Protective effect of Solanum torvum on monosodium glutamate-induced neurotoxicity in mice

Solanum torvum is a well known traditional herbal medicinal plant used in many neurological disorders. The objective of the study was to evaluate the effects of S. torvum on monosodium glutamate (MSG) induced neurotoxicity. Swiss albino mice received MSG (1000 mg/kg, p.o) followed by a methanolic and hydroalcoholic extract of S. torvum(100 and 300 mg/kg, p.o) for 14 days. MSG-treated mice showed significant (p<0.05) behavioural changes, decrease in relative organ weight of brain, a decrease in antioxidant enzyme levels and significant (p<0.05) increase in lipid peroxidation in brain tissue. Histopathological changes observed in brain tissue were vacuolated cells, pyknotic nuclei, decreased neuronal density and distorted layers of brain tissue. Both extracts of S. torvum (100 and 300 mg/kg) showed normal behavior, significant (p<0.05) increase in relative organ weight of brain, significant (p<0.05) decrease in lipid peroxidation (LPO) and significant (p<0.05) increase in reduced glutathione (RGSH), superoxide dismutase (SOD) and catalase (CAT) concentration in brain tissue as compared to MSG-treated mice. Treatment with S. torvum extracts reversed the histopathological changes induced by MSG. The study suggests that S. torvum seed extracts have the potential to ameliorate neuronal damage induced by MSG. Total flavonoid content of methanolic and hydroalcoholic extract of S. torvum was found to be44±1.2,and32±0.8 µg of rutin equivalent/mg of extracts and total phenolic content was found to be 70±0.28 and 52±0.62 µg of gallic acid equivalent/mg of extracts respectively

Protective efficacy of Murraya koenigii aqueous extract against monosodium glutamate-induced hepatotoxicity in Wistar rats

The present work was designed to study the potential effect of antioxidant rich aqueous extract of Murraya koenigii (AE-MK) on monosodium glutamate-induced hepatotoxicity in Wistar rats. The study was conducted on thirty adult Wistar rats, classified into six groups. MSG (1000 mg/kg, p.o) was administered to induce hepatotoxicity. The MSG treated group showed significant (P ˂0.05) increase in % change in body weight, relative organ weight, SOD, MDA, cholesterol, bilirubin, triglycerides, LDL levels; and AST, ALT activity while significant (P <0.05) decrease in glutathione peroxidase, albumin, HDL level and ALP activity in liver tissue as compared to control group. AE-MK (200, 400 mg/kg) significantly (P <0.05) reversed all the above parameters as compared to MSG treated rats. Histopathological changes observed in MSG treated rat liver tissue were cytoplasmic vacuolation, sinusoidal congestion, and cellular aggregates around the portal area. These changes were reversed with AE-MK (200, 400 mg/kg). The total phenol content was found to be 62 µg of gallic acid equivalent /mg of extract and free radical scavenging activity by DPPH method was found to be 74.16%. The study suggests that antioxidant rich aqueous extract of M. koenigii has protective effect against MSG-induced hepatotoxicity

Effect of SKB-Gutbiotic on acetic acid induced ulcerative colitis in male Wistar rats

Inflammatory bowel disease (IBD) is a chronic intestinal inflammation gaining increasing attention as it affects considerable number of humans. IBD is reported as ulcerative colitis (UC) and Crohn's disease (CD) Conventional therapies currently available are not satisfactory. Therefore, here, we investigated the effect of SKB-Gutbiotic on acetic acid induced ulcerative coltis (UC) in male Wistar rats. Male Wistar rats, 200-250 g were divided into six groups as follows: Gr. I (control) received 10 mL/kg of distilled water for 21 consecutive days. Gr. II received 2 mL of 4% acetic acid solution once intra rectally for induction of colitis. Gr. III received 2 mg/kg prednisolone as standard control. Groups IV, V & VI were treated with SKB-Gutbiotic @2×109, 20×109 and 50×109 Cfu/kg, respectively. All the animals from each group were sacrificed 24 h after the induction of colitis. Disease activity index, macroscopical damage, hematological parameters, level of superoxide dismutase (SOD), myeloperoxidase (MPO), reduced glutathione (GSH) and histopathological alterations were evaluated. Acetic acid-induced colitis significantly caused alteration in disease activity index, macroscopical damage, MPO and GSH levels (P <0.05) as compared to control group. SKB-Gutbiotic (20×109 and 50×109 Cfu/kg) administration significantly decreased disease activity index, MPO, SOD, increased GSH levels (P <0.05) as compared to colitis rats. In conclusion, SKB-Gutbiotic (20×109 and 50×109 Cfu/kg) significantly showed protective effects against acetic acid-induced colitis as a consequence of its anti-inflammatory and antioxidative properties

Bioanalytical Method Development and Validation: A Review

For various types of drug approval processes like INDs, NDAs, ANDAs, veterinary drug approval, the data related to bioanalytical method development and validation is needed to sponsors. Various agencies namely US FDA, American association of pharmaceutical scientists (AAPS), Health protection Branch (HPB), Association of analytical chemists (AOAC), Center for Veterinary Medicine (CVM), U.S. Department of Health and Human Services Food and drug Administration, Center for Drug Evaluation and Research (CDER), European Medicine Agency (EMA), China Food and Drug administration(CFDA), European Bioanalytical Forum (EBF), Global CRO council (GCC), ANVISA (Brazil), Japan Bioanalytical Forum (JBF) had done collective efforts at different timings to regulate and harmonize bioanalytical method development and validation

Effect of Solanum torvum Swartz on diabetic neuropathy in alloxan-induced diabetic rats

Solanum torvum Swartz is a well-known traditional herbal medicinal plant used in diabetes and diabetes-related complications. The objective of the study was to evaluate the effect of S. torvum on diabetic neuropathy in alloxan-induced diabetic rats. Diabetes was induced in Wistar rats by using a single intraperitoneal injection of alloxan monohydrate (150 mg/kg; i.p.). After confirmation of diabetes, rats received metformin (120 mg/kg, p.o.) and STME (30 and 100 mg/kg, p.o) for 5 weeks. Diabetic rats showed significant (P <0.05) behavioural changes, increase in blood glucose levels, decrease in relative organ weight of pancreas, significant (P <0.05) decrease in reduced glutathione (RGSH) and significant (P <0.05) increase in TBARS levels. While STME (100 mg/kg) treated diabetic rats significantly (P <0.05) reversed the above parameters as compared to diabetic rats. Treatment with STME (100 mg/kg) has also reversed histopathological changes as observed in diabetic control rats. The study suggests that methanolic extract of S. torvum ameliorates diabetic neuropathy in alloxan-induced diabetic rats

Effect of Solanum torvum Swartz on diabetic neuropathy in alloxan-induced diabetic rats

79-88Solanum torvum Swartz is a well-known traditional herbal medicinal plant used in diabetes and diabetes-related complications. The objective of the study was to evaluate the effect of S. torvum on diabetic neuropathy in alloxan-induced diabetic rats. Diabetes was induced in Wistar rats by using a single intraperitoneal injection of alloxan monohydrate (150 mg/kg; i.p.). After confirmation of diabetes, rats received metformin (120 mg/kg, p.o.) and STME (30 and 100 mg/kg, p.o) for 5 weeks. Diabetic rats showed significant (P P P P S. torvum ameliorates diabetic neuropathy in alloxan-induced diabetic rats

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Protective efficacy of Murraya koenigii aqueous extract against monosodium glutamate-induced hepatotoxicity in Wistar rats

188-196The present work was designed to study the potential effect of antioxidant rich aqueous extract of Murraya koenigii (AE-MK) on monosodium glutamate-induced hepatotoxicity in Wistar rats. The study was conducted on thirty adult Wistar rats, classified into six groups. MSG (1000 mg/kg, p.o) was administered to induce hepatotoxicity. The MSG treated group showed significant (P ˂0.05) increase in % change in body weight, relative organ weight, SOD, MDA, cholesterol, bilirubin, triglycerides, LDL levels; and AST, ALT activity while significant (P <0.05) decrease in glutathione peroxidase, albumin, HDL level and ALP activity in liver tissue as compared to control group. AE-MK (200, 400 mg/kg) significantly (P <0.05) reversed all the above parameters as compared to MSG treated rats. Histopathological changes observed in MSG treated rat liver tissue were cytoplasmic vacuolation, sinusoidal congestion, and cellular aggregates around the portal area. These changes were reversed with AE-MK (200, 400 mg/kg). The total phenol content was found to be 62 μg of gallic acid equivalent /mg of extract and free radical scavenging activity by DPPH method was found to be 74.16%. The study suggests that antioxidant rich aqueous extract of M. koenigii has protective effect against MSG-induced hepatotoxicity

Protective effect of Solanum torvum on monosodium glutamate-induced hepatotoxicity and nephrotoxicity in rats

31-42The objective of the study was to determine the protective effect of Solanum torvum on Monosodium glutamate (MSG) induced hepatotoxicity and nephrotoxicity in rats. Wistar rats received MSG (1000 mg/kilogram, per oral) followed by methanolic and hydroalcoholic extracts of S.torvum (100 & 300 mg/kg, p.o.) respectively for 14 days. Percentage change in body weight, relative organ weight of liver and kidney, liver function tests, kidney function tests and histopathological studies of liver and kidney tissues were observed in rats. In vitro antioxidant activity of S.torvum extracts was also performed. The results were analysed by One-way ANOVA followed by Dunnett’s test. The msg-treated group showed significant (p S. torvum extracts ameliorated the effects induced by MSG group. Total flavonoid content of methanolic & hydroalcoholic extract of S. torvum was found to be 44±1.2&32±0.8µg of rutin equivalent/mg of extract and total phenolic content was found to be 70±0.28 & 52±0.62 µg of gallic acid equivalent/mg of extract respectively. In vivo and In vitro antioxidant studies of both extracts showed that methanolic extract has more hepatoprotective, nephroprotective and anti-oxidant property than the hydroalcoholic extract of S.torvum fruits. It is concluded that S.torvum extract has a protective effect against MSG-induced hepatic and renal toxicity