Background: In India, on 30th January 2020, the first case of COVID-19 was reported, thereafter country has faced two waves with disastrous second wave. A total of about 34 million cases and 4.68 lakh deaths have been reported so far from India. Few studies have reported death rate as 5.7% among COVID-19 patients with at least one co-existing medical condition, as compared to 0.7% in patients without any comorbidity. Aims and Objectives: We aim to analyze the death audit data of 467 COVID-19 death cases considering factors of age, gender, area of residence, cause of death, related comorbidities, and relation with duration of hospital stay and presence or absence of comorbidity in COVID-19 death cases. Materials and Methods: This is an observational study from April 2020 to July 2021which is based on records obtained from death audit reports of a dedicated COVID-19 facility at a tertiary hospital, Agra, Uttar Pradesh. The state authorities introduced a standard “COVID-19 Death Audit Proforma” on a death audit portal to audit all deaths related from COVID-19 (SARS-CoV-2) infection. Statistical analysis used: The data were recorded in Microsoft Excel and analyzed using statistical software, Microsoft Excel (Version 16.49). The results are presented accordingly in form of descriptive statistics. Results: We have reported findings from 467 COVID-19 deaths from our dedicated COVID-19 facility in the present study. Median age of deceased was found to be 57 years with (71.9%) deaths in males, with predominantly 77.1% of patients residing in urban area. 74% of COVID-19 deaths were reported along with one or more comorbid illness at the time of admission with hypertension to be the most common comorbid disease (42.9%) followed by diabetes (34.5%). Median length of hospital stay is reported as 4 days. Conclusion: Our analysis from Uttar Pradesh dedicated COVID-19 facility found that comorbidities were present invariably in 74% of deaths from SAR-CoV-2 infection. Early diagnosis and timely aggressive management is pillar for reducing morbidity and mortality from COVID-19 disease.

Background: Vajeekarana deals with fertility, potency, and healthy offspring along with diseases like erectile dysfunction (ED). This is a widespread disease among men having negative impact on the quality of life of the patients and their partners. Aim: This study aims to prepare and characterize the formulation (Jeeva Rasa Churna [JRC]) used in ED. Materials and Methods: JRC has been prepared by homogeneous mixing of two mineral drugs, namely Shuddha Hingula and Shuddha Shilajatu and fine powder of five herbal ingredients, namely Akarakarabha, Ashwagandha, Shweta Mushali, Shatavari, and Vidarikanda. JRC was subjected to various physiochemical parameters such as moisture content, water-soluble extractive, thin-layer chromatography, and energy-dispersive X-ray spectroscopy (EDX) for its standardization. Results: The total of 3.750 kg of JRC was prepared using 150 g, Hingula and 3.600 kg of homogeneous mixture of Shuddha Shilajatu, Akarakarabha, Ashwagandha, Shweta Mushali, Shatavari, and Vidarikanda. It was observed that 5.6% moisture content and 1.80% water-soluble extractive were in JRC, respectively, and EDX study showed that formulation was free from heavy metals except mercury which is an ingredient of JRC. Conclusion: The physiochemical parameters of formulation JRC fall within the range of Ayurvedic pharmacopeia for Churna so it may be a safe and effective medicine for ED.

Cassia tora is a plant of medicinal importance. Medicinal plants from different localities are believed to differ in their therapeutic potency. In this study, six populations of C. tora with different eco-geographical origins were investigated genotypically (ISSR) and phytochemically (FTIR) to establish an integrated approach for population discrimination and authentication of the origin of this medicinal herb. CHS gene expression analysis and determination of flavonoid content were carried out to substantiate the study. A total of 19 population-specific authentication bands were observed in 11 ISSR fingerprints. Authentication codes were generated using six highly polymorphic bands, including three authentication bands. FTIR spectra revealed that the peaks at wavenumber 1623 cm −1 (carbonyl group) and 1034 cm −1 (>CO- group) were powerful in separating the populations. These peaks are assigned to flavonoids and carbohydrates, respectively, were more intense for Ranchi (highland) population. Variation in the transcript level of CHS gene was observed. The findings of FTIR and RT-PCR analyses were in agreement with the TFC analysis, where, the lowest amount of flavonoids observed for Lucknow (lowland) population. All the populations of C. tora have been authenticated accurately by ISSR analyses and FTIR fingerprinting, and the Ranchi site was observed to be more suitable for the potential harvesting of therapeutic bioactive compounds.

Curcuma longa (turmeric) and Withania somnifera (ashwagandha) are the two perennial herbs and have been used for many centuries as potential medicine to promote longevity and immunizing the body against various ailments. However, in Indian Ayurvedic system of medicine, rhizomes of C. longa and roots of W. somnifera are often used for the treatment of various metabolic disorders including diabetes and associated disorders. Since the beginning of the 20th century, a number of bioactivity-graded studies using different extracts of these two plants have been done and confirmed their therapeutic claims as anti-diabetic herbs. Efforts were also been made to further explore their bioactive metabolites like curcuminoids and withanolides to describe their anti-diabetic action. Recently, these two plants caught attention as potential treatment for diabetes. Information available on pharmacological and chemical studies has revealed that, these two plants are relatively safe and inexpensive natural products that reduces hyperglycemia and prevents the progression of other associated complications. Here, we reviewed the literature on the pharmacological applications of both turmeric and ashwagandha for diabetes and associated neurological disorders.

BACKGROUND:The objective of the study is to compare stress resistance-promoting effect of triethylene glycol (TEG) and root extract of Ashwagandha (Withania somnifera) i.e. withanolide-free root extract of Withania somnifera (WFWS).MATERIALS AND METHODS:Mice groups treated orally with 10 mg/kg TEG or WFWS (3.3, 10, 33.3, or 100 mg/kg) for 12 consecutive days were subjected to foot shock stress-triggered hyperthermia test on the 1st, 5th, 7th and 10th day and to marble-burying test on the following 2 days. Effects of treatment on stress-triggered alteration in body weight, core temperature, blood glucose, insulin and cortisol level were quantified and statistically analyzed.RESULTS:WFWS doses up to 10 mg/kg/day were as effective as TEG in affording protection against stress-triggered alteration in body weight, core temperature and marble-burying behavior. Protection against stress-triggered alteration in blood glucose and insulin level, as well as antidepressants or anxiolytic-like activities in the behavioral test, were observed in the higher two WFWS doses (33.3 and 100 mg/kg) treated groups only.CONCLUSION:Ashwagandha metabolites other than withanolides contribute to its stress resistance increasing effects. The observations suggest that modulation of physiological functions of gut microbiota may be involved in the mode of action of Withania somnifera root extracts.

Withania somnifera is an important Ayurvedic Rasayana herb, the roots of which are often used in traditionally known systems of medicine as tonic or for rejuvenation purposes. Effects of a single and ten daily oral doses (10, 20 and 40 mg/kg) of an analytically well standardized Withania somnifera root extract against foot shock stress triggered transient hyperthermia and hotplate test for analgesics in male mice were quantified. Body weights and basal rectal temperatures of animals were recorded on all observational days and on the 11th and 12th day of the experiment, all animals were subjected to tail suspension and pentobarbital hypnosis tests respectively. Daily dose dependent efficacy of the tested extract in stress induced hyperthermia test and in hot plate test increased with increasing number of treatment days, and its dose dependent inhibitory effect on immobility time in tail suspension were observed after its 11 daily oral doses. Daily handling and intermittent foot shock stress triggered body weight losses and elevations in basal core temperatures were almost completely prevented even by its lowest daily dose (10 mg/kg/day) tested. Repeated daily low oral doses of the Withania somnifera extract is effective in suppressing diverse stress responses, and its centrally acting analgesics and anxiolytics or antidepressants like efficacies increase with increasing numbers of treatment days. These observations reaffirm that Withania somnifera is an adaptogenic herb, and suggest that its effective therapeutic doses has to be adjusted according to the pre-existing allostatic load of patients.

Ayurveda, the science of living beings is the ancient system of medicine of India. Since Indian philosophy is reflected in Ayurveda, the principles of Ayurveda are very pervasive. The actual purpose of Ayurveda is to live the life with physical, mental, social and spiritual wellbeing. In Ayurveda numerous plants are described for fulfilling its purpose. One of those plants is Akarkara (Anacyclus pyrethrum L.) . Basically, Akarkara is described in Unani system of medicine as an amazing drug used in various ailments. Later on, due to its multidimensional uses, it also has been included in the Ayurvedic text written in u0026 after the medieval era. Shodhal Nighantu has described firstly Akarkara as one of the potent aphrodisiac drug. Here, an attempt is made to review its scattered multi-dimensional health benefits quoted in Ayurvedic and Unani treatises and validated through scientific researches in laboratories.

Aim: Withania somnifera root (WSR) extracts are often used in traditionally known Indian systems of medicine for prevention and cure of psychosomatic disorders. The reported experiment was designed to test whether low daily oral doses of such extracts are also effective in suppressing marble burying behavior in stressed mice or not. Materials and Methods: Groups of mice treated with 10, 20, or 40 mg/kg daily oral doses of WSR were subjected to a foot shock stress-induced hyperthermia test on the 1st, 5th, 7th, and 10th day of the experiment. On the 11th and 12th treatment days, they were subjected to marble burying tests. Stress response suppressing effects of low dose WSR were estimated by its effects on body weight and basal core temperature of animals during the course of the experiment. Results: Alterations in bodyweight and basal core temperature triggered by repeated exposures to foot shock stress were absent even in the 10 mg/kg/day WSR treated group, whereas the effectiveness of the extract in foot shock stress-induced hyperthermia and marble burying tests increased with its increasing daily dose. Conclusion: Marble burying test in stressed mice is well suited for identifying bioactive constituents of W. somnifera like medicinal plants with adaptogenic, anxiolytic and antidepressant activities, or for quantifying pharmacological interactions between them.

Objectives: To assess the antidiabetic potential of Shilajatvadi Lauha (SL) processed with Daruharidra (modified SL [MSL]) in streptozotocin (STZ)-nicotinamide (NA)-induced diabetic rats. Materials and Methods: Animals were divided into diabetic and nondiabetic groups. Type 2 diabetes in rats was induced with a single dose of STZ (65 mg/kg) NA (110 mg/kg) intraperitoneal diabetic rats were treated with formulation MSL (10, 30, and 100 mg/kg) and glibenclamide (10 mg/kg) once daily for 14 days orally. After 14 days treatment, fasting blood glucose and plasma insulin were assayed. Different biochemical parameters such as total cholesterol (TC), triglycerides (TGs), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and very LDL-C (VLDL-C) were also examined. Results: MSL significantly lowered the blood glucose and increases insulin level, which was comparable to the standard antidiabetic drug, glibenclamide. Treatment with MSL showed a significantly reduction in the levels of TC, TG, LDL-C, and VLDL-C and increases the level of HDL-C. Conclusion: MSL possess significant antidiabetic and antihyperlipidemic activity in Type 2 diabetes mellitus rats. The results are encouraging and further studies can be used to evaluate the exact mechanism of action to develop a novel molecule that will benefit the ailing.

Curcuma longa rhizomes (turmeric) are used as tonic in traditionally known Indian systems of medicine. Aim of this study was to compare stress response suppressing efficacies of a Curcuma longa extract (CLE) enriched in curcuminoids with those of curcumin and turmeric oil (TO). Effects of daily oral treatments with curcumin (5 mg/kg/day) or CLE (5, 20, and 80 mg/kg/day) or TO (1, 3, 10, 30 and 100 mg/kg/day) to male mice on their body weight and core temperature and in stress induced hyperthermia, tail suspension, and pentobarbital sleep tests were quantified. Although their single doses had no significant effects in foot shock stress induced hyperthermia test, curcumin like and dose dependant suppressing effects of CLE were observed after its repeated daily doses. Such effects of TO in the test was also observed after its higher tested daily doses only. Occasional foot shock stress triggered body weight losses and elevated basal core temperatures were also dose dependently antagonized by CLE and TO. Unlike for curcumin or CLE no effects of TO in tail suspension and pentobarbital sleep test were observed after its lower tested 11 daily doses. These observations reveal that volatile bioactive constituents of turmeric other than curcuminoids also possess stress resistance promoting properties and suggest that such efficacy of turmeric powder do not depend on their curcumin or curcuminoids contents only. Mouse bioassay procedure used in this study is well suited for pharmacological standardization of turmeric extracts and also for identifying their bioactive constituents.

Results of the very first experiments conducted to evaluate therapeutic potentials of a fumarate containing Fumaria indica extract and of fairly low daily oral doses of monomethyl fumarate for prevention of chronic unavoidable foot-shock stress-induced gastric ulcers, and possible involvement of diverse neuro-hormonal and oxidative process in their stress response desensitizing effects are reported and discussed in this article. Preventive effects of 21 daily oral 60, 120, and 240 mg/kg doses of a standardized 50 % methanolic F. indica extract (MFI) and 1.25, 2.50, and 5.00 mg/kg/day of pure monomethyl fumarate (MMF) were compared in rats subjected to one hour daily unavoidable foot-shocks. A pharmaceutically well-standardized Withania somnifera (WS) root extract was used as a reference herbal anti-stress agent in all experiments. Effects of the treatments on stress-induced alterations in body weight, adrenal and spleen weights, gastric ulcer and ulcer index, weight of glandular stomach, protective mucosal glycoprotein content, cellular proliferation, oxidative stress on stomach fundus, and brain tissues of male rats were quantified. Other parameters quantified were plasma corticosterone levels, brain monoamine levels, and expressions of the cytokines TNF-α, IL-10, and IL-1β in blood and brain of stressed and treated rats. Most but not every observed stress-induced anomalies were suppressed or completely prevented by both MFI and pure MMF treatments in dose-dependent manner. Qualitatively, the observed activity profiles of both of them were similar to those of WS dose tested. These results reveal that both MFI and MMF are potent gastro-protective agents against chronic unavoidable stress-induced ulcers and strongly suggest that they act as regulators or modulators of monoamine, corticosterone, and cytokine homeostasis.

Preclinical models with high prognostic power are a prerequisite for translational research. The closer the similarity of a model to myocardial infarction (MI), the higher is the prognostic value for clinical trials. An ideal MI model should present cardinal signs and pathology that resemble the human disease. The increasing understanding of MI stratification and etiology, however, complicates the choice of animal model for preclinical studies. An ultimate animal model, relevant to address all MI related pathophysiology is yet to be developed. However, many of the existing MI models comprising small and large animals are useful in answering specific questions. An appropriate MI model should be selected after considering both the context of the research question and the model properties. This review addresses the strengths, and limitations of current MI models for translational research.

AIMS:To compare analgesic and anti-inflammatory activities of aspirin and mono-hydroxybenzoic acids after their daily oral doses.MAIN METHODS:Efficacies of repeated daily stress response suppressing low oral doses (20mg/kg) of aspirin and 2-, 3-, and 4-hydroxybenzoic acids in mice hot plate test for centrally acting analgesics, and in acetic acid induced writing test were compared. Effects of their same daily doses and treatment regimen in cotton pellet granuloma and carrageenan edema test for anti-inflammatory drugs in stressed rats were compared in a second experiment. Effects of treatments on body weights, basal rectal temperatures, organ weights and plasma glucose, insulin and cortisol levels in stressed animals were compared also.KEY FINDINGS:Although stress response suppressing effects of aspirin and all the three hydroxybenzoic acids in both mice and rats were almost equal, effectiveness of 3- and 4-hydroxybenzoic acids as analgesic and anti-inflammatory agents were lower than those of aspirin or salicylic acid.SIGNIFICANCE:Observations made after single oral doses of aspirin or of mono-hydroxybenzoic acids are not very reliable predictors of their pharmacologically interesting bioactivity profiles and efficacies. Prostaglandin synthesis inhibition is not involved in low dose anti-inflammatory activities of 3- and 4-hydroxybenzoic acids. After their repeated daily low oral doses they are almost as potent stress response desensitizers as aspirin or salicylic acid.

The reported experimental study was conducted to compare the effects of repeated daily oral doses of curcuminoids (CLE) with metformin as potential antidepressants and analgesics. Effects of a single and ten daily oral doses of CLE (5, 20, 80 mg/kg/day) and of 50 mg/kg/day metformin (MET) were compared in mice hot plate test (HPT) for analgesics. On the 11th treatment day, all animals were subjected to foot shock stress triggered hyperthermia test, and on the 12th treatment day to tail suspension test (TST) for antidepressants. Immediately thereafter, their blood levels of glucose, insulin and cortisol were quantified. Dose dependent analgesic activity of CLE was observed in HPT, whereas the metformin dose tested suppressed only pain hypersensitivity in the test. But statistically significant effects of both of them were observed in TST, and both of them also afforded protections against body weight loss and slight elevation in core temperatures induced by daily handling and repeated testing. CLE or metformin had no significant effects in foot shock stress triggered transient hyperthermic responses or on blood glucose, insulin and cortisol levels. Reported results reveal that curcuminoids as well as metformin are stress response modifiers with antidepressants like activities, but only low dose curcuminoids possess centrally acting analgesics like activities. They suggest that the bio-assay system used in this study is well suited for identifying curcuminoids like plant metabolites with analgesic and anti-stress activities, and that low dose curcuminoids are more effective as analgesics than low dose metformin.

AIM:To compare stress resistance increasing and analgesic activities of piperlongumine and a methanolic Piper longum fruit extract (PLE).METHODS:Efficacies of a single and repeated daily oral doses (1-256 mg/kg/day) of PLE, piperlongumine, and 50 mg/kg/day doxycycline against foot shock stress triggered alteration in body weights and core temperatures, and of their 11 daily doses on antidepressants like activity in tail suspension test and on pentobarbital induced sedation in male mice were compared. In another experiment, analgesic activities of single and repeated daily 5 mg/kg oral doses of piperlongumine and PLE in mice hot plate test and in acetic acid induced writing tests were compared with those of aspirin and doxycycline.RESULTS:After their single oral doses no effects of piperlongumine or PLE or doxycycline were observed in the footshock stress induced hyperthermia test or in hot plate test. However, significant effects of piperlongumine and PLE in both the tests were observed after their 5 or more daily doses. Both of them also dose dependently suppressed daily handling and repetitive testing triggered alterations in body weights and core temperatures. Their doxycycline like antidepressant activity in tail suspension test and aspirin like analgesic effects in acetic acid writhing test were observed after their 11 daily 5 mg/kg oral dose.CONCLUSION:Piperlongumine is another bioactive secondary metabolite of P. longum and other plants of piper species with stress response suppressing, analgesic, and anti-inflammatory activities. Its bactericidal activities can also contribute to its therapeutically interesting bio-activity profile.

Cardioprotection represents one of the most important and realistic aspects of preventive therapy today. Quercetin, a naturally occurring dietary flavone, has been studied extensively for its antioxidant properties. The objective of present study is to find out the cardioprotective activity and to explore the underlying mechanisms of quercetin pretreatment (50 mg/kg body weight, orally) for 14 days against isoproterenol (ISO; 100 mg/kg body weight, subcutaneously) induced myocardial infarction in Wistar rats. Cardiac diagnostic markers, oxidative stress, inflammatory cytokines, histopathology along with gene expression analysis of calpain 1 and 2 were carried out in experimental rats. Quercetin pretreatment showed protective effects on heart by significantly attenuating the ISO-induced oxidative stress, inflammation, protecting heart architecture, and by downregulation of the expression of calpain. Overall, these findings revealed the cardio-protective potential of quercetin and its mechanism of action against ISO-inducedMI in rats.

Context: Shilajatvadi Lauha (SL) is used in Ayurveda as Indian traditional medicine for treating diabetes mellitus. Aims: To explore the anti-diabetic potential of SL in nicotinamide-streptozotocin induced diabetic rats. Materials and Methods: SL (10, 30, and 100 mg/kg) and glibenclamide (10 mg/kg) were orally administered once daily to diabetic rats for 14 days. Blood glucose, plasma insulin, total cholesterol (TC), triglycerides (TGs), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and very LDL-C (VLDL-C) were examined. Results: SL significantly lowered the blood glucose without any hypoglycemic effect on their control counterparts, which was comparable to that of the standard anti-diabetic drug, glibenclamide. SL also showed reduction in the levels of TC, TGs, LDL-C, VLDL-C, but it increases the levels of plasma insulin and HDL-C in diabetic rats. Conclusions: SL possesses anti-diabetic and anti-hyperlipidemic activities in Type 2DM rats, which seems to scientifically validate its traditional uses and might be a promising drug in the therapy of diabetes mellitus and its hyperlipidemic complications.

Context Andrographolide containing Andrographis paniculata (Burm. F.) Wall. Ex Nees (Acanthaceae) extracts is often used for treatments of diabetes and other inflammatory disorders commonly accompanying cognitive and other psychiatric disorders. Objective To compare the efficacies of a standardised A. paniculata extract (AP) and pure andrographolide on cognitive functions, oxidative stress and cholinergic function in diabetic rats. Materials and methods Streptozotocin-induced diabetic Charles Foster albino rats treated orally with a hydro-methanolic A. paniculata leaf extract (50, 100 and 200 mg/kg/day), or with pure andrographolide (15, 30 and 60 mg/kg/day) for 10 consecutive days, were subjected to Morris water maze test. After the test, acetylcholinesterase, superoxide dismutase (SOD), and catalase (CAT) activities and lipid peroxidation (LPO) in brain tissues were assessed. Results Acetylcholinesterase activity in pre-frontal cortex and hippocampus of diabetic rats was 2.1 and 2.6 times higher compared to nondiabetic rats. LPO was 1.6 times higher and decreased SOD (56.3%) and CAT (44.9%) activities in pre-frontal cortex of diabetic rats compared to nondiabetic rats. AP or andrographolide treatments dose dependently attenuated cognitive deficits, reduced acetylcholinesterase activity, oxidative stress, improved diabetic hyperglycemia and insulin deficiency. All observed effects of AP were quantitatively almost equal to those expected from its analytically quantified andrographolide content. Discussion and conclusion Reported observations are the very first ones suggesting beneficial effects of andrographolide against diabetes associated cognitive deficits, increased acetylcholinesterase activity and deteriorated antioxidative status. Efforts to exploit A. paniculata extracts enriched in andrographolide as preventive measures against such disorders can be warranted.

The aim of the present study was to prepare atorvastatin calcium (ATR) loaded poly(ε-caprolactone) nanoparticles (ALPNs) to enhance the oral bioavailability, efficacy and safety profile of drugs.

Atorvastatin calcium (ATR), a second generation statin drug, was encapsulated in eudragit RSPO-based polymeric nanoparticles. The effect of independent variables (polymer content, stabilizer concentration, volume of chloroform and homogenization speed) on response variables (mean diameter particle size and entrapment efficiency) were investigated by employing central composite experimental design. All the independent variables were found to be significant for determining the response variables. Solid-state characterization study indicated the absence of physicochemical interaction between drug and polymer in formulation. Morphological study exhibited homogenous spherical shape of formulated nanoparticles. In vitro release study in phosphate buffer (pH 7.4) demonstrated sustained release profile over 24 h. Pharmacokinetic study in Charles Foster rats showed significant enhancement in oral bioavailability as compared to pure drug suspension. Efficacy study (lipid profile and blood glucose level) significantly justified the effectiveness of formulation having 50% less dose of ATR as compared to pure drug suspension. The effectiveness of formulation was further justified with an improved plasma safety profile of treated rats. Hence, ATR encapsulated eudragit RSPO nanoparticles can serve as potential drug delivery approach to enhance drug bioavailability, efficacy and safety profiles to alter existing marketed drug products.