Synthesis of Some Benzofuran Derivatives Containing Pyrimidine Moiety as Potent Antimicrobial Agents.

In this investigation, the synthesis of 2-substituted pyrimidines by the reaction of benzofuran chalcones (3a-d) with urea, thiourea and guanidine hydrochloride was reported. The structures of title compounds (4a-d), (5a-d) and (6a-d) were established on the basis of analytical and spectral data. The synthesized compounds were screened for antimicrobial activity and molecular docking studies. Some of the compounds displayed excellent antimicrobial activity. The molecular docking analysis revealed that compounds 5a and 5c with the lowest binding energy in comparison to others suggesting its potential as best inhibitor of GluN-6-P. Consequently, it is confirmed from the above analysis that the compounds 5a and 5c might serve as a useful backbone scaffold for rational design, adaptation and investigation of more active analogs as potential broad spectrum antimicrobial agents.

Viper venom hyaluronidase and its potential inhibitor analysis: a multipronged computational investigation.

Viper venom hyaluronidase (VV-HYA) inhibitors have long been used as therapeutic agents for arresting the local and systemic effects caused during its envenomation. Henceforth, to understand its structural features and also to identify the best potential inhibitor against it the present computational study was undertaken. Structure-based homology modeling of VV-HYA followed by its docking and free energy-based ranking analysis of ligand, the MD simulations of the lead complex was also performed. The sequence analysis and homology modeling of VV-HYA revealed a distorted (ß/α)8 folding as in the case of hydrolases family of proteins. Molecular docking of the resultant 3D structure of VV-HYA with known inhibitors (compounds 1-25) revealed the importance of molecular recognition of hotspot residues (Tyr 75, Arg 288, and Trp 321) other than that of the active site residues. It also revealed that Trp 321 of VV-HYA is highly important for mediating π-π interactions with ligands. In addition, the molecular docking and comparative free energy binding analysis was investigated for the VV-HYA inhibitors (compounds 1-25). Both molecular docking and relative free energy binding analysis clearly confirmed the identification of sodium chromoglycate (compound 1) as the best potential inhibitor against VV-HYA. Molecular dynamics simulations additionally confirmed the stability of their binding interactions. Further, the information obtained from this work is believed to serve as an impetus for future rational designing of new novel VV-HYA inhibitors with improved activity and selectivity.

Multi-targeting Andrographolide and its Natural Analogs as Potential Therapeutic Agents.

Andrographis paniculata (A. paniculata) is a medicinal plant used in the Indian and Chinese traditional medicinal systems for its various beneficial properties of therapeutics. This is due to the presence of a diterpene lactone called 'andrographolide'. Several biological activities like antiinflammatory, antitumour, anti-hyperglycaemic, anti-fertility, antiviral, cardio protective and hepatoprotective properties are attributed to andrographolide and its natural analogs. The studies have shown that not only this diterpene lactone (andrographolide), but also other related terpenoid analogs from A. paniculata could be exploited for disease prevention due to their structural similarity with diverse pharmacological activities. Several scientific groups are trying to unveil the underlying mechanisms involved in these biological actions brough aout by andrographolide and its analogs. This review aims at giving an overview on the therapeutical and/or pharmacological activities of andrographolide and its derivatives and also exemplify the underlying mechanisms involved.

The effect of a plant extract enriched in stigmasterol and ß-sitosterol on glycaemic status and glucose metabolism in alloxan-induced diabetic rats.

Banana is an extensively cultivated plant worldwide, mainly for its fruit, while its ancillary product, the banana pseudostem, is consumed as a vegetable and is highly recommended for diabetics in the traditional Indian medicine system. The present study was aimed at elucidating the mechanism of antihyperglycaemia exerted by the ethanol extract of banana pseudostem (EE) and its isolated compounds viz., stigmasterol (C1) and ß-sitosterol (C2), in an alloxan-induced diabetic rat model. Diabetic rats which were administered with C1, C2 and EE (100 and 200 mg per kg b. wt.) for 4 weeks showed reduced levels of fasting blood glucose and reversal of abnormalities in serum/urine protein, urea and creatinine in diabetic rats compared to the diabetic control group of rats. Diabetic symptoms such as polyphagia, polydipsia, polyuria, urine glucose and reduced body weight were ameliorated in the diabetic group of rats fed with EE, C1 and C2 (100 mg per kg b. wt., once daily) for 28 days. The levels of insulin and Hb were also increased, while the HbA1c level was reduced. The altered activities of hepatic marker enzymes viz., aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP); glycolytic enzyme (hexokinase); shunt enzyme (glucose-6-phosphate dehydrogenase); gluconeogenic enzymes (glucose-6-phosphatase, fructose-1,6-bisphosphatase and lactate dehydrogenase) and pyruvate kinase were significantly reverted to normal levels by the administration of EE, C1 and C2. In addition, increased levels of hepatic glycogen and glycogen synthase and the corresponding decrease of glycogen phosphorylase activity in diabetic rats illustrated the antihyperglycaemic potential of EE and its components. The histological observations revealed a marked regeneration of the ß-cells in the drug treated diabetic rats. These findings suggest that EE might exert its antidiabetic potential in the presence of C1 and C2, attributable to the enhanced glycolytic activity, besides increasing the hepatic glucose utilization in diabetic rats by stimulating insulin secretion from the remnant ß-cells.

In vivo Toxicity Studies on Gall Extracts of Terminalia chebula (Gaertn.) Retz. (Combretaceae).

UNLABELLED: The galls of Terminala chebula (Gaertn.) Retz. (Combretaceae) are used for the treatment of various diseases in folk medicine and has been found to posses anti-inflammatory, anti-bacterial, anti-helmintic, anti-tyrosinase, and anti-aging activities. Considering the ethano-botanical and diverse pharmacological applications of galls of T. chebula, in this study, we investigate the possible toxic effects of different gall extracts of T. chebula by Brine shrimp (Artemia salina) toxicity assay. The cytotoxicity test of leaf gall extracts (petroleum ether, chloroform, ethanol, and aqueous) of T. chebula was evaluated by Brine shrimp (A. salina) toxicity assay, which is based on the ability to kill laboratory cultured Artemia nauplii (animals eggs) and also total content of polyphenols, flavonoids with other qualitative phytochemical analysis of the extract were determined. It was observed that the petroleum ether extract was virtually nontoxic on the shrimps, and exhibited very low toxicity with LC50 value of 4356.76 µg/ml. Furthermore, the chloroform extract exhibited very low toxicity, giving LC50 value of 1462.2 µg/ml. On the other hand, the ethanol extract was very toxic to brine shrimps with LC50 value of 68.64 µg/ml. The ethanol extract had the highest total phenolic and flavonoid content of 136 ± 1.5 mg of gallic acid equivalent/g d.w and 113 ± 1.6 mg of quercetin equivalent/g d.w, respectively. The higher toxicity effect was positively correlated to the high content of total polyphenols/flavonoids in the extract. This significant lethality of different extracts to brine shrimp is an indicative of the presence of potent cytotoxic components which warrants further investigation. SUMMARY: The present study investigates the toxicity effect of different extracts of galls of T. chebulla, which would serve as an index for formulation of drugs for treatment of various diseases. Presumably, these activities could be attributed in part to the polyphenolic features of the extract, as there was a strong correlation of higher toxic effect with that of high total phenolic and flavonoids content in the ethanolic leaf gall extracts of T. chebula.

Inhibition of Group IIA Secretory Phospholipase A2 and its Inflammatory Reactions in Mice by Ethanolic Extract of Andrographis paniculata, a Well-known Medicinal Food.

UNLABELLED: Andrographis paniculata Nees is an important medicinal plant found in the tropical regions of the world, which has been traditionally used in Indian and Chinese medicinal systems. It is also used as medicinal food. A. paniculata is found to exhibit anti-inflammatory activities; however, its inhibitory potential on inflammatory Group IIA phospholipases A2 (PLA2) and its associated inflammatory reactions are not clearly understood. The aim of the present study is to evaluate the inhibitory/neutralizing potential of ethanolic extract of A. paniculata on the isolated inflammatory PLA2 (VRV-PL-VIIIa) from Daboii rusellii pulchella (belonging to Group IIA inflammatory secretory PLA2 [sPLA2]) and its associated edema-induced activities in Swiss albino mice. A. paniculata extract dose dependently inhibited the Group IIA sPLA2 enzymatic activity with an IC50 value of 10.3 ± 0.5 µg/ml. Further, the extract dose dependently inhibited the edema formation, when co-injected with enzyme indicating that a strong correlation exists between lipolytic and pro-inflammatory activities of the enzyme. In conclusion, results of this study shows that the ethanolic extract of A. paniculata effectively inhibits Group IIA sPLA2 and its associated inflammatory activities, which substantiate its anti-inflammatory properties. The results of the present study warranted further studies to develop bioactive compound (s) in ethanolic extract of A. paniculata as potent therapeutic agent (s) for inflammatory diseases. SUMMARY: This study emphasis the anti-inflammatory effect of A. paniculata by inhibiting the inflammatory Group IIA sPLA2 and its associated inflammatory activities such as edema. It was found that there is a strong correlation between lipolytic activity and pro-inflammatory activity inhibition. Therefore, the study suggests that the extract processes potent anti-inflammatory agents, which could be developed as a potential therapeutic agent against inflammatory and related diseases.

Evaluating the Anticancer Potential of Ethanolic Gall Extract of Terminalia chebula (Gaertn.) Retz. (Combretaceae).

UNLABELLED: Plants have been an important source for discovery of anticancer compounds. With the current decline in the number of new molecular entities from the pharmaceutical industry, novel anticancer agents are being sought from traditional medicines; therefore the anticancer efficacy of many plants that are used in traditional medicine is yet to be verified. The objective of the study was to evaluate the cytotoxic potential of ethanolic leaf gall extract of Terminalia chebula are evaluated against buffalo rat liver 3A, MCF-7 (Human mammary gland adenocarcinoma) and A-549 (Human lung cancer) cell lines. The cytotoxic effect of the ethanolic extract was evaluated by MTT assay. The extract was potent and effective in inducing cytotoxic effects in all the cell lines with an IC50 value of 305.18 ± 1.7 µg/mL, 643.13 ± 4.2 µg/mL, and 208.16 ± 3.7 µ/mL, respectively. The extract was more effective against A549 cell lines when compared to others. The presences of phenolics, triterpenoids, and flavonoids were identified in the extract. The extract showed total phenolic and flavonoid content of 478 ± 2.2 mg of gallic acid equivalent/g d.w and 538 ± 1.4 mg of quercetinequivalent/g d.w, respectively. This higher content of total phenolics and flavonoids found in the ethanolic extract was directly associated to higher cytotoxicity activity. CONCLUSION: The ethanolic leaf gall extract of T. chebula showed effective cytotoxic activities; which might be attributed to the phenolics/flavonoids present in higher concentration. Future work will be interesting to know the chemical composition of the extract and also better understand the mechanism of action of the constituents present in the extract to develop it as drug for therapeutic application. SUMMARY: The present investigation establishes the anticancer activities of T. chebula leaf gall extracts on BRL3A, MCF-7, and A-549 cells. Presumably, these activities could be attributed in part to the phenolics/flavanoids features of the extract that has been demonstrated to act as cytotoxic agents. The experimental evidence obtained in the laboratory model could provide a rationale for the traditional use of plant as a source of easily available effective anticancer agents to the people, particularly in developing countries.

The standard aqueous stem bark extract of Mangifera indica L. inhibits toxic PLA2 - NN-XIb-PLA2 of Indian cobra venom.

The aqueous extract of Mangifera indica is known to possess diverse medicinal properties, which also includes anti-snake venom activities. However, its inhibitory potency and mechanism of action on multi-toxic snake venom phospholipases A2s are still unknown. Therefore, the objective of this study was to evaluate the modulatory effect of standard aqueous bark extract of M. indica on NN-XIb-PLA2 of Indian cobra venom. The in vitro sPLA2, in situ hemolytic and in vivo edema inhibition effect were carried out as described. Also the effect of substrate and calcium concentration was carried out. M. indica extract dose dependently inhibited the GIA sPLA2 (NN-XIb-PLA2) activity with an IC50 value of 7.6 µg/ml. M. indica extract effectively inhibited the indirect hemolytic activity up to 98% at ∼40 µg/ml concentration. Further, M. indica extract (0-50 µg/ml) inhibited the edema formed in a dose dependent manner. When examined as a function of increased substrate and calcium concentration, there was no relieve of inhibitory effect of M. indica extract on the NN-XIb-PLA2. Further, the inhibition was irreversible as evident from binding studies. The in vitro inhibition is well correlated with in situ and in vivo edema inhibiting activities of M. indica. As the inhibition is independent of substrate and calcium and was irreversible, it can be concluded that M. indica extract mode of inhibition could be due to direct interaction of components present in the extract with the PLA2 enzyme. The aqueous extract of M. indica effectively inhibits svPLA2 enzymatic and its associated toxic activities, which substantiate their anti-snake venom properties. Further in-depth studies on the role and mechanism of the principal constituents present in the extract, responsible for the anti-PLA2 activity will be interesting to develop them into potent antisnake component and also as an anti-inflammatory agent.

Therapeutic Potentials of Triterpenes in Diabetes and its Associated Complications.

Diabetes is a major chronic metabolic disorder globally and around of 285 million people are affected by the disease and the number is expected to double in the next two decades. The major focus of anti-diabetic therapies is to enhance insulin production, sensitivity and/or reduce the blood glucose level. Although several synthetic drugs have been developed as antidiabetic agents but their utility has been hampered due to their side effects and poor efficacy. In this scenario, research on natural products has been gained importance due their safety profile in toxicity studies. Terpenoids belong to an important class of natural products and several terpenoids have been reported as antidiabetic agents. Some of them are under various stages of pre-clinical and clinical evaluation to develop them as antidiabetic agents. These agents can inhibit enzymes responsible for the development of insulin resistance, normalization of plasma glucose and insulin levels and glucose metabolism. Triterpenes can act as promising agents in the treatment of diabetic retinopathy, neuropathy and nephropathy or in impaired wound healing by inhibiting several pathways involved in the diabetes and associated complications. However, efforts in understanding the biological actions and clinical studies involving the applications of triterpenes in treating diabetes are very limited. Hence, special attention is imperative to explore the therapeutic potential of these compounds and provide new information to the scientific community. This review aims to provide the recent advances in triterpenes chemistry, its derivatives, biological interventions and its therapeutic applications with special emphasis on diabetes and its associated disorders.

Anti-Lipoxygenase Activity of Leaf Gall Extracts of Terminalia chebula (Gaertn.) Retz. (Combretaceae).

UNLABELLED: Lipoxygenase (LOX) inhibitors are the promising therapeutic target for treating a wide spectrum of inflammatory-related diseases such as cancer, asthma, lymphoma, leukemia, and autoimmune disorders. In the present study, the photochemical constituents and the anti-LOX potential of leaf galls of Terminalia chebula are evaluated to exemplify its further potential development as medicine. Extracts of T. chebula galls were tested for anti-LOX activity using linoleic acid as substrate and lipoxidase as an enzyme and also the total content of polyphenols with phytochemical analysis of the extract were determined. The presence of highest total phenolic and flavonoid content of 141 ± 2.2 mg of gallic acid equivalent/g d.w and 125 ± 1.4 mg of quercetin equivalent/g d.w and maximal LOX inhibitory activity (52.67%) at 800 µg/mL concentrations were identified in the ethanolic extracts of leaf galls of T.chebula. The higher LOX inhibitory activity was positively correlated to the high content of total polyphenols/flavonoids. The results of this study confirm the folklore use of T. chebula leaves gall extracts as a natural anti-inflammatory agent and justify its ethnobotanical use. Therefore, the results encourage the use of T. chebula leave gall extracts for medicinal health, functional food, and nutraceuticals applications. SUMMARY: The present investigation demonstrated promising anti-LOX proper-ties of T. chebula leaves gall extracts. Presumably, these activities could be attributed in part to the polyphenolic features of the extract, as there was a strong correlation of higher LOX inhibiting activities with that of high total phenolic and flavonoid content in the methanolic leaf gall extracts of T. chebula. The results of this study confirm the folklore use of T. chebula leaves gall extracts as a natural anti-inflammatory agent and justify the ethnobotanical approach in the search for novel bioactive com-pounds.

The anti-inflammatory activity of standard aqueous stem bark extract of Mangifera indica L. as evident in inhibition of Group IA sPLA2.

The standard aqueous stem bark extract is consumed as herbal drink and used in the pharmaceutical formulations to treat patients suffering from various disease conditions in Cuba. This study was carried out to evaluate the modulatory effect of standard aqueous bark extract of M. indica on Group IA sPLA2. M. indica extract, dose dependently inhibited the GIA sPLA2 (NN-XIa-PLA2) activity with an IC50 value 8.1 µg/ml. M. indica extract effectively inhibited the indirect hemolytic activity up to 98% at ~40 µg/ml concentration and at various concentrations (0-50 µg/ml), it dose dependently inhibited the edema formation. When examined as a function of increased substrate and calcium concentration, there was no relieve of inhibitory effect on the GIA sPLA2. Furthermore, the inhibition was irreversible as evidenced from binding studies. It is observed that the aqueous extract ofM. indica effectively inhibits sPLA2 and it is associated inflammatory activities, which substantiate their anti-inflammatory properties. The mode of inhibition could be due to direct interaction of components present in the extract, with sPLA2 enzyme. Further studies on understanding the principal constituents, responsible for the anti-inflammatory activity would be interesting to develop this into potent anti-inflammatory agent.

Synthesis of new secretory phospholipase A2-inhibitory indole containing isoxazole derivatives as anti-inflammatory and anticancer agents.

Secretory phospholipase A2 (sPLA2) is an important enzyme that plays a key role in various inflammatory diseases including cancer and its inhibitors have been developed as preventive or therapeutic agents. In the present study, a series of new indole containing isoxazole derivatives (10a-10o) is synthesized and evaluated for their sPLA2 inhibitory activities. All compounds (10a-10o) showed significant sPLA2 inhibition activities both in vitro and in vivo studies which is substantiated in in silico studies. Among all the tested compounds, 10o showed potent sPLA2 inhibition activity, that is comparable or more to ursolic acid (positive control). Further studies demonstrated that 10o showed in vitro antiproliferative activity when tested against MCF-7 breast and DU145 prostate cancer cells. Furthermore, compounds 10a-10o obeyed lipinsky's rule of 5 and suggesting druggable properties. The in vitro, in vivo and in silico results are encouraging and warrant pre-clinical studies to develop sPLA2-inhibitory compound 10o as novel therapeutic agent for various inflammatory disorders and several malignancies.

Targeting arachidonic acid pathway by natural products for cancer prevention and therapy.

Arachidonic acid (AA) pathway, a metabolic process, plays a key role in carcinogenesis. Hence, AA pathway metabolic enzymes phospholipase A2s (PLA2s), cyclooxygenases (COXs) and lipoxygenases (LOXs) and their metabolic products, such as prostaglandins and leukotrienes, have been considered novel preventive and therapeutic targets in cancer. Bioactive natural products are a good source for development of novel cancer preventive and therapeutic drugs, which have been widely used in clinical practice due to their safety profiles. AA pathway inhibitory natural products have been developed as chemopreventive and therapeutic agents against several cancers. Curcumin, resveratrol, apigenin, anthocyans, berberine, ellagic acid, eugenol, fisetin, ursolic acid, [6]-gingerol, guggulsteone, lycopene and genistein are well known cancer chemopreventive agents which act by targeting multiple pathways, including COX-2. Nordihydroguaiaretic acid and baicalein can be chemopreventive molecules against various cancers by inhibiting LOXs. Several PLA2s inhibitory natural products have been identified with chemopreventive and therapeutic potentials against various cancers. In this review, we critically discuss the possible utility of natural products as preventive and therapeutic agents against various oncologic diseases, including prostate, pancreatic, lung, skin, gastric, oral, blood, head and neck, colorectal, liver, cervical and breast cancers, by targeting AA pathway. Further, the current status of clinical studies evaluating AA pathway inhibitory natural products in cancer is reviewed. In addition, various emerging issues, including bioavailability, toxicity and explorability of combination therapy, for the development of AA pathway inhibitory natural products as chemopreventive and therapeutic agents against human malignancy are also discussed.

Evaluating the inhibitory potential of Withania somnifera on platelet aggregation and inflammation enzymes: An in vitro and in silico study.

Context Withania somnifera (L.) Dunal is traditionally used for treating various ailments, but lacks scientific evaluation. Objective This study evaluates Withania somnifera (WS) for its effect on platelet activity and inflammatory enzymes. Materials and methods Aqueous and ethanolic (1:1) leaf extracts were subjected to in vitro indirect haemolytic activity using Naja naja venom, human platelet aggregation was quantified for lipid peroxidation using arachidonic acid (AA) as agonist and 5-lipoxygenase (5-LOX) levels were determined using standard spectrometric assays. Further, molecular docking was performed by the ligand fit method using molegro software package (Molegro ApS, Aarhus, Denmark). Results The study found that aqueous and ethanol extracts have very negligible effect (15%) with an IC50 value of 13.8 mg/mL on PLA2 from Naja naja venom. Further, extracts of WS also had very little effect (18%) with an IC50 value of 16.6 mg/mL on malondialdehyde (MDA) formation. However, a 65% inhibition of 5-LOX with an IC50 value of 0.92 mg/mL was observed in 1:1 ethanol extracts. The same was evident from SAR model with the active ingredient withaferin A binding predominantly on Phe 77, Tyr 98, Arg 99, Asp 164, Leu 168, Ser 382, Arg 395, Tyr 396 and Tyr 614 with an atomic contact energy value of -128.96 compared to standard phenidone (-103.61). Thus, the current study validates the application of WS for inflammatory diseases. Conclusion This study reveals the inhibitory potential of W. somnifera on inflammatory enzymes and platelet aggregation. Thus, WS can serve as a newer, safer and affordable medicine for inflammatory diseases.

Antibacterial potential of a basic phospholipase A2 (VRV-PL-VIIIa) from Daboia russelii pulchella (Russell's viper) venom.

BACKGROUND: Microbial/bacterial resistance against antibiotics poses a serious threat to public health. Furthermore, the side effects of these antibiotics have stimulated tremendous interest in developing new molecules from diverse organisms as therapeutic agents. This study evaluates the antibacterial potential of a basic protein, Vipera russellii venom phospholipase A2 fraction VIIIa (VRV-PL-VIIIa), from Daboia russelii pulchella venom against gram-positive and gram-negative bacteria. METHODS: The antibacterial potential of VRV-PL-VIIIa in the presence and absence of an inhibitor (p-bromophenacyl bromide) was tested against gram-positive and gram-negative bacteria and the minimum inhibitory concentration was determined by microdilution tests. RESULTS: VRV-PL-VIIIa demonstrated potent antibacterial activities against all the human pathogenic strains tested. It more effectively inhibited such gram-positive bacteria as Staphylococcus aureus and Bacillus subtilis, when compared to the gram-negative bacteria Escherichia coli, Vibrio cholerae, Klebsiella pneumoniae and Salmonella paratyphi. It inhibited bacterial growth at minimum inhibitory concentration values ranging from 11.1 to 19.2 µg/mL. The anti-bacterial potential of VRV-PL-VIIIa was comparable to the standards gentamycin, chlorophenicol and streptomycin. The PLA2's hemolytic and antibacterial activities were strongly correlated. Furthermore, even in the presence of p-bromophenacyl bromide, intense antibacterial activity was observed, suggesting a dissociation or partial overlapping of the bactericidal/antimicrobial domains. CONCLUSION: VRV-PL-VIIIa demonstrated potent antibacterial activities against all the human pathogenic strains tested. The study shows that despite a strong correlation between enzymatic and antimicrobial activities of VRV-PL-VIIIa, it may possess additional properties that mimic the bactericidal/membrane permeability-increasing protein. This study encourages further in-depth studies on the molecular mechanisms of antibacterial properties of VRV-PL-VIIIa, which would thereby facilitate development of this protein into a possible therapeutic lead molecule for treating bacterial infections.

Antioxidant activities of ficus glomerata (moraceae) leaf gall extracts.

An excess production or decreased scavenging of reactive oxygen species (ROS) has been implicated in the pathogenesis of diverse metabolic disorders such as diabetes, cancer, atherosclerosis and neurodegeneration. Hence the antioxidant therapy has gained an utmost importance in the treatment of such diseases linked to free radicals. The medicinal properties of plants have been investigated and explored for their potent antioxidant activities to counteract metabolic disorders. This research highlights the chemical composition and antioxidant potential of leaf gall extracts (aqueous and methanol) of Ficus glomerata (F. glomerata), which is extensively used in the preparation of traditional medications to treat various metabolic diseases. The presences of phenolics, flavonoids, phytosterols, terpenoids and reducing sugars were identified in both the extracts. In comparison to the aqueous extract, the methanol extract had the highest total phenolic and flavonoid content at 370 ± 3.2 mg of gallic acid equivalent per gram of dry weight (mg GAE/g dw) and 155 ± 3.2 mg of quercetin equivalent per gram of dry weight (mg QUE/g dw), respectively. The antioxidant activities of leaf gall extracts were examined using diphenylpicrylhydrazyl (DPPH), Nitric oxide scavenging, hydroxyl scavenging and ferric reducing power (FRAP) methods. In all the methods, the methanolic extract showed higher antioxidant potential than the aqueous extract. A higher content of both total phenolics and flavonoids were found in the methanolic extract and the significantly high antioxidant activity can be positively correlated to the high content of total polyphenols/flavonoids of the methanol extract. The results of this study confirm the folklore use of F. glomerata leaf gall extracts as a natural antioxidant and justify its ethnobotanical use. Further, the results of antioxidant properties encourage the use of F. glomerata leaf gall extracts for medicinal health, functional food and nutraceuticals applications. Future work will be interesting in knowing the chemical composition and better understand the mechanism of action of the antioxidants present for development as drug for its therapeutic application.

Protecting effect of caffeine against vinblastine (an anticancer drug) induced genotoxicity in mice.

Vinblastine a DNA non-intercalating agent has wide application against several human neoplasms, and found to cause cytogenotoxicity. In this study, clastogenotoxicity of vinblastine (1.5 mg/kg b w) and its prevention by caffeine at different doses (25, 50 and 100 mg/kg b w) administered intraperitoneally was assessed in in vivo mice. It was found that micronucleus level had decreased significantly (up to 28.8%) in 100 mg caffeine treated group at 30 h post treatment. However, it did not exhibit protective effect against chromosomal aberration in spaermatogonial cells at 24 h post treatment. The frequencies of aberrant primary spermatocytes had decreased significantly in 25 and 100 mg caffeine at 4th week of post treatment. Similarly, in 100 mg of caffeine administered, abnormal sperm level had reduced (4.01%) significantly at 8th week post treatment. Thus, caffeine decreased the vinblastine induced chromosomal aberrations and mitotic index in bone marrow cells. In conclusion, this study shows that caffeine exerts protective effect against vinblastin induced cytogenotoxicity. Further studies on molecular mechanism are interesting in order to develop it as an effective drug in cancer chemotherapy.

Antioxidant activities of leaf galls extracts of Terminalia chebula (Gaertn.) Retz. (Combretaceae).

BACKGROUND: Free radicals are implicated in several metabolic diseases and the antioxidant therapy has gained an utmost importance in the treatment. The medicinal properties of plants have been investigated and explored for their potent antioxidant activities to counteract metabolic disorders. In this study, the chemical composition and free radical scavenging potential of leaf gall extracts (ethanol, petroleum ether, chloroform and aqueous) of Terminelia chebula is evaluated, which is extensively used in the preparation of traditiona medications to treat various metabolic diseases. METHODS: The presences of phenolics, flavonoids, triterpens, saponins, glycosides, phytosterols, reducing sugars were identified in the extracts according to standard procedures. The free radical scavenging activities of the extract were also analysed by standard procedures. RESULTS: The methanol extract had the highest total phenolic and flavonoid content. The antioxidant activities of leaf gall extracts were examined using diphenylpicrylhydrazyl (DPPH), Super oxide radical scavenging, Hydroxyl scavenging and ferric reducing power (FRAP) methods. In all the methods, the ethanolic extract showed higher free radical scavenging potential than all the other extracts. CONCLUSIONS: As the higher content of both total phenolics and flavonoids were found in the ethanolic extract, so the significantly high antioxidant activity can be positively correlated to the high content of total polyphenols/flavonoids of the ethanol extract. The results of this study confirm the folklore use of T. chebula leaves gall extracts as a natural antioxidant and justify its ethnobotanical use. Further, the results of antioxidant properties encourage the use of T. chebula leave gall extracts for medicinal health, functional food and nutraceutical applications.

Antioxidant activity of insect gall extracts of Pistacia integerrima.

BACKGROUND: Pistacia integerrima (P. integerrina) insect galls are widely used in ayurveda and siddha system of medicine as karkatasringi. The use of leaf galls as a rejuvenator may be attributed to antioxidant property, however there is less scientific evidence. Therefore, the aim of this study was to evaluate the chemical composition and the antioxidant potential of leaf gall extracts (aqueous and ethanol) of P. integerrina, which is extensively used in the preparation of traditional medications. METHODS: The antioxidant activities of aqueous and ethanolic leaf gall extracts were examined using diphenylpicrylhydrazyl (DPPH), hydroxyl scavenging and ferric reducing power (FRAP) methods. RESULTS: The presences of phenolics, tannins, phytosterols, triterpenoids, saponins, flavonoids and reducing sugars were identified in both the extracts. In comparison to the aqueous extract, the ethanolic extract had the highest total phenolic and flavonoid content at 234 ±2.4 mg of GAE/g d.w. and 95.5 ±3.2 mg of QUE/g d.w., respectively. This higher content of total phenolics and flavonoids found in the ethanolic extract was directly associated with higher antioxidant activity. CONCLUSIONS: This study demonstrates the poetnet antioxidant activities of P. integerrima leaf gall extracts. Further, there was a strong association between the higher antioxidant activities with that of higher total phenolic and flavonoid content in the ethanolic leaf gall extracts of P. integerrima. The results encourage the use of P. integerrima leaf gall extracts for medicinal health, functional food and nutraceuticals applications, due to their antioxidant properties. Future work will be interesting to learn the chemical composition and better understand the mechanism of action of the antioxidants present in the extract for development as a drug for therapeutic application.

Antibacterial potential of a basic phospholipase A2(VRV-PL-VIIIa) from Daboia russelii pulchella (Russell's viper) venom

Background:Microbial/bacterial resistance against antibiotics poses a serious threat to public health. Furthermore, the side effects of these antibiotics have stimulated tremendous interest in developing new molecules from diverse organisms as therapeutic agents. This study evaluates the antibacterial potential of a basic protein, Vipera russellii venom phospholipase A2 fraction VIIIa (VRV-PL-VIIIa), from Daboia russelii pulchella venom against gram-positive and gram-negative bacteria.Methods:The antibacterial potential of VRV-PL-VIIIa in the presence and absence of an inhibitor (p-bromophenacyl bromide) was tested against gram-positive and gram-negative bacteria and the minimum inhibitory concentration was determined by microdilution tests.Results:VRV-PL-VIIIa demonstrated potent antibacterial activities against all the human pathogenic strains tested. It more effectively inhibited such gram-positive bacteria as Staphylococcus aureus and Bacillus subtilis, when compared to the gram-negative bacteria Escherichia coli, Vibrio cholerae, Klebsiella pneumoniae and Salmonella paratyphi. It inhibited bacterial growth at minimum inhibitory concentration values ranging from 11.1 to 19.2 μg/mL. The anti-bacterial potential of VRV-PL-VIIIa was comparable to the standards gentamycin, chlorophenicol and streptomycin. The PLA2's hemolytic and antibacterial activities were strongly correlated. Furthermore, even in the presence of p-bromophenacyl bromide, intense antibacterial activity was observed, suggesting a dissociation or partial overlapping of the bactericidal/antimicrobial domains.Conclusion:VRV-PL-VIIIa demonstrated potent antibacterial activities against all the human pathogenic strains tested. The study shows that despite a strong correlation between enzymatic and antimicrobial activities of VRV-PL-VIIIa, it may possess additional properties that mimic the bactericidal/membrane permeability-increasing protein. This study encourages further in-depth studies on the molecular mechanisms of antibacterial properties of VRV-PL-VIIIa, which would thereby facilitate development of this protein into a possible therapeutic lead molecule for treating bacterial infections.(AU)