Elucidation of plasma protein binding, blood partitioning, permeability, CYP phenotyping and CYP inhibition studies of Withanone using validated UPLC method: An active constituent of neuroprotective herb Ashwagandha

Singh, Sandeep K.; Valicherla, Guru R.; Bikkasani, Anil Kumar; Cheruvu, Srikanth H.; Hossain, Zakir; Taneja, Isha; Ahmad, Hafsa; Raju, K. Kanaka; Sangwan, Rajender Singh; Singh, Shio Kumar; Dwivedi, Anil Kumar; Wahajuddin, Mohammad; Gayen, Jiaur R.

doi:10.1016/j.jep.2021.113819

Cited by 14 publications

(6 citation statements)

References 48 publications

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“…None of the extracts inhibited β-esterase-dependent rifampicin metabolism in HLM or induced mRNA of CYP2B6 or CYP3A4 in HepG2 cells. In a detailed biopharmaceutical study of withanone, the compound was found to have IC 50 values >100 µM for CYP2C9/11 in rat and human liver microsomes and IC 50 values between 28.5 and 80 µM for other CYP isoenzymes (the lowest being 28.5 µM for CYP3A4 in human liver microsomes) [ 162 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Withania somnifera (Ashwagandha) on Stress and the Stress- Related Neuropsychiatric Disorders Anxiety, Depression, and Insomnia

Speers

Cabey

Soumyanath

et al. 2021

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Background: Withania somnifera (WS), also known as Ashwagandha, is commonly used in Ayurveda and other traditional medicine systems. WS has seen an increase in public use worldwide due to its reputation as an adaptogen. This popularity has elicited increased scientific study of its biological effects, including a potential application for neuropsychiatric and neurodegenerative disorders. Objective: This review aims to provide a comprehensive summary of preclinical and clinical studies examining the neuropsychiatric effects of WS, specifically its application in stress, anxiety, depression, and insomnia. Methods: Reports of human trials and animal studies of WS were collected primarily from the PubMed, Scopus, and Google Scholar databases. Results: WS root and leaf extracts exhibited noteworthy anti-stress and anti-anxiety activity in animal and human studies. WS also improved symptoms of depression and insomnia, though fewer studies investigated these applications. WS may alleviate these conditions predominantly through modulation of the hypothalamic-pituitary-adrenal and sympathetic-adrenal medullary axes, as well as through GABAergic and serotonergic pathways. While some studies link specific withanolide components to its neuropsychiatric benefits, there is evidence for the presence of additional yet unidentified active compounds in WS. Conclusion: While benefits were seen in the reviewed studies, significant variability in the WS extracts examined prevents a consensus on the optimum WS preparation or dosage from treating neuropsychiatric conditions. WS generally appears safe for human use; however, it will be important to investigate potential herb-drug interactions involving WS if used alongside pharmaceutical interventions. Further elucidation of active compounds of WS is also needed.

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Section: Discussionmentioning

confidence: 99%

Effects of Withania somnifera (Ashwagandha) on Stress and the Stress- Related Neuropsychiatric Disorders Anxiety, Depression, and Insomnia

Speers

Cabey

Soumyanath

et al. 2021

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“…Moreover, it was found that WS is predominantly active against many neurological conditions like AD, Parkinson's disease, and Huntington's disease [144,145]. Furthermore, the plant contains the active ingredient withanone, which has extraordinary pharmacological and neurological effects [146]. Ashwagandha has an ancient legacy of application in traditional medicine to improve memory and cognitive function.…”

Section: Convolvulus Pluricaulismentioning

confidence: 99%

Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights

Nagori,

Nakhate,

Yadav

et al. 2023

Future Pharmacology

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Alzheimer’s disease (AD) is a progressive, multifactorial, and unremitting neurodegenerative disease characterized by memory loss, personality changes, and cognitive impairment. It has become more prevalent in recent years. Therefore, understanding the pathophysiology of AD and developing efficient therapeutic strategies are essential. Moreover, the progression of the disease is unaffected by the pharmaceutical approaches discovered to date. Additionally, the failure of over 200 potential drug candidates in clinical trials over the past decade suggests the complexity and difficulty of both the disease and its underlying causes. Therefore, research focused on medicinal plant-based natural products in the search for novel neuroprotective therapeutic candidates for AD is essential. Indeed, several scientific investigations have demonstrated the efficacy of many medicinal plants and their principal phytochemicals in the treatment of AD. This review article covered the pathophysiological mechanisms of AD, the necessity for natural products as anti-AD treatments, and the most recent preclinical studies revealing the function of neuroprotective medicinal plants and their bioactive compounds in the effective management of AD. In addition, the review also presents clinical trial data of promising anti-AD formulations/agents of plant origin. Revealing recent findings and highlighting the clinical trial data related to the development of new treatments for AD would promote further research in this field and pave the way for the development of more effective and safe treatments for this debilitating disease.

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“…A total of 100 µL samples were aliquoted at predetermined time points (0, 5, 15, 30, 60, 90, 120 and 240 min), followed by SPE processing and analyzed using the validated LC-MS/MS method. The plasma stability was determined as the % drug remaining at different time points relative to the drug at 0 min [19].…”

Section: Plasma Stability Studymentioning

confidence: 99%

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

Valicherla

Katekar²,

Dadge³

et al. 2022

Molecules

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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. Samples were analyzed using the validated LC-MS/MS method. The solubility of PSTi8 was found to be 9.30 and 25.75 mg/mL in simulated gastric and intestinal fluids, respectively. The protein binding of PSTi8 was estimated as >69% in rat plasma. PSTi8 showed high stability in rat plasma and liver microsomes and the blood–plasma partitioning was >2. The bioavailability of PSTi8 after intraperitoneal and subcutaneous administration was found to be 95.00 ± 12.15 and 78.47 ± 17.72%, respectively, in rats. PSTi8 showed non-linear PK in dose proportionality studies, and has no gender difference in the PK behavior in rats. The high bioavailability of PSTi8 can be due to high water solubility and plasma protein binding, low clearance and volume of distribution. Our in vitro and in vivo findings support the development of PSTi8 as an antidiabetic agent.

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Elucidation of plasma protein binding, blood partitioning, permeability, CYP phenotyping and CYP inhibition studies of Withanone using validated UPLC method: An active constituent of neuroprotective herb Ashwagandha

Cited by 14 publications

References 48 publications

Effects of Withania somnifera (Ashwagandha) on Stress and the Stress- Related Neuropsychiatric Disorders Anxiety, Depression, and Insomnia

Effects of Withania somnifera (Ashwagandha) on Stress and the Stress- Related Neuropsychiatric Disorders Anxiety, Depression, and Insomnia

Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights

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

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