Tanshinone IIA alters the transforming growth factor-β1/Smads pathway in angiotensin II-treated rat hepatic stellate cells

Abstract

Objective To investigate the effects of tanshinone IIA on the transforming growth factor-β1 (TGF-β1)/Smads signaling pathway in angiotensin II-treated hepatic stellate cells (HSCs). Methods HSCs were cultured and treated with angiotensin II (10 μM) or angiotensin II (10 μM) plus tanshinone IIA (3, 10, or 30 μM). Cells were incubated for 48 hours and proliferation was determined with the Cell Counting Kit-8. The relative mRNA expression of TGF-β1, Smad4, and Smad7 was measured by quantitative real-time PCR, and the relative protein expression levels were investigated by western blotting. Results After angiotensin II treatment, cell proliferation was significantly accelerated. Furthermore, both the mRNA and protein expression of TGF-β1 and Smad4 was significantly up-regulated, while the mRNA and protein expression of Smad7 was significantly down-regulated compared with the control cells. Tanshinone IIA inhibited the observed effects of angiotensin II in a concentration-dependent manner, with significant inhibition exerted by tanshinone IIA at 10 and 30 μM. Conclusions Angiotensin II promotes the proliferation of HSCs, possibly by regulating the expression of components along the TGF-β1/Smads signaling pathway. Tanshinone IIA inhibits the angiotensin II-induced activation of this pathway, and may, therefore, have preventive and therapeutic effects in liver fibrosis.

Effect of Candesartan and Ramipril on Liver Fibrosis in Patients with Chronic Hepatitis C Viral Infection: A Randomized Controlled Prospective Study

“… 4 , 26 , 27 , 29 Angiotensin II was also reported to upregulate TGF-β1 mRNA expression in Kupffer cells. 29 , 30 Furthermore, there is a positive feedback in the liver, whereas TGF-β1 activates HSCs, and HSCs can produce much more TGF-β1. 31 , 32 Therefore, angiotensin II could promote hepatic fibrosis through activation of HSC via TGF-β1, among the most profibrotic cytokines that accumulate extracellular matrix and its noncollagenous glycoproteins, including HA.…”

Small-molecule natural products for reversing liver fibrosis based on modulation of HSCs activation: an update

“…Malvidin Inducing HSCs apoptosis via the endoplasmic reticulum stress pathway and mitochondrial pathway [192] Pelargonidin Suppressing the ROS-NLRP3-IL-1 β axis via activating the Nrf2 pathway [193] Isoliquiritigenin Alleviates LF through caveolin-1-mediated hepatic stellate cells ferroptosis [194] Kaempferol Regulating miR-26b-5p/Jag1 axis and Notch pathway [195] Dihydroartemisinin [128,196,197] Hesperidin Inhibiting NF-κB/IL-1β/IL-10 and TGFβ/Smad2/3/CTGF signaling pathways [198] Carvacrol Inhibiting TRPM7 and modulating the MAPK signal [199] Small Ellagic Acid Regulates inflammatory mediators to inhibit TGF-β-mediated HSC activation [223] Sulforaphane Through the Nrf2-mediated antioxidant response and acetaldehyde metabolization with inhibition of the LPS/TLR4 signaling pathway [224] Tanshinone IIA Intervening TGFβ/ Smad signaling pathway [225] Protocatechuic acid [265] Byakangelicin [266] Quercetin [267] Gooseberry anthocyanins [268] Naringin (NIN) [268] Germacrone [269] Small-molecule natural products…”

“…Apart from the above-mentioned natural products targeting HSC, natural products involved in the following related mechanisms: (1) Intervening in the TGFβ/Smad signaling pathway. The natural products involved are: Tanshinone IIA [225] , Protocatechuic acid [265] , Byakangelicin [266] , Quercetin [267] , Gooseberry anthocyanins [268] , Naringenin (NIN) [198] , Germacrone [269] , Brevilin A [270] , Curdione [271] , Limonin [272] , Piperlongumine [273] , Conophylline [274] , Apigenin [227] , Sal-B [219] , Taxifolin [275] , Vanillin [275] , Pterostilbene [276] , Sesamol [277] , Chelerythrine [278] , Physalin D [234] . (2) Reduced HSC activation by activating PPAR-g: Methoxyeugenol [226] , Apigenin [227] .…”