Hepatoprotective and pancreatoprotective effects of Arctium lappa root extract in valproic acid–induced toxicity: biochemical, histopathological, and immunohistochemical analysis
- 1Department of Biotechnology, School of Biosciences and Technology, VIT University
Abstract
Introduction: Valproic acid (VPA) is a widely used antiepileptic drug; however, its clinical use is limited by hepatotoxicity and pancreatitis, primarily mediated through oxidative stress and inflammation. Arctium lappa root extract (ALRE) has been reported to possess antioxidant, anti-inflammatory, and cytoprotective properties that may confer protection against VPA-induced organ toxicity.
Methods: Phytochemical profiling of ALRE was performed using GC-MS and HPLC. In vitro cytotoxic effects were assessed in Hep3B and PANC-1 cancer cell lines, while safety was assessed in THLE-2 normal hepatic epithelial cells and H6C7 normal pancreatic ductal epithelial cells using the MTT assay. The hepatoprotective and pancreatoprotective effects were investigated in VPA-induced toxicity in male Wistar albino rats through biochemical, oxidative stress, and histopathological analyses.
Results: ALRE exhibited low cytotoxicity towards THLE-2 and H6C7 cells, with IC50 values of 1,084.92 and 1,174.62 μg/mL, respectively. VPA administration markedly increased serum levels of ALT (127.67 ± 4.34 U/L), AST (153.67 ± 4.91 U/L), ALP (178.67 ± 5.21 U/L), GGT (7.67 ± 0.09 U/L), amylase (47.33 ± 2.91 U/L), and lipase (49.00 ± 3.79 U/L) compared with the control group (p < 0.05). These enzyme levels were considerably lowered by ALRE administration, especially at 500 mg/kg. Furthermore, ALRE restored antioxidant defences (SOD, CAT, and GSH), malondialdehyde levels were decreased, and the histological architecture of the liver and pancreas was improved.
Conclusion: ALRE effectively attenuated VPA-induced hepatic and pancreatic injury through antioxidant and cytoprotective mechanisms while exhibiting minimal toxicity towards normal hepatic and pancreatic cells. These findings support the potential therapeutic application of A. lappa as a natural protective against VPA-associated hepatotoxicity and pancreatitis. Further studies are warranted to elucidate the molecular mechanisms and pharmacokinetic interactions underlying the protective effects of ALRE.
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BibTeX
@article{shyam2026hepatoprotective,
title = {{Hepatoprotective and pancreatoprotective effects of Arctium lappa root extract in valproic acid–induced toxicity: biochemical, histopathological, and immunohistochemical analysis}},
author = {Mukul Shyam and Sabina Evan Prince},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1883451},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1883451/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Hepatoprotective and pancreatoprotective effects of Arctium lappa root extract in valproic acid–induced toxicity: biochemical, histopathological, and immunohistochemical analysis
AU - Mukul Shyam
AU - Sabina Evan Prince
PY - 2026
DA - 2026/10/16
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1883451
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1883451/full
AB - Introduction: Valproic acid (VPA) is a widely used antiepileptic drug; however, its clinical use is limited by hepatotoxicity and pancreatitis, primarily mediated through oxidative stress and inflammation. Arctium lappa root extract (ALRE) has been reported to possess antioxidant, anti-inflammatory, and cytoprotective properties that may confer protection against VPA-induced organ toxicity. Methods: Phytochemical profiling of ALRE was performed using GC-MS and HPLC. In vitro cytotoxic effects were assessed in Hep3B and PANC-1 cancer cell lines, while safety was assessed in THLE-2 normal hepatic epithelial cells and H6C7 normal pancreatic ductal epithelial cells using the MTT assay. The hepatoprotective and pancreatoprotective effects were investigated in VPA-induced toxicity in male Wistar albino rats through biochemical, oxidative stress, and histopathological analyses. Results: ALRE exhibited low cytotoxicity towards THLE-2 and H6C7 cells, with IC50 values of 1,084.92 and 1,174.62 μg/mL, respectively. VPA administration markedly increased serum levels of ALT (127.67 ± 4.34 U/L), AST (153.67 ± 4.91 U/L), ALP (178.67 ± 5.21 U/L), GGT (7.67 ± 0.09 U/L), amylase (47.33 ± 2.91 U/L), and lipase (49.00 ± 3.79 U/L) compared with the control group (p < 0.05). These enzyme levels were considerably lowered by ALRE administration, especially at 500 mg/kg. Furthermore, ALRE restored antioxidant defences (SOD, CAT, and GSH), malondialdehyde levels were decreased, and the histological architecture of the liver and pancreas was improved. Conclusion: ALRE effectively attenuated VPA-induced hepatic and pancreatic injury through antioxidant and cytoprotective mechanisms while exhibiting minimal toxicity towards normal hepatic and pancreatic cells. These findings support the potential therapeutic application of A. lappa as a natural protective against VPA-associated hepatotoxicity and pancreatitis. Further studies are warranted to elucidate the molecular mechanisms and pharmacokinetic interactions underlying the protective effects of ALRE.
SN - 1663-9812
ER -