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Ferulic acid attenuates liver fibrosis and hepatic stellate cell activation via inhibition of TGF-β/Smad signaling pathway.
Drug Des Devel Ther. 2018; 12:4107-4115.DD

Abstract

Purpose

Liver fibrosis is a worldwide health issue. Development of effective new drugs for treatment of this disease is of great importance. This study investigated the therapeutic effects of ferulic acid on liver fibrosis in vitro and in vivo.

Materials and methods

Human hepatic stellate cell line (HSC) LX-2 was used for in vitro assays. Transforming growth factor β1 (TGF-β1) was used to induce hepatic fibrosis in LX-2 cells. Western blot was used to detect protein levels of collagen I, fibronectin, α-smooth muscle actin (SMA), p-Smad2, p-Smad3, p-p38, and p-JNK. Gene expression was measured by RT-qPCR. Fluorescence staining was used to determine localization of Smad4. CCl4-induced hepatic fibrosis in SD rats was used as an in vivo model. Histological features were detected by hematoxylin and eosin staining. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hexadecenoic acid (HA), and hydroxyproline (Hyp) were measured by ELISA.

Results

TGF-β1 treatment significantly increased levels of collagen I, fibronectin, α-SMA, p-Smad2, p-Smad3, and Smad4 in LX-2 cells. Ferulic acid improved TGF-β1-induced hepatic fibrosis via regulation of the TGF-β1/Smad pathway. Consistent with in vitro data, CCl4 caused severe hepatic fibrosis in SD rats, as determined by ALT, AST, HA, and Hyp upregulation. Protein levels of p-Smad2 and p-Smad3 in liver tissues were significantly increased following treatment with CCl4. All CCL4-induced changes were markedly attenuated by ferulic acid treatment.

Conclusion

Ferulic acid potently improved hepatic fibrosis via inhibition of the TGF-β1/Smad pathway in vitro and in vivo. These findings provided evidence for potential use of ferulic acid to treat or prevent liver fibrosis.

Authors+Show Affiliations

Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China, jingyang_1981@126.com; xueke.zhao@yandex.com.Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.Department of Ultrasonography, The Maternity Hospital of Guizhou, Guiyang, Guizhou, China.Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China, jingyang_1981@126.com; xueke.zhao@yandex.com.Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China, jingyang_1981@126.com; xueke.zhao@yandex.com.Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China, jingyang_1981@126.com; xueke.zhao@yandex.com.Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China, jingyang_1981@126.com; xueke.zhao@yandex.com.Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China, jingyang_1981@126.com; xueke.zhao@yandex.com.Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China, jingyang_1981@126.com; xueke.zhao@yandex.com.Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China, jingyang_1981@126.com; xueke.zhao@yandex.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30584275

Citation

Mu, Mao, et al. "Ferulic Acid Attenuates Liver Fibrosis and Hepatic Stellate Cell Activation Via Inhibition of TGF-β/Smad Signaling Pathway." Drug Design, Development and Therapy, vol. 12, 2018, pp. 4107-4115.
Mu M, Zuo S, Wu RM, et al. Ferulic acid attenuates liver fibrosis and hepatic stellate cell activation via inhibition of TGF-β/Smad signaling pathway. Drug Des Devel Ther. 2018;12:4107-4115.
Mu, M., Zuo, S., Wu, R. M., Deng, K. S., Lu, S., Zhu, J. J., Zou, G. L., Yang, J., Cheng, M. L., & Zhao, X. K. (2018). Ferulic acid attenuates liver fibrosis and hepatic stellate cell activation via inhibition of TGF-β/Smad signaling pathway. Drug Design, Development and Therapy, 12, 4107-4115. https://doi.org/10.2147/DDDT.S186726
Mu M, et al. Ferulic Acid Attenuates Liver Fibrosis and Hepatic Stellate Cell Activation Via Inhibition of TGF-β/Smad Signaling Pathway. Drug Des Devel Ther. 2018;12:4107-4115. PubMed PMID: 30584275.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ferulic acid attenuates liver fibrosis and hepatic stellate cell activation via inhibition of TGF-β/Smad signaling pathway. AU - Mu,Mao, AU - Zuo,Shi, AU - Wu,Rong-Min, AU - Deng,Kai-Sheng, AU - Lu,Shuang, AU - Zhu,Juan-Juan, AU - Zou,Gao-Liang, AU - Yang,Jing, AU - Cheng,Ming-Liang, AU - Zhao,Xue-Ke, Y1 - 2018/12/03/ PY - 2018/12/26/entrez PY - 2018/12/26/pubmed PY - 2019/5/29/medline KW - CCl4 KW - Smad signaling pathway KW - TGF-β1 KW - ferulic acid KW - hepatic fibrosis SP - 4107 EP - 4115 JF - Drug design, development and therapy JO - Drug Des Devel Ther VL - 12 N2 - Purpose: Liver fibrosis is a worldwide health issue. Development of effective new drugs for treatment of this disease is of great importance. This study investigated the therapeutic effects of ferulic acid on liver fibrosis in vitro and in vivo. Materials and methods: Human hepatic stellate cell line (HSC) LX-2 was used for in vitro assays. Transforming growth factor β1 (TGF-β1) was used to induce hepatic fibrosis in LX-2 cells. Western blot was used to detect protein levels of collagen I, fibronectin, α-smooth muscle actin (SMA), p-Smad2, p-Smad3, p-p38, and p-JNK. Gene expression was measured by RT-qPCR. Fluorescence staining was used to determine localization of Smad4. CCl4-induced hepatic fibrosis in SD rats was used as an in vivo model. Histological features were detected by hematoxylin and eosin staining. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hexadecenoic acid (HA), and hydroxyproline (Hyp) were measured by ELISA. Results: TGF-β1 treatment significantly increased levels of collagen I, fibronectin, α-SMA, p-Smad2, p-Smad3, and Smad4 in LX-2 cells. Ferulic acid improved TGF-β1-induced hepatic fibrosis via regulation of the TGF-β1/Smad pathway. Consistent with in vitro data, CCl4 caused severe hepatic fibrosis in SD rats, as determined by ALT, AST, HA, and Hyp upregulation. Protein levels of p-Smad2 and p-Smad3 in liver tissues were significantly increased following treatment with CCl4. All CCL4-induced changes were markedly attenuated by ferulic acid treatment. Conclusion: Ferulic acid potently improved hepatic fibrosis via inhibition of the TGF-β1/Smad pathway in vitro and in vivo. These findings provided evidence for potential use of ferulic acid to treat or prevent liver fibrosis. SN - 1177-8881 UR - https://www.unboundmedicine.com/medline/citation/30584275/Ferulic_acid_attenuates_liver_fibrosis_and_hepatic_stellate_cell_activation_via_inhibition_of_TGF_β/Smad_signaling_pathway_ L2 - https://dx.doi.org/10.2147/DDDT.S186726 DB - PRIME DP - Unbound Medicine ER -