Mechanistic Study of Purple Sweet Potato Anthocyanins: Multifaceted Anti-Fibrotic Effects and Targeting of PDGFRβ in Liver Fibrosis

The purple sweet potato anthocyanins (PSPA) are known for their diverse health benefits, yet their hepatoprotective effects and the mechanisms by which they combat liver fibrosis have not been thoroughly investigated. This study aimed to elucidate these effects by employing a carbon tetrachloride (CCl₄)-induced mouse model of liver fibrosis. We conducted a comprehensive analysis of the effects of PSPA on liver injury, oxidative stress, inflammation, and fibrosis-related signaling pathways. Our results demonstrate that PSPA can mitigate liver damage in mice, regulate key antioxidant enzymes such as catalase and SOD, and reduce oxidative stress as indicated by lowered MDA levels. PSPA also decrease the expression of inflammatory proteins, including CD3, CD4, CD45, IL-1β, TNF-α, and IL-17A, and reduce the accumulation of fibrotic markers like type I and III collagens and α-SMA. Additionally, PSPA have demonstrated the ability to inhibit key fibrogenic signaling proteins, including TGFβR2, p-Smad2, p-Smad3, p-PDGFRβ, p-AKT, p-ERK1/2, p-JNK1/2, and p-p38. Furthermore, we identified two potent monomers, PSPA-1 and PSPA-2, which directly target the PDGFRβ, a key player in fibrosis. The mechanism of action involves the inhibition of PDGF-B binding to PDGFRβ, thus disrupting the PDGF-B/PDGFRβ signaling pathway. These findings suggest that the hepatoprotective and antifibrotic effects of PSPA are due to their multifunctional bioactivities and the presence of specific active components that can effectively target fibrogenic protein.