Preclinical pharmacokinetics, absolute bioavailability and dose proportionality evaluation of bioactive phytochemical Withanone in rats.

Withanone (WN), a bioactive phytochemical isolated from the medicinal herb Withania somnifera, has shown multiple pharmacological and therapeutic successes, including neuroprotective and anti-cancer activities. However, detailed pharmacokinetic (PK) properties of pure WN were not well defined. Pharmacokinetic (PK) characteristics, dose proportionality, and absolute bioavailability of pure WN were explored in rats using an efficient, reliable, and sensitive LC-MS/MS assay to address this gap.

Assessment of Perception of Dental Students to OSCE Exams: A Cross-Sectional Study.

Aims And Objective: To assess the knowledge as well as attitude of dental students to OSCE exams.

Materials And Methods: With the aim of evaluating the knowledge and attitude of dental students to OSCE exams, the present study was planned and it consisted of total 1000 dental students (Third year, Final year, and Interns) who have taken the OSCE examinations. The survey included a questionnaire in addition to a subsection on participants' demographic information.

Therapeutic Role of ELOVL in Neurological Diseases.

Fatty acids play an important role in controlling the energy balance of mammals. De novo lipogenesis also generates a significant amount of lipids that are endogenously produced in addition to their ingestion. Fatty acid elongation beyond 16 carbons (palmitic acid), which can lead to the production of very long chain fatty acids (VLCFA), can be caused by the rate-limiting condensation process.

ACE2/ANG-(1-7)/Mas receptor axis activation prevents inflammation and improves cognitive functions in streptozotocin induced rat model of Alzheimer's disease-like phenotypes.

Activation of the renin-angiotensin system (RAS), by Angiotensin converting enzyme/Angiotensin II/Angiotensin receptor-1 (ACE/Ang II/AT1 R) axis elicits amyloid deposition and cognitive impairment. Furthermore, ACE2 induced release of Ang-(1-7) binds with the Mas receptor and autoinhibits ACE/Ang II/AT1 axis activation. Inhibition of ACE by perindopril has been reported to improve memory in preclinical settings.

Formulation and Characterization of Phytosomes as Drug Delivery System of Formononetin: An Effective Anti-Osteoporotic Agent.

Background: Formononetin (FNT), a methoxy isoflavone, is a potential phytoconstituent utilized for refurbishing fractures in bone tissue. Conceding to its involvement in first-pass metabolism followed by glucuronidation, its absorption efficacy is limited. Hence, it belongs to the BCS class II classification.

Nanomedicines targeting the inflammasome as a promising therapeutic approach for cell senescence.

Technological advancements in the present era have enhanced drug discovery and development. Nanomedicines are valuable pharmacotherapeutic tools against several diseases and disorders including aging related disorders. The mechanistic association between nanomedicines and molecular modulation have been investigated by many researchers.

4-Phenylbutyrate Mitigates the Motor Impairment and Dopaminergic Neuronal Death During Parkinson's Disease Pathology via Targeting VDAC1 Mediated Mitochondrial Function and Astrocytes Activation.

Parkinson's disease (PD) is a progressive motor neurodegenerative disorder significantly associated with protein aggregation related neurodegenerative mechanisms. In view of no disease modifying drugs, the present study was targeted to investigate the therapeutic effects of pharmacological agent 4-phenylbutyric acid (4PBA) in PD pathology. 4PBA is an FDA approved monocarboxylic acid with inhibitory activity towards histone deacetylase and clinically treats urea cycle disorder.

Self-Fluorescent Lone Tryptophan Nanoparticles as Theranostic Agents Against Alzheimer's Disease.

Aggregation of β-amyloid (Aβ42) peptide in the neural extracellular space leads to cellular dysfunction, resulting in Alzheimer's disease (AD). The hydrophobic core of the amyloidogenic Aβ42 peptide contains aromatic residues that play an important role in the self-assembly and subsequent aggregation of the peptide. Hence, targeting these hydrophobic core residues by potent low molecular agents can be a promising therapeutic approach toward AD.

Evaluation of Bioactive Metabolites and Antioxidant-Rich Extracts of Amaranths with Possible Role in Pancreatic Lipase Interaction: In Silico and In Vitro Studies.

Fat/carbohydrate-rich diet consumption or elevated secretion of pancreatic lipase (PL) in pancreatic injury results in increased fat digestion and storage. Several metabolites in plant-based diets can help achieve the requirements of nutrition and fitness together. Presently, nutritional metabolites from , , and were assessed and predicted for daily intake.

Isoformononetin, a dietary isoflavone protects against streptozotocin induced rat model of neuroinflammation through inhibition of NLRP3/ASC/IL-1 axis activation.

Aims: Isoformononetin (IFN), a methoxyl isoflavone present in most of human dietary supplements. However, being a highly potent antioxidant and anti-inflammatory molecule, its activity against neuronal oxidative stress and neuroinflammation has not been explored till now. The present study was inquested to assess the antioxidant, anti-apoptotic and anti-inflammatory activity of IFN against streptozotocin induced neuroinflammation in different brain regions of rat.

Mechanism for antiParkinsonian effect of resveratrol: Involvement of transporters, synaptic proteins, dendrite arborization, biochemical alterations, ER stress and apoptosis.

The present study was undertaken to evaluate the mechanism for antiParkinsonian effect of resveratrol employing 6-hydroxydopamine (6-OHDA) induced experimental model of Parkinson's disease (PD). Resveratrol treatment significantly protects the PD related pathological markers like level of tyrosine hydroxylase, dopamine and apoptotic proteins (Bax and cleaved caspase-3). Disease pathology involves significantly decreased level of dopamine transporter, synaptophysin and postsynaptic density protein 95 (PSD-95) along with augmented level of vesicular monoamine transporter and considerably affected the dendrite arborization.

Chronic unpredictable stress negatively regulates hippocampal neurogenesis and promote anxious depression-like behavior via upregulating apoptosis and inflammatory signals in adult rats.

Psychological and physical stress play a pivotal role in etiology of anxiety and depression. Chronic psychological and physical stress modify various physiological phenomena, as a consequence of which oxidative stress, decreased neurotransmitter level, elevated corticosterone level and altered NSC homeostasis is observed. However, the precise mechanism by which chronic stress induce anxious depression and modify internal milieu is still unknown.

Piperine and Celecoxib synergistically inhibit colon cancer cell proliferation via modulating Wnt/β-catenin signaling pathway.

Background: Celecoxib (CXB), a selective COX-2 inhibitor NSAID, has exhibited prominent anti-proliferative potential against numerous cancers. However, its low bioavailability and long term exposure related cardiovascular side effects, limit its clinical application. In order to overcome these limitations, natural bioactive compounds with lower toxicity profile are used in combination with therapeutic drugs.

N-acetyl-cysteine in combination with celecoxib inhibits Deoxynivalenol induced skin tumor initiation via induction of autophagic pathways in swiss mice.

Deoxynivalenol is a trichothecene mycotoxin which naturally contaminates small grain, cereals intended for human and animal consumption. Investigations for dermal toxicity of DON has been needed and highlighted by WHO. Previous studies on dermal toxicity suggest that DON has DNA damaging potential leading to skin tumor initiation in mice skin.

Celecoxib reduces Deoxynivalenol induced proliferation, inflammation and protein kinase C translocation via modulating downstream targets in mouse skin.

Exposure to mycotoxins is mostly by ingestion but also occurs by the dermal and inhalation routes. The present study for the first time demonstrated that mycotoxin Deoxynivalenol (DON), permeates through Swiss albino mice skin, which demands awareness of health risks in people who are dermally exposed to mycotoxins especially agricultural farmers. Despite the widespread contamination of DON in food commodities studies to alleviate DON's toxicity are sparsely reported.

Mechanistic exploration of quercetin against metronidazole induced neurotoxicity in rats: Possible role of nitric oxide isoforms and inflammatory cytokines.

Aim: Metronidazole, a nitroimidazole derived antibiotic used to treat many bacterial infections, is reported to penetrate the blood brain barrier after long term administration resulting into neuronal toxicity. Further, quercetin, a polyphenol flavonoid is reported to exhibit neuroprotective activity but its pharmacodynamics interaction against metronidazole induced neurotoxicity. Therefore, the present study was designed to evaluate the postulated mechanism of metronidazole induced neurotoxicity and potential neuroprotective role of quercetin.

LC-ESI-MS/MS method for the simultaneous determination of isoformononetin, daidzein, and equol in rat plasma: Application to a preclinical pharmacokinetic study.

Isoformononetin (methoxy isoflavone) is a potent osteogenic isoflavone abundantly present in Butea monosperma, Pisum sativum, Mung bean, Machaerium villosum, Medicago sativa, and Glycine max. In the current study, an LC-ESI-MS/MS method for the simultaneous evaluation of isoformononetin (IFN), daidzein (DZN) and equol (EQL) was developed and validated in rat plasma using biochanin A as an internal standard. IFN, DZN, and EQL separation was achieved by using acetonitrile and acetic acid (0.

Dopamine receptor activation mitigates mitochondrial dysfunction and oxidative stress to enhance dopaminergic neurogenesis in 6-OHDA lesioned rats: A role of Wnt signalling.

Nigral dopaminergic (DAergic) cell degeneration and depletion of dopamine neurotransmitter in the midbrain are cardinal features of Parkinson's disease (PD). Dopamine system regulates different aspects of behavioural phenotypes such as motor control, reward, anxiety and depression via acting on dopamine receptors (D1-D5). Recent studies have shown the potential effects of dopamine on modulation of neurogenesis, a process of newborn neuron formation from neural stem cells (NSCs).

Neuropharmacokinetics: a bridging tool between CNS drug development and therapeutic outcome.

WHO classified neurological disorders to be among 6.3% of the global disease burden. Among the most central aspects of CNS drug development is the ability of novel molecules to cross the blood-brain barrier (BBB) to reach the target site over a desired time period for therapeutic action.

Bioavailability Enhancement of Poorly Soluble Drugs: The Holy Grail in Pharma Industry.

Background: Bioavailability, one of the prime pharmacokinetic properties of a drug, is defined as the fraction of an administered dose of unchanged drug that reaches the systemic circulation and is used to describe the systemic availability of a drug. Bioavailability assessment is imperative in order to demonstrate whether the drug attains the desirable systemic exposure for effective therapy. In recent years, bioavailability has become the subject of importance in drug discovery and development studies.

Formononetin and biochanin A protects against ritonavir induced hepatotoxicity via modulation of NfκB/pAkt signaling molecules.

Aims: Ritonavir (RIT) is a human immune deficiency virus (HIV) protease inhibitor (PI) active against HIV-1 and HIV-2. Among various adverse effects of PIs, hepatotoxicity is a very common adverse reaction of RIT which is concentration dependent. Red clover isoflavones are found to possess anti-inflammatory, antioxidant and anti-apoptosis activity.

New therapeutic activity of metabolic enhancer piracetam in treatment of neurodegenerative disease: Participation of caspase independent death factors, oxidative stress, inflammatory responses and apoptosis.

Piracetam, a nootropic drug that has been clinically used for decades but remains enigmatic due to no distinct understanding of its mechanism of action. The present study aimed to investigate the role of caspase independent pathway in piracetam mediated neuroprotection. LPS administration caused significant alterations in oxidative stress related parameters like glutathione, glutathione reductase and increased lipid peroxidation.

Development and validation of UPLC-MS/MS assay for quantification of cladrin: Absolute bioavailability and dose proportionality study in rats.

Cladrin, an isoflavone is a major bioactive constituent found in stem bark of Butea monosperma with remarkable osteogenic activity. A speedy and sensitive UPLC coupled tandem mass spectrometry (UPLC-MS/MS) method was developed, validated and successfully applied to bioavailability, blood partitioning, plasma protein binding, intravenous and multiple-dose oral pharmacokinetics of cladrin in rats. Separation was done on C18 column (5.

Therapeutic Targeting of NLRP3 Inflammasomes by Natural Products and Pharmaceuticals: A Novel Mechanistic Approach for Inflammatory Diseases.

Inflammasomes are multiprotein complexes having nucleotide-binding domain and leucine-rich repeat consisting members along with pyrin and HIN domain family. An inflammasome mainly consists of cytoplasmic sensor molecule, such as NLRP3, the adaptor apoptosisassociated speck-like protein containing caspase recruitment domain) protein along with effector procaspase-1. The inflammasome regulates caspase-1 activation, resulting in secretion of interleukin- 1β and interleukin-18.