Prasad G. Jamkhande

Therapeutic approaches to drug targets in atherosclerosis

Non-communicable diseases such as cancer, atherosclerosis and diabetes are responsible for major social and health burden as millions of people are dying every year. Out of which, atherosclerosis is the leading cause of deaths worldwide. The lipid abnormality is one of the major modifiable risk factors for atherosclerosis. Both genetic and environmental components are associated with the development of atherosclerotic plaques. Immune and inflammatory mediators have a complex role in the initiation and progression of atherosclerosis. Understanding of all these processes will help to invent a range of new biomarkers and novel treatment modalities targeting various cellular events in acute and chronic inflammation that are accountable for atherosclerosis. Several biochemical pathways, receptors and enzymes are involved in the development of atherosclerosis that would be possible targets for improving strategies for disease diagnosis and management. Earlier anti-inflammatory or lipid-lowering treatments could be useful for alleviating morbidity and mortality of atherosclerotic cardiovascular diseases. However, novel drug targets like endoglin receptor, PPARα, squalene synthase, thyroid hormone analogues, scavenger receptor and thyroid hormone analogues are more powerful to control the process of atherosclerosis. Therefore, the review briefly focuses on different novel targets that act at the starting stage of the plaque form to the thrombus formation in the atherosclerosis.

Plant profile, phytochemistry and pharmacology of Cordia dichotoma (Indian cherry): a review.

More than half of the worlds population relies on the traditional medicine and major role of the traditional medicine including the use of plant extract and their active constituents. Among them, Cordia dichotoma Forst., a small to moderate size plant of family Boragenaceae, commonly called bhokar, lasura, gonda, Indian cherry and shlesmataka. Plant parts such as leaves, fruit, bark and seed have been reported for possessing antidiabetic, antiulcer, anti-inflammatory, immune-modulator and analgesic activity. Screening of fruit, leaves and seed shows the presence of pyrrolizidine alkaloids, coumarins, flavonoids, saponins, terpenes and sterols. Present review focuses on details of geographical distribution, physicochemical parameters, phytoconstituents and pharmacological properties of Cordia dichotoma reported so far.

In silico PASS analysis and determination of antimycobacterial, antifungal, and antioxidant efficacies of maslinic acid in an extract rich in pentacyclic triterpenoids

Objective/background: Microbial infections such as tuberculosis is a major cause of mortality worldwide. Plant-derived phytochemicals have a long history of providing much-needed novel therapeutics. Triterpenoids are among the prominent phytochemicals that possess numerous biological activities. Among them is maslinic acid (MA), a biologically active olean-type pentacyclic triterpenoid. In search of a novel antimicrobial agent, we aimed to evaluate the antimicrobial potential of MA. Methods: Antibacterial and antifungal activity was evaluated through the agar well diffusion method. Antitubercular activity was analysed through the agar well diffusion and disc diffusion methods, respectively. Antioxidant capacity was determined through assays for total antioxidant capacity, 2,2-diphenyl-1-picrylhydrazyl radical scavenging, hydrogen peroxide radical scavenging, and Fe3+ reducing power. The program Prediction of Activity Spectra for Substances was used to calculate the possible biological activity of MA. Results: MA showed dose-dependent antioxidant activity similar to that of ascorbic acid. It had no inhibitory effect on bacterial strains, but it had moderate activity against the fungi Aspergillus flavus and Ustilago maydis, with Aspergillus niger being the most sensitive to MA. MA also exhibited strong antimycobacterial activity. Probable antioxidant, antibacterial, and antifungal activity of MA based on software calculations are 0.479, 0.363 and 0.589 respectively. Conclusion: This work provides scientific evidence of the antioxidant, antifungal, and antimycobacterial activities of MA, showing its potential application in the development of natural antioxidants and antimicrobial agents for the agro-food and pharmaceutical industries.

Marine bioactive agents: a short review on new marine antidiabetic compounds

Abstract From medicinal point of view, marine environment is a diversified source of several biologically active compounds that are relatively untapped. Exploitation of marine resources may provide valuable leads which carry economic and scientific potential. Diabetes is a metabolic disorder and a major cause of mortality and morbidity in both developed and developing countries. Several antidiabetics are available but the major limitations of these synthetic drugs are cost, effectiveness and adverse effects. The relative safety of drugs from natural source is the main reason behind exploring marine resources as a source of therapeutic, food and nutritional compounds. Marine resources provide many compounds including polyphenols, peptides, pigments, phlorotannins and sterols that could be used for the treatment of diabetes and associated complications. The present review focuses on potential marine resources that provide bioactive agents for diabetes treatment.

Annona reticulata Linn. (Bullock's heart): Plant profile, phytochemistry and pharmacological properties

From the beginning of human civilization plants and plant based chemicals are the most important sources of medicines. Phytochemical and different products obtained from plant are used as medicines, pharmaceuticals, cosmetics and food supplements. Annona reticulata Linn. (牛心果 niú xīn guǒ; Bullocks heart) is a versatile tree and its fruits are edible. Parts of A. reticulata are used as source of medicine and also for industrial products. It possesses several medicinal properties such as anthelmintic, analgesic, anti-inflammatory, antipyretic, wound healing and cytotoxic effects. It is widely distributed with phytochemicals like tannins, alkaloids, phenols, glycosides, flavonoids and steroids. Present article is an attempt to highlight over taxonomy, morphology, geographical distribution, phytoconstituents and pharmacological activities of A. reticulata reported so far.

Assessment of Annona reticulata Linn. leaves fractions for invitro antioxidative effect and antimicrobial potential against standard human pathogenic strains

Abstract Since from long time the plant, Annona reticulata Linn. is known for its beneficial effects. Leaves of A. reticulata were screened for phytochemicals and in vitro antioxidant, antibacterial and antifungal activity. The shade dried leaves were extracted with methanol and aqueous methanolic extract was partitioned successively with n-butanol, chloroform and acetone solvents. Methanolic extract was subjected to antioxidant screening using DPPH free radical scavenging activity and H2O2 scavenging activity. Antibacterial and antifungal activity of extract and fractions were analyzed on eight different clinical bacterial and fungal strains using agar well diffusion method and broth dilution method (MIC and MMC determination). The antioxidant activity showed that the extracts exhibited scavenging effect in concentration-dependent manner. The extract showed potent inhibitory effect against Bacillus subtilis and Escherichia coli bacterial strains while in case of fungal strains the maximum effect was observed against Candida blanki. The maximum zone of inhibition of n-butanol, chloroform and acetone fractions was observed against B. subtilis, and E. coli respectively while all fractions exhibited potent inhibitory effect against C. blanki. MIC and MBC values were determined for active samples, methanol extract and chloroform fraction against Staphylococcus aureus, B. subtilis, E. coli and Pseudomonas aeruginosa which revealed lower MIC and MBC values. The fungal strains Candida albicans, Saccharomyces cerevisiae and C. blanki were used to calculate MIC and MFC values for methanol extract and acetone fraction which demonstrated lower MIC and MFC values. The results provided evidence that the plant is richly supplied with numerous phytoconstituents that might indeed be potential sources of natural antioxidant, antimicrobial agents and supplementary food.

Teratogenicity: a mechanism based short review on common teratogenic agents

Abstract Teratogenicity or reproductive and developmental toxicity has increasingly been recognized as a most important part of overall toxicology. Each compound has its own unique toxicological profile and mechanism of teratogenicity. The present view-point was to explore and review the teratogenic mechanism and common teratogenic effects of teratogenic compounds, biological agents and physical agents. Every year millions of different chemicals are produced and used in the world which contaminate environment and consequently are exposed to human. Many of these chemicals have ability to penetrate into human tissue and developing foetus, negatively impacting the reproductive health of human. Many of the teratogenic effects occur because of biological and physical factors like infection and radiation respectively.

In vitro anthelmintic efficacy of Borassus flabellifer Linn. (Palmae) against Pheretima posthuma

Abstract Objective To investigate the anthelmintic activity of Borassus flabellifer ( B. flabellifer ) Linn. leaves against Indian adult earth worms ( Pheretima posthuma ). Methods The B. flabellifer leaves and Indian adult earth worms ( Pheretima posthuma ) were collected and authenticated. Earth worms were grouped and treated with extract at 10, 20 and 50 mg/mL concentration, albendazole (10 mg/mL) as a standard and normal saline. The paralysis time and mortality time was considered as indicator of anthelmintic efficacy. Results All the extracts showed concentration dependent activity but significant activity was observed at 50 mg/mL. At concentration 50 mg/mL extract pertained better activity with paralysis time (13.3 min) and death times (17.92 min) when compared to standard albendazole. Conclusions The study findings reveal that the methanolic extract of B. flabellifer leaves has effective anthelmintic activity against Indian adult earth worms.

Evaluation of anthelmintic activity and in silico PASS assisted prediction of Cordia dichotoma (Forst.) root extract.

Background: Worm infection and associated complications are severe problems that afflict a large population worldwide. Failure of synthetic drugs in worm infections because of drug resistance has made alternative drug therapy desirable. Cordia dichotoma (Forst.) is an ethnomedicinal plant which is rich in several secondary metabolites. Traditionally, the plant has been claimed to have high medicinal properties including antimicrobial activity and cytotoxicity. Materials and Methods: The study begun with an aim to explore plant-based natural anthelmintic agents against Pheretima posthuma, an Indian earthworm. Methanol extract of the drug was obtained by successive soxhlet extraction. The extract was tested for different phytochemicals. Worms were exposed to 10 mg/ml, 25 mg/ml, 50 mg/ml, and 75 mg/ml concentrations of extract and standard drug, albendazole. A software-based tool, prediction of activity spectra for substances was used to estimate anthelmintic efficacy of plant metabolites. Result: The phytochemical analysis revealed presence of alkaloids, tannins, glycosides, saponins, flavonoids, and phenols. The extract showed dose-dependent effects, affecting worm motility, viability, and mortality. It was also found that the biological activity spectrum of the plant phytoconstituents such as octacosanol, lupeol, caffeic acid, and hentricontanol were >0.5 (probable activity > 0.5). Conclusion: The findings of the present work suggest that the extract of C. dichotoma significantly interferes with motility pattern of P. posthuma. The paralysis and mortality of P. posthuma might be due to the combined effects different phytoconstituents. The extract of C. dichotoma promises natural sources to control worm infection.

Role of norepinephrine reuptake inhibitors in attention deficit hyperactivity disorder: A mechanism-based short review

Prevalence of neurobehavioral disorder is increasing worldwide. Attention deficit hyperactivity disorder (ADHD) is among the most common neurobehavioral disorder observed in the children. It is associated with behavioral symptoms such as hyperactivity, attention deficit, impulsivity, and excessive motor activity. The wide range of conditions and factors produces abnormality in neuronal functioning. Alteration in the prefrontal cortex and its links to the striatum and cerebellum; and change in the level of catecholamine are predominantly responsible for ADHD. Dopamine (DA) and norepinephrine (NE) released in these areas regulate network activity. Physiological actions of catecholamine are regulated through activation of receptors such as α1, α2 , β1, β2 , β3 , and D1. The less release of DA or NE leads to insufficient activation of postsynaptic D 1 and α2 A receptors, whereas overstimulation of these catecholamines in conditions such as stress creates abnormal behavioral response and attention. NE reuptake inhibitors selectively enhance the level of catecholamine by interfering with transport proteins, metabolizing enzyme, blocking different sites on receptor and neuronal activity index. The present review gives insights of the role of NE reuptake inhibitors in ADHD.