Perceived Utility of Jan Aushadhi Outlets and Awareness of Generic Medicines at the Andaman and Nicobar Islands: A Cross-Sectional Study.

BACKGROUND: Despite being the leading exporter of generic medicines to the world, affordable medicines are still beyond the reach of most patients in India. Analysis of the National Sample Survey data showed that in one year, more than 55 million Indians became poor only because they had to spend their own money to purchase medicines. The Jan Aushadhi Scheme launched by the Government of India is an ambitious step to make quality generic drugs affordable to the common man of the country. OBJECTIVE: This study aimed to assess the knowledge, attitude, and perceptions of patients at a tertiary care teaching hospital in the Andaman and Nicobar Islands about Jan Aushadhi Kendras and generic medicines. MATERIALS AND METHODS: The study was a questionnaire-based cross-sectional study. A prevalidated self-made questionnaire was distributed to 200 patients visiting the OPD of different clinical departments in the hospital. Participants' knowledge, attitude, and perception of Jan Aushadhi Kendras and generic medicines were evaluated. Analysis of collected data was done using descriptive statistical measures such as mean and percentages. RESULTS: It was found that most of the participants were not fully aware of the Jan Aushadhi Scheme and the facts about generic medicines. The majority of the participants were under the notion that generics were not similar in quality to the branded ones. CONCLUSION: The study observed that the patients had a very poor understanding of the Jan Aushadhi Scheme and generic medicines with the majority being ignorant and having incorrect information. To fill this gap, a more proactive approach by the healthcare workers and authorities is needed to disseminate the scheme-related facts, dispel the myths regarding generics, and accept the program wholeheartedly by the common man.

Identification and characterization of a novel decalin derivative with anti-Candida activity from Streptomyces chrestomyceticus strain ADP4.

A novel decalin derivative, trans-1-oxo-2,4-diacetylaminodecalin (1) with anti-Candida activity, had been isolated from Streptomyces chrestomyceticus strain ADP4. The structure of the compound was determined from the analysis of spectral data (LCMS/MS, UV, FTIR, 1D- and 2D-NMR). The anti-Candida activity of 1 was specific to Candida albicans and Candida auris. Further, it displayed inhibition of the early-stage biofilm of C. albicans. In-silico analysis of the compound revealed its drug likeness properties without any violations and PAINS alert when investigated for ADME properties. Along with the overall bioavailability, compound 1 did not show any predicted bioaccumulation and mutagenicity in the analysis by TEST software. Non-cytotoxic property was further confirmed by in-vitro assay on the HepG2 cell line.

Phenyl Pentyl Ketone and m-isobutyl Methoxy Benzoate Produced by Streptomyces Chrestomyceticus ADP4 are Potent Antimicrobial Agents Displaying Broad Spectrum Activities.

Isolation and identification of two antimicrobial compounds, a phenyl pentyl ketone (CP1) and m-isobutyl methoxy benzoate (CP2), from Streptomyces chrestomyceticus ADP4 have been reported. Structure of the compounds were elucidated from analyses of spectral data that included LCMS/MS, NMR, FTIR and UV spectroscopies. Both the compounds displayed significant inhibition of albicans and non-albicans species of Candida (NAC) pathogens including C. auris, which is currently a pathogen of global concern. Also, the compounds showed potent antagonistic activity against Staphylococcus aureus, another significant human pathogen. No in-vitro cytotoxicity against HePG2 cells was observed with either of the compounds. Both displayed favourable drug likeness properties as determined by in-silico ADME and toxicological studies. Also, this is the first report on production of these anti-microbial compounds by an actinobacterium. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01068-7.

Anti-Candida attributes and in-silico drug-likeness properties of phenyl 2'ß, 6'ß-trimethyl cyclohexyl ketone and phenyl nonanyl ether produced by Streptomyces chrestomyceticus ADP4.

AIM: To isolate and characterize anti-Candida compounds from soil actinobacterium Streptomyces chrestomyceticus ADP4 and to assess their drug likeness. METHODS AND RESULTS: Two anti-Candida compounds, Phenyl 2'α, 2'ß, 6'ß-trimethyl cyclohexyl ketone (1PB1) and Phenyl nonanyl ether (1PB2), were isolated from the metabolites produced by Streptomyces chrestomyceticus ADP4. Their structures were deduced by extensive analyses of spectral data obtained from liquid chromatography with tandem mass spectrometry (LCMS/MS), nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FTIR) and ultraviolet (UV) spectroscopies. While both the compounds inhibited growth of the Candida spp., 1PB2 was effective in inhibiting biofilm formed by Candida albicans ATCC 10231. The compounds did not show any cytotoxicity against HepG2 cells and were found to be safe when predicted theoretically on rat model, bioaccumulation and mutagenicity by using the software: toxicity estimation software tool (TEST). The compounds displayed drug-like properties when analyzed by using SwissADME software. CONCLUSIONS: 1PB1 and 1PB2 are being reported for the first time from any natural source along with their anti-Candida properties. In-silico studies revealed their druggability and suitability to take up further work on the compounds for their possible application in treating Candida-associated infections. SIGNIFICANCE AND IMPACT OF THE STUDY: The increasing prevalence of Candidiasis associated with drug-resistant strains of Candida spp. highlighted the urgent need for discovery of new compounds with anti-Candida properties that could hold promise as potential drug candidate.

Knowledge, attitude, and perception of Indian population toward coronavirus disease (COVID-19).

BACKGROUND: Coronavirus disease (COVID-19) has spread very fast worldwide as a pandemic causing unprecedented morbidity and mortality. Most countries in the world have undergone emergency lockdown in an attempt to flatten the curve and reduce the load on healthcare systems. OBJECTIVE: This study was done to assess the knowledge, attitude, and perception toward the disease among the home-bound Indian population during the lockdown. METHODOLOGY: This was a questionnaire-based descriptive cross-sectional study conducted online. Compilation and assessment of the online data in the form of responses were done as for descriptive studies. RESULTS: Among the 320 participants of the study, the awareness about the epidemiological features, including the signs and symptoms of the disease, was very good (more than 99% in some aspects). The attitude toward the measures for prevention of disease at home and outside was also very good (more than 97%) in some aspects, with a scope of improvement in a few others. Only one-third had the knowledge of online (e-consultation) services floated by governments and hospitals for medical advice. Ten percent had the potential to misuse drugs as prophylaxis. Most of the participants perceived that they had no predictable idea about the shape of disease epidemiology in the near future and only hoped for things to get better. CONCLUSION: This study reflects that aggressive awareness drives have played an important role in the dissemination of knowledge and the development of informed positive attitude toward COVID-19. Few gaps in knowledge and practices related to disease epidemiology, safe practices, mobile app for tracking and the availability of e-resources for medical advice, still remain. These should be addressed more aggressively, to strengthen the efforts to overcome this unprecedented crisis.

Chemistry and Antioxidant Potential of Phytoconstituents from Aegle Marmelos Fruit-Shell.

BACKGROUND: Oxidative stress is among the main causes of metabolic disorders. Hence, there is a need to discover potent antioxidants for therapeutic applications. OBJECTIVE: The objective of this study has been to investigate the phytoconstituents of the methanolic extract of the hard shell of Aegle marmelos fruit and their antioxidant potential. METHODS: Methanolic extract was fractionated using different solvents by liquid-liquid extraction. Characterization of the phytoconstituents was done by using phytochemical tests and GC-MS analysis. The free radical scavenging activity, total reducing power, lipid peroxidation inhibition and cell protection assays against oxidative stress were performed with methanolic extract and its fractions. RESULTS: Therapeutically significant class of compounds, for example, polyphenols, glycosides and sterols were revealed in the hard-shell extract. Differential separation of compounds was achieved by liquid-liquid extraction using different solvents. Six compounds: 4-Hydroxybenzeneacetic acid; 5-Oxo-pyrrolidine-2-carboxylic acid methyl ester; 1-[3-Methyl-3-Butenyl] Pyrrolidine; Trans-sinapyl alcohol; 5-[Hydroxymethyl]-2-furaldehyde and 2,4- Dihydroxy-2,5-dimethyl-3[2H]-furan-3-one, identified in the fruit-shell extract, are being reported for the first time from this plant. Strong antioxidant potential of the extract was evident from efficient scavenging of free radicals. The extract also conferred protection to yeast cells against oxidative damage. CONCLUSION: Results showed that the hard shell of the Aegle marmelos fruit was a potent source for antioxidant compounds, which can be developed for therapeutic applications in the control and management of metabolic diseases.

Isolation and Characterization of a New Endophytic Actinobacterium Streptomyces californicus Strain ADR1 as a Promising Source of Anti-Bacterial, Anti-Biofilm and Antioxidant Metabolites.

In view of the fast depleting armamentarium of drugs against significant pathogens, like methicillin-resistant Staphylococcus aureus (MRSA) and others due to rapidly emerging drug-resistance, the discovery and development of new drugs need urgent action. In this endeavor, a new strain of endophytic actinobacterium was isolated from the plant Datura metesl, which produced secondary metabolites with potent anti-infective activities. The isolate was identified as Streptomyces californicus strain ADR1 based on 16S rRNA gene sequence analysis. Metabolites produced by the isolate had been investigated for their antibacterial attributes against important pathogens: S. aureus, MRSA, S. epidermis, Enterococcus faecium and E. faecalis. Minimum inhibitory concentration (MIC90) values against these pathogens varied from 0.23 ± 0.01 to 5.68 ± 0.20 µg/mL. The metabolites inhibited biofilm formation by the strains of S. aureus and MRSA (Biofilm inhibitory concentration [BIC90] values: 0.74 ± 0.08-4.92 ± 0.49 µg/mL). The BIC90 values increased in the case of pre-formed biofilms. Additionally, the metabolites possessed good antioxidant properties, with an inhibitory concentration (IC90) value of 217.24 ± 6.77 µg/mL for 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging. An insight into different classes of compounds produced by the strain ADR1 was obtained by chemical profiling and GC-MS analysis, wherein several therapeutic classes, for example, alkaloids, phenolics, terpenes, terpenoids and glycosides, were discovered.

Molecules and Metabolites from Natural Products as Inhibitors of Biofilm in Candida spp. pathogens.

BACKGROUND: Biofilm is a critical virulence factor associated with the strains of Candida spp. pathogens as it confers significant resistance to the pathogen against antifungal drugs. METHODS: A systematic review of the literature was undertaken by focusing on natural products, which have been reported to inhibit biofilms produced by Candida spp. The databases explored were from PubMed and Google Scholar. The abstracts and full text of the manuscripts from the literature were analyzed and included if found significant. RESULTS: Medicinal plants from the order Lamiales, Apiales, Asterales, Myrtales, Sapindales, Acorales, Poales and Laurales were reported to inhibit the biofilms formed by Candida spp. From the microbiological sources, lactobacilli, Streptomyces chrestomyceticus and Streptococcus thermophilus B had shown the strong biofilm inhibition potential. Further, the diverse nature of the compounds from classes like terpenoids, phenylpropanoid, alkaloids, flavonoids, polyphenol, naphthoquinone and saponin was found to be significant in inhibiting the biofilm of Candida spp. CONCLUSION: Natural products from both plant and microbial origins have proven themselves as a goldmine for isolating the potential biofilm inhibitors with a specific or multi-locus mechanism of action. Structural and functional characterization of the bioactive molecules from active extracts should be the next line of approach along with the thorough exploration of the mechanism of action for the already identified bioactive molecules.

Natural Polyphenols: Chemical Classification, Definition of Classes, Subcategories, and Structures.

Background: Polyphenols are natural compounds synthesized exclusively by plants with chemical features related to phenolic substances and eliciting strong antioxidants properties. Objective: The aim of this paper is to give a reliable overview of the chemical classification of natural polyphenols. Methods: Literature survey was done through google scholar, pubmed and scopus search engine. Results and Discussion: These molecules or classes of natural substances are characterized by two phenyl rings at least and one or more hydroxyl substituents. This description comprehends a large number of heterogeneous compounds with reference to their complexity. Therefore, polyphenols can be simply classified into flavonoids and non-flavonoids, or be subdivided in many sub-classes depending on the number of phenol units within their molecular structure, substituent groups, and/or the linkage type between phenol units. Polyphenols are widely distributed in plant tissues where they mainly exist in form of glycosides or aglycones. The structural diversity of flavonoid molecules arises from variations in hydroxylation pattern and oxidation state resulting in a wide range of compounds: flavanols, anthocyanidins, anthocyanins, isoflavones, flavones, flavonols, flavanones, and flavanonols.

Phenolic Substances in Foods: Health Effects as Anti-Inflammatory and Antimicrobial Agents.

Background: The interest in phenolic compounds present in foods of vegetable origin has shown a notable increase in recent decades. This interest is due to the growing number of scientific studies concerning their beneficial role in human health. The interest in polyphenols has been supported by the current and growing awareness, and attention of consumers to food from a food safety viewpoint and also because of the beneficial effects ascribed to polyphenols. Objective: The aim of this article is to highlight antibacterial, antifungal, and anti-inflammatory activities of various phenolic compounds normally found in certain foods. Conclusions: Phenolic compounds exert different biological functions, such as antioxidant activity, modulation of detoxifying enzymes, stimulation of the immune system, reduction of platelet aggregation, modulation of hormonal metabolism, reduction of blood pressure, and anti-inflammatory, antibacterial, antiviral, and antifungal activities.

A pharmacoeconomic analysis to compare cost-effectiveness of metformin plus teneligliptin with metformin plus glimepiride in patients of type-2 diabetes mellitus.

BACKGROUND: With the available evidence of early combined oral drug therapies being more effective in lowering blood glucose levels than maximal doses of a single drug, many clinicians are taking the aggressive approach of adding a sulfonylurea or a dipeptidyl peptidase-4 (DPP-4) inhibitor to metformin as the initial therapy in type 2 diabetes mellitus (T2DM). Pharmacotherapy for a chronic disease like diabetes has substantial economic implications for patients especially in a developing country like India. So it is important to scientifically evaluate the cost-effectiveness of these commonly practiced combination therapies in the management of T2DM. MATERIALS AND METHODS: This was a prospective observational randomized comparative study conducted over 8 weeks on patients of T2DM who were prescribed either of the two therapies of metformin (500 mg) plus glimepiride (1 mg) or metformin (500 mg) plus teneligliptin (20 mg). Cost-effectiveness analysis was done by calculating the expense incurred on 0.1% reduction in HbA1 c and 1 mg/dl reduction in fasting plasma glucose (FPG)/post-prandial plasma glucose (PPG) levels after 8 weeks and compared for both the groups. The same was also evaluated for differences in BMI levels. RESULTS: The cost-effectiveness for per unit reduction in HbA1c and FPG was significant in metformin plus glimepiride group as compared to the metformin plus teneligliptin group though it was comparable for both the groups for per unit PPG reduction. There was no significant change in BMI levels between the groups. CONCLUSION: Compared to metformin plus teneligliptin, metformin plus glimepiride is a significantly cost-effective therapy when used as an initial combination therapy in patients of T2DM in lowering HbA1c and FPG.

Isolation and Characterization of Nuciferoic Acid, a Novel Keto Fatty Acid with Hyaluronidase Inhibitory Activity from Cocos nucifera Linn. Endocarp.

BACKGROUND: Inflammation and oxidative stress are very closely related to pathophysiological processes and linked to multiple chronic diseases. Traditionally, the coconut fruits were used in Guatemala for treatment of dermatitis and inflammation. Isolation of the anti-inflammatory agent from the hard shell of the coconut fruit was targeted in the current study. METHODS: Fractionation of ethanolic extract of the coconut hard shell was done by using column chromatography, solvent treatments and TLC that led to the isolation of a molecule. RESULTS AND DISCUSSION: Spectral characterization of the molecule by LC-MS/MS QTOF, FTIR, 1HNMR, 13C-NMR, HMQC and HMBC indicated that it is a novel keto fatty acid, which is named as nuciferoic acid. Hyaluronidase inhibitory potential of the nuciferoic acid was found to be moderate. It was further docked in all the ten cavities of hyaluronidase and was compared with the substrate hyaluronic acid. Cavity 1 and cavity 4 could be the probable sites of action on hyaluronidase for nuciferoic acid. ADME and toxicological characterization suggested that the key sites of metabolism on nuciferoic acid are C1, C2, C14 and C17. Toxicity prediction against 55 toxicological endpoints revealed that nuciferoic acid does not have any indication of existing toxicological features. CONCLUSION: A novel keto fatty acid, nuciferoic acid, from C. nucifera hard shell has been isolated and characterized. It was found to inhibit hyaluronidase activity, which indicated its potential application as an anti-inflammatory drug or as an adjuvant.

Diversity and Applications of Endophytic Actinobacteria of Plants in Special and Other Ecological Niches.

Actinobacteria are wide spread in nature and represent the largest taxonomic group within the domain Bacteria. They are abundant in soil and have been extensively explored for their therapeutic applications. This versatile group of bacteria has adapted to diverse ecological habitats, which has drawn considerable attention of the scientific community in recent times as it has opened up new possibilities for novel metabolites that may help in solving some of the most challenging problems of the day, for example, novel drugs for drug-resistant human pathogens, affordable means to maintain ecological balance in various habitats, and alternative practices for sustainable agriculture. Traditionally, free dwelling soil actinobacteria have been the subject of intensive research. Of late, symbiotic actinobacteria residing as endophytes within the plant tissues have generated immense interest as potential source of novel compounds, which may find applications in medicine, agriculture, and environment. In the light of these possibilities, this review focuses on the diversity of endophytic actinobacteria isolated from the plants of extreme habitats and specific ecological niches. Furthermore, an attempt has been made to assign chemical class to the compounds obtained from endophytic actinobacteria. Potential therapeutic applications of these compounds and the utility of endophytic actinobacteria in agriculture and environment are discussed.

Inhibition of Biofilm and Virulence Factors of Candida albicans by Partially Purified Secondary Metabolites of Streptomyces chrestomyceticus Strain ADP4.

BACKGROUND: Despite several advancements in antifungal drug discovery, fungal diseases like Invasive Candidiasis (IC) still remain associated with high rates of morbidity and mortality worldwide. Thus there is an enormous need for anti-Candida drugs. OBJECTIVE: The main objectives of the work included: 1. To investigate therapeutically significant classes of secondary metabolites produced by S. chrestomyceticus strain ADP4. 2. To investigate and analyze inhibition of significant virulence attributes of C. albicans, such as, biofilm and secretory hydrolytic enzymes by ADP4 secondary metabolites. 3. Mechanistic analysis of probable compounds for their site of action on Secretary Aspartyl Proteinase 3 (Sap3). METHODS: Metabolite extract-SDB (MESDB) of S. chrestomyceticus strain ADP4 was fractionated on silica gel column chromatography. Fractions were analyzed for anti-Candida activity by disc diffusion assay. Active fractions were further purified by differential solvent treatment. MIC90 values were determined by broth dilution method. MFC was based on counting viable cells. Inhibition of yeast to hyphae transition and that of production of hydrolytic enzymes were estimated by plate assays. GC-MS of MESDB and Partially Purified Metabolite preparations (PPMs) was done. GRIP docking studies with Sap 3 of C. albicans was done using VLife MDS 4.6 software. RESULTS: Chemical profiling showed that ADP4 secondary metabolites contained alkaloids, flavonoids, polyphenols, terpenoids and triterpenes. The MESDB and the PPMs showed low or no cytotoxicity but were able to effectively contain virulence attributes of Candida pathogen. Docking studies revealed that some of the probable compounds have affinity for aspartic acid residue in Sap3 enzyme of C. albicans. CONCLUSION: Secondary metabolite of strain ADP4 included important classes of therapeutically important compounds. Their anti-Candida activity was mediated by inhibition of critical virulence factors of the pathogen.

Enhanced White Matter Integrity in Corpus Callosum of Long-Term Brahmakumaris Rajayoga Meditators.

Meditation has a versatile nature to affect cognitive functioning of human brain. Recent researches demonstrated its effects on white matter (WM) properties of human brain. In this research, we aim to investigate WM microstructure of corpus callosum (CC) in long-term meditators (LTMs) of rajayoga meditation using diffusion tensor imaging. For this cross-sectional analysis, 22 LTMs and 17 control participants of age ranging from 30 to 50 years were recruited. Results show high fractional anisotropy values with low mean diffusivity in whole as well as different segments of CC in the LTM group. Also the experience of meditation was correlated with WM properties of CC tracts. Findings may suggest rajayoga meditation to bring potential changes in microstructure of CC segments. Further studies are suggested in clinical population to check its validity and efficacy against disorders involving agenesis of WM.

In Silico Studies Revealed Multiple Neurological Targets for the Antidepressant Molecule Ursolic Acid.

BACKGROUND: Ursolic acid, a bioactive pentacyclic triterpenoid had been evaluated for its interaction with the neurological targets associated with antidepressant drugs. Current study was to mechanistically analyze the probable site of action for ursolic acid on the target proteins. METHODS: Ursolic acid has been docked with monoamine oxidase isoforms: MAO-A and MAO-B, LeuT (homologue of SERT, NET, DAT) and Human C-terminal CAP1 using GRIP docking methodology. RESULTS: Results revealed its non-selective antidepressant action with strong binding affinity towards LeuT and MAO-A proteins, which was found to be comparable with the reference ligands like chlorgyline, clomipramine, sertraline and deprenyl/selegiline. CONCLUSION: Significant binding affinity of ursolic acid was seen with MAO-A, which indicated its potential role in other neurological disorders, for example, Alzheimer's disease and Parkinson disease besides depression.

Anti-biofilm activity of the metabolites of Streptomyces chrestomyceticus strain ADP4 against Candida albicans.

Candida albicans is a commensal but a significant opportunistic pathogen. It forms biofilms, which protect them against anti-Candida compounds. Therefore, an agent capable of disrupting the Candida biofilms will be useful in the treatment of such infections. The metabolites of Streptomyces chrestomyceticus strain ADP4 displayed strong anti-Candida activity, hence were investigated further for their ability to inhibit biofilm. Strong inhibition of biofilms produced by several reference strains of C. albicans was observed with BIC90 values ranging from 4 to 8 µg/mL. The anti-biofilm activity of ADP4 metabolites appeared to involve membrane disruption and leakage of cellular materials. Also, it effectively inhibited Candida cells from adhering to polystyrene surface and inhibited their conversion to the hyphal state, thereby preventing further development of the biofilm by the adherent cells. This is the first such report on the metabolites produced by any strain of S. chrestomyceticus.

Suvorexant: The first orexin receptor antagonist to treat insomnia.

Primary insomnia is mainly treated with drugs acting on benzodiazepine receptors and a few other classes of drugs used for different co-morbidities. A novel approach to treat insomnia has been introduced recently, with the approval of suvorexant, the first in a new class of orexin receptor antagonists. Orexin receptors in the brain have been found to play an important role in the regulation of various aspects of arousal and motivation. The drugs commonly used for insomnia therapy to date, have often been associated with adverse effects, such as, day-time somnolence, amnesia, confusion, and gait disturbance, apart from the risk of dependence on chronic use. Suvorexant has not shown these adverse effects because of its unique mechanism of action. It also appears to be suitable as a chronic therapy for insomnia, because of minimal physical dependence. The availability of this new drug as an effective and safe alternative is an important and welcome development in insomnia management.