Mechanistic Study\nof Purple Sweet Potato Anthocyanins:\nMultifaceted Anti-Fibrotic Effects and Targeting of PDGFRβ in\nLiver Fibrosis

The purple sweet potato anthocyanins (PSPA) are known\nfor their\ndiverse health benefits, yet their hepatoprotective effects and the\nmechanisms by which they combat liver fibrosis have not been thoroughly\ninvestigated. This study aimed to elucidate these effects by employing\na carbon tetrachloride (CCl<sub>4</sub>)-induced mouse model of liver\nfibrosis. We conducted a comprehensive analysis of the effects of\nPSPA on liver injury, oxidative stress, inflammation, and fibrosis-related\nsignaling pathways. Our results demonstrate that PSPA can mitigate\nliver damage in mice, regulate key antioxidant enzymes such as catalase\nand SOD, and reduce oxidative stress as indicated by lowered MDA levels.\nPSPA also decrease the expression of inflammatory proteins, including\nCD3, CD4, CD45, IL-1β, TNF-α, and IL-17A, and reduce the\naccumulation of fibrotic markers like type I and III collagens and\nα-SMA. Additionally, PSPA have demonstrated the ability to inhibit\nkey fibrogenic signaling proteins, including TGFβR2, p-Smad2,\np-Smad3, p-PDGFRβ, p-AKT, p-ERK1/2, p-JNK1/2, and p-p38. Furthermore,\nwe identified two potent monomers, PSPA-1 and PSPA-2, which directly\ntarget the PDGFRβ, a key player in fibrosis. The mechanism of\naction involves the inhibition of PDGF-B binding to PDGFRβ,\nthus disrupting the PDGF-B/PDGFRβ signaling pathway. These findings\nsuggest that the hepatoprotective and antifibrotic effects of PSPA\nare due to their multifunctional bioactivities and the presence of\nspecific active components that can effectively target fibrogenic\nprotein.