Simultaneous estimation of five biomarkers of neuroprotective herb Ashwagandha NMITLI-118R AF1 in rat plasma and brain using LC-ESI-MS/MS: Application to its pharmacokinetic and stability studies.

Withania Somnifera (WS) is a popular nutritional supplement in the USA, Europe, and Asia, known for its pharmacological effects on neurological disorders. However, the bioanalytical method development, validation, and pharmacokinetics of WS NMITLI-118R AF1 biomarkers Withanolide A (WLD A), Withanone (WNONE), Withanolide B (WLD B), Withaferin A (WF A), and 12 Deoxywithastramonolide (12 DEOXY) in rats have not been comprehensively explored. This study aimed to develop and validate a sensitive and selective LC-ESI-MS/MS method for these biomarkers in male Sprague Dawley rats plasma and brain matrix.

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.

LC-MS/MS method for quantification of raspberry ketone in rat plasma: application to preclinical pharmacokinetic studies.

Raspberry ketone (RK), derived from red raspberry fruit (, family Rosaceae), is a reported potent antiobesity agent. This study aims to investigate method development, validation, and and pharmacokinetics in rats. LC-MS/MS was used to conduct method development, validation, stability, and oral PK samples of RK in plasma analyses.

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.

Augmented experimental design for bioavailability enhancement: a robust formulation of abiraterone acetate.

Abiraterone acetate (ABRTA) is clinically beneficial in management of metastatic castration-resistant prostate cancer (PC-3). With highlighted low solubility and permeability, orally hampered treatment of ABRTA necessitate high dose to achieve therapeutic efficacy. To triumph these challenges, we aimed to develop intestinal lymphatic transport facilitating lipid-based delivery to enhance bioavailability.

Correction: Simultaneous quantification of five biomarkers in ethanolic extract of Linn. stem using liquid chromatography tandem mass spectrometry: application to its pharmacokinetic studies.

[This corrects the article DOI: 10.1039/C9RA07482A.].

Approaches to minimize the effects of P-glycoprotein in drug transport: A review.

P-glycoprotein (P-gp) is a transporter protein that is come under the ATP binding cassette family of proteins. It is situated on the surface of the intestine epithelium, where P-gp substrate binds to the transporter and is pumped into the intestine lumen by the ATP-driven energy-dependent process. In this review, we summarize the role of the P-gp efflux transporter situated on the intestine, the clinical importance of P-gp related drug interactions, and approaches to minimize the effect of P-gp in drug transport.

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.

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.

Challenges of peptide and protein drug delivery by oral route: Current strategies to improve the bioavailability.

Advancement in biotechnology provided a notable expansion of peptide and protein therapeutics, used as antigens, vaccines, hormones. It has a prodigious potential to treat a broad spectrum of diseases such as cancer, metabolic disorders, bone disorders, and so forth. Protein and peptide therapeutics are administered parenterally due to their poor bioavailability and stability, restricting their use.

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.

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.

A butanolic fraction from the standardized stem extract of Cassia occidentalis L delivered by a self-emulsifying drug delivery system protects rats from glucocorticoid-induced osteopenia and muscle atrophy.

We recently reported that a butanol soluble fraction from the stem of Cassia occidentalis (CSE-Bu) consisting of osteogenic compounds mitigated methylprednisone (MP)-induced osteopenia in rats, albeit failed to afford complete protection thus leaving a substantial scope for further improvement. To this aim, we prepared an oral formulation that was a lipid-based self-nano emulsifying drug delivery system (CSE-BuF). The globule size of CSE-BuF was in the range of 100-180 nm of diluted emulsion and the zeta potential was -28 mV.

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.

Development and validation of LC-MS/MS method for quantification of novel PP2A - β-catenin signalling inhibitor, S011-2111 in mice plasma: Application to its preclinical pharmacokinetic studies.

S011-2111 is a semicarbazone and chalcone hybrid demonstrating antiproliferative tumor cell-selective effects along with unique antimetastatic potential by mitigating PP2A-β-catenin signalling pathway. The present study envisaged to explore the in vitro and in vivo pharmacokinetics of S011-2111. A sensitive and selective liquid chromatography-tandem mass spectrometry bioanalytical method was developed and validated to determine S011-2111.

Pharmacokinetics and brain targeting of -resveratrol loaded mixed micelles in rats following intravenous administration.

Trans-Resveratrol (T-RES) is a compound with wide therapeutic applications that shows low bioavailability and distribution across blood-brain barrier. The purpose of our study was to develop T-RES loaded mixed micelle (T-RES-MM) for its enhanced systemic availability and targeting to the brain. T-RES-MMs were formulated using Pluronic F-127 (PF-127) and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) by using film hydration process.

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.