Comparative evaluation of antifibrotic activity of Salvadora persica extracts in CCl4-induced liver fibrosis in rats by reducing oxidative stress and inflammation via transcriptional modulation associated with TGF-β1/Smad signaling pathway
7 affiliations
- 1Faculty of Medicine, Qilu Institute of Technology
- 2Department of Chemistry, College of Science, King Saud University
- 3Faculty of Medicine and Allied Health Sciences, The Islamia University of Bahawalpur
- 4Department of Zoology, Division of Science and Technology, University of Education
- 5College of Pharmacy, University of Sargodha
- 6Department of Eastern Medicine, Government College University Faisalabad
- 7College of Medicine, Qatar University
Abstract
Plant Salvadora persica (SP) is well-known for its pharmacological activities, including its role in oral hygiene. In the present study, we investigated, the in vivo comparative hepatoprotective potential of SP root extracts against chronic liver injury fibrosis. In Wistar albino rats, liver fibrosis was induced by intraperitoneal injection of carbon tetrachloride (CCl4) in olive oil (1:1 v/v) at 1 mL/kg, twice weekly for 9 weeks. Liver damage was evaluated by measuring serum liver biochemical parameters, antioxidant enzyme levels, and lipid peroxidation marker in liver homogenate. The mRNA expression level of inflammatory and profibrotic markers in liver tissue and histopathology of liver tissue by H&E staining and collagen deposition by Masson’s trichrome, and Van Gieson’s staining were determined. SP extracts, including aqueous (SP-AQ), ethanolic (SP-E), and petroleum ether (SP-PE), were analyzed by Gas Chromatography-Mass Spectrometry (GC-MS), followed by multivariate principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). The findings demonstrated that SP extracts demonstrated significant hepatoprotective effects by improving rats’ body weight without significant increase in liver index, reducing liver biochemical markers, and reducing oxidative stress by increasing SOD and GPx levels and decreasing MDA level. In liver tissue, the mRNA expression levels of the inflammatory markers IL-1β, IL-6, and TNF-α and profibrotic markers TGF-β1, Smad2, Smad3, α-SMA, and Collagen1A1 were downregulated by modulating the genes expression levels related with the TGF-β1/Smad signaling pathway. Histopathology showed recovery from liver damage and reduced collagen deposition. Comparatively, antifibrotic activity was greater by SP-PE, modest by SP-E and lowest by SP-AQ extracts. Furthermore, phytochemical analysis of the SP extracts demonstrated considerable diversity in their phytoconstituent profiles due to difference in solvent polarity, with PCA and PLS-DA analyses confirming distinct clustering and discrimination among SP extracts. SP-PE extract, greater efficacy can be attributed to selection of a non-polar solvent and 4-propenyl-2,6-dimethoxyphenol, along with other dominant phytochemicals, which exerted synergistic biological effects. The SP extracts showed significant hepatoprotective activity with consistent biological effects in reducing oxidative stress, inflammation, and fibrosis in CCl4-induced liver fibrosis in rats. However, further studies of major individual compounds of SP-PE are warranted for clinical use in liver fibrosis.
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BibTeX
@article{latif2026comparative,
title = {{Comparative evaluation of antifibrotic activity of Salvadora persica extracts in CCl4-induced liver fibrosis in rats by reducing oxidative stress and inflammation via transcriptional modulation associated with TGF-β1/Smad signaling pathway}},
author = {Fouzia Latif and Bilal Ahmed and Hamad Z. Alkhathlan and Muhammad Saad Majeed and Afia Muhammad Akram and Qurat-ul-ain Ahmad and Shehla Akbar and Sabira Sultana and Hailing Ding and Farhan Sachal Cyprian and Merajuddin khan},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1900981},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1900981/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Comparative evaluation of antifibrotic activity of Salvadora persica extracts in CCl4-induced liver fibrosis in rats by reducing oxidative stress and inflammation via transcriptional modulation associated with TGF-β1/Smad signaling pathway
AU - Fouzia Latif
AU - Bilal Ahmed
AU - Hamad Z. Alkhathlan
AU - Muhammad Saad Majeed
AU - Afia Muhammad Akram
AU - Qurat-ul-ain Ahmad
AU - Shehla Akbar
AU - Sabira Sultana
AU - Hailing Ding
AU - Farhan Sachal Cyprian
AU - Merajuddin khan
PY - 2026
DA - 2026/10/08
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1900981
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1900981/full
AB - Plant Salvadora persica (SP) is well-known for its pharmacological activities, including its role in oral hygiene. In the present study, we investigated, the in vivo comparative hepatoprotective potential of SP root extracts against chronic liver injury fibrosis. In Wistar albino rats, liver fibrosis was induced by intraperitoneal injection of carbon tetrachloride (CCl4) in olive oil (1:1 v/v) at 1 mL/kg, twice weekly for 9 weeks. Liver damage was evaluated by measuring serum liver biochemical parameters, antioxidant enzyme levels, and lipid peroxidation marker in liver homogenate. The mRNA expression level of inflammatory and profibrotic markers in liver tissue and histopathology of liver tissue by H&E staining and collagen deposition by Masson’s trichrome, and Van Gieson’s staining were determined. SP extracts, including aqueous (SP-AQ), ethanolic (SP-E), and petroleum ether (SP-PE), were analyzed by Gas Chromatography-Mass Spectrometry (GC-MS), followed by multivariate principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). The findings demonstrated that SP extracts demonstrated significant hepatoprotective effects by improving rats’ body weight without significant increase in liver index, reducing liver biochemical markers, and reducing oxidative stress by increasing SOD and GPx levels and decreasing MDA level. In liver tissue, the mRNA expression levels of the inflammatory markers IL-1β, IL-6, and TNF-α and profibrotic markers TGF-β1, Smad2, Smad3, α-SMA, and Collagen1A1 were downregulated by modulating the genes expression levels related with the TGF-β1/Smad signaling pathway. Histopathology showed recovery from liver damage and reduced collagen deposition. Comparatively, antifibrotic activity was greater by SP-PE, modest by SP-E and lowest by SP-AQ extracts. Furthermore, phytochemical analysis of the SP extracts demonstrated considerable diversity in their phytoconstituent profiles due to difference in solvent polarity, with PCA and PLS-DA analyses confirming distinct clustering and discrimination among SP extracts. SP-PE extract, greater efficacy can be attributed to selection of a non-polar solvent and 4-propenyl-2,6-dimethoxyphenol, along with other dominant phytochemicals, which exerted synergistic biological effects. The SP extracts showed significant hepatoprotective activity with consistent biological effects in reducing oxidative stress, inflammation, and fibrosis in CCl4-induced liver fibrosis in rats. However, further studies of major individual compounds of SP-PE are warranted for clinical use in liver fibrosis.
SN - 1663-9812
ER -