PMID- 38461536 OWN - NLM STAT- Publisher LR - 20240310 IS - 2831-090X (Electronic) IS - 2831-0896 (Linking) DP - 2024 Mar 10 TI - Echinacoside ameliorates hepatic fibrosis and tumor invasion in rats with thioacetamide-induced hepatocellular carcinoma. LID - 10.17305/bb.2024.10367 [doi] AB - 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 alpha-fetoprotein (AFP) and examining liver sections stained with Masson trichrome or anti-transforming growth factor (TGF)-beta1 antibodies. The hepatic expression of mRNA and protein levels of TGF-beta1, beta-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-beta1, beta-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-beta1, beta-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. FAU - Albalawi, Ajwan Z AU - Albalawi AZ AD - PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia. FAU - Alatawi, Areej S AU - Alatawi AS AD - PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia. FAU - Al-Atwi, Shekha M AU - Al-Atwi SM AD - PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia. FAU - Alhwyty, Lama S AU - Alhwyty LS AD - PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia. FAU - Alharbi, Kadi M AU - Alharbi KM AD - PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia. FAU - Alshehri, Shahad A AU - Alshehri SA AD - PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia. FAU - Almarwani, Wasayf A AU - Almarwani WA AD - PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia. FAU - Aljohani, Khulud K AU - Aljohani KK AD - PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia. FAU - Hassan, Hanan M AU - Hassan HM AD - Department of Pharmacology and Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa City, Egypt. FAU - Al-Gayyar, Mohammed M H AU - Al-Gayyar MMH AD - Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia. LA - eng PT - Journal Article DEP - 20240310 PL - Bosnia and Herzegovina TA - Biomol Biomed JT - Biomolecules & biomedicine JID - 9918522188506676 SB - IM EDAT- 2024/03/10 18:42 MHDA- 2024/03/10 18:42 CRDT- 2024/03/10 16:12 PHST- 2024/02/12 00:00 [received] PHST- 2024/03/06 00:00 [accepted] PHST- 2024/03/10 18:42 [medline] PHST- 2024/03/10 18:42 [pubmed] PHST- 2024/03/10 16:12 [entrez] AID - 10.17305/bb.2024.10367 [doi] PST - aheadofprint SO - Biomol Biomed. 2024 Mar 10. doi: 10.17305/bb.2024.10367.