Heavy metals are natural constituents of the earth's crust, but indiscriminate human activities have drastically altered their geochemical cycles and biochemical balance. This results in accumulation of metals in plant parts having secondary metabolites, which is responsible for a particular pharmacological activity. Prolonged exposure to heavy metals such as cadmium, copper, lead, nickel, and zinc can cause deleterious health effects in humans. Molecular understanding of plant metal accumulation has numerous biotechnological implications also, the long term effects of which might not be yet known.

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The 2019-novel coronavirus (nCoV) is a major source of disaster in the 21^th century. However, the lack of specific drugs to prevent/treat an attack is a major need at this current point of time. In this regard, we conducted a systematic review to identify major druggable targets in coronavirus (CoV). We searched PubMed and RCSB database with keywords HCoV, NCoV, corona virus, SERS-CoV, MERS-CoV, 2019-nCoV, crystal structure, X-ray crystallography structure, NMR structure, target, and drug target till Feb 3, 2020. The search identified seven major targets (spike protein, envelop protein, membrane protein, protease, nucleocapsid protein, hemagglutinin esterase, and helicase) for which drug design can be considered. There are other 16 nonstructural proteins (NSPs), which can also be considered from the drug design perspective. The major structural proteins and NSPs may serve an important role from drug design perspectives. However, the occurrence of frequent recombination events is a major deterrent factor toward the development of CoV-specific vaccines/drugs.

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. Levamisole hydrochloride in low concentration (5 ng/mI) stimulated the movements of the whole worm as well as of the nerve-muscle complex of Setario cervi suspended in an isolated organ bath. At higher concentration (25 ng/mI) the response was biphasic consisting of initial stimulation followed by irreversible paralysis. The initial stimulant effect is not due to release of ACh as it is not blocked by prior addition of d-tubocurarine to the bath fluid. Levamisole in 5 x 25 mg/kg daily dose caused disappearance of microfilariae from the peripheral circulation in 7 of the 8 rats treated: The drug at this dose level had some macrofilaricidal action as well. A higher dose of 5 x 50 mg/kg daily caused complete disappearance of microfilariae from peripheral circulation of all the rats and produced a significant lethal effect on the adult worms The antifilarial efficacy of the drug needs evaluation in domestic animals and men.

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OBJECTIVE: To evaluate the antibacterial potential of aqueous and acetone extracts of galls of Quercus infectoria by determination of Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values. MATERIALS AND METHODS: The extracts from the galls of Q. infectoria at 10 mg/ml were screened against three Gram-positive bacteria (Staphylococcus aureus ATCC 25923, Staphylococcus epidermidis and Bacillus subtilis) and three Gram-negative bacteria (Escherichia coli NCTC 12079 serotype O157:H7, Salmonella typhimurium NCTC 74 and Pseudomonas aeruginosa ATCC 27853). The MIC of the extracts were then determined using the twofold serial microdilution technique at a concentration ranging from 5 mg/ml to 0.0024 mg/ml. The MBC values were finally obtained from the MIC microtiter wells which showed no turbidity after 24 hrs of incubation by subculturing method. RESULTS: Out of the six bacterial species tested, S. aureus was the most susceptible. On the other hand, the extracts showed weak inhibitory effect against S. epidermidis, B. subtilis, S. typhimurium and P. aeruginosa while there was no inhibition zone observed for E. coli O157. The MIC values of the extracts ranged from 0.0781 mg/ml to 1.25 mg/ml whereas the MBC values ranged from 0.3125 mg/ml to 2.50 mg/ml. The MBC values of aqueous extract against S. aureus and S. typhimurium were higher than their MIC values. The MBC value of acetone extract against S. aureus was also higher than its MIC value. Interestingly, however, the MIC and MBC values of acetone extract against S. typhimurium were the same (1.25 mg/ml). CONCLUSION: The aqueous and acetone extracts displayed similarities in their antimicrobial activity on the bacterial species and as such, the galls of Quercus infectoria are potentially good source of antimicrobial agents.

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Objective: To study the effects of neem kernel powder(NP) and glibenclamide. alone or in combination, on alloxan diabetic rats. Methods: The diabetic rabbits were given with NP alone or in combination with glibenclamide for thirty days and at the end of thirty days the serum lipid levels, blood glucose and activities of some serum, liver and intestinal enzymes were assessed. Results: Administration of NP alone (500 mg/kg) as well as the combination of NP (250mg/kg) with glibenclamide (0.25mg/kg) significantly decreased the concentration of serum lipids, blood glucose and activities of serum enzymes like alkaline phosphatase (alk P), acid phosphatase (acid P), lactate dehydrogenase (LDH), liver glucose 6-phosphatase (G6P) and HMG CoA reductase activity in liver and intestine of alloxan diabetic rabbits. However, all the treatments produced an increased liver hexokinase activity. The changes observed were significantly greater when the treatment was given in combination of NP and glibenclamide than with NP alone. Conclusion: Our data suggest a significant antidiabetic and antihyperlipaemic effect of NP in alloxan diabetic rabbits.

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Bacopa monniera Linn. (Brahmi) has been used since times immemorial as nerve tonic for Improvement of memory The authentication of the traditional claims of brahmi was initiated by investigating the effect of an alcoholic extract of this plant on acquisition, consolidation and retention of three newly acquired behavioural responses in albino rats, viz.. a foot-shock motivated brightness discrimination response, active conditioned avoidance response and Sidman continuous avoidance response. The facilitatory effect of the brahmi extract (40 mg/kg, p o. x 3d) was manifest in all the three learning responses as it augmented both the cognitive function and mental retention capacity. The chemical constituent responsible for the facilitator) effect of brahmion learning schedules was identified as a mixture of two saponins designated as bacosides A and B.The bacosides significantly improved the acquisition, consolidation and retention in the shock-motivated brightness discrimination response, active conditioned avoidance response and produced a dose-dependent facilitation of discretion between an aversive (LiCL) and palatable fluid (sucrose) in the conditioned taste aversion (CTA) response. Bacosides also attenuated the retrograde amnesia produced by Immobilisation induced stress, E C S and scopolamine. They also enhanced protein kinase activity and produced an Increase in protein in hippocampus. Bacosides were also found to be safe in regulatory pharmacological and toxicological studies and were well tolerated by normal healthy male human volunteers in single dose (20-300 mg) and multiple doses (100 and 200 mg) administered for 4 weeks double blind placebo controlled and non-crossover regulatory Phase-I clinical trial.

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Extensive scientific research on curcumin, a natural compound present in the rhizomes of plant Curcuma longa Linn., demonstrated its antiinflammatory action. Curcumin was found to inhibit arachidonic acid metabolism, cyclooxygenase, lipoxygenase, cytokines (Interleukins and tumour necrosis factor) Nuclear factor-kB and release of steroidal hormones. Curcumin was reported to stabilize lysosomal membrane and cause uncoupling of oxidative phosphorylation besides having strong oxygen radical scavenging activity, which was responsible for its antiinflammatory property. In various animal studies, a dose range of 100-200 mg/kg body weight exhibited good antiinflammatory activity and seemed to have negligible adverse effect on human systems. Oral LD50 in mice was found to be more than 2.0 g/kg body weight.

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Objective: The objective of the present study was to provide an in-vitro evidence for the potential inhibitory activity of extracts and fractions of Adiantum caudatum Linn. and Celosia argentea Linn. on α-amylase and α-glucosidase enzymes . Materials and Methods: The plant extracts were prepared, first with cold maceration (70% v/v ethanol) and then by Soxhlation techniques (95% v/v ethanol). Subsequently, the combined extracts were subjected for fractionation. Different concentrations (0.1, 0.2, 0.3, 0.4, and 0.5 mg/ml) of extract and fractions were subjected to α-amylase and α-glucosidase inhibitory assay. The absorbance was measured at 540 and 405 nm using multiplate reader and the percentage of α- amylase and α- glucosidase inhibitory activity and IC ₅₀ values of extract and fractions were calculated. Results: Fraction 2 of A. caudatum and fraction 4 of C. argentea has shown highest α-amylase and α-glucosidase inhibitory potential with IC ₅₀ values of 0.241, 0.211 and 0.294, 0.249 mg/ml, respectively, which was comparable with acarbose (0.125 and 0.93 mg/ml). Whereas, extracts and remaining fractions of both the plants have shown lesser activity. Conclusion: The results of the present study indicate that, fraction 2 of A. caudatum, rich in triterpenoids and phenolics and fraction 4 of C. argentea, rich in flavonoids, are effective α- amylase and α- glucosidase inhibitors, which may be helpful to reduce the postprandial glucose levels. Hence, further studies may throw light on the antidiabetic potential of A. caudatum and C. argentea, especially in the management of type 2 diabetes.

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. A flavonoid fraction (XE) extracted from the bark of pterocarpus marsupium Roxb. (Leguminoceae) was studied for the hypoglycaemic activity normal and alloxanised albino rats. The drug XE did not show a consistent effect on normal blood sugar levels but it effectively reversed the alloxan-induced changes in the blood sugar level and the beta-cell population in the pancreas. It also showed a protective effect when it was given prior to alloxan administration. The novel action of drug on the pancreatic beta-cells and absence of acute toxicity may offer a new hope to the diabetics in future.

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A phytotherapeutic approach to modern drug development can provide many invaluable drugs from traditional medicinal plants. Search for pure phytochemicals as drugs is time consuming and expensive. Numerous plants and polyherbal formulations are used for the treatment of liver diseases. However, in most of the severe cases, the treatments are not satisfactory. Although experimental evaluations were carried out on a good number of these plants and formulations, the studies were mostly incomplete and insufficient. The therapeutic values were tested against a few chemicals-induced subclinical levels of liver damages in rodents. Even common dietary antioxidants can provide such protection from liver damage caused by oxidative mechanisms of toxic chemicals. However, experiments have clearly shown that plants such as Picrorrhiza kurroa, Andrographis paniculata, Eclipta alba, Silibum marianum, Phyllanthus maderaspatensis and Trichopus zeylanicus are sufficiently active against, at least, certain hepatotoxins. Screening plants for antihepatitis activities remains in its infancy. P.kurroa, E. alba, Glycyrrhiza glabra, A. paniculata and P. amarus are likely to be active against Hepatitis B virus. In the case of severe liver damage, most of the liver cells die or turn into fibrotic state. In this case, the treatment should include in addition to the therapeutic agents, agents which can stimulate liver cell proliferation. For developing satisfactory herbal combinations to treat severe liver diseases, plants have to be evaluated systematically for properties such as antiviral activity (Hepatitis B, Hepatitis C, etc), antihepatotoxicity* (antioxidants and others), stimulation of liver regeneration and choleretic activity. The plants with remarkable activities for each of the above properties have to be identified. Single plant may not have all the desired activities. A combination of different herbal extracts/'fractions is likely to provide desired activities to cure severe liver diseases. Development of such medicines with standards of safety and efficacy can revitalise treatment of liver disorders. * hepatoprotective activity.

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Objectives: Ellagic acid (EA) has shown antinociceptive and anti-inflammatory effects. Inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2) enzymes and also cytokines play a key role in many inflammatory conditions. This study was aimed to investigate the mechanisms involved in the anti-inflammatory effect of EA. Materials and Methods: Carrageenan-induced mouse paw edema model was used for induction of inflammation. Results: The results showed that intraplantar injection of carrageenan led to time-dependent development of peripheral inflammation, which resulted in a significant increase in the levels of tumor necrosis factor α (TNF-α) and interleukin 1 (IL-1) β, nitric oxide (NO) and prostaglandin E ₂ (PGE ₂ ) and also iNOS and COX-2 protein expression in inflamed paw. However, systemic administration of EA (1-30 mg/kg, intraperitoneal [i.p.]) could reduce edema in a dose-dependent fashion in inflamed rat paws with ED50 value 8.41 (5.26-14.76) mg/kg. It decreased the serum concentration of NO, PGE ₂ , aspartate aminotransferase and alanine aminotransferase, and suppress the protein expression of iNOS, COX-2 enzymes, and attenuated the formation of PGE _2, TNF-α and IL-1 β in inflamed paw tissue. We also demonstrated that EA significantly decreased the malondialdehyde (MDA) level in liver at 5 h after carrageenan injection. Moreover, histopathological studies indicated that EA significantly diminished migration of polymorphonuclear leukocytes into site of inflammation, as did indomethacin. Conclusions: Collectively, the anti-inflammatory mechanisms of EA might be related to the decrease in the level of MDA, iNOS, and COX-2 in the edema paw via the suppression of pro-inflammatory cytokines (TNFα, IL1 β), NO and PGE ₂ overproduction.

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Silymarin, a flavonolignan from the seeds of 'milk thistle' (Silybum marianum), has been widely used from ancient times because of its excellent hepatoprotective action. It is a mixture of mainly three flavonolignans, viz, silybin, silidianin, and silychristine, with silybin being the most active. Silymarin has been used medicinally to treat liver disorders, including acute and chronic viral hepatitis, toxin/drug-induced hepatitis, and cirrhosis and alcoholic liver diseases. It has also been reported to be effective in certain cancers. Its mechanism of action includes inhibition of hepatotoxin binding to receptor sites on the hepatocyte membrane; reduction of glutathione oxidation to enhance its level in the liver and intestine; antioxidant activity; and stimulation of ribosomal RNA polymerase and subsequent protein synthesis, leading to enhanced hepatocyte regeneration. It is orally absorbed but has very poor bioavailability due to its poor water solubility. This review focuses on the various pharmacological activities of silymarin including the clinical trials. For the first time, the review also looks at the formulation work that has been done to enhance its solubility, so as to increase its bioavailability and thus, its hepatoprotective action.

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Objectives : This study was aimed to evaluate the chemical composition, antioxidant potential in vitro and in vivo, anti-inflammatory, and antinociceptive activity of turmeric oil. Materials and Methods : Chemical analysis of turmeric oil was done by gas chromatography/mass spectrometry. Antioxidant activities in vitro was done by six different methods and in vivo antioxidant activity was determined by measuring superoxide generation from macrophages treated with phorbol-12-myristate-13-acetate (PMA) as well as determining antioxidant level after feeding the oil orally for one month. Anti-inflammatory activity was studied in mice using carrageenan, dextran, and formalin. Antinociceptive activity was evaluated by using acetic acid-induced writhing movement in mice. Results : The main constituent of essential oil of turmeric was found to be ar-turmerone (61.79%), curlone (12.48%), and ar-curcumene (6.11%). Turmeric oil was found to have in vitro antioxidant activity and IC ₅₀ for scavenging superoxides, hydroxyl radicals, and lipid peroxidation were 135 mg/ml, 200 mg/ml, and 400 mg/ml, respectively. The ferric-reducing activity for 50 mg of turmeric essential oil was found to be 5 mM. Intraperitoneal administration of oil was found to inhibit PMA-induced superoxide radicals elicited by macrophages. Oral administration of turmeric oil for one month to mice significantly increased superoxide dismutase, glutathione, and glutathione reductase enzyme levels in blood and glutathione-S-transferase and superoxide dismutase enzymes in liver. Turmeric oil showed significant reduction in paw thickness in carrageenan, dextran-induced acute inflammation, and formalin-induced chronic inflammation. The drug produced significant antinociceptive activity (P < 0.001) at all doses studied. Conclusions : These results demonstrated that turmeric oil has potential health benefits as it can scavenge the free radicals and produce significant anti-inflammatory and antinociceptive activities.

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Objectives: To study the preventive role of curcumin against doxorubicin (Dox)-induced myocardial toxicity in rats. Materials and Methods: Cardiotoxicity was produced by cumulative administration of Dox (15 mg/kg for two weeks). Curcumin (200 mg/kg, po) was administered as pretreatment for two weeks and then for two alternate weeks with Dox. The general observations, mortality, histopathology, biomarker enzymes like lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), biochemical parameters such as aspartate aminotransferase (AST) alanine aminotransferase (ALT) and alkaline phosphatase (ALP), antioxidant enzymes such as glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were monitored after three weeks of last dose. Results: The repeated administration of Dox induced cardiomyopathy associated with an antioxidant deficit and increased level biomarkers. Pretreatment with the curcumin significantly protected myocardium from the toxic effects of Dox by reducing the elevated level of biomarker enzymes like LDH and CPK and biochemical parameters such as AST, ALT and ALP back to normal. Curcumin increased the reduced level of GSH, SOD and CAT and decreased the elevated level of malondialdehyde (MDA) in cardiac tissue. Conclusion: The biochemical and histopathology reports support the cardioprotective effect of curcumin which could be attributed to antioxidant.

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Endocan is a novel endothelium derived soluble dermatan sulfate proteoglycan. It has the property of binding to a wide range of bioactive molecules associated with cellular signaling and adhesion and thus regulating proliferation, differentiation, migration, and adhesion of different cell types in health and disease. An increase in tissue expression or serum level of endocan reflects endothelial activation and neovascularization which are prominent pathophysiological changes associated with inflammation and tumor progression. Consequently, endocan has been used as a blood-based and tissue-based biomarker for various cancers and inflammation and has shown promising results.

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Efforts to discover and develop new antimalarial drugs have increased dramatically in recent years mainly because of resistance to existing antimalarial drugs. Selection of candidate drugs for clinical trials in man and the design of clinical protocols are based upon consideration of data from a battery of preclinical test systems. All compounds are assessed initially in one or more primary screening models. A compound which is considered 'active' by well established criteria in primary screening test is considered for further evaluation in successively more clinical tests. At the end of each stage of testing, a decision is taken to advance the compound to the next stage or discontinue it. Primary screening tests should have optimal sensitivity, a high degree of reproducibility, high throughput, requiring a minimum quantity of test compound and should bear low cost. As there is growing need for newer and more efficacious antimalarial drugs especially in tropical countries, more sensitive and economical screening models are needed. This review is an update of various conventional and latest in vitro and in vivo screening methods being used for evaluation of antimalarial compounds.

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Objectives: To assess the safety and efficacy of TCE in human immuno-deficiency virus positive patients. Materials and Methods: Efficacy of Tinospora cordifolia extract (TCE) in HIV positive patients was assessed in randomized double blind placebo controlled trial. 68 HIV positive participants were randomly assigned to two groups to receive either TCE or placebo for six months. After clinical examination TLC, DLC, ESR, platelet count, hemoglobin and CD4 count were done. The hematological investigations were repeated at bimonthly intervals and CD4 count was repeated at the end of the study. Patients were clinically reviewed at monthly intervals for compliance, refill and ADR monitoring. The drugs were decoded at the end of the trial. Results: TCE treatment caused significant reduction in eosinophil count and hemoglobin percentage. 60% patients receiving TCE and 20% on placebo reported decrease in the incidence of various symptoms associated with disease. Some of the common complaints reported by patients on TCE were anorexia, nausea, vomiting and weakness. Conclusion: Tinospora cordifolia extract, a plant derived immunostimulant, significantly affected the symptoms of HIV. This was validated by clinical evaluation. However not all of the objective parameters studied by us, back this up. Tinospora cordifolia could be used as an adjunct to HIV/AIDS management.

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The use of cosmeceuticals has drastically risen in recent years. This significantly increases the armamentarium of the clinician in improving the treatment of skin, hair, and other conditions. They are at the juncture where wellness meets beauty and growing use by consumers is indicative of their popularity. This article focuses on skin, hair, and other cosmeceuticals and their regulatory aspects.

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Objectives: Andrographis paniculata (Burm. f.) Nees originates from India and grows widely in many areas in Southeast Asian countries. Andrographis paniculata (Burm. f.) Nees has shown an antidiabetic effect in type 1 DM rats. The present study investigates the purified extract of the plant and its active compound andrographolide for antidiabetic and antihyperlipidemic effects in high-fructose-fat-fed rats, a model of type 2 DM rats. Materials and Methods: Hyperglycemia in rats was induced by high-fructose-fat diet containing 36% fructose, 15% lard, and 5% egg yolks in 0.36 g/200 gb.wt. 55 days. The rats were treated with the extract or test compound on the 50 ^th day. Antidiabetic activity was measured by estimating mainly the pre- and postprandial blood glucose levels and other parameters such as cholesterol, LDL, triglyceride, and body weight. Results: The purified extract and andrographolide significantly (P<0.05) decreased the levels of blood glucose, triglyceride, and LDL compared to controls. However, no changes were observed in serum cholesterol and rat body weight. Metformin also showed similar effects on these parameters. Conclusions: Andrographis paniculata (Burm. f.) Nees or its active compound andrographolide showed hypoglycemic and hypolipidemic effects in high-fat-fructose-fed rat.

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