Synthetic heterocyclic derivatives as promising xanthine oxidase inhibitors: An overview.

Inhibition of xanthine oxidase (XO) is an effective and most prominent therapeutic approach for the management of gout. Discovery of its association in the pathophysiology of diabetes, cardiovascular disorders, etc., widened its therapeutic horizons. Limited drug candidates in clinical practice along with side effects forced researchers to develop more efficacious and safer XO inhibitors for the management of gout and other disorders associated with XO hyperactivity. In this regard, this review focus on (a) various drug candidates in clinical practice and under clinical trials, (b) Development of various heterocyclic motifs as XO inhibitors in last two decades and (c) various patented synthetic XO inhibitors.

Evaluation of antimicrobial potential of successive extracts of Ulmus wallichiana Planch.

BACKGROUND: The plant Ulmus wallichiana Planch. is found in hills of Uttarakhand, India. Bark of U. wallichiana is commonly used as traditional healer for bone fracture of animals as well as human beings and also used as wound healer remedy. OBJECTIVE: The present study was designed to evaluate antimicrobial potential of various extracts of U. wallichiana bark. MATERIALS AND METHODS: Soxhlet extraction method was used for preparation of different extracts viz. petroleum ether, chloroform, ethyl acetate, ethanol and aqueous. Antioxidant activity was determined by DPPH and FRAP assay method. In vitro antimicrobial activity was evaluated using agar well diffusion method. RESULTS: Ethyl acetate extract exhibited the highest significant antioxidant activity. Antibacterial activity was performed against Escherichia coli, Bacillus subtilis, Staphylococcusaureus and Pseudomonas aeruginosa. Amongst the various extracts tested, only ethyl acetate exhibited highest zone of inhibition as compared to other extracts and greater than standard drug. Chloroform extract also showed moderate zone of inhibition. Antifungal activity was evaluated against Aspergillus fumigates and Aspergillus flavus. The ethyl acetate extract showed maximum zone of inhibition as compared to other extracts. Chloroform extract showed mild antifungal activity. Chloramphenicol and nystatin were used as a positive control as antibacterial and antifungal agent respectively. Furthermore, the highest percentage of phenolic and flavonoid compounds was estimated in ethyl acetate extract. CONCLUSION: The ethyl acetate extract of U. wallichiana showed the highest antimicrobial activity, and should be further investigated for isolating active compound(s) responsible for antimicrobial activity.

Evaluation of antioxidant and free-radical scavenging potential of Artemisia absinthium.

CONTEXT: Currently there has been an increased global interest to identify antioxidant compounds for use in preventive medicine and the food-industry that are pharmacologically potent and have low or no side effects. As plants produce significant amount of antioxidants to prevent oxidative stress, they represent a potential source of new compounds with antioxidant activity. OBJECTIVE: The current study was designed to evaluate the methanol extract of Artemisia absinthium Linn. (Asteraceae; MAB) for its in vitro free-radical scavenging effects using different classical assays, and in vivo antioxidant activity using global cerebral ischemia and reperfusion (I/R)-induced oxidative stress in mice. MATERIALS AND METHODS: The in vitro scavenging activity was studied on the superoxide anions, hydrogen peroxide, hydroxyl, nitric oxide radical, and reducing power. Further, in the in vivo studies, the animal model of global cerebral I/R was established by occluding the bilateral carotid artery for 15 min followed by 24-h reperfusion. The thiobarbituric acid reactive substances (TBARS) concentration, superoxide dismutase (SOD) activity and glutathione (GSH) content were determined by colorimetric assays. RESULTS: In the in vitro assays, methanol extract of A. absinthium showed significant (p<0.05) superoxide anion, hydrogen peroxide, hydroxyl and nitric oxide radical scavenging activities, and significant reducing power. Furthermore, in the in vivo studies, oral administration of MAB (100 or 200 mg/kg) inhibited cerebral I/R-induced oxidative stress by decreasing TBARS, and restoring levels of SOD and GSH. CONCLUSION: The results indicated that A. absinthium possess potent antioxidant properties, and may be used as a protective agent against disorders associated with oxidative stress.

Role of Ocimum basilicum L. in prevention of ischemia and reperfusion-induced cerebral damage, and motor dysfunctions in mice brain.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Ocimum (Lamiaceae) has a long history of use as culinary and medicinal herbs. Many species are used for their antioxidant and neuroprotective activity in various parts of the world. Ocimum basilicum Linn. has been used traditionally for the treatment of anxiety, diabetes, cardiovascular diseases, headaches, nerve pain, as anticonvulsant and anti-inflammatory, and used in a variety of neurodegenerative disorders. AIM OF THE STUDY: The present study is designed to investigate the effect of ethyl acetate extract of Ocimum basilicum leaves on ischemia and reperfusion-induced cerebral damage, and motor dysfunctions in mice. MATERIALS AND METHODS: Global cerebral ischemia was induced by bilateral carotid artery occlusion for 15 min followed by reperfusion for 24h. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. The concentration of thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) content was determined by colorimetric assay. Short-term memory was evaluated using elevated plus-maze. Inclined beam walking was employed to assess motor coordination. Bilateral carotid artery occlusion followed by reperfusion produced significant increase in cerebral infarct size and lipid peroxidation (TBARS), and reduced GSH content, and impaired short-term memory and motor coordination. RESULTS: Pre-treatment with standardized ethyl acetate extract of Ocimum basilicum (100 and 200mg/kg, p.o.) markedly reduced cerebral infarct size and lipid peroxidation, restored GSH content, and attenuated impairment in short-term memory and motor coordination. CONCLUSION: The results of the study suggest that Ocimum basilicum could be useful clinically in the prevention of stroke.

Evaluation of Antioxidant and Cerebroprotective Effect of Medicago sativa Linn. against Ischemia and Reperfusion Insult.

Antioxidants have been the focus of studies for developing neuroprotective agents to be used in the therapy for stroke, which is an acute and progressive neurodegenerative disorder. Medicago sativa (MS) has a long tradition of use as ayurvedic and homoeopathic medicine in central nervous system disorders. The plant has been reported to have antioxidant, anti-inflammatory and antidiabetic effects. Therefore, the present study was designed to investigate the neuroprotective effect of methanol extract of MS on ischemia and reperfusion-induced cerebral injury in mice. Bilateral carotid artery occlusion (BCAO) for 15 min followed by 24-h reperfusion, resulted in significant elevation in infarct size, xanthine oxidase (XO) activity, superoxide anion (O(•-) (2)) production and thiobarbituric acid-reactive substance (TBARS) levels, and significant depletion in endogenous antioxidant [reduced glutathione (GSH), superoxide dismutase (SOD) and total tissue sulfhydryl (T-SH) groups] systems in mice brain. Further, BCAO led to impairment in short-term memory and motor coordination. Pre-treatment with MS (100 or 200 mg kg(-1), p.o.) markedly reduced cerebral infarct size, XO, O(•-) (2) and TBARS levels, significantly restored GSH, SOD and T-SH levels and attenuated impairment in short-term memory and motor coordination. In addition, MS directly scavenged free radicals generated against a stable radical 1,1-diphenyl-2-picrylhydrazyl and O(•-) (2) generated in phenazine methosulphate-nicotinamide adenine dinucleotide systems, and also inhibited XD/XO conversion and resultant O(•-) (2) production. The data from this study suggest that treatment with MS enhances the antioxidant defense against BCAO-induced global cerebral ischemia and exhibits neuroprotective activity.

The genus Artemisia: a comprehensive review.

CONTEXT: Medicinal plants are nature's gift to human beings to make disease free healthy life, and play a vital role to preserve our health. They are believed to be much safer and proven elixir in the treatment of various ailments. The genus Artemisia (Astraceae) consists of about 500 species, occurring throughout the world. The present review comprises the ethnopharmacological, phytochemical and therapeutic potential of various species of Artemisia. OBJECTIVE: The aim of this this review is to bring together most of the available scientific research conducted on the genus Artemisia, which is currently scattered across various publications. Through this review the authors hope to attract the attention of natural product researchers throughout the world to focus on the unexplored potential of Artemisia species. METHODS: This review has been compiled using references from major databases such as Chemical Abstracts, Medicinal and Aromatic Plants Abstracts, ScienceDirect, SciFinder, PubMed, King's American Dispensatory, Henriette's Herbal Homepage, Dr. Duke's Phytochemical and Ethnobotanical Databases. RESULTS: An exhaustive survey of literature revealed that the different species of Artemisia have a vast range of biological activities including antimalarial, cytotoxic, antihepatotoxic, antibacterial, antifungal and antioxidant activity. Some very important drug leads have been discovered from this genus, notably artemisinin, the well known antimalarial drug isolated from the Chinese herb Artemisia annua. Terpenoids, flavonoids, coumarins, caffeoylquinic acids, sterols and acetylenes constitute major classes of phytoconstituents of the genus. CONCLUSION: Various species of Artemisia seems to hold great potential for in-depth investigation for various biological activities, especially their effects on the central nervous and cardiovascular systems.

Phytochemical and pharmacological potential of Medicago sativa: a review.

CONTEXT: Many herbal remedies have so far been employed for the treatment and management of various ailments since the beginning of human civilization. Medicago is an extensive genus of the family Leguminosae, comprising about 83 different species. Medicago sativa (Linn.) has long been used as traditional herbal medicine in China, Iraq, Turkey, India and America for the treatment of a variety of ailments. OBJECTIVES: The aim of this review was to collect all available scientific literature published and combine it into this review. The present review comprises the ethnopharmacological, phytochemical and therapeutic potential of M. sativa. METHODS: The present review includes 117 references compiled from major databases as Chemical Abstracts, Science Direct, SciFinder, PubMed, Dr. Dukes Phytochemical and Ethnobotany, CIMER, and InteliHealth. RESULTS: An exhaustive survey of literature revealed that saponins, flavonoids, phytoestrogens, coumarins, alkaloids, amino acids, phytosterols, vitamins, digestive enzymes and terpenes constitute major classes of phytoconstituents of this plant. Pharmacological reports revealed that it is used as neuroprotective, hypocholesterolemic, antioxidant, antiulcer, antimicrobial, hypolipidemic, estrogenic, and in the treatment of atherosclerosis, heart disease, stroke, cancer, diabetes and menopausal symptoms in women. CONCLUSION: M. sativa seems to hold great potential for in-depth investigation for various biological activities, especially their effects on central nervous and cardiovascular system. Through this review, the authors hope to attract the attention of natural product researchers throughout the world to focus on the unexplored potential of M. sativa, and it may be useful in developing new formulations with more therapeutic value.

Cerebroprotective effect of Ocimum gratissimum against focal ischemia and reperfusion-induced cerebral injury.

CONTEXT: Oxidative stress is believed to increase delayed neuronal death in the brain following ischemia. As a consequence, many attempts to reduce the damage resulting from cerebral ischemia under more highly oxidized conditions have focused on treatments aimed at maintaining the redox equilibrium of the local environment. Many antioxidants were shown to be neuroprotective in experimental models of cerebral ischemia and reperfusion. OBJECTIVE: The present study was designed to investigate the potential protective effects of ethanol extract of Ocimum gratissimum Linn. (Lamiaceae) (EEOg) against focal ischemia and reperfusion (I/R) insult in rat brain. MATERIALS AND METHODS: The animal model of focal I/R was established by occluding the middle cerebral artery (MCA) of male Wistar rats for 2 h, followed by 24 h reperfusion. The thiobarbituric acid reactive substances concentration, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity were determined by colorimetric assays. The characterization and quantitative analysis of phenolic content was determined using HPLC. RESULTS: MCA occlusion led to significant rise in cerebral infarct volume and lipid peroxidation, and depletion in SOD and GPx in brain. The neurological deficits were also significantly elevated by MCA occlusion. All the brain oxidative stress, damage and neurological deficits were significantly attenuated by pre-treatment with EEOg (150 or 300 mg/kg, p.o.). CONCLUSION: The overall finding suggests the neuroprotective potential of O. gratissimum in cerebral ischemia, and is mediated through its antioxidant activity. Therefore, O. gratissimum should be investigated further as a possible strategy against cerebral stroke.

Neuroprotective effect of Artemisia absinthium L. on focal ischemia and reperfusion-induced cerebral injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia absinthium L. has long been used as traditional herbal medicine in China, Europe and Pakistan for the treatment of gastric pain, cardiac stimulation, to improve memory and for the restoration of declining mental function. AIM OF THE STUDY: The present study was designed to investigate the potential protective effects of Artemisia absinthium on cerebral oxidative stress and damage as well as behavioral disturbances induced by cerebral ischemia and reperfusion injury in rats. MATERIALS AND METHODS: Focal ischemia and reperfusion were induced by middle cerebral artery occlusion (MCAO) for 90 min, followed by 24 h reperfusion. MCAO led to significant rise in infarct size and lipid peroxidation, and depletion in glutathione content, superoxide dismutase and catalase activity in brain. Further, behavioral deficits like motor incoordination and impairment of short-term memory were also significantly impaired by MCAO as compared with sham group. RESULTS: The brain oxidative stress and damage, and behavioral deficits were significantly attenuated by pre-treatment with the methanol extract of Artemisia absinthium (100 mg/kg and 200 mg/kg, p.o.). CONCLUSION: These findings suggested that Artemisia absinthium is neuroprotective and may prove to be useful adjunct in the treatment of stroke.