Agnuside from Vitex negundo L. Attenuates Hepatocellular Lipid Accumulation: Association with the AMPK/SREBP1/FASN/HMGCR/PPARα/UCP2 Signaling Network
4 affiliations
- 1Institute of Advanced Study in Science & Technology , , , ,
- 2Academy of Scientific and Innovative Research (AcSIR) , ,
- 3Tezpur University , , , ,
- 4National Institute of Pharmaceutical Education and Research (NIPER) , , , ,
Abstract
Vitex negundo L. (VN) is a medicinal plant known for its anti-inflammatory and hepatoprotective properties, commonly used as a vegetable in northeastern Indian communities. However, its role in treating nonalcoholic fatty liver disease (NAFLD) is still underexplored. This study evaluates the therapeutic potential of VN and its bioactive compounds in reducing lipid accumulation in CC1 hepatocytes. A crude extract of VN and its n-butanol fraction (VNBU) were tested on palmitate-induced CC1 hepatocytes to evaluate lipid accumulation. Key compounds Agnuside, 5-hydroxy-3,6,7,3́,4́-pentamethoxyflavone, and Vitexilactone were isolated. Agnuside’s effects on lipogenesis, cholesterol accumulation, and fatty acid oxidation were assessed using biochemical assays and Western blot analysis. Molecular docking and dynamics simulations were conducted to explore its interactions with 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Agnuside treatment was associated with reduced lipid accumulation by modulating Adenosine monophosphate-activated protein kinase (AMPK), HMGCR, Sterol regulatory element-binding transcription factor 1 (SREBP1), Fatty acid synthase (FASN), Peroxisome Proliferator-activated receptors (PPARα), and uncoupling protein (UCP2), suggesting a favorable shift in lipid metabolism. Computational studies indicated that Agnuside binds stably to HMGCR, similar to statins. In summary, these findings suggest that VN and Agnuside exert protective effects in hepatocytes, accompanied by favorable shifts in lipid metabolism markers. Further studies are needed to confirm the causal role of this signaling network.
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BibTeX
@article{saikia2026agnuside,
title = {{Agnuside from Vitex negundo L. Attenuates Hepatocellular Lipid Accumulation: Association with the AMPK/SREBP1/FASN/HMGCR/PPARα/UCP2 Signaling Network}},
author = {Abhipsha Saikia and Semim Akhtar Ahmed and Kangkon Saikia and Pranamika Sarma and Devi Basumatary and Ashis K. Mukherjee and Jagat Chandra Borah and Asis Bala},
journal = {ACS Omega},
year = {2026},
month = oct,
doi = {10.1021/acsomega.6c06583},
url = {https://pubs.acs.org/acsodf/article/doi/10.1021/acsomega.6c06583/5460505/Agnuside-from-Vitex-negundo-L-Attenuates},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Agnuside from Vitex negundo L. Attenuates Hepatocellular Lipid Accumulation: Association with the AMPK/SREBP1/FASN/HMGCR/PPARα/UCP2 Signaling Network
AU - Abhipsha Saikia
AU - Semim Akhtar Ahmed
AU - Kangkon Saikia
AU - Pranamika Sarma
AU - Devi Basumatary
AU - Ashis K. Mukherjee
AU - Jagat Chandra Borah
AU - Asis Bala
PY - 2026
DA - 2026/10/28
JO - ACS Omega
DO - 10.1021/acsomega.6c06583
UR - https://pubs.acs.org/acsodf/article/doi/10.1021/acsomega.6c06583/5460505/Agnuside-from-Vitex-negundo-L-Attenuates
AB - Vitex negundo L. (VN) is a medicinal plant known for its anti-inflammatory and hepatoprotective properties, commonly used as a vegetable in northeastern Indian communities. However, its role in treating nonalcoholic fatty liver disease (NAFLD) is still underexplored. This study evaluates the therapeutic potential of VN and its bioactive compounds in reducing lipid accumulation in CC1 hepatocytes. A crude extract of VN and its n-butanol fraction (VNBU) were tested on palmitate-induced CC1 hepatocytes to evaluate lipid accumulation. Key compounds Agnuside, 5-hydroxy-3,6,7,3́,4́-pentamethoxyflavone, and Vitexilactone were isolated. Agnuside’s effects on lipogenesis, cholesterol accumulation, and fatty acid oxidation were assessed using biochemical assays and Western blot analysis. Molecular docking and dynamics simulations were conducted to explore its interactions with 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Agnuside treatment was associated with reduced lipid accumulation by modulating Adenosine monophosphate-activated protein kinase (AMPK), HMGCR, Sterol regulatory element-binding transcription factor 1 (SREBP1), Fatty acid synthase (FASN), Peroxisome Proliferator-activated receptors (PPARα), and uncoupling protein (UCP2), suggesting a favorable shift in lipid metabolism. Computational studies indicated that Agnuside binds stably to HMGCR, similar to statins. In summary, these findings suggest that VN and Agnuside exert protective effects in hepatocytes, accompanied by favorable shifts in lipid metabolism markers. Further studies are needed to confirm the causal role of this signaling network.
SN - 2470-1343
ER -