TY - JOUR T1 - Notoginsenoside Ft1 promotes fibroblast proliferation via PI3K/Akt/mTOR signaling pathway and benefits wound healing in genetically diabetic mice JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther DO - 10.1124/jpet.115.229369 SP - jpet.115.229369 AU - Eryun Zhang AU - Bo Gao AU - Li Yang AU - Xiaojun Wu AU - Zhengtao Wang Y1 - 2015/01/01 UR - http://jpet.aspetjournals.org/content/early/2015/11/13/jpet.115.229369.abstract N2 - Wound healing requires the essential participation of fibroblasts, which is impaired in diabetic foot ulcers (DFU). Notoginsenoside Ft1 (Ft1), a saponin from Panax notoginseng, can enhance platelet aggregation by activating signaling network mediated through P2Y12, and induce proliferation, migration, and tube formation in cultured human umbilical vein endothelial cells. However, whether it can accelerate fibroblast proliferation and benefit wound healing, especially DFU, has not been elucidated. In the present study, on human dermal fibroblast HDF-a, Ft1 increased cell proliferation and collagen production in the presence of high glucose via PI3K/Akt/mTOR signaling pathway. On the excisional wound splinting model established on db/db diabetic mouse, topical application of Ft1 significantly shortened the wound closure time by 5.1 days in contrast with PBS treatment (15.8 days vs. 20.9 days). Meanwhile, Ft1 increased the rate of re-epithelialization and the amount of granulation tissue at day 7 and day 14. The molecule also enhanced mRNA expressions of COL1A1, COL3A1, TGFβ1, TGFβ3 and fibronectin, the genes that contributed to collagen expression, fibroblast proliferation and consecutively scar formation. Moreover, Ft1 facilitated the neovascularization accompanied with elevated VEGF, PDGF and FGF at either mRNA or protein levels, and alleviated the inflammation of infiltrated monocytes indicated by reduced TNF-α and IL- 6 mRNA expressions in the diabetic wounds. Altogether, these results indicated that Ft1 might accelerate diabetic wound healing by orchestrating multiple processes, including promoting fibroblast proliferation, enhancing angiogenesis and attenuating inflammatory response, which provided a great potential application of it in clinics for patients with DFU. ER -