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Ethnopharmacological Relevance: Calotropis procera (Ait.) R.Br. is one of an ancient traditional shrub, which has been used for the treatment of diabetes, pain and inflammation for thousands of years in India. The root extract of Calotropis procera has been widely used by the tribal׳s of district Udaipur, Rajasthan (India) for treatment of diabetes mellitus and its associated complications like diabetic neuropathy. The present study was performed to explore the protective effect of root, stem and leaf extracts of Calotropis procera in diabetes and diabetic neuropathy against tactile allodynia, mechanical hyperalgesia and thermal hyperalgesia in streptozotocin induced diabetic rats., Materials and Methods: Diabetes and peripheral neuropathy were induced in Wistar rats by injection of streptozotocin (45 mg/kg/intraperitoneally). The roots, stem and leaves of Calotropis procera were sequentially extracted with petroleum ether, chloroform, ethyl acetate and methanol. All the extracts were assessed by oral administration at 100 and 250 mg/kg in streptozotocin diabetic rats. The following compounds were used as positive controls: insulin NPH (1 IU/kg/day), metformin (500 mg/kg/day), glibenclamide (2.5 mg/kg/day) and a combination of acarbose (20 mg/kg/day) with methylcobalamine (500 µg/kg/day). In contrast, the streptozotocin induced untreated diabetic rats termed as negative control. Thermal hyperalgesia, mechanical hyperalgesia and tactile allodynia were evaluated in all groups of streptozotocin diabetic rats to assess the extent of neuropathy by Eddy׳s hot plate, tail immersion, Randall-Selitto and Von Frey hair tests. The basal nociceptive thresholds were assessed in week 4 of post streptozotocin injection. All groups received their treatment on a regular basis from 28 to 42 days following a confirmation of diabetic neuropathy. The nociceptive thresholds were assessed in all groups in week 5 and 6. The histopathology of pancreas and biochemical estimations of plasma insulin and glycosylated haemoglobin (HbA1C%) levels were also performed in week 6 of post streptozotocin injection., Results: The negative control rats developed diabetes and diabetic neuropathy after 6 week of streptozotocin administration distinguished by significant (p<0.01) hyperalgesia and tactile allodynia with enhanced HbA1C% level compared to normoglycemic rats. Chronic administration of root methanol, stem methanol and leaf ethyl-acetate extracts of Calotropis procera for 2 weeks at 100 and 250 mg/kg doses significantly (p<0.01) attenuated the diabetes induced mechanical hyperalgesia, thermal hyperalgesia, tactile allodynia and HbA1C% level in streptozotocin diabetic rats as compared to negative control rats. Further, the root methanol extract of Calotropis procera in 100mg/kg dose showed the regeneration capability of β cells in the histology of pancreas with significant (p<0.01) improvement in plasma insulin level in streptozotocin diabetic rats compared to negative control rats., Conclusion: Root methanol extract of Calotropis procera (100mg/kg) has shown ameliorative effect in diabetic neuropathy which may be attributed by its multiple actions including potent hypoglycemic and antioxidant., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: The whole plant of Fagonia schweinfurthii (Hadidi) Hadidi (Family: Zygophyllaceae) is used in variety of diseases including hepatic ailments in deserts and dry areas of India., Aim of the Study: To evaluate antioxidant and hepatoprotective activity of ethanolic extract from Fagonia schweinfurthii (Hadidi) Hadidi (FSEE) in carbon tetrachloride (CCl4) induced hepatotoxicity in HepG2 cell line and rats., Materials and Methods: In vitro antioxidant activity was determined by DPPH, ABTS radicals and hydrogen peroxide methods. In vitro cytotoxicity and hepatoprotective potential of FSEE were evaluated using HepG2 cells. Based on the cytotoxicity assay, FSEE (50, 100, 200 µg/ml) was assessed for hepatoprotective potential against CCl4 induced toxicity in HepG2 cell line by monitoring cell viability, aspartate aminotransferase (AST), alanine aminotransaminase (ALT), lactate dehydrogenase (LDH) leakage, lipid peroxidation (LPO) and glutathione level (GSH). Further, in vivo hepatoprotective activity of FSEE was evaluated against CCl4 induced hepatotoxicity in male Wistar albino rats. Rats were pre-treated with FSEE (200 mg, 400 mg kg(-1) day(-1) p.o.) for 7 days followed by a single dose of CCl4 (1.0 ml/kg, i.p.) on 8th day. Silymarin was used as positive control. After 24h of CCl4 administration, various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransaminase (ALT), alkaline phosphatase (ALP), total bilirubin (TB) and total protein (TP) levels were estimated in serum. The antioxidant parameters like superoxide dismutase (SOD) activity, catalase (CAT) activity, glutathione (GSH) content and malondialdehyde (MDA) level in the liver homogenate were determined. Histopathological changes in the liver of different groups were also studied., Results: The FSEE possessed strong antioxidant activity in vitro. The results indicated that CCl4 treatment caused a significant decrease in cell viability. The CCl4-induced changes in the HepG2 cells were significantly ameliorated by treatment of the FSEE. FSEE significantly prevented CCl4 induced elevation of AST, ALT, ALP, TB, and CCl4 induced decrease in total protein in rats. FSEE treated rat liver anti-oxidant parameters (SOD, CAT, MDA and GSH,) were significantly antagonized for the pro-oxidant effect of CCl4. Histopathological studies also supported the protective effect of FSEE., Conclusion: The results of this study revealed that FSEE has significant hepatoprotective activity. This effect may be due to the ability of the extract to inhibit lipid peroxidation and increase in the anti-oxidant enzymatic activity., (© 2013 Elsevier Ireland Ltd. All rights reserved.)

Ziziyphus nummularia (family: Rhamnaceae) is a thorny small bush, grows in abundance in the grazing lands of the arid areas of Rajasthan, India. It is an important ethnomedicinal plant of the Thar Desert; local inhabitants use every part of the plant as medicine. Kernels are prescribed in pregnancy as soporific, antiemetic and for relieving abdominal pain. The insect gall is powered and given orally with water to cure bone fracture. Crushed root is applied on the paining shoulder of the bullock. The decoction of leaves is used for the treatment of cough and cold; leaves are also regarded as diaphoretic and prescribed in typhoid. Paste of leaves is used for healing of cuts, boils and cutaneous disease. It is widely used in pain and inflammatory conditions. Z. nummularia contains a unique group of alkaloids known as cyclopeptide alkaloids, in continuation of our work carried out on the leaves of Z. nummularia , present study was initiated to explore antiinflammatory and analgesic potential of cyclopeptide alkaloids isolated from the leaves of Z. nummularia (IFZN). Anti-inflammatory activity was tested against rat paw oedema, mouse peritonitis and cotton pellet granuloma. For screening of analgesic activity, acetic acid induced writhing, tail flick and hot plate test were performed. IFZN 30 mg/kg shows the anti-oedematogenic effect against paw oedema induced by carrageenan, dextran, serotonin and histamine; IFZN 20 and 30 mg/kg were found to have highly significant anti-nociceptive effects. Result of pharmacological studies indicated that IFZN is a potent and efficacious analgesic agent. The analgesic activity of IFZN is mediated by the peripheral as well as central pathways.

Ethnopharmacological Relevance: [corrected] Euphorbia caducifolia is a Euphorbiaceae species native to Thar Desert of India, where latex of E. caducifolia (ECL) is used by the local inhabitants for treatment of bleeding wound, cutaneous eruption and other skin diseases. Looking to the medicinal importance of the plant, it was considered worthwhile to scientifically evaluate the ECL for the wound healing activity., Material and Methods: In vitro methods, clotting of platelet free plasma and angiogenesis in chick chorioallantoic membrane (CCM) were used for studying effect of ECL on clotting and angiogenesis. Excision and incision wounds model were used to study effect of ECL on wound contraction, tensile strength and hydroxyproline and DNA content., Results: ECL treatment stimulates the blood vessel formation in CCM, at the all dose levels. 56.77, 74.48 and 78.09% increase in area of angiogenesis was observed in ECL 2.5, 5.0 and 10mg/ml treated groups respectively. The excised skin of ECL 5.0 and 10mg/ml treated animals found to have higher content of hydroxyproline and DNA, when compared with control group. An acceleration of the wound closure was observed with an enhanced number of fibroblasts and collagen content in ECL treated mice., Conclusion: Result of in vitro and in vivo experiments indicate that ECL exerts significant wound healing activity, demonstrating its relevant therapeutic potential., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: Generic drugs are identical or bioequivalent versions of the brand name drugs. They are the economic alternative of the costlier brand name drugs. This article presents a general overview of the procedure and regulatory aspects relating to generic drug approval in the US., Methods: A computerized search was conducted to find literature on generic drug approval in the US. The literature was searched using the following key words: generic drug, brand name drug, Hatch-Waxman Act, Medicare Act, NDA, ANDA, CTD and exclusivity., Findings: The search results were filtered for the literature describing and analyzing the procedure and regulatory provisions for generic drug approval in the US. After the screening total 19 applicable literature remained., Conclusion: In the US standardized procedures for the recognition of generic drugs have been laid down under the Drug Price Competition and Patent Term Restoration Act, 1984 (the Hatch-Waxman Act). Provisions of this Act such as patent challenge, patent term extension and data exclusivity have created profound effects on the approval, sale and distribution of the pharmaceuticals in the US. The Hatch-Waxman Act is an excellent piece of legislation that takes care of the rights of both the brand name and generic drug companies. This article presents only an overview of generic drug approvals and for all practical purposes official resources should be referred.

A new reverse phase high performance liquid chromatography method for the simultaneous estimation of frusemide and amiloride hydrochloride in tablet formulation is developed. The determination was carried out on a HIQ SIL, C18 (250×4.6 mm, 5 µm) column using a mobile phase of 50 mM phosphate buffer solution:acetonitrile (50:50 v/v, pH 3.0). The flow rate was 1.0 ml/min with detection at 283 nm. The retention time for frusemide was 3.038 min and for amiloride hydrochloride 10.002 min. Frusemide and amiloride hydrochloride showed a linear response in the concentration range of 20-200 µg/ml and 10-100 µg/ml, respectively. The results of analysis have been validated statistically and by recovery studies. The mean recoveries found for frusemide was 99.98% and for amiloride hydrochloride was 100.09%. Developed method was found to be simple, accurate, precise and selective for simultaneous estimation of frusemide and amiloride hydrochloride in tablets.

A new simple, sensitive, precise, and accurate high-performance liquid chromatography (HPLC) method of analysis for artemether both as a bulk drug and in capsule formulations was developed and validated. The method employed mobile phase acetonitrile (ACN) and buffer in the ratio 65:35 of pH 6.5 adjusted with tryethylamine. The linear regression analysis data for the calibration plots showed good linear relationship with r(2) = 0.9996 in the concentration range 250-750 μg/ml. The mean value slope and intercept were 9355.5 and -93.5, respectively. The method was validated for precision, accuracy, and recovery studies. Limit of detection (LOD) and Limit of quantitation (LOQ) for artemether were found to be 21.83-750 μg/ml, respectively. The method has been successfully applied in the analysis of marketed capsule formulations. The presented method was found to be reliable to separate all the degradents from all the stress conditions with resolution of more than 1.5 showing that it is a stability indicating method.

A series of 4-aryl substituted semicarbazones of pyridyl carbaldehyde and pyridyl methyl ketone were designed and synthesized to meet the structural requirements essential for anticonvulsant activity. The structure of synthesized compounds were confirmed by IR spectroscopy, PMR spectroscopy and nitrogen estimation. All the compounds were evaluated for anticonvulsant activity and neurotoxicity. Anticonvulsant activity was determined after intraperitoneal (i.p.) administration to mice by maximal electroshock (MES) and subcutaneous metrazol (ScMet) induced seizure methods and minimal motor impairment was determined by rotorod test. Majority of compounds exhibited significant anticonvulsant activity after intraperitoneal administration. The results obtained showed that 85.7 % of the compounds afforded protection in the MES test and 64.2 % of the total compounds afforded protection in ScPTZ test. Some of them also showed good activity after oral administration. In this study (Methyl-4- pyridyl) ketone -N(4)- (p- chloro phenyl) substituted semicarbazone emerged as most active derivative showing activity at 100 mg/kg in both the test with prolonged duration of action. In the present study semicarbazones of pyridyl containing carbonyl compounds emerges as the lead molecule, showing broad spectrum of activity with low neurotoxicity and prolong duration of action on oral administration. Thus these may be utilized for the future development of novel anticonvulsants with broad spectrum of anticonvulsant activity.

Capparis decidua (frock) Edgew (family Capparidaceae) is a xerophytic shrub, commonly known as karrel or ker, whose bark and shoot are used as analgesic, anti-inflammatory, hypolipidemic, and antidiabetic agents. The plant contains generous quantities of alkaloids. An alcoholic extract of aerial parts of C. decidua, including flowers and fruits, was screened for central nervous system (CNS) activity using conventional behavioral animal models. In the open field test all doses of C. decidua extract tested decreased the number of rearings, grooming, and fecal bolus (P < 0.001) when compared with control. In the barbiturate-induced sleeping test a significant (P < 0.001) a decrease in latency of sleeping and increase in sleeping time were observed at all doses (100, 200, and 300 mg/kg). C. decidua extract increased the percentage of animals exhibiting motor deficit in the rotarod test. In the pentylenetetrazole-induced seizures test the C. decidua extract dose-dependently decreased (P < 0.05) the number of animals with convulsions and increased convulsion latency (P < 0.001); none of the animals treated with extract died in the test. C. decidua extract decreased the duration of tonic hind leg extension in maximal electroshock-induced seizures (P < 0.001) when compared with control. The findings of the present animal study suggested that C. decidua has CNS depressant and anticonvulsant activities.