Delving into the Latest Updates on Withanolide A with Synapse

Overview

Basic Info

Drug Type

Chemical drugs

Synonyms-

Target

APP

Action

inhibitors

Mechanism

APP inhibitors(Beta amyloid A4 protein inhibitors)

Therapeutic Areas

Nervous System Diseases

Active Indication

Alzheimer Disease

Inactive Indication-

Originator Organization

Indian Institute of Technology New Delhi

Active Organization

Indian Institute of Technology New Delhi

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Two genes encoding GTs (WsGT4 and WsGT6) from W. somnifera were identified and characterized using Escherichia coli expressed recombinant proteins and in-planta studies. Biochemical assays with recombinant proteins showed that WsGT4 catalyzed product formation using withanolide A, withanolide B, withanone, and 12-deoxywithastramonolide as substrates and UDP-glucose serving as the glucose donor. While, WsGT6 catalyzed the product formation only with withaferin A as a substrate employing either UDP-glucose or UDP-galactose as sugar donors. Quantitative real-time analysis showed that transcripts of WsGT4 and WsGT6 were induced in response to methyl jasmonate treatment and prominent in leaves as compared to other tissues. Modulating the expression of WsGT4 and WsGT6 by virus-induced gene silencing (VIGS) and transient overexpression significantly affected the levels of withanolides and withanosides in the leaves. Furthermore, silencing either WsGT4 or WsGT6 in W. somnifera reduced the tolerance to Pseudomonas syringae DC3000 growth, while their overexpression enhanced the tolerance to the bacterium.

CONCLUSIONS:

Our results indicate the role of WsGT4 and WsGT6 in withanoside biosynthesis and in defense against a bacterial pathogen in W. somnifera. These GTs could be utilized for targeted modulation of withanolides in cell cultures or at the whole-plant level and for enhancing tolerance against bacterial pathogens and improving the yield of withanosides.

01 Oct 2025·ADVANCES IN THERAPY

Superior Bioavailability of a Novel 1.5% Ashwagandha Formulation (Zenroot™): A Randomized, Double-Blind, Single-Dose, Comparative, Oral Bioavailability Study in Healthy Adults

Article

Author: Thomas, Jestin V ; Ramapalaniappan, Abiraamasundari ; Morde, Abhijeet ; Padigaru, Muralidhara ; Patni, Paras ; Loganathan, Vijayakrishnan ; Joshua, Lincy

INTRODUCTION:

Ashwagandha has multiple medicinal properties and is widely used as a supplement to address various health conditions including stress and anxiety. The bioavailability of Ashwagandha bioactives provide critical information on the biological effects in humans after oral supplementation.

METHODS:

A randomized, double-blind, single-dose, cross-over comparative oral bioavailability study was conducted in 20 healthy, adult human subjects under fasting conditions. All subjects consumed single dose of ZEN 1.5 (Zenroot™ Ashwagandha 1.5% 125 mg), ASH 5 (Reference product 1-Ashwagandha 5% 600 mg) and ASH 10 (Reference product 2-Ashwagandha 10% 500 mg) as per a randomization schedule. Blood samples were collected at 0.00 h, and at 00.25, 00.50, 00.75, 01.00, 02.00, 03.00, 04.00, 05.00, 06.00, 09.00, 12.00, and 24.00 h post-dose. Total withanolides (consisting of withanoside IV, withanolide A, 12-deoxywithastramonolide, and withaferin A) were quantified in plasma using the LC-MS/MS method and pharmacokinetics parameters like area under the curve, AUC_0-t, C_max, T_max, t_½ and test/reference (T/R) ratio for test product, ZEN 1.5, versus reference products, ASH 5 and ASH 10, were used for statistical comparisons.

RESULTS:

Subjects in the ZEN 1.5 group showed significantly (P < 0.05) higher total withanolides concentration in plasma at all post-dose time points except 12.00 and 24.00 h compared to ASH 5. In addition, subjects in Ashwagandha ZEN 1.5 group showed significantly higher (P < 0.05) total withanolides concentration in plasma at 0.25, 1.00, 2.00, 3.0, and 4.00 h compared to ASH 10. Further, ZEN 1.5 showed significantly higher bioavailability for total withanolides compared to ASH 5 and ASH 10 with significantly higher (P < 0.05) C_max and AUC_0-t parameters, T/R ratio, and 90% CI. ZEN 1.5 at 125-mg dose showed 2.1-fold higher bioavailability compared to ASH 5 at 600 mg, and 1.3-fold higher bioavailability compared to ASH 10 at 500 mg. ZEN 1.5 was well tolerated during the study period.

CONCLUSION:

A low dose of 125 mg of ZEN 1.5 showed greater total withanolides bioavailability compared to reference products. The C_max and AUC parameters were significantly higher than the 80-125% criteria established by the FDA for bioequivalence confirming superior bioavailability of ZEN 1.5. In addition, ZEN 1.5 was well tolerated by subjects throughout the study duration. Further studies are warranted for evaluating the health benefits of ZEN 1.5.

TRIAL REGISTRATION:

CTRI/2022/11/047039.

01 Aug 2025·Nanomedicine-Nanotechnology Biology and Medicine

Withaferin A and Withanolide A-mediated silver nanoparticles target bacterial motility, metabolism, and stress adaptation in E. coli

Article

Author: Goswami, Anamitra ; Nag, Moupriya ; Mukherjee, Nabanita ; Goswami, Arunava ; Sil, Moumita ; Lahiri, Dibyajit ; Polikarpov, Igor ; Mukherjee, Dipro

Biogenic silver nanoparticles (Bio-AgNPs) were synthesized using Withania somnifera root extract and evaluated for their antimicrobial and biosafety profiles. LC-MS confirmed key withanolides, including Withaferin A. The nanoparticles exhibited a UV-Vis peak at 446 nm, a crystalline core size of ∼15.65 nm, a hydrodynamic diameter of ∼134.85 nm, and a zeta potential of -25.29 mV. Bio-AgNPs showed potent antibacterial activity against Escherichia coli K12, with MICs between 156.25 and 312.5 ppm and superior efficacy to AgNO₃. RNA-seq analysis revealed downregulation of flagellar genes (flgD, flgG, fliC), maltose transporters (malK, malF, lamB), and citrate metabolism (citT, citD), indicating impaired motility and nutrient uptake. Upregulation of metal efflux (cusF, cusB) and electron transport (fixA, fixB) genes reflected oxidative stress response. Cytotoxicity assays on WI-38 and HEK-293 cells showed >80 % viability up to 156.25 ppm. These findings support Bio-AgNPs as biocompatible, plant-derived antimicrobials effective against Gram-negative bacteria.

100 Deals associated with Withanolide A

Login to view more data