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9,12,15-Octadecatrienoic acid (ODA) a carboxylic acid composed of 18 carbon atoms and three cis double bonds. ODA is a plant derived essential fatty acid indispensable to the human system. ODA refers to many different structural and conformational isomers, that differ in the position of the double bonds along the backbone and on whether they are in cis ('Z') or trans ('E') conformation. It has been well established that ODA can only be outsourced from food and then converted into eicosa-pentaenoic acid (EPA) and docosa-hexaenoic acid (DHA) in the human system. However, this metabolic process is highly limited and the rate of conversion is influenced by several factors such as dose, gender, and disease. Studies suggest that ODA is associated with reduced risk of fatal ischemic heart disease. Further, higher intake may reduce the risk of sudden death among prevalent myocardial infarction in patients consistent with induced antiarrhythmic effect. ODA significantly reduces blood clots. Traditional usage of ODA is attributed to its cardiovascular-protective, anti-cancer, neuro-protective, anti-osteoporotic, anti-inflammatory, and anti-oxidative properties. Recent pharmacological indicate that ODA has anti-metabolic syndrome, anticancer, anti-inflammatory, anti-oxidant, anti-obesity, neuro-protective, and more specifically involved in the regulation of gut-micro-floral functionalities. Studies, both experimental and clinical trials indicate that ODA has anti-metabolic syndrome effects. In short, ODA is potentially used to treat many diseases, but in-depth ADMET studies are required to firmly re-establish its clinical efficacy and market potential. Keywords: ADMET; Moringa oleifera; Secondary Metabolites; Natural Products (NPs); Bioactive Substances; Octadecatrienoic acid (ODA); Eicosa-Pentaenoic Acid (EPA); Docosa-Hexaenoic Acid (DHA)

Plant Based Natural Products (PBNPs) have been subject of interest since ancient time due to their use in food, industrial and biomedical applications. Research attention has further augmented to explore their phytochemical composition, properties, and potential application in the post-COVID era. In the present study phytochemical screening has been carried out with Methanolic Leaf Extracts of Moringa oleifera (MLEMO) followed by Gas Chromatography-Mass Spectrometry (GCMS) analysis. Phytochemical analysis of MLEMO revealed the presence of Alkaloids, Carbohydrates, Coumarins, Flavonoids, Glycosides, Phenol, Proteins, Quinones, Saponins, Steroids, Tannins and Terpenoids. Further, GCMS analysis revealed the presence of 41 compounds of which Dihydroxyacetone; Monomethyl malonate; 4H-Pyran-4-one,2,3-dihydro-3,5-dihydroxy-6-methyl; 1,3-Propanediol, 2-ethyl-2-(hydroxymethyl); Propanoic acid, 2-methyl-, octyl ester; 3-Deoxy-d-mannoic lactone; Sorbitol; Inositol; Cyclohexanemethanol, alpha-methyl-4-(1-methylethyl), Hexadecanoic acid, Methyl palmitate; n-Hexadecanoic acid (Palmitic acid); 9-Octadecenoic acid, methyl ester; Phytol; 9,12,15-Octadecatrienoic acid; Octadecanoic acid; 9-Octadecenamide were prominent. Most of the compounds in the list are bioactive and possess medicinal properties that are expected to serve as a baseline lead for the development of therapeutic agents. Keywords: Phytochemical screening; GCMS; Bioactive Natural Products; Moringa oleifera; MLEMO; Biomedical application

Wide-reaching interest in use of plant derived secondary metabolites (PDSMs) has been growing world over. This implies that the beneficial effects of plant based natural products (PBNPs) being rediscovered and harnessed for the development of novel drugs; drug-leads and structural background for drug design. Survey of literature on the indigenous use of traditional medicinal knowledge bestows ethnopharmacological potentials of PBNPs that has inspired drug design and development through research in drug discovery; PBNPs provide baseline for the development of drug leads against various pharmacological targets. Studies indicate that Cymbopogon martini Essential Oil (CMEO) exhibits a wide range of biological activities (anticancer, antidiabetic, antibacterial, antifungal, antioxidant, hepatoprotective and insecticide) attributed to the presence of bio-active secondary metabolites (BASM). However, wide-spread application of CMEO is limited because of typical odor, color and taste. In the present study, In-silico Absorption, Distribution, Metabolism, Elimination, Toxicity (ADMET) studies of β-caryophyllene (BCP) from Cymbopogon martinii is envisaged. β-caryophyllene enhances wound healing through multiple routes therefore, Non AMES toxic, Non-carcinogens, and biodegradable nature of β-caryophyllene prospects this compound as considered as an apt lead for the development of drugs for the treatment of cuts and wounds besides other diseases viz., diabetics, cancer, metabolic inflammation and other long term complications associated with these diseases. In particular, BCP inhibits cytochrome P450 isoforms (CYP3A4) that metabolize xenobiotics and results in adverse effects. Pharmacokinetic properties and predicted score values of β-caryophyllene have highlighted that both pharmacological and toxicological aspects need to be further investigated before put to clinical trials. Keywords: ADMET; β-caryophyllene; Cymbopogon martinii; Cardiotoxicity; Cytotoxicity; Drugability; Pharmacokinetics; Bioactivity; Essential Oil

Plant Based Natural Products (PBNPs) are the primary source of natural antioxidants capable of neutralizing or eliminating harmful Reactive Oxygen Species (ROS). Oxidative stress contributes not only to the pathogenesis of type 2 diabetes (T2DM) but also to diabetic related vascular complications by lipid peroxidation. Oxidation induced DNA and protein damage leads to development of vascular complications like coronary heart disease, CVD, stroke, neuropathy, retinopathy, nephropathy, CKD, and other long term complications associated with diabetics. Likewise Multidrug resistance (MDR) is one of the major clinical challenges in cancer treatment and compromises the effectiveness of conventional anticancer chemotherapeutics. P-glycoprotein (P-gp) has been characterized as a major mechanism of MDR. Ellagic acid (EA) is a bioactive secondary metabolite widely distributed in vegetables and fruits (Strawberry, Grapes, Blackberry, Raspberry, Plums etc.) Chemically, EA is 2,3,7,8-tetrahydroxychromeno [5,4, -cde] chromene-5, 10-dione, a heterotetracyclic dimer of Gallic Acid (GA) molecules formed by oxidative aromatic coupling involving intramolecular lactonization. EA is associated with pharmacological activities such as anti-inflammatory, neuroprotective, cardio-protective, antioxidant, anti-mutagenic, multidrug resistance etc. EA has been marketed as a dietary supplement with claimed benefits against cancer, CVD, CKD and other metabolic disorders. However, pharmacological limitation of EA is attributed to its low solubility in water and reduced bioavailability. In the present study, bimolecular potential of EA has been bioprospected in the revised framework of ADMET pharmacoinformatics to further widen its biomedical applications. Keywords: ADMET; Pharmacoinformatics; Ellagic Acid; Gallic Acid; Syzygium cumini; Alagarkovil Reserve Forest (ARF); Reactive Oxygen Species (ROS)

Quercetin (3,3′,4′,5,7-Pentahydroxyflavone) is the one among the bioactive secondary metabolite (BASM) in neem seed of Azadirachta indica A. Juss. Quercetin (Que) and its derivatives hold promising pharmacological effects. Antidiabetic, anti-inflammatory, antioxidant, antimicrobial, anti-Alzheimer’s, antiarthritic, cardiovascular, and wound-healing effects of Que have been extensively investigated, recently lot of work has been carried out on its anticancer activity against different cancer cell lines. Recently, in silico/ in vitro studies have demonstrated that Que interferes with different stages of coronavirus entry and replication cycle (PLpro, 3CLpro, and NTPase/helicase). Due to its pleiotropic effects in human health and disease and lack of systemic toxicity, Que and its derivatives could be tested for their efficacy on human target system in future clinical trials. In the present study, an attempt has been made to evaluate the physicochemical, druggable properties of Que from A. indica to prospect its ADMET properties. Keywords: NEEM; Azadirachta indica; Quercetin; Pharmacoinformatics; ADMET; Drug-Likeness; Toxicology

Purpose : Sorafenib is the sole FDA approved drug conventionally used for the treatment of advanced hepatocellular carcinoma (HCC). Despite of the beneficial use of sorafenib in the treatment of HCC, multidrug resistance still remains a challenge. HCC is inherently known as chemotherapy resistant tumor due to P-glycoprotein (P-gp)-mediated multidrug resistance. Methods: We studied the interaction energy of kaempferol with human multidrug resistance protein-1 (RCSB PDB ID: 2CBZ) using in silico method with the help of BIOVIA Discovery Studio. HepG2 and N1S1 liver cancer cell lines were treated in suitable cell culture media to evaluate the efficacy of kaempferol in chemo-sensitizing liver cancer cells towards the effect of sorafenib. Cell viability study was performed by MTT assay. Results: In silico analysis of kaempferol showed best docking score of 23.14 with Human Multi Drug Resistant Protein-1 (RCSB PDB ID: 2CBZ) compared with positive control verapamil. In in-vitro condition, combination of sub-toxic concentrations of both kaempferol and sorafenib produced 50% cytotoxicity with concentration of 2.5 µM each which indicates that kaempferol has the ability to reverse the MDR by decreasing the over-expression of P-gp. Conclusion: Kaempferol is able to sensitize the HepG2 and N1S1 against the sub-toxic concentration of sorafenib. Hence, we consider that the efficacy of sorafenib chemotherapy can be enhanced by the significant approach of combining the sub-toxic concentrations of sorafenib with kaempferol. Thus, kaempferol can be used as a better candidate molecule along with sorafenib for enhancing its efficacy, if validated through preclinical studies.

Astaxanthin is a naturally occurring carotenoid which is derived from the microalgae Haematococcuspluvialis. As well as being the most powerful antioxidant known to science, it also has potent anti-inflammatory properties. Naturalastaxanthin´s distinct advantage in comparison to other antioxidants, is its ability to span the entire lipid bilayer of the cell membrane, thus providing superior protection from the inside out. Natural astaxanthin has a strong ability to both balance and strengthen the immune system. This article reviews the current available scientific literature regarding the effect of astaxanthin from the algae Haematoccus pluvialis in Astashine capsules as a natural immune booster in COVID-19 infections.

A prebioticis defined as “a non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon” Modification by prebiotics of the composition of the colonic micro-flora leads to the predominance of a few of the potentially health-promoting bacteria. The scientific data showing that prebiotics may positively affect various physiologic functions in ways that will permit them now or in the future to be classified as functional foods for which health claims (of enhanced function or of reduction in disease risk) will be authorized. The present paper Reviews the Role of Maxfibe Sachets developed by R&D cell of Lactonova Nutripharm Pvt Ltd. Hyderabad.

An ideal colon specific drug delivery system needs to perform multiple functions like greater bio availability, less toxicity and higher therapeutic efficacy, all of which require high degree of smartness. This article focuses on the overview of the stimuli-responsive polymers and various nanodrug delivery systems which have found applications in colon specific delivery of drugs as this system provide a link between therapeutic need and drug delivery. These polymers exhibit a non-linear response to a small stimulus leading to a macroscopic alteration in their structure/properties. Stimuli responsive polymers display a significant physio chemical change in response to small changes in their environment (temperature, pH, light etc.). Colonic drug delivery has gained increased importance in treating diseases like Crohn’s disease, ulcerative colitis, colon cancer etc. The expansion in the development of polymers based system with greater flexibility, versatility and unexplored potential enables new opportunities for them in uplifting bio medicine. Applying the concepts of smartness in the context of clinically relevant therapeutic and diagnostic systems, it can prelude in a new era of ‘smart’ therapeutics that can improve the health care fields. In particular, due to its high sensitivity to the stimuli, this system has been identified as a sensible platform for releasing drug at suitable site and at appropriate time.

Alzheimer's disease (AD) is a neurodegenerative disorder affecting the central nervous system (CNS) characterized by the overproduction of amyloid beta proteins and its inability to clear from the brain resulting in its self-aggregation to form toxic oligomers, fibrils and plaques. Studies show that the incidence of AD would double in every 2 decade showing an increase from 66 million to 115 million by 2050. Currently therapies address systemic administration for treating Alzheimer's disease by appropriate manipulations in neutrophins, the neutrophic enhancing factors. In addition, therapeutic strategies using cholinesterase inhibitors, N-methyl-D-aspartate (NMDA) receptor blockage, or by drugs that remove amyloid plaques frombrain. Fluid biomarkers improve diagnostic accuracy in predementia phase as drugs would be effective only in initial stages. However, a major challenge in the CNS drug delivery being the blood brain barrier (BBB) and that nanotechnological approaches have been designed to facilitate drug delivery across this physiological barrier. This review addresses the current challenges and strategies as well as the significance of nanotechnology for a better understanding and delivery of drugs across the BBB to reach damaged areas of the CNS in patients.

Chaulmoogra oil based methotrexate loaded nanoemulsion was prepared via emulsification technique using tween 80 and ethanol as surfactants. The formulation was characterized by FTIR and TEM. The prepared nanoemulsion has an average particle size of 34 nm with negative surface charge and has pH compatible to skin. Rheological studies revealed the shear thinning non-Newtonian visco-elastic behavior of the formulation as explained by the Herschel Bulkley model. The formulation was cytocompatible towards mouse dermal fibroblast L929 cells when tested by MTT assay and was stable in refrigerator for the tested period of 3 months. The in-vitro release mechanism of methotrexate from formulation followed zero order release kinetics with non Fickian diffusion mechanism. The ex-vivo skin permeation studies done by Franz diffusion cell apparatus using porcine skin revealed the improved skin permeation and retention of drug in deep skin layers when compared with control drug solution. The in vivo anti-psoriatic studies done on imiquimod psoriatic model revealed superior anti-psoriatic efficacy, with effective skin retention and lesser serum and tissue accumulation when compared with orally administered methotrexate tablet.

This paper analyzes a family of high step up single switch switched capacitor boost converters and Z-source/quasi Z-source dc-dc converters to provide high output dc voltage gain with single stage conversion having low voltage stress on active switches, capacitors, and diodes. The operating principles, parameters design guideline of these converters are presented along with simulation results. The discussed topologies in this paper are aimed to increase the conversion system reliability and efficiency with decreased cost, volume, and weight. These power converter topologies are used for various applications such as photovoltaic (PV) systems, wind energy conversion, fuel cells, uninterruptible power systems, motor drives, energy storage systems, electric vehicle and power factor correction. Simulations are carried out in MATLAB/Simulink environment.

Chitosan is a natural polymer having much use in drug delivery applications. The polymer is characterized by its biocompatibility, biodegradability, muco-adhesiveness, antimicrobial activity, non-toxicity and positive charge. Insolubility of chitosan in water and other common organic solvents limits its utility. This problem can be solved by chemical modification of its reactive functional groups; NH2 and –OH to form derivatives with improved solubility. The transdermal drug delivery systems which can control the drug release process have got substantial importance in drug delivery research areas. Chitosan and its derivatives are reported to enhance the skin permeability via a variety of molecular mechanisms. Low molecular weight chitosan is often employed as permeability enhancer in transdermal drug delivery system (TDDS). Various chitosan based transdermal drug delivery systems like composite films, vesicular systems, dendrimers, microspheres, microneedles and other nanocarriers like nanoparticles, nanogel, nanoemulsion, nanolipid carriers with benefits achieved are detailed in this review.

Chitosan, a polymer from chitin family has gained considerable pharmaceutical and biomedical importance due to variety of advantages like easy availability, nontoxicity, biocompatibility, biodegradability, rich functionalities, and high drug-loading capacity. Versatility of chitosan allows for the development of systems such as nanoparticles, hydrogels, scaffolds, microspheres, etc. for drug delivery applications. Its cationic nature helps to target negatively charged cell surface receptors expressed at tumor sites and the pH-dependent swelling property ensures the drug’s release in the acidic tumor environment. Chitosan is reported to possess bacteriostatic, fungistatic, antiinflammatory properties and is reported to promote tissue granulation. The porous nature, gel-forming properties, ease of chemical modification, and wound-healing activity of chitosan make it a promising supporting material for tissue engineering applications. This chapter deals with the use of chitosan-based drug delivery systems for infectious, inflammatory, and neoplastic diseases along with tissue engineering applications of chitosan-based materials for bone, skin, liver, and nerve tissue regeneration.

Methotrexate loaded chitin nanogel (MCNG) was formulated for its topical use in psoriasis. MCNG was characterized by DLS, TEM and FTIR. The MCNG particles were spherical in shape with size of 196±14nm, having surface charge of +9.21±0.42 mv. MCNG exhibited greater swelling and drug release at acidic pH than neutral and alkaline conditions. The treatment with MCNG showed significant level of toxicity on HaCaT and THP-1 cells and was taken up well by HaCaT cells as revealed by fluorescent microscopy. MCNGs exhibited significant anti-inflammatory activity as revealed by the inhibitory effects observed on the activity of COX-2 and LOX-5 enzymes expressed in THP-1 cells. Skin permeation studies revealed an increased trasdermal flux of methotrexate from MCNG with loosened stratum corneum and other epidermal layers of skin in comparison with control methotrexate solution treated samples. Significant anti-psoriatic efficacy on imiquimod (IMQ) induced model of psoriasis without any dermal and systemic toxicities suggest that it as an ideal delivery platform for topical delivery of methotrexate in psoriasis. Thus it is expected to become a better alternative for the oral delivery of methotrexate in the selected disease.

The anti-psoriatic efficacy of orally administered methotrexate loaded chitin nanogel (MCNG) was evaluated (two doses- 2.715 mg/kg and 5.143 mg/kg) and compared against orally administered methotrexate tablet MTX (5.143 mg/kg). MCNG at both dose levels of 2.715 mg/kg and 5.143 mg/kg exhibited significant anti-psoriatic activity which is very much comparable with MTX, caused normalization of histological features and inflammatory score associated with induced psoriasis. Biodistribution studies revealed the presence of drug in serum and in vital organs at all the three cases with highest amount in MCNG at 5.143 mg/kg dose, followed by MTX tablet and are lowest in MCNG at 2.715 mg/kg dose. MCNG at the highest dose of 5.143 mg/kg caused liver, lung and kidney toxicities on sub acute toxicity studies and MTX tablet was found to be toxic on liver and lung on sub chronic toxicity studies. MCNG 2.715 mg/kg was found to be safe on both sub acute and sub chronic administrations, suggesting that it can provide sufficient serum and tissue level of methotrexate necessary to clear psoriatic lesions, without inducing systemic toxicity and expected to be a better alternative for orally administered conventional methotrexate tablet for patients who need systemic medications for psoriasis.

In the present study chitin nanogel loaded with anti-psoriatic drug clobetasol was developed (CLCNG) for its topical delivery in psoriasis. CLCNG had the particle size of 132±14nm, with gel like consistency, stability in refrigerator, having higher drug release properties at acidic pH. CLCNG exhibited significant toxicity towards HaCaT and THP-1cell lines by MTT assay. The uptake of nanogel by HaCaT cell lines was confirmed by fluorescent microscopy. CLCNG at 0.35mg/ml exhibited significant anti-inflammatory activity with an average of 65% and 70% inhibition in COX and LOX activities expressed in THP-1 cells. In vitro skin permeation studies revealed the increased transdermal flux with fragmented stratum corneum and loosened epidermal layers in CLCNG treated samples, compared with control drug solution. The in vivo anti-psoriatic studies done on imiquimod model confirmed the potential benefits of the nanogel for the topical delivery of clobetasol in psoriasis.

This paper analyzes a family of high step up single switch switched capacitor boost converters and Z-source/quasi Z-source dc-dc converters to provide high output dc voltage gain with single stage conversion having low voltage stress on active switches, capacitors, and diodes. The operating principles, parameters design guideline of these converters are presented along with simulation results. The discussed topologies in this paper are aimed to increase the conversion system reliability and efficiency with decreased cost, volume, and weight. These power converter topologies are used for various applications such as photovoltaic (PV) systems, wind energy conversion, fuel cells, uninterruptible power systems, motor drives, energy storage systems, electric vehicle and power factor correction. Simulations are carried out in MATLAB/Simulink environment.