Echinacoside ameliorates hepatic fibrosis and tumor invasion in rats with thioacetamide-induced hepatocellular carcinoma

Ajwan Z Albalawi; Areej S Alatawi; Shekha M Al-Atwi; Lama S Alhwyty; Kadi M Alharbi; Shahad A Alshehri; Wasayf A Almarwani; Khulud K Aljohani; Hanan M Hassan; Mohammed M H Al-Gayyar

doi:10.17305/bb.2024.10367

Authors

Ajwan Z Albalawi PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia https://orcid.org/0009-0004-8327-8418
Areej S Alatawi PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia https://orcid.org/0009-0009-5650-2716
Shekha M Al-Atwi PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia https://orcid.org/0009-0008-1225-8531
Lama S Alhwyty PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia
Kadi M Alharbi PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia https://orcid.org/0009-0003-6064-0923
Shahad A Alshehri PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia https://orcid.org/0009-0006-6521-5186
Wasayf A Almarwani PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia https://orcid.org/0009-0008-4553-1100
Khulud K Aljohani PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia https://orcid.org/0009-0000-3819-6414
Hanan M Hassan Department of Pharmacology and Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa City, Egypt https://orcid.org/0000-0003-0464-0809
Mohammed M H Al-Gayyar Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia https://orcid.org/0000-0003-4777-3919

DOI:

https://doi.org/10.17305/bb.2024.10367

Keywords:

β-catenin, cellular communication network factor 2 (CCN2), E-cadherin, echinacoside, fascin, matrix metalloproteinase-9 (MMP9), mammalian target of rapamycin (mTOR), phosphoinositide 3-kinases (PI3K), platelets derived growth factor (PDGF)-B, transforming growth factor (TGF)-β1

Abstract

Hepatocellular carcinoma (HCC) affects approximately 800,000 individuals globally each year. Despite advancements in HCC treatments, there is still a pressing need to identify new drugs that can combat resistance. One potential option is echinacoside, a natural caffeic acid glycoside with antioxidant, anti-inflammatory, antidepressant, and antidiabetic properties. Therefore, we aimed to investigate the ability of echinacoside to exhibit antitumor activity against HCC in rats through ameliorating hepatic fibrosis and tumor invasion. Rats were given thioacetamide to induce HCC, and some were given 30 mg/kg of echinacoside twice a week for 16 weeks. The liver impairment was assessed by measuring serum α-fetoprotein (AFP) and examining liver sections stained with Masson trichrome or anti-transforming growth factor (TGF)-β1 antibodies. The hepatic expression of mRNA and protein levels of TGF-β1, β-catenin, SMAD4, matrix metalloproteinase-9 (MMP9), phosphoinositide 3-kinases (PI3K), mammalian target of rapamycin (mTOR), connective tissue growth factor 2 (CCN2), E-Cadherin, platelets derived growth factor (PDGF)-B and fascin were also analyzed. Echinacoside improved the survival rate of rats by decreasing serum AFP and the number of hepatic nodules. Examination of micro-images indicated that echinacoside can reduce fibrosis. It also significantly decreased the expression of TGF-β1, β-catenin, SMAD4, MMP9, PI3K, mTOR, CCN2, PDGF-B, and fascin while enhancing the expression of E-Cadherin. In conclusion, echinacoside exhibits a protective effect against HCC by increasing survival rates and decreasing tumor growth. It also acts as an inhibitor of the hepatic tissue fibrosis pathway by reducing the expression of TGF-β1, β-catenin, SMAD4, PI3K, CCN2, PDGF-B and mTOR. Additionally, it prevents tumor invasion by suppressing MMP9 and fascin, and increasing the expression of E-Cadherin.