The DPP-4 inhibition is an interesting target for the development of antidiabetic agents which promotes the longevity of GPL-1(Glucagon-like peptide 1). The current study was intended to assess DPP-4(Dipeptidyl Peptidase-4) inhibition mediated antidiabetic effect of phytocompounds of an aqueous fruit extract of Withania coagulans (Stocks) Dunal by in-vitro, in-silico and in-vivo approaches. The phytoconstituents screening was executed by LCMS (Liquid Chromatography with tandem mass spectrometry). The in-vitro and in-vivo, DPP-4 assays were performed by using available kits. The in-vitro DPP-4 activity was inhibited up to 68.3% by the test extract. Accordingly, in-silico determinations of molecular docking, molecular dynamics and pharmacokinetics were performed between the target enzyme DPP-4 and leading phytocompounds. The molecular dynamics authenticated the molecular docking data by crucial parameters of cytosolic milieu by the potential energy, RSMD (Root Mean Square Deviation), RSMF (Root Mean Square Fluctuation), system density, NVT (Number of particles at fixed volume, ensemble) and NPT (Number of particles at fixed pressure, ensemble). Accordingly, ADMET predictions assessed the druggability profile. Subsequently, the course of the test extract and the sitagliptin (positive control), instigated significant (p ≤ 0.001) ameliorations in HOMA indices and the equal of antioxidants in nicotinamide-streptozotocin induced type 2 diabetic animal model. Compassionately, the histopathology represented increased pancreatic cellular mass which caused in restoration of histoarchitectures. It has been concluded that phytoconstituents in W. coagulans aqueous fruit extract can regulate DPP-4, resulting in improved glucose homeostasis and enhanced endocrinal pancreatic cellular mass.Communicated by Ramaswamy H. Sarma.

BACKGROUND:Convolvulus pluricaulis is a native plant that is commonly mentioned in Ayurveda as a Rasayana and is primarily recommended for use in mental stimulation and rejuvenation therapy. Convolvulus pluricaulis is used as a brain tonic. The plant is reported to be a prominent memory-improving drug. It is used as a psychostimulant and tranquilizer. It is reported to reduce mental tension.OBJECTIVE:The present study aimed to explore the protective effect of hydroalcoholic extract from the leaves of Convolvulus pluricaulis along with CNS depressant and anti-anxiety activities, in models of mice.METHODS:The extract from leaves of Convolvulus pluricaulis were sequentially isolated with a mixture of water and alcohol solution in the soxhlet apparatus. An acute toxicity study was conducted as per OECD guidelines no. 423, in which 18 Albino male mice were treated with different doses (1, 10, 100, 500, 1000, and 2000 mg/kg) of hydroalcoholic extract of Convolvulus pluricaulis and assessed for toxicity parameters for 14 days. Various psychomotor activities of hydroalcoholic extract from leaves of Convolvulus pluricaulis for 100, 200, and 300 mg/kg doses were performed in mice by using various tests like actophotometer, open field, rota-rod, grip strength tests, elevated plus maze, hole board test, inclined plane, chimney test.RESULTS:The hydroalcoholic extract from leaves of Convolvulus pluricaulis was found to fall under category 4 in the acute toxicity study. Therefore, 100, 200, and 300 mg/kg doses of hydroalcoholic extract of leaves of Convolvulus pluricaulis were selected for the further pharmacological study. The results of psychomotor tests (actophotometer, open field, rota-rod, grip strength, hole board test, inclined plane, chimney test, elevated plus maze, light-dark model) for test doses 100, 200, and 300 in mice showed CNS depressant and anti-anxiety effects.CONCLUSION:Hydroalcoholic extract from leaves of Convolvulus pluricaulis at the 100, 200, and 300 mg/kg doses has shown CNS depressant and anti-anxiety effects in mice models.

Typical firefighter protective clothing consists of a helmet, outer garments, gloves, trousers, and boots. The most common natural fibres used for manufacturing thermal protective clothing for firefighters include cotton, wool, silk, and flax. Wool possesses pyrolyzing temperature and limiting oxygen index (LOI) values of ∼245°C and 25.2%, respectively; cotton has pyrolyzing temperature and LOI values of 300°C and 18.4%, respectively; silk has pyrolyzing temperature and LOI values of 320°C and 23.1%, respectively; while flax has an LOI value of 19%. Since these natural fibres have low pyrolyzing temperature and LOI values, chemical modification of these fibres is required to make them suitable for manufacturing thermal protective clothing. However, even after chemical modification, these fibres exhibit an average LOI of ∼30% and are not self-extinguishing. Therefore, chemically modified natural fibre-based thermal protective clothing can only be used as by wildfire hazard or vehicle hazard firefighters, where there is a less intense thermal environment.

Since its discovery, liposomes have been vastly studied and applied in the field of pharmaceutical, food, and nutraceutical industry. Being a delivery vesicle, liposomes are capable of effectively transporting drugs, food, or nutraceuticals into the body by facilitating absorption directly in the mouth while protecting the encapsulated substance from degradation by the acidic environment of the stomach. Their ability to incorporate both hydrophobic and hydrophilic drugs as well as their biocompatibility, reduced risk of 166toxic side effects made them the most extensively studied drug delivery system. The application of liposomes in the food industry was first published in the early 1980’s. The initial application of liposome included the controlled release of enzymes in the making of cheese. Further, both lipid and aqueous soluble food ingredients were delivered by liposomal technology. However, designing food and nutraceuticals into liposomal delivery system comes with its own challenges. This chapter details about the techniques in developing liposomal based food and nutraceuticals, formulations, and characterization of liposomal products in functional food and nutraceuticals, challenges in formulating functional food and nutraceuticals into liposomal systems, global market of liposomal system in functional food and nutraceutical products and recent patents related to liposomal technology in functional food and nutraceuticals.

At present, people and patients worldwide are relying on the medicinal plant as a therapeutic agent over pharmaceuticals because the medicinal plant is considered safer, especially for chronic disorders. Several medicinal plants and their components are being researched and explored for their possible therapeutic contribution to CNS disorders. Thymoquinone (TQ) is one such molecule. Thymoquinone, one of the constituents of Plant Nigella Sativa, is effective against several neurodegenerative diseases like, Alzheimer's, Depression, Encephalomyelitis, Epilepsy, Ischemia, Parkinson's, and Traumatic. This review article presents the neuropharmacological potential of TQ's, their challenges, and delivery prospects, explicitly focusing on neurological disorders along with their chemistry, pharmacokinetics, and toxicity. Since TQ has some pharmacokinetic challenges, scientists have focused on novel formulations and delivery systems to enhance bioavailability and ultimately increase its therapeutic value. In the present work, the role of nanotechnology in neurodegenerative disease and how it improves the bioavailability and delivery of a drug to the site of action has been discussed. There are a few limitations to developing novel drug formulations, including solubility, pH, and compatibility of nanomaterials. Since here we are targeting CNS disorders, the bloodbrain barrier (BBB) becomes an additional challenge. Hence, the review summarized the novel aspects of delivery and biocompatible nanoparticles-based approaches for targeted drug delivery into CNS, enhancing TQ bioavailability and its neurotherapeutic effects.

The objective of the current research is to develop ZnO-Manjistha extract (ZnO-MJE) nanoparticles (NPs) and to investigate their transdermal delivery as well as antimicrobial and antioxidant activity. The optimized formulation was further evaluated based on different parameters. The ZnO-MJE-NPs were prepared by mixing 10 mM ZnSO4·7H2O and 0.8% w/v NaOH in distilled water. To the above, a solution of 10 mL MJE (10 mg) in 50 mL of zinc sulfate was added. Box–Behnken design (Design-Expert software 12.0.1.0) was used for the optimization of ZnO-MJE-NP formulations. The ZnO-MJE-NPs were evaluated for their physicochemical characterization, in vitro release activity, ex vivo permeation across rat skin, antimicrobial activity using sterilized agar media, and antioxidant activity by the DPPH free radical method. The optimized ZnO-MJE-NP formulation (F13) showed a particle size of 257.1 ± 0.76 nm, PDI value of 0.289 ± 0.003, and entrapment efficiency of 79 ± 0.33%. Drug release kinetic models showed that the formulation followed the Korsmeyer–Peppas model with a drug release of 34.50 ± 2.56 at pH 7.4 in 24 h. In ex vivo studies ZnO-MJE-NPs-opt permeation was 63.26%. The antibacterial activity was found to be enhanced in ZnO-MJE-NPs-opt and antioxidant activity was found to be highest (93.14 ± 4.05%) at 100 µg/mL concentrations. The ZnO-MJE-NPs-opt formulation showed prolonged release of the MJE and intensified permeation. Moreover, the formulation was found to show significantly (p < 0.05) better antimicrobial and antioxidant activity as compared to conventional suspension formulations.

Isopropyl Isothiocyanate (IPI) is a poorly water-soluble drug used in different biological activities. So, the present work was designed to prepare and evaluate IPI loaded vesicles and evaluated for vesicle size, polydispersity index (PDI) and zeta potential, encapsulation efficiency, drug release, and drug permeation. The selected formulation was coated with chitosan and further assessed for the anti-platelet and anti-thrombotic activity. The prepared IPI vesicles (F3) exhibited a vesicle size of 298 nm ± 5.1, the zeta potential of −18.7 mV, encapsulation efficiency of 86.2 ± 5.3% and PDI of 0.33. The chitosan-coated IPI vesicles (F3C) exhibited an increased size of 379 ± 4.5 nm, a positive zeta potential of 23.5 ± 2.8 mV and encapsulation efficiency of 77.3 ± 4.1%. IPI chitosan vesicle (F3C) showed enhanced mucoadhesive property (2.7 folds) and intestinal permeation (~1.8-fold) higher than IPI vesicles (F3). There was a significant (p < 0.05) enhancement in size, muco-adhesion, and permeation flux achieved after coating with chitosan. The IPI chitosan vesicle (F3C) demonstrated an enhanced bleeding time of 525.33 ± 12.43 s, anti-thrombin activity of 59.72 ± 4.21, and inhibition of platelet aggregation 68.64 ± 3.99%, and anti-platelet activity of 99.47%. The results of the study suggest that IPI chitosan vesicles showed promising in vitro results, as well as improved anti-platelet and anti-thrombotic activity compared to pure IPI and IPI vesicles.

Cancer is considered as one of the most life-threatening diseases, wherein uncontrolled growth of abnormal cells takes place. Nutraceutical is any compound which is a nutritious food or a fraction of nutritious food which gives health or clinical boons, together with the prevention and treatment of disease. This chapter aims to provide to its readers a key scientific knowledge about how important are these nutraceuticals in terms of effectively preventing and treating various types of cancer via a novel nanocarrier strategy. Various types of lipid type, polymeric type, and inorganic nanocarriers have been investigated to improve the bioaccessibility and therapeutic success of nutraceuticals. It is also briefly explained in this chapter in its subsections, the importance of the combination approach of nutraceuticals and chemotherapeutic agents utilizing nanocarriers, over simple nutraceutical loaded 106nanocarriers. Regardless of efficient manufacturing procedures of nano-nutraceutical delivery systems, the caliber, strength, potency, and untoward effects should work out and discourse on top preference. To make use of the full prospective of nanocarriers, additional preclinical and clinical investigations are required for nanoformulation nutraceuticals. It is apprehended that the continued attempts in the field of nutraceutical delivery using the variety of novel nanocarriers would yield many rewarding outcomes.

Heera Ram1* , Chandra kala1, Karishma Sen1, Anita Sakarwal1, Jaykaran Charan2, Paras Sharma3 , Rajsekhar Roy4, Surajit Ghosh4 1Department of Zoology, Jai Narain Vyas University, Jodhpur, India. 2Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur, India. 3Department of Pharmacognosy, BVM College of Pharmacy, Gwalior, India. 4Department of Bioscience Bioengineering, Indian Institute of Technology Jodhpur, Jodhpur, India.

Aim: The present work deals with the GC-MS-analysis of chemical constituents of hydroalcoholic extract of Cissampelos pareira leaves and thier anti-diabetic activity. Methods: GC-MS analysis of extract was performed using Shimadzu QP-2010 plus with thermal desorption system 20. Acute oral toxicity of extract was done using the Organization of Economic Co-operation and Development (OECD) guideline 423. Diabetes was induced by single dose of streptozotocin 65 mg/kg, i.p. to all the rats except in rats of control group. Following which oral glucose tolerance test was performed and the rats were divided into various experimental groups. Various treatments continued for 21 days. Parameters such as blood glucose level, body weight, liver enzymes, lipid profiles and oxidative markers were checked. Results: GC-MS analysis of the extract identified 25 compounds present in it. Based on acute oral toxicity study three doses of hydroalcoholic extract of Cissampelos pareira leaves viz 100, 200 and 400 mg/kg were selected for evaluation of anti-diabetic activity. The extracts at doses 200 and 400 mg/kg BW were able to reduce blood sugar level, liver enzymes, total cholesterol, total triglyceride, low density lipoprotein and Malondialdehyde; and enhance body weight, high density lipoprotein and Glutathione significantly when compared to rats of negative control group. The effect of extract at dose 400 mg/kg was comparable to standard Glibenclamide. Conclusion: Results conclude that the chemical constituents present in the hydroalcoholic extract of Cissampelos pareira contained some anti-diabetic compounds possessing strong anti-diabetic activity.

The aim of the current study was to develop the phytosomal gel of aloe vera extract for improved topical delivery. Aloe vera extract loaded phytosomal system was developed by fixing the amount of aloe vera extract and ethanol and by varying the concentration of lecithin (0.15-0.25% w/v) and speed of rotation (80-120 rpm). Different formulation batches were prepared as per the Design expert software. A 2(2) Factorial design was applied to optimize the formulation on the basis of vesicular size and entrapment efficiency. Developed formulations were evaluated for vesicular size, entrapment efficiency, PDI, zeta potential and in-vitro release. Further stability studies were also performed. For the optimized formulation (F09), vesicular size, entrapment efficiency and PDI were found as 123.1 +/- 1.44 nm, 95.67 +/- 0.27% and 0.98 +/- 0.06. Zeta potential of -11.9 mV and drug release of 56.91 +/- 4.1% obtained in 24 h. Drug release kinetics from the phytosomes follows Higuchi model. TEM micrograph confirms the uniform structure of phytosomes. Phytosomal gel of optimized phytosomal formulation (F09) was developed with 1% Carbopol 934 and physically characterized on the basis of pH, viscosity, homogeneity and drug content. Ex-vivo permeation study showed the better permeation and flux profile of phytosomal gel with the conventional aloe vera extract gel. Also, studies on phytosomal formulation and gel showed stability up-to 3 months. Thus overall, it can be concluded that the phytosomal gel is a good carrier for topical delivery of herbal extract such as aloe vera.

High lipophilicity, low bioavailability, and hostile gastrointestinal (GI) environment is the major concern in oral administration of thymoquinone (TQ). Herein, we developed chitosan (CS) modified solid lipid nanoparticles (SLNs) to improve oral bioavailability. SLNs were systematically optimized by using a three-factor three-level QbD approach. The optimized TQ-CS-SLNs were successfully evaluated for various in vitro and ex vivo experiments and further evaluated for its bioavailability in Wistar albino rats. The developed TQ-CS-SLNs showed particle size, polydispersity index, and drug entrapment in the range between 135.61 and 211.36 nm, 0.17-0.29, and 65.14-91.78 %. The zeta potential of TQ-CS-SLNs was found to be +12.52 +/- 1.21 mV. Moreover, TQ-CSSLNs showed a controlled release profile during 24 h of study. In addition, optimized TQ-CS-SLNs showed excellent mucoadhesion with 67.26 +/- 2.18 % mucoadhesive efficiency. The intestinal permeation and confocal microscopy revealed higher permeation of TQ-CS-SLNs compared to TQ suspension. Furthermore, bioavailability results revealed that the optimized TQ-CS-SLNs represents many fold improved oral bioavailability of TQ compared to TQ suspension. Therefore, from the findings, it was concluded that the CS-SLNs could be an effective nanoplatforms for improved oral bioavailability of TQ.

Background: COVID-19 is an infectious disease caused by SARS-CoV-2. The disease has hit hard around the globe and is now a pandemic. As of April 01, 2020, a total of 875,560 cases have been reported and the figures are increasing day by day. Currently, there is no treatment or vaccine available for curing COVID-19 and pharmaceutical companies are racing toward the common goal of achieving the cure. Methods: Scientific databases, including Science direct, Pub med, Elsevier, Scopus, and Nature, were explored. Data has also been accessed from case reports, newspaper reports, internet data, World Health Organisation (WHO) reports, and Centre of Disease Control (CDCs) reports. The US National Library of Medicine, Clinicaltrials.gov, were accessed to get information about the ongoing clinical trials. The literature survey started in the first week of February 2020 and was completed in the first week of April 2020. Additional literature survey was done in the second week of June 2020. Results: The epicentre of COVID-19 is Wuhan City, Hubei Province, China. Coronavirus belongs to Order Nidovirale and is subdivided into four groups alpha, beta, gamma, and delta. Coronavirus 229E, NL63, HKU1, MERS-CoV and SARS-CoV are known to infect humans. It is an enveloped, nonsegmented positive-sense RNA virus of size 30-32 kb with several structural and accessory proteins. The pathogenesis of COVID-19 involves attachment of Spike (S) protein of SARS-CoV-2 to the angiotensin- converting enzyme 2(ACE2) receptor present on the host cell membrane. Clinical manifestation of COVID-19 include fever, cough, complicated dyspnoea, pneumonia, etc. Real-time -PCR is a sensitive test for the detection of SARS-CoV. Remdesivir, Bevacizumab, Darunavir and cobicistat, lopinavirritonavir, Oseltamavir, hydroxychloroquine, Sarilumab, mRNA -1273, Ad5-nCoV are some of the drugs under the clinical phase of the trial. People with A-positive blood group, with comorbidities like diabetes, hypertension, chronic pulmonary obstructive disease, substance abuse disorders, immunocompromised individuals, health care workers, and older adults are at high risk of getting infected with SARS-CoV-2. Conclusion: This article gives insight into the occurrence of COVID-19, classification and structure of SARS-CoV-2, pathogenesis, pathological findings, clinical manifestation, diagnosis, potential treatment options and prevention, and people at risk of COVID-19.

Aim: The study is aimed at determining the characters of roots of Aerva javanica (A.javanica) assessing acute oral toxicity of hydroalcoholic extract of roots of Aerva javanica. Place and Duration of Study: the physicochemical and phytochemical evaluation was carried out at Faculty of Pharmacy, Maulana Azad University Jodhpur, Rajasthan. Acute Oral Toxicity was studied at Bilwal Medchem and Research Laboratory, Jaipur Rajasthan. The duration of study June 2021 – July 2021 Methodology: The pharmacognostical characters were evaluated in terms of organoleptic property, physico-chemical parameters, and preliminary phytochemical investigation. The acute oral toxicity was determined using the 423, OECD guideline for testing of chemical, acute toxic class method. Results: The physico-chemical analysis revealed total ash; water soluble ash and, acid insoluble ash to be 6.36 ± 0.26%, 0.79 ±0.23 % and, 1.23 ± 0.34%. The water, alcohol and petroleum ether soluble extractive values were found to be 17.88± 3.54 %, 15.58 ± 1.13% and, 0.3 ± 0.13 %. The percentage yield of hydroalcoholic extract of root of A.javanica was found to be 24%. The phytochemical screening of hydroalcoholic extract revealed the presence of carbohydrates, flavonoids, steroids, alkaloids, tannins, proteins, and fixed oil. The acute oral toxicity of hydroalcoholic extract of root of A.javanica revealed that the extract was found to be safe till 2000 mg/kg BW. Conclusion: The results of the present study will furnish data helpful in the correct identification and authentication of roots of A.javanica. The extractive value shed light on the most suitable solvent to be chosen to obtain extract rich in phytoconstituents. The physicochemical screening furnished data on important phytoconstituents present in the hydroalcoholic extract which could be helpful in isolation and purification of desired phytoconstituents. Acute oral toxicity study revealed that the extract is safe till 2000 mg/kg BW which could be helpful in selection of dose for future pharmacological activities.

BACKGROUND:Putranjiva roxburghii Wall is traditionally known to cure many pathological conditions including epilepsy.OBJECTIVE:The present study is aimed at determining bioactive compounds in ethanolic extract of Putranjiva roxburghii test extract (PRTE) seeds by GCMS analysis and to assess its antiepileptic potential using various experimental models of epilepsy.METHODS:The ethanolic extract of seeds of Putranjiva roxburghii was subjected to GC-MS analysis to detect the bioactive phytoconstituents. Acute oral toxicity of the extract was performed using OCED guideline 420. Pentylenetetrazol (PTZ) kindling model of epilepsy and Maximal electroshock epilepsy (MES) model of epilepsy were used to determine anti-epileptic potential.RESULTS:The GC-MS analysis of the extract revealed the presence of 20 phytoconstituents. The major phytoconstituents included n-Propyl heptyl ether (25.25%), 5-Ethyl hydantoin (8%), octadec- 9-enoic acid (16.25%) and 1, 2-Benzene dicarboxylic acid (11.86%). The PRTE (50 mg/kg and 100 mg/kg) afforded a significant and dose-dependent protection against PTZ-induced kindling epilepsy and MES induced epilepsy (p<0.001 and p<0.01).CONCLUSION:Based on the above findings, it is evident that Putranjiva roxburghii seeds contain biologically active compounds. It can also be concluded that the extract possesses anti-epileptic potential.

Wipe-outs of cancerous cells with fewer toxicity effects on the body can be achieved by application of nanotechnology; this technique helps to enhance the selectivity and potency of chemical, physical, and biological interactions with the tumor cells. The nanodevice target the cancerous cells through mechanisms of active and passive targeting, either independently or simultaneously, have high specificity. Nanotechnology has been growing and massively focusing on research; earlier imaging is impossible with several devices but is possible with the application of nanotechnology. The most challenging task to detect cancerous cells in the early stage can be overcome by using nanotechnology. Treatment of cancer by a nanodevice has been proved to be a blessing as it targets only the cancerous cells with minimum toxicities to healthy cells. Several devices are used for the treatment of cancer like nanoshells, nanotubes, and quantum dots, among others. This chapter summarizes the advantages and applications of nanotechnology-based devices for the treatment of cancer.

Immunotherapy is considered as one of the emerging tools for the treatment of cancer. Immunotherapy deals with the manipulation of our immune system to kill cancerous cells. Components of innate and adaptive immunity play vital roles in the recognition and killing of cancer cells. Among these components, CD8+ cytotoxic T lymphocytes (CTLs) are the most important to kill cancerous cells. There are various costimulatory and coinhibitory checkpoints that stimulate or inhibit immunogenic signaling against cancer. Targeting these checkpoints has revolutionized cancer treatment. However, there are multiple hurdles which need to be overcome to make it successful as chemotherapy, radiotherapy, and surgery. Currently most of the cancer immunotherapeutic agents are under clinical trials. This chapter summarizes the mechanism of modulation of various stimulatory and inhibitory checkpoints, drugs under trails, and the limitations of cancer immunotherapy.