Simultaneous Estimation of Quercetin and -Resveratrol in Extract in Rat Serum Using Validated LC-MS/MS Method: Application to Pharmacokinetic and Stability Studies.

is a nutrient-rich plant with a history of use in traditional medicine. It boasts a diverse range of polyphenols, including quercetin, resveratrol, β-sitosterol, myricetin, and other compounds. We developed and validated a sensitive LC-MS/MS method to quantify quercetin and -res biomarkers in rat serum and applied this method to pharmacokinetic and stability studies.

Pancreastatin deteriorates hepatic lipid metabolism via elevating fetuin B in ovariectomized rats.

Hepatic steatosis is an important mstetabolic complication in women encountering postmenopausal phase of life. Pancreastatin (PST), has previously been investigated in diabetic and insulin resistant rodents. The present study highlighted the role of PST in ovariectomized rats.

Hesperidin inhibits NOX4 mediated oxidative stress and inflammation by upregulating SIRT1 in experimental diabetic neuropathy.

Hesperidin possesses myriads of pharmacological benefits, including anti-inflammatory and antioxidant properties. Herein, we speculated that the described pharmacological benefits of hesperidin might be due to its potentiating action on SIRT1; thereby, inhibition of NOX4. We developed diabetic neuropathy in Sprague-Dawley rats by feeding them a high-fat diet (HFD) for 12 weeks.

Evaluation of mutagenic, cytotoxic, mitochondrial dysfunction, apoptotic activity, and acute toxicity of ethanolic extract of Cissus quadrangularis.

Recent studies have focused on exploring the efficacy of Cissus quadrangularis extract (EECQ) against various metabolic disorders involving the liver as the prime target organ, suggesting a considerable threat of hepatotoxicity in the person encountering it. Consequently, the current study was aimed to unravel the mutagenic, cytotoxic, mitochondrial dysfunction, apoptotic activity in HepG2 cells, and acute toxicity of EECQ. MTT, SRB, trypan blue dye exclusion, and lactate dehydrogenase (LDH) assay were performed in HepG2 cell lines to determine the cytotoxicity of the extract.

extract mitigates diabetic cardiomyopathy by inhibiting RAAS activation, inflammation and oxidative stress.

Background: Diabetic cardiomyopathy (DCM) is an age-related disease, and its progression is accompanied by hyperglycaemia, cardiac dysfunction, and myocardial structural and functional abnormalities. , a traditional medicinal plant, contains polyphenols, flavonoids, phytosterols, carbohydrates and ascorbic acid. It is used to treat osteoporosis, asthma, haemorrhoids and menstrual disorders.

Evaluation of the Pharmacokinetics of the Pancreastatin Inhibitor PSTi8 Peptide in Rats: Integration of In Vitro and In Vivo Findings.

PSTi8 is a pancreastatin inhibitory peptide that is effective in the treatment of diabetic models. This study investigates the pharmacokinetic (PK) properties of PSTi8 in Sprague Dawley rats, for the first time. In vitro and in vivo PK studies were performed to evaluate the solubility, stability in plasma and liver microsomes, plasma protein binding, blood-plasma partitioning, bioavailability, dose proportionality, and gender difference in PK.

Polyphenolic-rich Cissus quadrangularis extract ameliorates insulin resistance by activating AdipoR1 in peri-/post-menopausal rats.

Insulin resistance (IR) is a significant complication in menopausal women, which predisposes them to cardiovascular disorder, obesity, and diabetes. Cissus quadrangularis is a polyphenolic plant rich in nutrients and is used as an edible vegetable in Nigeria. Previously, we investigated that C.

Ethanolic extract of improves vasoreactivity by modulation of eNOS expression and oxidative stress in spontaneously hypertensive rats.

Background: Endothelial dysfunction is related to the reduced bioavailability of nitric oxide (NO) and plays a significant role in developing hypertension. The intake of a diet rich in antioxidants decreases the threat of hypertension. possesses antioxidant, anti-inflammatory, and hypocholesterolemic activities.

Pancreastatin induces hepatic steatosis in type 2 diabetes by impeding mitochondrial functioning.

Aims: Mitochondrial dysfunction is among the key factors for the advancement of hepatic steatosis to NAFLD and NASH. Pancreastatin (PST: human ChgA250-301) is a dysglycemic hormone, previously reported to promote steatosis and inflammation in various animal models of metabolic disorders. Recently, we observed PST deregulates energy expenditure and mitochondrial functioning in perimenopausal rats.

Cissus quadrangularis extract attenuates diabetic nephropathy by altering SIRT1/DNMT1 axis.

Objectives: Hyperglycemia-induced SIRT1, DNMT1, SODs, as well as oxidative stress, play a pivotal role in the progression of diabetic nephropathy. Cissus quadrangularis, holds antioxidant and hypoglycemic activity; however, a direct link between its activity and prevention of diabetic nephropathy has not been ascertained yet. Accordingly, we aimed to delineate the protective effect of ethanolic extract of Cissus quadrangularis (EECQ) against high-fat diet/streptozotocin (HFD/STZ) induced diabetic nephropathy rats.

Pancreastatin mediated regulation of UCP-1 and energy expenditure in high fructose fed perimenopausal rats.

Aims: Pancreastatin (PST) is a crucial bioactive peptide derived from chromogranin A (CHGA) proprotein that exhibits an anti-insulin effect on adipocytes. Herein, we investigated the effects of PST on brown adipose tissues (BAT) and white adipose tissue (WAT) in connection with uncoupling protein-1 (UCP-1) regulated energy expenditure in high fructose diet (HFrD) fed and vinylcyclohexenediepoxide (VCD) induced perimenopausal rats.

Material And Methods: We administered VCD in rats for 17 consecutive days and fed HFrd for 12 weeks.

Pancreastatin induces islet amyloid peptide aggregation in the pancreas, liver, and skeletal muscle: An implication for type 2 diabetes.

Recent findings suggest that the accumulation of misfolded aggregates of islet amyloid peptide (IAPP) plays an essential role in pancreatic damage and type 2 diabetes (T2D). Pancreastatin (PST), a chromogranin derived peptide, instigates insulin resistance (IR) and promotes T2D. Here, we aimed to investigate whether PST induces IAPP aggregation in the pancreas, liver, and skeletal muscles.

in Neurological Disorders: Ethnopharmacological Evidence, Mechanism of Action and its Progress in Delivery Systems.

Background: The underlying cause of major neurodegenerative disorders remains a healthcare mystery. The thoroughly investigated causes include oxidative stress, inflammation, environmental factor, mitochondrial dysfunction, and irregular neuronal protein aggregation. Withania somnifera has been used for more than 2500 years as a useful medicinal plant to improve disease defense, prevent aging, rejuvenate the body in a vulnerable situation, and generate a feeling of mental well-being.

PSTi8 with metformin ameliorates perimenopause induced steatohepatitis associated ER stress by regulating SIRT-1/SREBP-1c axis.

Aims: Hepatic steatosis in women confronting menopause is the manifestation of substantial fructose consumption and forms a positive feedback loop to develop endoplasmic reticulum (ER) stress. Previously pancreastatin inhibitor peptide-8 (PSTi8) and Metformin (Met) combination effectively ameliorated hepatic lipid accumulation in high fructose diet (HFrD) fed diabetic mice models at reduced doses. Moreover, SIRT-1 plays a crucial role in the regulation of SREBP-1c.

Combination of Pancreastatin inhibitor PSTi8 with metformin inhibits Fetuin-A in type 2 diabetic mice.

In the preceding study, we delineated that high-fat diet (HFD) consumption in mice increases the circulatory level of pancreastatin (PST), which additionally enhances the free fatty acid (FFA) concentration in circulation. Consequently, the aggravated FFA activates Fetuin-A, which facilitates hepatic lipid accumulation, insulin resistance (IR), and culminates in type 2 diabetes (T2D). Metformin (Met) is a widely known first-line drug for the treatment of T2D.

Naringin ameliorates type 2 diabetes mellitus-induced steatohepatitis by inhibiting RAGE/NF-κB mediated mitochondrial apoptosis.

Aims: Recent findings have instituted the role of hyperglycemia-related AGE/RAGE and NF-κB in instigating reactive oxygen species (ROS) mediated mitochondrial dysfunction and apoptosis of hepatocyte, which leads to steatohepatitis. Naringin, a flavanone glycoside found to possess myriads of pharmacological benefits along with its antioxidant and anti-inflammatory properties. Consequently, we aimed to decipher the effect of naringin on RAGE/NF-κB mediated mitochondrial apoptosis in type 2 diabetes mellitus (T2DM)-induced steatohepatitis.

Pancreastatin inhibitor PSTi8 protects the obesity associated skeletal muscle insulin resistance in diet induced streptozotocin-treated diabetic mice.

Pancreastatin (PST), a chromogranin A (CHGA) derived peptide connects obesity with insulin resistance by inducing inflammation. Previously, we have evaluated potential activity of PST inhibitor (PSTi8) in liver and adipose tissue in type 2 diabetic mice model. In this study we further explore the therapeutic effect of PSTi8 on glucose metabolism in skeletal muscle cells/tissue and its effect on energy homeostasis in diet induced diabetic mice model.

LC-ESI-MS/MS assay development and validation of a novel antidiabetic peptide PSTi8 in mice plasma using SPE: An application to pharmacokinetics.

PSTi8 is a 21 amino acid pancreastatin inhibitory peptide that demonstrated potent antidiabetic activity in insulin resistant rodent models. The goal of the current work is to establish and validate the LC-ESI-MS/MS bioanalytical assay of PSTi8 in mice plasma in order to unveil its pharmacokinetic (PK) behaviour for the first time. The MS detection of PSTi8 and diprotin A (internal standard, IS) was conducted with Q1/Q3 SRM transitions at 607.

Pancreastatin inhibitor PSTi8 attenuates hyperinsulinemia induced obesity and inflammation mediated insulin resistance via MAPK/NOX3-JNK pathway.

Pancreastatin (PST), a chromogranin A derived peptide has anti-insulin effects and plays a significant role in obesity-induced insulin resistance. In obesity and type 2 diabetes mellitus, both insulin and PST level are elevated, but it is not clearly understood how anti-insulin effect of PST get regulated in hyperinsulinemic state. Simultaneously we have explored pancreastatin inhibitor PSTi8 against the native PST in the same hyperinsulinemic state.

Pancreastatin inhibitor, PSTi8 ameliorates metabolic health by modulating AKT/GSK-3β and PKCλ/ζ/SREBP1c pathways in high fat diet induced insulin resistance in peri-/post-menopausal rats.

Increase in the prevalence of insulin resistance (IR) in peri-/post-menopause women is mainly due to hormone deficiency and lifestyle. PSTi8 (PEGKGEQEHSQQKEEEEEMAV-amide) is a pancreastatin inhibitor peptide which showed potent antidiabetic activity in genetic and lifestyle induced type 2 diabetic mice. In the present work, we have investigated the antidiabetic activity of PSTi8 in rat models of peri-/post-menopausal IR.

Pancreastatin inhibitor activates AMPK pathway via GRP78 and ameliorates dexamethasone induced fatty liver disease in C57BL/6 mice.

Aims: To investigate the role of pancreastatin inhibitor (PSTi8) in lipid homeostasis and insulin sensitivity in dexamethasone induced fatty liver disease associated type 2 diabetes.

Main Methods: Glucose releases assay, lipid O staining and ATP/AMP ratio were performed in HepG2 cells. Twenty four mice were randomly divided into 4 groups: Control group (saline), DEX (1 mg/kg, im) for 17 days, DEX+PSTi8 (acute 5 mg/kg and chronic 2 mg/kg, ip) for 10 days.

Determination of permeability, plasma protein binding, blood partitioning, pharmacokinetics and tissue distribution of Withanolide A in rats: A neuroprotective steroidal lactone.

Preclinical Research & Development Withanolide A (WA), a steroidal lactone is a major bioactive constituent of Withania somnifera (L.) with remarkable neuropharmacological activity. In this study, we investigated the permeability, plasma protein binding (PPB), blood partitioning, intravenous (i.

Evaluation of oral pharmacokinetics, in vitro metabolism, blood partitioning and plasma protein binding of novel antidiabetic agent, S009-0629 in rats.

S009-0629 [methyl-8-(methylthio)-2-phenyl-6-p-tolyl-4,5-dihydro-2H-benzo[e]indazole-9-carboxylate] is a novel antidiabetic agent with PTP1B inhibitory activity. In this study, we have investigated the in vitro metabolic stability, plasma protein binding, blood partitioning, and oral pharmacokinetic study of S009-0629 in rats. The plasma protein binding, blood partitioning, and metabolic stability were determined by HPLC method.

Discovery of pancreastatin inhibitor PSTi8 for the treatment of insulin resistance and diabetes: studies in rodent models of diabetes mellitus.

Pancreastatin (PST) is an endogenous peptide which regulates glucose and lipid metabolism in liver and adipose tissues. In type 2 diabetic patients, PST level is high and plays a crucial role in the negative regulation of insulin sensitivity. Novel therapeutic agents are needed to treat the diabetes and insulin resistance (IR) against the PST action.

Cardioprotective Effect of Planchon in β-Adrenergic Agonist Induced Cardiac Hypertrophy.

Planchon (Family: Ulmaceae), a traditional medicinal plant, was used in fracture healing in the folk tradition of Uttarakhand, Himalaya, India. The present study investigated the cardioprotective effect of ethanolic extract (EE) and butanolic fraction (BF) of in isoprenaline (ISO) induced cardiac hypertrophy in Wistar rats. Cardiac hypertrophy was induced by ISO (5 mg/kg/day, subcutaneously) in rats.