Notoginsenoside Ft1

NotoginsenosideFt1 is a saponin found in Panax notoginseng. Notoginsenoside Ft1 inhibits the PI3K/AKT/mTOR signaling pathway, activates the p38 MAPK and ERK1/2 signaling pathways, and increases the proportion of CD8⁺ T cells, thereby inducing apoptosis and lysosomal cell death in various cancer cells, and promoting angiogenesis. Notoginsenoside Ft1 causes vasodilation by activating glucocorticoid receptors (GR) and estrogen receptor beta (ERβ) in endothelial cells. Notoginsenoside Ft1 increases intracellular Ca²⁺ accumulation, reduces cAMP levels by activating a signaling network mediated through P2Y₁₂ receptors, and promotes platelet aggregation, thereby exerting a procoagulant effect. Notoginsenoside Ft1 inhibits ferroptosis (ferroptosis) in renal tubular epithelial cells by activating the TGR5 receptor, thereby demonstrating a renal protective effect. Notoginsenoside Ft1 acts as a TGR5 agonist and an FXR antagonist to combat obesity and insulin resistance^{[1][2][3][4][5][6][7][8]}. In Vitro:Notoginsenoside Ft1 (0-10 μM, 0-48 h) significantly promotes HUVECs proliferation and migration, promotes the transition of the cell cycle from G1 to S phase, significantly promotes the formation of tubular structures of HUVECs, and promotes VEGF expression and secretion by inhibiting the PI3K/AKT/mTOR pathway and the Raf/MEK/ERK pathway^[1].
Notoginsenoside Ft1 (0-250 μM) promotes platelet aggregation in a dose-dependent manner in Wistar rats (EC₅₀ = 56.42 μM) and exhibits comprehensive procoagulant effects in both human (240 μg/mL, 5 min) and rat plasma (80 μg/mL, 5 min), affecting extrinsic and common coagulation pathways^[2].
Notoginsenoside Ft1 (56.4 μM) induces an increase in intracellular Ca^²⁺ in platelets and P2Y12-HEK293 cells, significantly inhibits the production of cAMP and induces the phosphorylation of PI3K and Akt^[2].
Notoginsenoside Ft1 (1 nM-10 mM, 30 min) stimulates endothelial GRs and ERbs with subsequent activation of the PI3K/Akt and ERK1/2 pathways in rat mesenteric arteries, resulting in phosphorylation of eNOS and the release of NO, which activates soluble guanylyl cyclase in the vascular smooth muscle cells leading to vasodilatation^[3].
Notoginsenoside Ft1 (0.1-100 μM, 24 h) inhibits the proliferation of SH-SY5Y cells (IC₅₀ = 45 μM), causes cell cycle arrest and induces apoptosis involving regulating the p38 MAPK and ERK1/2 pathways^[4].
Notoginsenoside Ft1 (0.1-10 μM, 0.5-24 h) significantly activates the luciferase activity of TGR5 and increases the level of cAMP in Tgr5-HEK293 cells and promotes the secretion of GLP-1 in NCI-H716 cells^[5].
Notoginsenoside Ft1 (10 μM, 24 h) significantly inhibits the FXR target genes in Caco-2 cells and inhibits the FXR activity induced by GW4064 (HY-50108) in HEK293T cells^[5].
Notoginsenoside Ft1 (10 μM, 24 h) has inhibitory effects on HepG2 (IC₅₀ = 46.3 μM), Huh7 (IC₅₀ = 35.2 μM), and PLC/PRF/5 (IC₅₀ = 58.9 μM) cells, but not on THLE-2 (IC₅₀ = 82.2 μM) cells^[6].
Notoginsenoside Ft1 (12.5-50 μM, 12-24 h) induces apoptosis by inhibiting the PI3K/AKT/mTOR pathway and promotes lysosomal cell death by activating TFEB in HepG2 cells^[6].
Notoginsenoside Ft1 (0-100 μM, 24 h-14 d) inhibits the growth of MC38, CT26, HT29 cell with IC₅₀ of 32.87, 30.75 and 27.59 μM, inhibits clone formation of MC38 cells and significantly inhibits the migration ability of MC38 and CT26 cells and inhibits colony number^[7].
Notoginsenoside Ft1 (5 μM, 24 h) successfully inhibits the ferroptosis model in HK2 cells, as demonstrated by increased cell viability, suppressed ROS accumulation, improved mitochondrial dysfunction, and altered expression of ferroptosis marker proteins^[8].
In Vivo:Notoginsenoside Ft1 (1-25 μM for Matrigel plug assay and 0.25-25 mg/kg for ear wound healing assay, i.p., single dose and every other day for 28 days, respectively) promotes the formation of blood vessels in Matrigel plug and wound healing in mice^[1].
Notoginsenoside Ft1 (1.25 mg/kg, i.v., single dose) significantly increases thrombosis and shortens the bleeding time in Wistar rats^[2].
Notoginsenoside Ft1 (50-100 mg/100 g diet, p.o., for 6 weeks) ameliorates obesity, improves glucose disorder in high fat diet (HFD) mice by activating Tgr5 and enhances hepatic bile acids (BA) synthesis by antagonizing FXR^[5].
Notoginsenoside Ft1 (25-50 mg/kg, p.o., once daily for 3 weeks) shows anti-cancer effects in HepG2 xenograft tumor mice model^[6].
Notoginsenoside Ft1 (10-30 mg/kg, i.p., once daily for 24 days) markedly inhibits subcutaneous tumor formation in colorectal cancer (CRC) and enhances the proportion of CD8⁺ T cells in tumor-bearing mice, thus restraining tumor growth^[7].
Notoginsenoside Ft1 controls blood sugar in mice, reduces renal tubular damage, and intervenes in the occurrence of renal ferroptosis by activating the JUN signaling pathway^[8].