTs recommended by the World Health Organization (WHO) for treatment of falciparum malaria. Due to the increasing resistance to artemisinin derivatives, CSIR-CDRI has developed a prospective short acting, trioxane antimalarial derivative, CDRI 97-78. In the present study, a liquid chromatography-electrospray ionization-tandem mass spectrometry (LC–ESI-MS/MS) method for the simultaneous quantification of piperaquine (PPQ) and 97-63, the active metabolite of CDRI 97-78 found in vivo, was developed and validated in 100 μL rat plasma using halofantrine as internal standard. PPQ and 97-63 were separated using acetonitrile:methanol (50:50, v/v) and ammonium formate buffer (10 mM, pH 4.5) in the ratio of 95:5(v/v) as mobile phase under isocratic conditions at a flow rate of 0.65 mL/min on Waters Atlantis C18 (4.6 × 50 mm, 5.0 µm) column. The extraction recoveries of PPQ and 97-63 ranged from 90.58 to 105.48%, while for the internal standard, it was 94.27%. The method was accurate and precise in the linearity range 3.9–250 ng/mL for both the analytes, with a correlation coefficient (r) of ≥ 0.998. The intra- and inter-day assay precision ranged from 2.91 to 8.45% and; intra- and inter-day assay accuracy was between 92.50 and 110.20% for both the analytes. The method was successfully applied to study the effect of oral co-administration of PPQ on the pharmacokinetics of CDRI 97-78 in Sprague-dawley rats and vice versa. The co-administration of CDRI 97-78 caused significant decrease in AUC0–∞ of PPQ from 31.52 ± 2.68 to 14.84 ± 4.33 h*µg/mL. However, co-administration of PPQ did not have any significant effect on the pharmacokinetics of CDRI 97-78. Copyright © 2015 John Wiley & Sons, Ltd.

Recently, inhibition of poly (ADP-ribose) polymerase-1 (PARP1) was shown to be protective in experimental pulmonary hypertension (PH) and prevented right ventricular hypertrophy (RVH) associated with it. However, molecular mechanism behind cardioprotection by PARP1 inhibition in PH still needs detailed exploration. Therefore, effect of inhibition of PARP1 on the right ventricle (RV) dysfunction was studied in monocrotaline (MCT) induced PH model. Following a single dose administration of MCT (60 mg/kg, s.c.), male Sprague-Dawley rats were treated with PARP1 inhibitor 1,5-Isoquinolinediol (ISO, 3 mg/kg, i.p.) for 35 days for preventive study and from day 21-35 for curative study. RV pressure (RVP) and RVH were measured after 35 days. Histophathological studies, PARP1 activity, mRNA and protein expression were studied in isolated RV. Oxidative and nitosative stress, inflammation and Matrix metalloproteinases (MMPs)/Tissue inhibitor of metalloproteinase 2 (TIMP2) were also assessed. Mitochondrial dysfunction was studied by mitochondrial membrane permeability and estimation of Nicotinamide adenine dinucleotide (NAD) and Adenosine triphosphate (ATP). Apoptosis in RV was assessed by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), caspase 3 activity and cleaved PARP1 expression. PARP1 inhibition significantly reversed the increase in RVP and RVH in both preventive and curative treatment in the MCT-injected rats. ISO lowered oxidative and nitrosative stress and inflammation and restored the balance of MMPs/TIMP2 expression. PARP1 inhibition prevented mitochondrial dysfunction and the release of cell death factors from mitochondria. ISO also decreased apoptosis by decreasing number of TUNEL positive cells, caspase 3 activity and PARP1 cleavage in RV. Thus, PARP1 inhibition ameliorated PH induced RV hypertrophy and may emerge as a new therapeutic target for PH.

Ethnopharmacological relevance: Andrographis paniculata (Acanthaceae) is given from ancient times in Indian traditional medicine like Ayurveda and Unani for the treatment of gastrointestinal tract disorders, bronchial diseases, fevers, inflammatory diseases, liver disorders, parasitic diseases and snake poisoning. Aim of the study: Investigation of hydromethanolic extract of Andrographis paniculata in the treatment of ulcer by Indomethacin and Indomethacin plus pylorus ligation induced gastric ulcer in rats. Materials and methods: The antiulcer activity of hydromethanolic extract of Andrographis paniculata (APE) was investigated using 36 rats. The first group was subjected as control, the second group was subjected to pylorus ligation on 6th day under ether anesthesia, and the third group was subjected to Indomethacin (20 mg/kg) for 5 days + pylorus ligation on 6th day under ether anesthesia. The fourth and fifth groups were administered with the 50% hydromethanolic extract of Andrographis paniculata (200 and 400 mg/kg/day, respectively). The sixth group served as reference antiulcer drug omeprazole (10 mg/kg/day). All animals were deprived of food (but not water) for 24 hours prior to being subjected to ulcerogenic challenge. At the end of study, the stomach tissue was cut, washed with ice cold saline. The tissue was fixed in 10% buffered neutral formalin solution for histopathological examination. Ulcer Index, pH, titrable acidity, gastric mucus, antioxidant activity, and gastric pepsin activity was evaluated by using tissue and gastric juice. Results: APE showed dose-dependent ulcer protective effect in indomethacin plus pylorus ligation induced gastric ulcer. The % protection was found in group IV (19.32% & 30.75%), group V (62.17% & 67.47% %) and group VI (70.38% & 74.57%) when compared to PL group II and IND+PL group III, respectively. The APE showed highly significant enhancement of gastric wall mucus at the dose of 400 mg/kg. The TBARS level was significantly increased in group II rats and IND+PL group III rats respectively, while the level of GSH was significantly decreased as compared to control group. The pH was significantly increased with subsequently decrease in acidity with the treatment of APE. APE showed a marginal increase in pepsin activity compared to control group I rats. These observations were in good corroboration with the histopathological studies results. Conclusions: The results of our study revealed that the extracts of Andrographis paniculata possess significant dose dependent gastroprotective and antisecretory effects by strengthening the gastric mucosa, decreasing the acidity of gastric juice and pepsin activity as well as restore the imbalance antioxidant activity. Further studies on other factors like H. pylori, PGs and cAMP, which play important role in ulcerogenisis may provide more insights on the antiulcerogenic activity of Andrographis paniculata.

Coleus forskohlii is an important ancient root drug of Indian origin, commonly known as gander in indian ayurvedic system of medicine. A lot of research work has been done on Coleus forskohlii regarding various cardiovascular disorders but no work has been done to find out its cardioprotective activity. Wistar albino rats were divided into five main groups having 5 animal each: Group 1 termed as Normal control (NC) received 0.5ml of normal saline throughout experimental period and served as control. Group 2 termed as Isoprenaline group (ISO) received 0.5ml of normal saline for 28 day and received Isoprenaline (85mg/kg, s.c.) on 29th and 30th day at an interval of 24 hours. Group 3 termed as Standard group (STD) received Metoprolol (pure) (10 mg/kg/day, p.o.) for 28 day and received Isoprenaline (85mg/kg, s.c.) on 29th and 30th day at an interval of 24 hours. Group 4 termed as Test group 1 (TG 1) and Group 5 termed as Test group 2 (TG 2) received Coleus forskohlii (50 mg/kg/day, p.o.) (100 mg/kg/day, p.o.) for 28 day and received Isoprenaline (85mg/kg, s.c.) on 29th and 30th day at an interval of 24 hours respectively. The experiment was terminated on 31st day and animal were sacrificed by cervical decapitation after an overnight fast. Blood was collected for estimation of biochemical parameter and heart was dissected out for grading, heart/weight ratio and histopathological examination.the the level of marker enzyme in serum as AST, ALT, LDH, CK, Troponin-I were significantly decreased (P 0.001) in rats pretreated with Coleus forskohlii when compared to that of group which received isoprenaline alone. Further, histopathological examination showed the reduction of necrosis, edema and inflammation following Coleus forskohlii pretreatment. Based on present findings, it is concluded that Coleus forskohliil may be a potential preventive and therapeutic agent against the myocardial necrosis associated ischemic heart disease.

Objective The aim of the current study was to evaluate the hepatoprotective action of the leaves of Adenanthera pavonina against isoniazid (INH) and rifampicin (RIF)-induced liver damage in experimental animals. Methods Five groups of six rats each were selected for the study. A methanolic (50%) extract of A. pavonina at a dose of 100 and 200 mg/kg as well as silymarin 100 mg/kg were administered orally once daily for 28 days in INH + RIF treated groups. The serum levels of glutamic oxaloacetic transaminase (SGOT), glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), bilirubin, total protein, albumin and lactate dehydrogenase (LDH) were estimated along with activities of superoxide dismutase (SOD), catalase, glutathione, thiobarbituric acid reactive substances (TBARS). Histopathological analysis was carried out to assess injury to the liver tissue. Result The methanolic extract of A. pavonina was safe up to a dose of 2000 mg/kg. The significantly elevated serum enzymatic activities of SGOT, SGPT, ALP, bilirubin and LDH due to INH + RIF treatment were restored to near normal in a dose dependent manner after the treatment with methanolic extract of leaves of A. pavonina. Also the increased level of total protein and albumin towards normal by extract of A. pavonina leaves. In the anti-oxidant studies a significant increase in the levels of glutathione, catalase and superoxide dismutase was observed. In addition, methanolic extract also significantly prevented the elevation of hepatic malondialdehyde formation in the liver of INH + RIF intoxicated rats in a dose dependent manner. The biochemical observations were supplemented with histopathological examination of rat liver sections. Conclusions These findings suggested that the methanolic extract of leaves of A. pavonina exhibited hepatoprotective effects against INH + RIF induced hepatic damage in rats as compared to standard drug silymarin.

1. S002-333, (2-(4'-methoxy-benzenesulfonyl)-2,3,4,9-tetrahydro-1H-pyrido (3,4-b) indole-3-carboxylic acid amide) is a novel potent antithrombotic molecule currently under development phase. It is the racemic mixture of two enantiomers, namely S004-1032 (R-form) and S007-1558 (S-form). 2. The contribution of five major isoenzymes, namely CYP2B6, 2C9, 2C19, 2D6 and 3A4 was quantified using recombinant P450s in the phase-I metabolism through relative activity factor approach. CYP2C19 was found to be the major contributor for S002-333 and S007-1558, while CYP3A4 showed greater involvement in S004-1032 metabolism. Chemical inhibition and immunoinhibition studies reconfirmed the results in human liver microsomes (HLM). 3. Four major phase-I metabolites of S002-333; M-1 and M-3 (oxidative), M-2 (O-demethylated) and M-4 (dehydrogenated) were characterized in HLM. These metabolites constituted 11.2, 11.3 and 21.5% of the parent in comparison with the net phase-I metabolism of 29.9, 31.4 and 38.3% of S002-333, S004-1032 and S007-1558, respectively. 4. Among CYP2C9, 2C19 and 3A4, the relative contribution of CYP2C9 was found to be maximum during M-1 through M-4 formation. Enzyme kinetic analysis for detected metabolites indicated that M-1 to M-3 followed classical hyperbolic kinetics, whereas M-4 showed evidence of autoactivation. In conclusion, the results suggest prominent role of CYP2C9, 2C19 and 3A4 isoforms for enantioselective disposition of S002-333 in vitro.

Coadministration of 2 or more drugs may result in unexpected toxicity. This study aimed to evaluate the effect of carbamazepine coadministration on the pharmacokinetics of CDRI-97/78, an 1,2,4-trioxane antimalarial agent. Firstly, 97/78 was administered alone and then 97/78 and carbamazepine were coadministered to male and female rats. An revalidated LC-MS/MS method was used for quantitation of 97/63 since 97/78 is instantly and completely converted to 97/63 (an in-vivo active metabolite). The Tmax and Cmax values of 97/63 were 1.75±0.77 h and 862±306 ng/mL in male rats whereas in female rats they were 5.45±0.76 h and 662.75±95.09 ng/mL after a single dose of 97/78 alone. However, following coadministration of 97/78 and carbamazepine, the values for Tmax and Cmax were 1.06±0.16 h and 533±153 ng/mL in male rats and 2.23±1.93 h and 636.5±112.4 ng/mL in female rats. The half life of 97/63 following a single oral dose of 97/78 or coadministration with carbamazepine to male rats was 6.98±0.63 h and 6.64±0.54 h, respectively; the values in female rats were 7.5±0.5 h and 5.48±0.37 h. A statistically insignificant difference (P>0.05) was observed with the student t-test for the pharmacokinetic parameters of 97/63 following oral administration of 97/78 alone or coadministration of 97/78 and carbamazepine except for MRT in female rats. Intersex statistical comparison also showed an insignificant difference for 97/63 following oral administration of 97/78 alone or in combination with carbamazepine except for MRT, which supports coadministration of 97/78 and carbamazepine.

Anti-platelet therapy is a useful strategy to prevent acute thromboembolic artery occlusions. This study was designed to assess the efficacy of seselin derivatives against murine pulmonary thromboembolism, bleeding time, platelet activation and thrombosis. Administration of C3 (16 mg/kg) offered 70% protection against collagen- and epinephrine-induced pulmonary thromboembolism and 30% protection against arachidonic acid-induced death in mice, without adversely affecting bleeding time. No significant difference was observed by C3 in ferric chloride-induced arterial thrombosis in rats. Significant reduction in thrombus weight was observed in arteriovenous shunt model. In rat PRP, C3 reduced ADP and collagen-induced platelet aggregation. In chronic hamster model of dyslipidemia, administration of C3 (16 mg/kg p.o. for 90 days) had no effect on plasma lipids, vasoreactivity and platelet adhesion. C3 fed hamsters showed reduced whole-blood aggregation response to ADP and collagen compared to HC-fed hamsters. In addition, C3 augmented thrombin time; however, time to occlusion was not increased. These results convincingly demonstrated that C3 is a novel molecule that reduces the risk of thrombosis and alleviates prothrombotic state associated with hyperlipidemia without any adverse effect on bleeding time. The high benefit/risk ratio of this compound makes it a suitable candidate for future valid studies.

Particle engineering is the prime focus to improve pulmonary drug targeting with the splendor of nanomedicines. In recent years, submicron particles have emerged as prettyful candidate for improved fludisation and deposition. For effective deposition, the particle size must be in the range of 0.5-5 μm. Inhalers design for the purpose of efficient delivery of powders to lungs is again a crucial task for pulmonary scientists. A huge number of DPI devices exist in the market, a significant number are awaiting FDA approval, some are under development and a large number have been patented or applied for patent. Even with superior design, the delivery competence is still deprived, mostly due to fluidisation problems which cause poor aerosol generation and deposition. Because of the cohesive nature and poor flow characteristics, they are difficult to redisperse upon aerosolization with breath. These problems are illustrious in aerosol research, much of which is vastly pertinent to pulmonary therapeutics. A technical review is presented here of advances that have been utilized in production of submicron drug particles, their in vitro/in vivo evaluations, aerosol effects and pulmonary fate of inhaled submicron powders.

Repaglinide (RPG) is a fast-acting prandial glucose regulator. It acts by stimulating insulin release from pancreatic β-cells. Recurrent dosing of RPG before each meal is burdensome remedy. Hence the plan of the present study was to evaluate nanoemulsion as a hopeful carrier for RPG for persistent hypoglycemic effect. The drug was incorporated into oil phase of nanoemulsion to give improved biopharmaceutical properties as compared to the lipid-based systems. Pseudo ternary phase diagrams were prepared by aqueous titration method. Formulations were selected at a difference of 5% w/w of oil from the o/w nanoemulsion region of phase diagrams. The optimized nanoemulsion formulation constituted sefsol-218 (5% v/v) as an oil phase, 30% v/v of Tween-80 and transcutol as a surfactant and co-surfactant to restrain nanodroplet size and low viscosity and distilled water (65%). In vitro dissolution studies showed higher drug release (98.22%), finest droplet size (76.23 nm), slightest polydispersity value (0.183), least viscosity (21.45 cps) and immeasurable dilution capability from the nanoemulsion as compared with existing oral tablet formulation. The optimized RPG nanoemulsion formulation showed better hypoglycemic effect in comparison to tablet formulation in experimental diabetic rats. No significant variations were also observed in the optimized formulation when subjected to accelerated stability study at different temperature and relative humidity over a period of 3 months.

Background: Erythrina indica Lam. traditionally used in the treatment of laxative, diuretic, worm infestation, liver ailment and joints pain. Objective: To evaluate the antihepatotoxic potential of Erythrina indica against isoniazid (INH) and rifampicin (RIF) induced hepatotoxicity in rats. Methods and material: Liver toxicity was induced by antitubercular drugs (INH+ RIF) at dose level of 50 mg/kg each, p.o for 28 days. 50% methanolic extract of Erythrina indica (100 and 200 mg/kg) were administered orally once daily for 28 days. The hepatoprotective activity was assessed using various biochemical parameters SGOT, SGPT, ALP, bilirubin, total protein, albumin and LDH. Meanwhile, in vivo antioxidant activities as SOD, CAT, GSH and, LPO were measured in liver homogenate also histological examinations were carried out to assess hepatoprotective activity. Statistical analysis used: The values were subjected to one way analysis of variance (ANOVA) followed by Tukey multiple compare test. Results were considered statistically significant when P < 0.05. Results: Obtained results demonstrated that the treatment with Erythrina indica (E. indica) significantly prevented drug induced increase in serum levels of hepatic enzymes. Furthermore, Erythrina indica significantly reduced the lipid peroxidation (P < 0.01 tp P < 0.001) in the liver tissue and restored activities of defense antioxidant enzymes GSH (2.15 ± 0.08 to 2.48 ± 0.99; P < 0.05), SOD (2.69 ± 0.752 to 3.712 ± 0.056; P < 0.05 to P < 0.01) and CAT (10.20 ± 0.58 to 12.59 ± 0.42; P < 0.05 to P < 0.001) towards normal. Histopathology of liver tissue showed that Erythrina indica attenuated the hepatocellular necrosis, regeneration and repair of cells toward normal. Conclusion: The results of this study strongly indicate the protective effect of Erythrina indica against liver injury which may be attributed to its hepatoprotective activity, and there by scientifically support its traditional use.

Reports regarding drug toxicity and adverse events resulting from coadministration of multiple drugs are increasing at an alarming rate. CDRI-97/78 is an 1,2,4-trioxane antimalarial agent under development which gets metabolized to the in vivo active metabolite 97/63. In order to assess its drug interaction potential, CDRI-97/78 was administered alone and in combination with lamotrigine to male and female rats via the oral route. Quantification of the active metabolite 97/63 in rat plasma was achieved with an LC-MS/MS assay. After oral administration of 97/78, the Tmax and Cmax values of 97/63 in male rats were 1.75±0.77 h and 862±306 ng/mL while female rats showed values for Cmax of 622.75±95.09 ng/mL and for Tmax of 7.5±0.5 h. Coadministration of 97/78 and lamotrigine resulted in decreased Tmax and Cmax values in both male and female rats (Tmax and Cmax of 0.77±0.16 h and 58.58±6.43 ng/mL in male rats; 1.13±0.22 h and 62.95±12.00 ng/mL in female rats, respectively). A statistically significant difference (P

Objective To evaluate the acute and subacute toxicity of 50% ethanolic extract of Tephrosia purpurea (T. purpurea) in rodents. Methods The acute toxicity test was conducted in Swiss albino mice. The extract of T. purpurea was administrated in single doses of 50, 300 and 2000 mg/kg and observed for behavioral changes and mortality, if any. In subacute toxicity study, Wistar rats of either sex were administered two doses of T. purpurea i.e., 200 and 400 mg/kg (One-tenth and one-fifth of the maximum tolerated dose), p.o. for 4 weeks. During 28 days of treatment, rats were observed weekly for any change in their body weight, food and water intake. At the end of 28 days, rats were sacrificed for hematological, biochemical and histopathology study. Results In the acute toxicity study, T. purpurea was found to be well tolerated upto 2000 mg/kg, produced neither mortality nor changes in behavior in mice. In subacute toxicity study, T. purpurea at dose level of 200 and 400 mg/kg did not produce any significant difference in their body weight, food and water intake when compared to vehicle treated rats. It also showed no significant alteration in hematological and biochemical parameters in experimental groups of rats apart from a decrease in aspartate transaminase, alanine transaminase and alkaline phosphate content at the dose of 400 mg/kg. Histopathological study revealed normal architecture of kidney and liver of T. purpurea treated rats. Conclusions These results demonstrated that there is a wide margin of safety for the therapeutic use of T. purpurea and further corroborated the traditional use of this extract as an anti hepatocarcinogenic agent.

Objectives The chemopreventive potential of Tephrosia purpurea extract (TPE) on N-nitrosodiethylamine (NDEA)-induced hepatocellular carcinoma (HCC) in Wistar rats was assessed. Methods HCC was induced by a single intraperitoneal injection of NDEA (200 mg/kg) followed by subcutaneous injections of CCl4 (3 ml/kg per week) for six weeks. After administration of the carcinogen, 200 and 400 mg/kg TPE were administered orally once a day throughout the study. Key findings The levels of liver cancer markers, including α-fetoprotein and carcinoembryonic antigen, were substantially increased by NDEA treatment. TPE treatment significantly reduced liver injury and restored the entire liver cancer markers. Additionally, TPE markedly normalized the activity of antioxidant enzymes, namely lipid peroxidation, reduced glutathione, catalase, superoxide dismutase, glutathione peroxidase and glutathione-S-transferase in the liver of NDEA-treated rats. Treatment with TPE significantly reduced the nodule incidence and multiplicity in the carcinogen-bearing rats. Histological observations of the liver tissues correlated with the biochemical observations. Conclusions These findings powerfully support that T. purpurea prevented lipid peroxidation, suppressed the tumour burden, and promoted enzymatic and nonenzymatic antioxidant defence systems during NDEA-induced hepatocarcinogenesis. This might have been due to modulating the antioxidant defence status, which contributed to its anticarcinogenic potential.

Objective To investigation the chemopreventive efficiency of Fumaria indica extract (FIE) on the antioxidant status of N-nitrosodiethylamine (NDEA) and CCl 4 -induced hepatocarcinogenesis in Wistar rats. Methods The experimental animals were divided into six groups ( n = 6). HCC was induced by single intraperitoneal injection of NDEA in normal saline at a dose of 200 mg/kg body weight followed by weekly subcutaneous injections of CCl 4 (3 mL/kg/week) for 6 weeks, as the promoter of carcinogenic effect. After administration of the carcinogen, 200 and 400 mg/kg of FIE were administered orally once a day throughout the study. At the end of 20 weeks, the body weight, liver weight and relative liver weight were measured. The level of hepatic malondialdehyde (MDA) formation, reduced glutathione (GSH) and the activities of antioxidant enzymes viz. CAT, SOD, GPx, and GST in the liver of NDEA and CCL 4 -treated rats were assessed. Results Obtained results demonstrated that the cotreatment with FIE (200 and 400 mg/kg) significantly prevented the decrease of the body weight and also increased in relative liver weight caused by NDEA and CCl4 administration. FIE also significantly prevented hepatic malondialdehyde (MDA) formation and reduced glutathione (GSH) in NDEA-treated rats which were dose dependent. Additionally, FIE also markedly increased the activities of antioxidant enzymes such as CAT, SOD, GPx, and GST in the liver of NDEA and CCL 4 -treated rats. Conclusions These finding powerfully supports that Fumaria indica exert a chemopreventive effect by reversing the oxidant-antioxidant imbalance during hepatocarcinogenesis induced by NDEA and CCl 4 .

Objective To evaluation the weight reduction and hypercholesteremic potential of punarnava root extract induced with high fat diets in experimental rodents by administrating oral doses (50, 100, 200 mg/kg). Methods Thirty six female Sprague-Dawley rats were divided in six groups and each group had six animals. Group-I administered laboratory diet, control obese group-II induced with high fat diet (HFD), group-III standard drug plus HFD rats (5 mg/kg) and Boerhaavia diffusa root extract (BDRE) were administered (50, 100 and 200 mg/kg) plus HFD rats (group-IV, V and VI). After the end of experimental period (60 days) the body weight, organ fat pad weight, lipid profile, liver and kidney marker enzyme were estimated along with histopathological examination in experimental groups of animals. Results The obtained results showed that the significant reduction on administration of BDRE (100 and 200 mg/kg) in body weight, visceral fat pad (P Conclusions The results of this study scientifically supported its traditional uses of Boerhaavia diffusa as antiobesity activity by normalizes the elevated body weight and organ fat pad weight as well as antilipidemic property by lowering the altered levels of lipid profile in female Sprague-Dawley rats.

Citrus limetta risso (Rutaceae) has been frequently used in Indian traditional medicine for the treatment of hyperlipidemia and promotion of weight loss. Studies also indicated towards the antihyperlipidemic potential of Metformin. This study was performed on high fat diet (HFD) induced hyperlipidemia in murine models in both presence and absence of diabetes which was induced by dose of 30mg/kg. Hyperlipidemia was induced by feeding rats with HFD for 28 days. Antihyperlipidemic effect of Citrus limetta peel extract (400mg/kg) and its main terpene component D-limonene (400mg/kg) was evaluated and compared with the effect of Metformin (200mg/kg) by the measurement of body weight gain, body mass index(BMI), food efficiency ratio, fasting blood glucose, Lee's index, heart to body weight ratio, serum lipid profiles (triglycerides, total cholesterol, HDL-Cholesterol, LDL-Cholesterol, VLDL-Cholesterol), end organ weights (Liver, heart, kidneys and visceral fat pad) and antioxidant enzymes such as Thiobarbituric acid (TBARS), Superoxide dismutase (SOD), Catalase (CAT) and Glutathione (GSH). Histomorphological studies were also carried out. Citrus limetta extract, Dlimonene and Metformin significantly reduced the weight gain percentage, total cholesterol, LDL and VLDL and increased the level of HDL-cholesterol and antioxidant enzyme level in liver tissue, also controlled the other parameters’ value within their normal ranges. Histomorphological study of fat tissue shows the normalization of swollen and slight deteriorated cells in the treated groups as compared to control groups. This study concludes that Citrus limetta extract and D-limonene have the antihyperlipidemic activity.

BACKGROUND Traditional remedies employ herbal drugs for the treatment of liver ailments and hepatoprotection. Thus, the present study was designed to evaluate the hepatoprotective effect of "extract of Anacyclus pyrethrum Linn" (APE) against antitubercular drug-induced hepatotoxicity in rats. METHODS Group I rats (normal control) received vehicle (1 % CMC), while group II rats (hepatotoxic control) isoniazid (INH) plus rifampicin (RIF) each 50 mg/kg/day po, for 28 days. Group III, IV and V rats were administered with APE 200, APE 400 and silymarin 100 mg/kg/day po, respectively, for 28 days. Concurrently, hepatotoxicity was tried to induce by coadministration of INH and RIF each 50 mg/kg/day po for 28 days in group III, IV and V rats. After 24 h of the last dosing, blood was obtained under light anesthesia and the rats were killed. Hepatoprotective effect was assessed by liver weight, relative liver weight and biochemical parameters such as serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), serum bilirubin, cholesterol, total protein and albumin levels. RESULTS Group IV rats showed significant (p

1. S002-333 [(2-(4'-methoxy-benzenesulfonyl)-2,3,4,9-tetrahydro-1H-pyrido (3,4-b) indole-3-carboxylic acid amide)] is a novel and potent antithrombotic active agent. The present work investigates the pharmacokinetics, bioavailability, dose proportionality and permeability of the racemate, S002-333 in male New Zealand White (NZW) rabbits. 2. Rabbits were administered single intravenous (i.v.) (2 mg/kg) and three oral doses of 10, 20 and 40 mg/kg of S002-333, respectively, at different occasions to evaluate dose proportionality. Serial blood samples were collected and analyzed by a liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Since S002-333 is a racemate consisting of S004-1032 (R) and S007-1558 (S), same samples were analyzed using a chiralcel column so as to evaluate the respective enantiomers. 3. The peak plasma concentration, after oral administration, occurred at ∼10 h post-dose. The clearance (CL) and volume of distribution (Vd) after i.v. dose were found to be 3.05 ± 0.09 l/h/kg and 6.73 ± 1.16 l/kg, respectively. The absolute oral bioavailability of S002-333 was 16.32%, whereas it was 6.62 and 5.90% for R- and S-enantiomers, respectively. The absolute bioavailability of 10, 20 and 40 mg/kg doses were found to be 27.91, 14.39 and 16.91%, respectively. The PAMPA (parallel artificial membrane permeability assay) assay shows that S002-333 has a low-passive permeability at gastric and intestinal environment. 4. In conclusion, S002-333 has low-passive permeability, low CL and large Vd. The R-enantiomer has a "slightly" greater bioavailability than the S-enantiomer.

Increased sympathetic nervous system (SNS) activity is associated with cardiovascular diseases but its role has not been completely explored in pulmonary hypertension (PH). Increased SNS activity is distinguished by elevated level of norepinephrine (NE) and activity of γ-Amino butyric acid Transminase (GABA-T) which degrades GABA, an inhibitory neurotransmitter within the central and peripheral nervous system. Therefore, we hypothesized that GABA-T may contribute in pathophysiology of PH by modulating level of GABA and NE. The effect of daily oral administration of GABA-T inhibitor, Vigabatrin (GVG, 50 and 75 mg/kg/day, 35 days) was studied following a single subcutaneous administration of monocrotaline (MCT, 60 mg/kg) in male SD rats. The pressure and hypertrophy of right ventricle (RV), oxidative stress, inflammation, pulmonary vascular remodelling were assessed after 35 days in MCT treated rats. The expression of GABA-T and HIF-1α was studied in lung tissue. The levels of plasma NE (by High performance liquid chromatography coupled with electrochemical detector; HPLC-ECD) and lung GABA (by liquid chromatography-mass spectrometry) were also estimated. GVG at both doses significantly attenuated increased in pressure (35.82 ± 4.80 mm Hg, p < 0.001; 28.37 ± 3.32 mm Hg, p < 0.001 respectively) and hypertrophy of RV, pulmonary vascular remodelling, oxidative stress and inflammation in lungs of MCT exposed rats. GVG also reduced the expression of GABA-T and HIF-1α in MCT treated rats. Increased NE level and decreased GABA level was also reversed by GVG in MCT exposed rats. GABA-T plays an important role in PH by modulating SNS activity and may be considered as a therapeutic target in PH.

Diabetes mellitus is a worldwide epidemic disease that eventually advances to a chronic stage and affects different vital organs by intensifying the underlying pathological factors, and through the remodeling of the tissues by the generation of reactive oxygen species leading to the development of respective organ failure. Two such complications are painful neuropathy and cardiomyopathy; both of which are common and progressive complications of diabetes. The symptoms of peripheral neuropathy include tingling, burning, lancinating pain, hyperesthesia, and allodynia. The course of the disease progression may vary from intermittent, mild symptoms to severe chronic, and daily pain; which culminates into poor quality of life. Another complication of diabetes mellitus, diabetic cardiomyopathy, is defined as a ventricular dysfunction disorder that occurs in diabetic patients. The development of the disease is characterized by a hidden subclinical period, during which cellular, structural changes and abnormalities lead to diastolic dysfunction, followed by systolic dysfunction, and terminating into heart failure. Left ventricular hypertrophy, metabolic abnormalities, extracellular matrix changes, small vessel disease, cardiac autonomic neuropathy, insulin resistance, oxidative stress, and apoptosis are the most important pathological advancements that lead to diabetic cardiomyopathy. Various pharmaceutical agents from different pharmacological categories have been proposed for the symptomatic treatment of painful diabetic neuropathy; however, it is a herculean task to select a drug due to the wide range of choices and lack of consistent guidelines for treatment. Similarly, treatment of cardiomyopathy is based on the general therapeutic rules of management of heart failure and no specifications have yet been addressed for this condition. Therefore, more studies are required to improve our knowledge of these complex syndromes. From this perspective, this review is designed to delineate a general overview of neuropathy and cardiomyopathy, referring to the conventional therapies in use and possible unconventional, natural, herbal, and safe treatments for both the above-mentioned complications of diabetes.

Objective: Onosma echioides (OE) L. , family Boraginaceae, is most recurrently used remedial herb, which is extensively dispersed all over India. It is used as purgative, bladder obstacle, liver chaos, kidney obstruction, sciatic pain, and gout. The study was meant to carry out the physicochemical, phytochemical, and high-performance thin layer chromatography (HPTLC) analysis on root bark of OE . Methods: The physicochemical parameters were carried out as per the World Health Organization guideline. The preliminary chemical test was performed as per pharmacopeia and conventional methods. Camag HPTLC system equipped with TLC autosampler 4 applicator, TLC scanner 3 and win CATS 1.4.4. Software was used for HPTLC analysis of plant extract with standard, i.e., shikonin. The extracts were developed using toluene:ethyl acetate:formic acid (5:4:0.3) as a mobile phases using standard procedures and scanned under ultraviolet 254 nm and 366 nm. Results: OE is composed of sterols, tannins, alkaloids, flavonoids, glycoside, saponin, and carbohydrates. The plant was found to be free from adulteration and contamination. The fluorescence characteristics of leaf powder were studied both in visible light and ultraviolet light (254 nm and 365 nm) after treatment with various reagents. The TLC plate showed several spots at different Rf when viewed under 254 nm, 366 nm. The HPTLC profile showed several peaks that indicated the presence of various phytochemicals along with its active constituent, i.e., shikonin. Conclusion: The study provides referential information for the standardization of the plant. The HPTLC profile will help in authentication and standardization of the plant.

Objective : We sought to investigate the protective activity of candesartan against memory impairment, oxidative stress and cholinergic dysfunction induced by activation of the central renin-angiotensin system. Methods : Male Swiss albino mice were divided into eight groups. Group 1 received vehicle (1.0% w/v gum acacia), orally for 14 d. Group 2 received intracerebrally ( i. c. ) artificial cerebrospinal fluid (aCSF, the vehicle of colchicine) and treated with vehicle for 14 d. Group 3, 4 and 5 injected with i. c. colchicine in the doses of 1µg, 2µg, 3µg respectively and treated with vehicle for 14 d. Group 6 and 7 received i. c colchicine (3 µg) and treated with candesartan (0.05 and 0.1 mg/kg respectively) orally for 14 d. Group 8 received i. c colchicine (3 µg) and treated with standard drug donepezil 5 mg/kg (PO) for 14 d. Learning and memory behavior was assessed by using morris water maze. Biochemical parameters of oxidative stress and cholinergic function were estimated in the brain on day 18. Parameters of oxidative stress and cholinergic function were estimated after the completion of behavioral studies Results: Treatment with a higher dose of colchicines (3µg/mice) caused memory deficit as shown by no significant decrease in escape latency time throughout all the sessions. Results of biochemical estimation showed a marked increase in malondialdehyde (MDA), nitrite level, reduced glutathione (GSH) level, cholinotoxic effect of colchicines has been correlated by marked decrease in acetyl cholinesterase (AChE) activity. Colchicine in a dose of 3 µg/mice has been validated. Pretreatment with candesartan in doses 0.05 and 0.1 mg/kg reverses oxidative stress which can be measured by decreased MDA, nitrite level and increased GSH level. Increased AChE activity may imply protection of cholinergic neurons hence improvement in learning and memory behavior. Conclusion: Preventive treatment with angiotensins receptor blocker, candesartan showed that memory impairment induced by colchicines may be mediated by alteration of central rennin angiotensins system and loss of cholinergic neurons. This study highlighted a number of clinical findings which support marked neuroprotection by blocked of the central AT1 receptor.

In a focused exploration, thiazolidin-4-ones with different C-2 and N-3 substituent groups were synthesized and evaluated as non-nucleoside reverse transcriptase inhibitors against HIV-1. This has led to new active compounds sporting heteroaryls at both C-2 and N-3 positions prompting to view them in the backdrop of nevirapine. To assign the molecular attributes for the activity, the compounds are investigated by docking them into non-nucleoside inhibitor-binding pocket of HIV-1 reverse transcriptase (RT). The most active compounds of this series (7d and 7f) shared spatial features with nevirapine with added molecular flexibility. Furthermore, in molecular dynamics simulations carried out for up to 10 ns, the compounds 7d and 7f showed consistency in their interactions with non-nucleoside inhibitor-binding pocket of HIV-1 RT and suggested Tyr319 and Val106 as potential residues for H-bond interaction with these molecules. These results open new avenues for the exploration of 2,3-diheteroaryl thiazolidin-4-ones for prevention of HIV-1.

Background Lumefantrine is the mainstay of anti-malarial combination therapy in most endemic countries presently. However, it cannot be used alone owing to its long onset time of action. CDRI 97–78 is a promising trioxane-derivative anti-malarial candidate that is currently being investigated as a substitute for artemisinin derivatives owing to their emerging resistance. Methods In the present study, a sensitive, simple and rapid high-performance liquid chromatography coupled with positive ion electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed for the simultaneous determination of lumefantrine and CDRI 97-78’s metabolite, 97–63, in rat plasma using halofantrine as an internal standard. Lumefantrine and 97–63 were separated on a Waters Atlantis C18 (4.6 × 50 mm, 5.0 μm) column under isocratic condition with mobile phase consisting of acetonitrile: methanol (50:50, v/v) and ammonium formate buffer (10 mM, pH 4.5) in the ratio of 95:5 (v/v) at a flow rate of 0.65 mL/min. Results The method was accurate and precise within the linearity range 3.9-500 ng/mL for both lumefantrine and 97–63 with a correlation coefficient (r2) of ≥0.998. The intra- and inter-day assay precision ranged from 2.24 to 7.14% and 3.97 to 5.90%, and intra- and inter-day assay accuracy was between 94.93 and 109.51% and 96.87 and 108.38%, respectively, for both the analytes. Upon coadministration of 97–78, the relative bioavailability of lumefantrine significantly decreased to 64.41%. Conclusions A highly sensitive, specific and reproducible high-throughput LC-ESI-MS/MS assay was developed and validated to quantify lumefantrine and CDRI 97–78. The method was successfully applied to study the effect of oral co-administration of lumefantrine on the pharmacokinetics of 97–78 in male Sprague–Dawley rats and vice versa. Co-administration of 97–78 significantly decreased the systemic exposure of lumefantrine. Electronic supplementary material The online version of this article (doi:10.1186/s12936-015-0684-5) contains supplementary material, which is available to authorized users.

Withania somnifera (Linn.) Dunal (Solanaceae), a clinically used herbal drug in Ayurveda, shows potent antioxidant, anti-inflammatory, pro-apoptotic, and cardioprotective effects. However, the efficacy of W. somnifera in pulmonary hypertension (PH), a cardiopulmonary disorder, remains unexplored.The present study investigates the effect of W. somnifera root powder on monocrotaline (MCT)-induced PH in rats.In preventive studies, W. somnifera root powder (50 and 100 mg/kg/d, p.o.) was administered from day 1 following single administration of MCT (60 mg/kg, s.c.) in Sprague-Dawley (SD) rats. After 35 d, right ventricular pressure (RVP) was measured in anesthetized rats. Various physical markers of right ventricular hypertrophy (RVH) were measured in isolated hearts. Markers of endothelial function, inflammation, and oxidative stress were estimated in lung homogenate. Vasoreactivity of pulmonary arteries was also studied. In therapeutic treatment, W. somnifera (50 and 100 mg/kg/d, p.o.) was administered from day 21 to 35 post-MCT administration.Preventive treatment with 50 and 100 mg/kg W. somnifera significantly reduced the RVP (32.18 ± 1.273 mm Hg and 29.98 ± 1.119 mm Hg, respectively, versus 42.96 ± 1.789 mm Hg of MCT) and all markers of RVH in MCT-challenged rats. There was an improvement in inflammation, oxidative stress and endothelial dysfunction, and attenuation of proliferative marker and apoptotic resistance in lungs. Therapeutic treatment with W. somnifera (100 mg/kg) also reduced RVP and RVH.This study demonstrated that W. somnifera significantly protected against MCT-induced PH due to its antioxidant, anti-inflammatory, pro-apoptotic, and cardioprotective properties.

Metformin (MTF) improves hyperglycemia primarily by suppressing glucose production by the liver. The objective of our investigation was to evaluate nanoemulsion as a promising carrier for MTF for sustained hypoglycemic effect. The drug was incorporated into oil phase of nanoemulsion, which finally improved biopharmaceutical properties achieved when compared with lipid based systems. Pseudo ternary phase diagrams were prepared by aqueous titration method. Formulations were selected at a difference of 5% v/v of oil from the o/w nanoemulsion region of phase diagrams, and then thermodynamic stability and dispersibility tests were performed. The composition of optimized formulation was hydrogenated castor oil (5% v/v), 30% v/v of surfactant (tween 80), co-surfactant (transcutol) and distilled water (65% v/v) as an aqueous phase. The preparation showed maximum drug release (98.70%), optimal globule size (92.25 nm), lowest polydispersity value (0.172), lesser viscosity (22.124 cps) and infinite dilution capability. The antidiabetic activity of optimized MTF nanoemulsion formulation evaluated by blood glucose estimation showed significant hypoglycemic effect which was comparable to that observed with conventional marketed formulation in experimental diabetic rats. Optimized formulation was subjected to stability studies at different temperature and relative humidity and was found to be stable. No significant variations were observed in the formulation over a period of 3 months at accelerated storage conditions.

The synthesis and SAR studies of 10 new chemical entities (NCEs) that have shown BMP-2 stimulation and osteoblast differentiation are reported. Among these, 2-((1-(benzyl(2-hydroxy-2-phenylethyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamoyl)benzoic acid (11) was the most effective while its analogue 13 also showed good activity in inducing osteoblast BMP-2 production. Compound 11 induced osteoblast differentiation in vitro, and this effect was abrogated by a physiological BMP-2 inhibitor, noggin. It also exhibited dose dependent increase in nascent bone formation (2.16- and 3.12-fold more than the control at 1 and 5 mg/kg dose, respectively) at the fracture site in rats. At the maximum osteogenic concentration, compound 11 significantly inhibited osteoblastic proteosomal activity. This compound was safe, as it had no effect on BMP synthesis in cardiovascular tissue.

Traditional knowledge and ethno-botanical use of plants have been widely acknowledged all over the world. Certain people of India, using whole plant of Euphorbia hirta L . as an effective remedy for varities of diseasese. The documentation of traditional knowledge from eastern Uttar pardesh area reveals that it is highly widely used in Ayurveda . Pharmacological and physico- chemical details of E.hirta not available in authentic litrature including API (Ayurvedic Pharmacopea of India) So the validation and standardisation of whole plant of Euphorbia hirta . was carried out to establish its macro- and microscopical standards, physicochemical parameters, preliminary phytochemical investigation and TLC profiles to evaluate the characters of the plant. Macroscopic characters of E. hirta leaves shows composition of leaf is simple with dark green color about 2-6cm. long in size, T.S. of the leaf revealed the presence of stomata, upper and lower epidermis, vascular bundle. Powder characteristics revealed the presence of starch gran-ules, covering trichomes. The various diagnostic characteristic of leaf powder was coarse, dark green, which revealed the presence of lignified xylem vessel,anomocytic type of sto-mata, Physicochemical parameters were also evaluated. Preliminary phytochemical analysis indicated a high percentage of quercetine and flavonoids and this may be one of the reasons behind the anti diabatic and hepatoprotective activity of this plant. The above parameters, which are being reported for the first time in this plant, are significant towards establishing the pharmacognostic standards for future identification and authentication of genuine plant material used Ayurveda for various diaeases in eastern UP.