Licorice treatment prevents oxidative stress, restores cardiac function, and salvages myocardium in rat model of myocardial injury.

The present study examined the effects of licorice on antioxidant defense, functional impairment, histopathology, and ultrastructural alterations in isoproterenol (ISP)-induced myocardial injury in rats. Myocardial necrosis was induced by two subcutaneous injection of ISP (85 mg/kg) at an interval of 24 h. Licorice was administered orally for 30 days in the doses of 100, 200, 400, or 800 mg/kg. ISP-treated rats showed impaired hemodynamics, left ventricular dysfunction, and caused depletion of antioxidants and marker enzymes along with lipid peroxidation from myocardium. ISP also induced histopathological and ultrastructural alterations in myocardium. Pretreatment with licorice prevented the depletion of endogenous antioxidants and myocyte injury marker enzymes, inhibited lipid peroxidation, and showed recovery of hemodynamic and ventricular functions. Licorice treatment also reduced myonecrosis, edema, and infiltration of inflammatory cells and showed preservation of subcellular and ultrastructural components. Our results demonstrate that licorice exerts cardioprotection by reducing oxidative stress, augmenting endogenous antioxidants, and restoring functional parameters as well as maintaining structural integrity.

Naringin ameliorates pentylenetetrazol-induced seizures and associated oxidative stress, inflammation, and cognitive impairment in rats: possible mechanisms of neuroprotection.

Oxidative stress and cognitive impairment are associated with PTZ-induced convulsions. Naringin is a bioflavonoid present in the grapefruit. It is a potent antioxidant, and we evaluated its effect on PTZ-induced convulsions. Rats were pretreated with normal saline, naringin (20, 40, and 80 mg/kg, i.p.), or diazepam (5mg/kg, i.p.) 30 min prior to the administration of PTZ. The administration of PTZ induced myoclonic jerks and generalized tonic-clonic seizures (GTSs). We observed that naringin significantly prolonged the induction of myoclonic jerks dose-dependently. Naringin (80 mg/kg, i.p.) pretreatment protected all rats, and this protective effect was annulled by the GABAA receptor antagonist, flumazenil. In addition, naringin reduced brain MDA and TNF-α levels and conserved GSH. The pretreatment also enhanced the performance of rats in the passive avoidance task. Our observations highlight the antioxidant, antiinflammatory, and anticonvulsant potential of naringin. Also, naringin modulates the GABAA receptor to produce anticonvulsant effects and to ameliorate cognitive impairment.

Examining the determinants of health and long-term care for older adults in India through a socio-ecological model - A qualitative assessment.

Background: Ageing is associated with multiple long-term health problems and requires medication management, support with activities of daily living, and attention to psychological needs. This study aimed at exploring the enablers and barriers and psychosocial determinants of long-term care. Methods: A qualitative study, using semi-structured interviews and thematic analysis, was carried out from February to June 2018. One-on-one in-depth interviews were carried out with 28 participants, including care recipients (n = 12), caregivers (n = 12), and primary-care physicians (n = 4) at the Community Health Centre in the state of Jammu and Kashmir of India. Results: Attention from family members, leisure activities, faith in the healthcare provider, and a positive attitude towards life were found to be enablers of long-term care. Resource constraints and alienation from the community were barriers. Incorporating the psychosocial needs of care recipients and problems faced by family caregivers is essential in providing good quality care to individuals with chronic illness. Conclusion: The lack of a targeted, nationwide policy has resulted in considerable variability in long-term care services across the country. There is an urgent need to make long-term care an integral part of the Indian health system utilizing a holistic framework to address the health needs of older adults and implementing it through an equitable community-based comprehensive primary health and community-based model.

Akt/GSK-3ß/eNOS phosphorylation arbitrates safranal-induced myocardial protection against ischemia-reperfusion injury in rats.

PURPOSE: Traditional medicine has been appropriately identified as the most productive soil for the cultivation and harvesting of modern medicines. Herein, we postulate that safranal, an active constituent of Crocus sativus, owing to its strong antioxidant and anti-apoptotic potential, could be a valuable molecule in alleviating myocardial ischemia-reperfusion (IR) injury. METHODS: To evaluate this hypothesis, safranal (0.1-0.5 mL/kg/day, i.p.) or saline were administered to rats for 14 days, and on 15th day, one-stage ligation of left anterior descending coronary artery for 45 min was performed, followed by 60 min reperfusion. RESULTS: We concluded that safranal not only significantly decreased infarct size, but also improved left ventricular functions and the overall hemodynamic status of the myocardium. Interestingly, safranal enhanced phosphorylation of Akt/GSK-3ß/eNOS and suppressed IKK-ß/NF-κB protein expressions in IR-challenged myocardium. Our findings also imply that safranal exhibits strong anti-apoptotic potential, as evidenced by upregulated Bcl-2 expression and downregulated Bax and caspase3 expression with decreased TUNEL positivity. Moreover, safranal dose-dependently normalized myocardial antioxidant and nitrotyrosine levels, cardiac injury markers (LDH and CK-MB), and decreased TNF-α level in IR-insulted myocardium. Histopathological and ultrastructural findings correlated with the functional and biochemical outcomes showing preserved myocardial architecture and decreased inflammatory cells and edema. CONCLUSIONS: Taken together, these results provide convincing evidence of safranal as an invaluable molecule in myocardial IR setting probably due to its fortified antioxidant and anti-apoptotic potential.

Protective effect of Emblica officinalis (amla) on isoproterenol-induced cardiotoxicity in rats.

Emblica officinalis, commonly known as amla, is an important medicinal plant reputed for its dietary and therapeutic uses. The aim of the present study was to investigate the protective role of E. officinalis against isoproterenol (ISP)-induced cardiotoxicity in rats and elucidate the possible mechanism involved. Rats were administered E. officinalis (100, 250 and 500 mg/kg, p.o.) or vehicle (normal saline) for 30 days, with concurrent subcutaneous injections of ISP (85 mg/kg, at 24 h interval) on 29th and 30th day. ISP-induced cardiac dysfunction as evidenced by decreased mean arterial pressure, heart rate, contractility (+LVdP/dt) and relaxation (-LVdP/dt) along with increased left ventricular end diastolic pressure. ISP significantly (p < 0.05) decreased antioxidant enzymes, superoxide dismutase, catalase and glutathione peroxidase and myocyte-injury-specific marker enzymes, creatine phosphokinase-MB and lactate dehydrogenase in heart. A significant (p < 0.05) depletion of reduced glutathione and increase in thiobarbituric acid reactive substances along with histopathological alteration has further indicated the oxidative damage of myocardium. However, pretreatment with E. officinalis exhibited restoration of hemodynamic and left ventricular function along with significant preservation of antioxidants, myocytes-injury-specific marker enzymes and significant inhibition of lipid peroxidation. Furthermore, histopathological salvage of myocardium reconfirmed the protective effects of E. officinalis. Results of the present study demonstrate cardioprotective potential of E. officinalis attributed to its potent antioxidant and free radical scavenging activity as evidenced by favorable improvement in hemodynamic, contractile function and tissue antioxidant status.

Andrographis paniculata extract protect against isoproterenol-induced myocardial injury by mitigating cardiac dysfunction and oxidative injury in rats.

Present study evaluated the cardioprotective effect of Andrographis paniculata (100, 200 or 400 mg/kg) against isoproterenol (85 mg/kg, b.w.)-induced cardiotoxicity referred as myocardial infarction in rats. Isoproterenol significantly (p < 0.05) decreased mean arterial pressure, heart rate, contractility and relaxation and increased left ventricular end diastolic pressure. Isoproterenol also significantly (p < 0.05) decreased antioxidants, superoxide dismutase, catalase, glutathione peroxidase, glutathione and increased leakage of cardiac injury markers; creatine phosphokinase-MB isoenzyme, lactate dehydrogenase concomitant to increased lipid peroxidation and histopathological perturbations. However, pretreatment with A. paniculata favorably restored hemodynamic parameters and left ventricular function and significantly (p < 0.05) prevented the depletion of endogenous antioxidants and myocyte marker enzymes as well as inhibited lipid peroxidation. Significant (p < 0.05) reversal of almost all the hemodynamic, biochemical and histopathological parameters by A. paniculata pretreatment in isoproterenol-induced cardiotoxicity depicted the cardioprotective effect of A. paniculata. Results showed that A. paniculata protected heart against cardiotoxic effects of isoproterenol by boosting endogenous antioxidant network, restoring ventricular function and maintaining structural integrity of heart.

Studies on effects of Emblica officinalis (Amla) on oxidative stress and cholinergic function in scopolamine induced amnesia in mice.

Emblica officinalis, commonly known as amla, is an important medicinal plant of India. Its fruits have potent antioxidant activity due to the presence of tannoids, tannins, vitamin C and flavonoids. The aim of this study was to investigate the beneficial effect of the hydroalcoholic extract of the fruits of Emblica officinalis (EO) on memory impairment in Swiss albino mice. Scopolamine (1 mg kg(-1), i.p)was administered to induce amnesia and the memory was evaluated by using elevated plus-maze and passive avoidance tests. Piracetam (200 mg kg(-1), i.p.) was used as a standard nootropic agent. The EO extract was administered intraperitoneally in four graded doses (150, 300, 450 and 600 mg kg(-1)) for 7 consecutive days to different groups of mice. The mice were sacrificed on the 8th day following assessment of memory. The brain malondialdehyde (MDA) and glutathione (GSH) as well as acetylcholinesterase (AchE)) activity was determined. It was observed that EO extract reversed the amnesia induced by scopolamine. The mean transfer latency and retention latency in the EO extract 600 mg kg(-1) group vs the vehicle treated scopolamine group was 13.46 sec (p<0.001) and 134.4 sec (p<0.001) vs 23.99 sec and 44.55 sec, respectively. EO extract treatment also significantly (p<0.001) ameliorated the oxidative stress induced by scopolamine administration. The mice brain MDA and GSH levels in the EO extract 600 mg kg(-1) group vs the scopolamine group were 29.95 nmol g(-1) of wet tissue and 51.87 microg g(-1) tissue vs 55.22 nmol g(-1) of wet tissue and 28.33 microg g(-1) tissue, respectively. Further, EO extract (300, 450 and 600 mg kg(-1), i.p) significantly (p<0.001) reversed the rise in brain acetyl cholinesterase (AchE) level induced by scopolamine. The mice brain Ach E levels in the EO extract 600 mg kg(-1) group as compared to the scopolamine group was 70.23 vs 151.49 U mg(-1) protein(-1), respectively. These results suggestthat EO possesses memory enhancing, antioxidant and anti-cholinesterase activity. It may be useful for the treament of cognitive impairments induced by cholinergic dysfunction. Its potential in the management of dementia and Azheimer disease needs to be further explored.

Healthcare worker resilience during the COVID-19 pandemic: A qualitative study of primary care providers in India.

Since 2020, the world saw a myriad of creative health-care policy responses to the COVID-19 pandemic. This article studied the experience of rural primary care providers (PCPs) in India deputized for COVID-19 care in urban areas. In-depth interviews were conducted with PCPs (n = 19), who served at COVID-19 facilities. Lack of epidemic management and intensive tertiary care experience, limited and inadequate training, and fear of infection emerged as the primary sources of distress, in addition to absent systemic mental health support and formalized recognition. Even so, resilience among the respondents emerged as a result of encouragement from their families, peers, and mentors through various means including social media, and from individual recognition from communities and local governments. Rural PCPs expressed an eagerness to serve at the frontlines of COVID-19 and demonstrated indomitable spirit in the face of an acutely understaffed health system, growing uncertainty, and concerns about personal and family health. It is imperative to reconfigure health-care education and continuing professional development, and equip all health-care professionals with mental health support and the ability to deal with public health emergencies and build a more resilient health workforce.

Time trends in tuberculosis mortality across the BRICS: an age-period-cohort analysis for the GBD 2019.

Background: Tuberculosis is the leading cause of death from a single infectious agent among the HIV-negative population and ranks first among the HIV-positive population. However, few studies have assessed tuberculosis trends in Brazil, Russia, India, China and South Africa (BRICS) or with an emphasis on HIV status. This study assesses the time trends of tuberculosis mortality across the BRICS with an emphasis on HIV status from 1990 to 2019. Methods: We obtained tuberculosis data from the Global Burden of Disease 2019 study (GBD 2019). We calculated the relative proportion of tuberculosis to all communicable, maternal, neonatal, and nutritional diseases by HIV status across the BRICS. We used age-period-cohort modelling to estimate cohort and period effects in tuberculosis from 1990 to 2019, and calculated net drift (overall annual percentage change), local drift (annual percentage change in each age group), longitudinal age curves (expected longitudinal age-specific rate), and period (cohort) relative risks. Findings: There were 549,522 tuberculosis deaths across the BRICS in 2019, accounting for 39.3% of global deaths. Among HIV-negative populations, the age-standardised mortality rate (ASMR) of tuberculosis in BRICS remained far higher than that of high-income Asia Pacific countries, especially in India (36.1 per 100 000 in 2019, 95% UI [30.7, 42.6]) and South Africa (40.1 per 100 000 in 2019, 95% UI [36.8, 43.7]). China had the fastest ASMR reduction across the BRICS, while India maintained the largest tuberculosis death numbers with an annual decrease much slower than China's (-4.1 vs -8.0%). Among HIV-positive populations, the ASMR in BRICS surged from 0.24 per 100 000 in 1990 to 5.63 per 100 000 in 2005, and then dropped quickly to 1.70 per 100 000 in 2019. Brazil was the first country to reverse the upward trend of HIV/AIDS-tuberculosis (HIV-TB) mortality in 1995, and achieved the most significant reduction (-3.32% per year). The HIV-TB mortality in South Africa has realised much progress since 2006, but still has the heaviest HIV-TB burden across the BRICS (ASMR: 70.0 per 100 000 in 2019). We also found unfavourable trends among HIV-negative middle-aged (35-55) adults of India, men over 50 in the HIV-negative population and whole HIV-positive population of South Africa, and women aged 45-55 years of Russia. China had little progress in its HIV-positive population with worsening period risks from 2010 to 2019, and higher risks in the younger cohorts born after 1980. Interpretation: BRICS' actions on controlling tuberculosis achieved positive results, but the overall improvements were less than those in high-income Asia Pacific countries. BRICS and other high-burden countries should strengthen specified public health approaches and policies targeted at different priority groups in each country. Funding: National Natural Science Foundation of China (82073573; 72074009), Peking University Global Health and Infectious Diseases Group.

Naringin protects against kainic acid-induced status epilepticus in rats: evidence for an antioxidant, anti-inflammatory and neuroprotective intervention.

The effect of naringin, a bioflavanoid, with potent antioxidant activity was studied on kainic acid (KA)-induced seizures, cognitive deficit and oxidative stress. Rats were administered KA (10 mg/kg intraperitoneally (i.p.)) and observed for behavioral changes and incidence and latency of convulsions over 4 h. The rats were thereafter sacrificed and oxidative stress parameters like malondialdehyde (MDA) and glutathione (GSH) were estimated in the brain. The level of proinflammatory cytokine, tumor necrosis factor (TNF)-α was also determined in the rat brain. It was observed that pretreatment with naringin (20, 40, 80 mg/kg, i.p.) significantly (p<0.001) increased the latency of seizures as compared to the vehicle treated-KA group. Naringin (40, 80 mg/kg) also significantly prevented the increase in MDA and fall in GSH levels due to KA. In addition, naringin dose-dependently attenuated the KA-induced increase in the TNF-α levels of brain. The pretreatment with naringin also significantly increased retention latency in the passive avoidance task. This shows that naringin reduced the cognitive deficit induced by KA. The results of our study suggest that naringin has therapeutic potential since it suppresses KA-induced seizures, cognitive impairment and oxidative stress in the brain. These neuroprotective effects are a result of its antioxidant and anti-inflammatory activity.

Hydroalcoholic extract of Emblica officinalis protects against kainic acid-induced status epilepticus in rats: evidence for an antioxidant, anti-inflammatory, and neuroprotective intervention.

CONTEXT: Emblica officinalis (Euphorbiaceae), commonly known as amla, is traditionally used for central nervous system (CNS) disorders. OBJECTIVE: In the present study, the effect of standardized hydroalcoholic extract of E. officinalis fruit (HAEEO), an Indian medicinal plant with potent antioxidant activity, was studied against kainic acid (KA)-induced seizures, cognitive deficits and on markers of oxidative stress. MATERIALS AND METHODS: Rats were administered KA (10 mg/kg, i.p.) and observed for behavioral changes, incidence, and latency of convulsions over 4 h. The rats were thereafter sacrificed for estimation of oxidative stress parameters: thiobarbituric acid-reactive substances (TBARS) and glutathione (GSH). The proinflammatory cytokine tumor necrosis factor alpha (TNF-α) was also determined in the rat brain. RESULTS: Pretreatment with HAEEO (500 and 700 mg/kg, i.p.) significantly (P < 0.001) increased the latency of seizures as compared with the vehicle-treated KA group. HAEEO significantly prevented the increase in TBARS levels and ameliorated the fall in GSH. Furthermore, HAEEO dose-dependently attenuated the KA-induced increase in the TNF-α level in the brain. HAEEO also significantly improved the cognitive deficit induced by KA, as evidenced by increased latency in passive avoidance task. DISCUSSION AND CONCLUSION: HAEEO at the dose of 700 mg/kg, i.p., was most effective in suppressing KA-induced seizures, cognitive decline, and oxidative stress in the brain. These neuroprotective effects may be due to the antioxidant and anti-inflammatory effects of HAEEO.

Cardioprotective effects of Commiphora mukul against isoprenaline-induced cardiotoxicity: a biochemical and histopathological evaluation.

Commiphora mukul commonly known as Guggul is one of the oldest and commonly consumed herb for promoting heart and vascular health. Present study was undertaken to evaluate cardioprotective potential of Commiphora mukul against isoprenaline-induced myocardial necrosis in rats. Wistar albino rats were divided into three main groups: sham (saline only), isoprenaline control (saline and isoprenaline) and Commiphora mukul treated (Commiphora mukul and isoprenaline) groups. Commiphora mukul was administered in three doses 100, 200 and 400 mg kg(-1) p.o. for 30 days. On 29th and 30th day, the animals of isoprenaline control and Commiphora mukulpretreatment groups were administered isoprenaline (85 mg kg(-1); s.c.), consecutively at an interval of 24 hr. Isoprenaline administration produced a significant (p < 0.05) decrease in myocardial antioxidants; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx), reduced glutathione (GSH), and myocyte injury marker enzymes creatine-phosphokinase-MB (CK-MB) and lactate dehydrogenase (LDH) along with enhanced lipid peroxidation; malondialdehyde (MDA) in heart. Commiphora mukul pretreatment reversed the isoprenaline-induced oxidative changes in rat myocardium by significant (p < 0.05) increase in SOD, CAT, GSHPx, GSH and reduction of MDA. In addition to improving myocardial antioxidant status, Commiphora mukul also prevented the leakage of LDH and CK-MB from heart. Further, histopathological examination showed the reduction of necrosis, edema and inflammation following Commiphora mukul pretreatment. Based on present findings, it is concluded that Commiphora mukul may be a potential preventive and therapeutic agent against the oxidative stress associated ischemic heart disease owing to antioxidant and antiperoxidative activity.

Curcumin protects rat myocardium against isoproterenol-induced ischemic injury: attenuation of ventricular dysfunction through increased expression of Hsp27 along with strengthening antioxidant defense system.

This investigation examines the role of heat shock protein (Hsp) 27 and its modulation by curcumin in isoproterenol-induced myocardial ischemic injury in rats. Evidence from hemodynamic functions and oxidative stress parameters were also included in the study. The animals were divided into control, isoproterenol, and curcumin 100, 200, and 400 mg/kg treatment groups. Curcumin was administered orally for 15 days to all the treated groups. On 13th and 14th day, isoproterenol (85 mg/kg, s.c.) was injected to curcumin-treated and isoproterenol group. On day 15, hemodynamic parameters were recorded. Thereafter, animals were sacrificed and hearts were kept for biochemical and Western blot analysis. We found dose-dependent increase in the expression of Hsp27 with drastic fall at highest dose. Hemodynamically, the lower 2 doses also restored the cardiac function as evident by improved contractile functions, decreased left ventricular end-diastolic pressure, restored arterial pressures, and heart rate. In addition, there was an increase in then level of superoxide dismutase, catalase, reduced glutathione, and decreased production of thiobarbituric acid reactive substances and leakage of cardiac necroenzyme creatine kinase-MB isoenzyme and lactate dehydrogenase in curcumin 100 and 200 mg/kg group as compared with isoproterenol. However, at a dose of 400 mg/kg, there was ineffectual protection against isoproterenol-induced myocardial damage. Our results suggested 200 mg/mg as the most optimum therapeutic dose showing improved cardiac function due to stabilization of cytoskeleton structure which in turn is attributed to Hsp27 expression along with fortified antioxidant defense system.