Notoginsenoside Ft1 Promotes Fibroblast Proliferation via PI3K/Akt/mTOR Signaling Pathway and Benefits Wound Healing in Genetically Diabetic Mice

Abstract

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 P 2 Y 12 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 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 phosphate-buffered saline (PBS) treatment (15.8 versus 20.9 days). Meanwhile, Ft1 increased the rate of reepithelialization and the amount of granulation tissue at day 7 and day 14. The molecule also enhanced mRNA expressions of COL1A1, COL3A1, transforming growth factor (TGF)-b1 and TGF-b3 and fibronectin, the genes that contributed to collagen expression, fibroblast proliferation, and consequent scar formation. Moreover, Ft1 facilitated the neovascularization accompanied with elevated vascular endothelial growth factor, platelet-derived growth factor, and fibroblast growth factor at either mRNA or protein levels and alleviated the inflammation of infiltrated monocytes indicated by reduced tumor necrosis factor-a and interleukin-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.

Panax Notoginseng Saponins attenuates sevoflurane-induced nerve cell injury by modulating AKT signaling pathway

“…An earlier study reported that PNS alters the activity of PI3K/AKT signaling pathway molecules, and then regulated the cell proliferation and apoptosis (23). In the current study, the results indicated that nerve cells stimulated with sevoflurane had significantly decreased phosphorylation of AKT.…”

Effects of Dietary Supplementation of Lauric Acid on Lactation Function, Mammary Gland Development, and Serum Lipid Metabolites in Lactating Mice

“…The activation of the PI3K/Akt signaling pathway is coupled with regulating the proliferation of various cells [38][39][40]. The PI3K/Akt signaling pathway has effects on regulating mammary gland development [41,42].…”

Total saponins of panaxnotoginseng promotes lymphangiogenesis by activation VEGF-C expression of lymphatic endothelial cells

“…Previously, it was reported that PNS promote wound repair of anterior cruciate ligament through phosphorylation of PI3K, AKT and ERK (Yu et al, 2015), promote osteogenic differentiation of bone marrow stromal cells through the ERK and P38 MAPK (Linares and Gisbert, 2011), and activate PI3K/Akt pathway in cardiomyocytes (Chen et al, 2011). In addition, Its effective components Notoginsenoside R1-mediated neuroprotection through estrogen receptor-dependent crosstalk between Akt and ERK1/2 pathways (Meng et al, 2014), while Notoginsenoside Ft1 promotes fibroblast proliferation via PI3K/Akt/mTOR signaling pathway (Zhang et al, 2015b). Those above results suggested that PNS stimulate ERK, PI3K and P38MAPK signaling pathway to exert biological activity.…”