Phytoformulation with hydroxycitric acid and capsaicin protects against high-fat-diet-induced obesity cardiomyopathy by reducing cardiac lipid deposition and ameliorating inflammation and apoptosis in the heart.

Background and aim: Phytoformulation therapy is a pioneering strategy for the treatment of metabolic disorders and related diseases. The aim of the present study was to investigate the protective effect of a phytoformulation consisting of hydroxycitric acid and capsaicin against obesity-related cardiomyopathy. Experimental procedure: Sprague-Dawley rats were fed HFD for 21 weeks, and phytoformulation (100 mg/kg body weight) was administered orally for 45 days starting at week 16. Results and conclusion: We found that HFD supplementation resulted in significant hyperglycemia and caused an increase in cardiac lipid deposition, inflammation and apoptosis in the heart. Phytoformulation therapy not only significantly decreased blood levels of glucose, cholesterol, triglycerides, free fatty acids, and inflammatory cytokines in obese rats, but also protected cardiac tissue, as shown by histological analysis. Conversely, phytoformulation therapy decreased mRNA levels for sterol regulatory element-binding factor 1, fatty acid synthase, acetyl-CoA carboxylase, and fatty acid binding protein 1 genes involved in fatty acid synthesis and absorption in obese rats. It increased the levels of lysosomal acid lipase, hormone-sensitive lipase, and lipoprotein lipase genes involved in fatty acid degradation in the heart. In addition, the phytoformulation improved cardiac inflammation and apoptosis by downregulating the genes nuclear factor kappa-light-chain enhancer of activated B cells (NF-kB), tumour necrosis factor α, interleukin-6, toll-like receptor-4 (TLR-4), BCL2-associated X and caspase-3. In conclusion, our results show that the phytoformulation improved insulin sensitivity and attenuated myocardial lipid accumulation, inflammation, and apoptosis in the heart of HFD-induced obese rats by regulating fatty acid metabolism genes and downregulating NF-kB/TLR-4/caspase-3.

Linalool attenuates lipid accumulation and oxidative stress in metabolic dysfunction-associated steatotic liver disease via Sirt1/Akt/PPRA-α/AMPK and Nrf-2/HO-1 signaling pathways.

INTRODUCTION: Linalool is a monoterpene that occurs naturally in various aromatic plants and is identified in our previous study as a potential candidate for protection against high-fat diet (HFD)-induced metabolic dysfunction-associated steatotic liver disease (MASLD). However, little is known about its direct effects on hepatic lipid metabolism and oxidative stress. Therefore, this study aims to investigate the therapeutic effect of linalool against MASLD and the underlying mechanism. METHODS: To establish a rat model of MASLD, male Wistar rats were fed HFD for 16 weeks and orally administered linalool (100 mg/kg body weight) for 45 days starting from week 14. RESULTS: Linalool significantly reduced HFD-induced liver lipid accumulation and restored altered adipokine levels. Mechanistically, linalool downregulated the mRNA expression of sterol regulatory element binding protein 1 and its lipogenesis target genes fatty acid synthase and acetyl-CoA carboxylase, and upregulated the mRNA expression of genes involved in fatty acid oxidation (peroxisome proliferator-activated receptor (PPAR)-alpha [PPAR-α], lipoprotein lipase and protein kinase B [Akt]) as well as the upstream mediators sirtuin 1 (Sirt1) and AMP-activated protein kinase (AMPK) in the liver of MASLD rats. In addition, linalool also curbed oxidative stress by increasing antioxidant enzymes and activating nuclear erythroid-2-related factor 2 (Nrf-2) and its downstream target genes involved in antioxidant properties. CONCLUSION: Therefore, this study concludes that linalool attenuates lipid accumulation in the liver by inhibiting de novo lipogenesis, promoting fatty acid oxidation, and attenuating oxidative stress by regulating Sirt1/Akt/PPRA-α/AMPK and Nrf-2/ HO-1 signaling pathways.

Phenolic fraction extracted from Kedrostis foetidissima leaves ameliorated isoproterenol-induced cardiotoxicity in rats through restoration of cardiac antioxidant status.

In this study, the cardioprotective effects of partially purified phenolic fraction of Kedrostis foetidissima leaves (PFK) were evaluated in isoproterenol (ISO)-induced myocardial infarction rat model. ISO induction to experimental rats for two consecutive days significantly increased the levels of triglycerides, cholesterol, phospholipids, free fatty acids, low-density lipoproteins, and cardiac biomarker enzymes, and decreased the levels of high-density lipoproteins and antioxidant enzyme activity. Pretreatment of experimental rats with PFK for 45 days led to a significant elevation in antioxidant enzyme activity. PFK-pretreated rats exhibited significantly reduced levels of circulating lipids and cardiac-specific biomarker enzymes compared to ISO-treated rats. Thus, the present study demonstrated that PFK ameliorated ISO-induced cardiotoxicity through the augmentation of the endogenous cardiac antioxidant system, thereby modulating the lipid peroxidation caused by ISO-induced free radicals, and prevented the myocardial damage, which was confirmed through histopathological analysis. PRACTICAL APPLICATIONS: Kedrostis foetidissima is edible medicinal plant and phenolic fraction extracted from the leaves of this plant may help the common man in the protection of heart. The phenolic fraction shows significant antioxidant activity, so this might be referred to as dietary supplement and also helps to develop new pharmaceutical formulations.

Evaluation of Anti-diarrheal Potential of Hydro-alcoholic Extracts of Leaves of Murraya koenigii in Experimental Animals.

BACKGROUND: The indigenous medical system of India mentions the use of Murraya koenigii leaves for the treatment of different types of diarrheas over ages. OBJECTIVE: To evaluate the anti-diarrheal activity of hydro-alcoholic extracts of leaves of Murraya koenigii and to check its effects on intestinal transits in experimental rat model. MATERIALS AND METHODS: The hydro-alcoholic extract of Murraya koenigii leaves was obtained with Soxhlet extraction method. Animals were divided into four groups (n = 6) receiving daily for three consecutive days: vehicle, standard drug atropine (3mg/kg, i.p.), leaf extracts 200 & 400 mg/kg respectively in oral route. Effects of the drugs on normal defecation were noted and then castor oil induced diarrhea was used to measure the effects of leaf extract on stool frequency and consistency. Finally, charcoal meal test was used to evaluate the effect of the extract on intestinal transit. Statistical evaluation was done using SPSS version 17, one way ANOVA followed by Dunnett's t-test was done and P< 0.001 was considered as significant. RESULTS: Murraya koenigii leaf extracts in 200 and 400 mg/kg dose reduced stool frequency, increased stool consistency and increased small intestinal transit time. CONCLUSION: Hydro-alcoholic extract of Murraya koenigii leaves possesses significant anti-diarrheal activity due to its inhibitory effect on gastrointestinal motility, making it useful for a wide number of gastrointestinal diseases.

Evaluation of anticonvulsant, sedative, anxiolytic, and phytochemical profile of the methanol extract from the aerial parts of Swertia corymbosa (Griseb.) wight ex C.B. Clarke.

The objective of the present study was to evaluate the anxiolytic, antidepressant, and anticonvulsant activity of the methanolic extract of Swertia corymbosa (SCMeOH). After acute toxicity test, oral treatment with SCMeOH at doses of 125, 250, and 500 mg/kg behavioral models of open field, elevated-plus-maze, actophotometer, rotarod, pentylenetetrazole, isoniazid, and maximal electroshock induced seizure models were utilized. In open field test, SCMeOH (125, 250, and 500 mg/kg) (P < 0.01, P < 0.001) increased the number of rearings. However, the number of central motor and ambulation (P < 0.01, P < 0.001) were reduced. Likewise, the number of entries and the time spent in open arm were increased while the number of locomotion was decreased (P < 0.001) in elevated-plus-maze and actophotometer test, respectively. SCMeOH (125-500 mg/kg) protected the mice against the pentylenetetrazole and isoniazid induced convulsions; it causes significant (P < 0.01 and P < 0.001) dose dependent increase in latency of convulsion. Treatment with SCMeOH reduced the duration of the tonic hind limb extension induced by electroshock. Two major compounds such as gentiopicroside and swertianin were analyzed by HPLC system.

RETRACTED: Anti-diabetic activity of Swertia corymbosa (Griseb.) Wight ex C.B. Clarke aerial parts extract in streptozotocin induced diabetic rats.

ETHNOPHARMACOLOGICALS RELEVANCE: Swertia corymbosa locally called as Shirattakuchi have a long history of use in Ayurveda herbal preparations in Indian traditional system of medicine. It has been used in folklore medicine for the treatment of diabetes. AIM OF THE STUDY: The present study aimed to investigate the effect of the methanolic extract of Swertia corymbosa (SC) in diabetic and to analyze its chemical composition by HPLC-ESI/MS that may correlate with their pharmacological activities. MATERIALS AND METHODS: The in vitro anti-diabetic activity of the extracts was measured by using α-glucosidase and α-amylase enzyme inhibitory activity. The methanolic extract of Swertia corymbosa were administered orally (125, 250 and 500 mg/kg, for 28 days) to streptozotocin-induced diabetic rats. Hypoglycemic effects, oral glucose tolerance test, change in body weight and lipid profile, biochemical analysis and histopathological examination were assessed. High-performance liquid chromatography-electrospray ionization/mass spectrometry (HPLC-ESI/MS) method was also developed to analyze the chemical composition. RESULTS: In vitro anti-dabetic study, the methanol extract of SC is found to be a potent inhibitor of α-glucosidase and α-amylase activity. Oral administration of SC and standard drug for 28 days caused a significant decrease in the concentrations of blood glucose level, total cholesterol (TC), serum triglycerides (TGs), low-density lipoprotein-cholesterol (LDL-C), malondialdehyde (MDA) and significant increase in the concentrations of high density lipoprotein-cholesterol (HDL-C), serum insulin and body weight. Furthermore, activities of antioxidative enzymes, including SOD, GPx, GSH and CAT were enhanced dosed dependently with SC. Histopathological studies of the pancreas showed the regeneration of the ß-cells by extract which were earlier necrosed by streptozotocin. Ten major compounds such as loganic acid (1), swertiamarin (2), sweroside (3), gentiopicroside (4), isovitexin (5), amoroswertin (6), amarogentin (7), gentiacaulein (8), decussatin (9) and swertianin (10) were analyzed by HPLC-ESI/MS system. CONCLUSIONS: These results demonstrate that SC aerial parts of methanolic extract is an effective anti-diabetic and antioxidant activities which provides the scientific proof for the folklore medicine.

Cardioprotective activity of Amaranthus viridis Linn: effect on serum marker enzymes, cardiac troponin and antioxidant system in experimental myocardial infarcted rats.

BACKGROUND: Cardiovascular diseases (CVDs) have a high prevalence in developing and developed countries and myocardial infarction accounts for majority of deaths and disabilities. The current study dealt with the protective role of Amaranthus viridis Linn on isoproterenol (ISO)-induced myocardial infarction (MI) in rats. METHODS: Subcutaneous injection of ISO (20 mg/kg body weight in 1 ml saline) to rats for two consecutive days offered significant alteration in cardiac marker enzymes (AST, ALT, LDH and CPK), cardiac troponin, lipid peroxidation products (TBARS and hydroperoxide) and antioxidant system (CAT, SOD, GPx, GST, GSH and GSSG). ISO-induced myocardial damage was indicated by increased activities of marker enzymes in serum and the levels of cardiac troponin in the serum. In addition to these diagnostic markers, the levels of lipid peroxidation products in the heart were significantly (p<0.05) increased and the activities of enzymic antioxidants and non-enzymic antioxidant such as glutathione in the heart was significantly (p<0.05) decreased and GSSG in the heart was increased in ISO-induced rats. RESULTS: Effect of Amaranthus viridis oral treatment (100, 200 and 300 mg/kg body weight) for 45 days elicited a significant cardio protective activity by lowering the levels of serum marker enzymes, cardiac troponin, GSSG and lipid peroxidation and elevated the levels of antioxidant enzymes and GSH. The effect at a dose of 300 mg/kg of A. viridis was more pronounced than that of the dose 100 mg/kg and 200mg/kg and brought back all the parameters to near normal. The effect produced by A. viridis was compared with α-tocopherol. CONCLUSIONS: The present findings have demonstrated that the cardioprotective effects of A. viridis in ISO-induced oxidative damage may be due to an augmentation of the endogenous antioxidants and inhibition of lipid peroxidation of membrane.

Hepatoprotective activity of Clerodendrum inerme against CCl4 induced hepatic injury in rats.

The ethanolic extract of Clerodendrum inerme leaves were screened for its hepatoprotective activity in CCl4 (0.5 ml/kg, i.p) induced liver damage in Swiss albino rats at a dose of 200 mg /kg bw. The ethanolic extract of C. inerme significantly (P<0.001) decreases the serum enzyme alanine amino transferase (ALT), asparate amino transferase (AST), alkaline phosphates (ALP), triglycerides (TGL), total cholesterol (TC) and significantly increased the glutathione level. Silymarin (25 mg/kg), a known hepatoprotective drug used for comparison exhibited significant activity (P<0.001). The extract did not shown any mortality up to a dose of 2000 g/kg bw.

Pathophysiology of sea nettle (Chrysaora quinquecirrha), envenomation in a rat model and the effects of hyperbaric oxygen and verapamil treatment.

The effect of lethal sea nettle envenomation on the morphology and blood flow in various rat organs was characterized and the influence of two antidotes (hyperbaric oxygen and verapamil) was compared. Either antidote slightly prolonged survival, but the protective effects were not statistically significant. The venom caused no histologic alterations in brain, heart, or lungs but induced hepatic and renal necrosis. Hepatocytes in mid-zonal regions and renal tubular epithelium were the cell types predominantly affected. Hyperbaric oxygen and verapamil did not decrease the hepatic injury. The venom did not influence central hemodynamics until preterminally and it diminished blood flow to brain, but not to liver or kidney. Hyperbaric oxygenation protected against venom-induced decreases in blood flow to the brain. These results add toxic hepatic and renal necrosis and cerebral ischemia to the pathophysiology of envenomation in this model.