Notoginsenoside R2

Notoginsenoside R2 (20(S)-Notoginsenoside R2; Ginsenoside Ng-R2) is an orally active notoginsenoside. Notoginsenoside R2 activates P90RSK and Nrf2 via the MEK1/2-ERK1/2 pathway to inhibit 6-OHDA-induced apoptotic damage in nerve cells. Notoginsenoside R2 upregulates SOX8/β-catenin by reducing miR-27a, thereby suppressing Aβ_25-35-induced neuronal apoptosis and inflammatory responses. Notoginsenoside R2 alleviates lipid accumulation and mitochondrial dysfunction in diabetic nephropathy by inhibiting c-Src. Notoginsenoside R2 alleviates hepatic fibrosis by inducing hepatic stellate cell senescence and inhibiting the inflammatory microenvironment via JAK/STAT3 suppression. Notoginsenoside R2 can be used in research related to Parkinson's disease, Alzheimer's disease, diabetic nephropathy and hepatic fibrosis^{[1][2][3][4][5]}. In Vitro:Notoginsenoside R2 (20 μM; 24 h) protects SH-SY5Y cells against 6-OHDA (HY-B1081)-induced cell death, with reduced counts of TUNEL-positive cells and decreased overall apoptosis rate^[1].
Notoginsenoside R2 (20 μM; 24 h) reduces 6-OHDA-induced LDH release in SH-SY5Y cells, PC12 cells, and primary cortical neurons^[1].
Notoginsenoside R2 (20 μM; 24 h) inhibits 6-OHDA-induced oxidative stress in SH-SY5Y cells, as evidenced by decreased intracellular ROS production and MDA levels, and reverses mitochondrial membrane depolarization in cells^[1].
Notoginsenoside R2 (20 μM) increases the activities of HO-1, GSH-PX and GR in SH-SY5Y cells, and pre-incubation for 24 h reverses the 6-OHDA-induced decreases in the activities of these enzymes and the reduced nuclear accumulation level of Nrf2^[1].
Notoginsenoside R2 (20 μM; 4-24 h) activates the MEK1/2-ERK1/2 signaling pathway in SH-SY5Y cells, thereby inducing the activation of downstream P90RSK and Nrf2. The latter mediates the inhibition of 6-OHDA-induced apoptotic protein expression. Notably, the activation of the aforementioned pathway depends on MEK1/2-ERK1/2 signal transduction, but is independent of JNK, p38 or PI3K/Akt signal transduction^[1].
Notoginsenoside R2 (10-30 μM) dose-dependently attenuates Aβ_25-35 (HY-P0128)-induced apoptosis of primary rat cortical neurons, reduces the expression levels of activated caspase-3 and miR-27a, downregulates COX-2 expression, upregulates the mRNA and protein expression of SOX8, and increases the expression of total β-catenin protein and nuclear β-catenin protein^[2].
Notoginsenoside R2 (10-40 μM; 24 h) attenuates lipid accumulation, oxidative stress, mitochondrial dysfunction and apoptosis in HK-2 cells stimulated with high glucose and palmitic acid (HGPA) by inhibiting c-Src activation^[3].
Notoginsenoside R2 (10-100 μM; 24 h) inhibits the proliferation of HSC-T6 cells^[5].
Notoginsenoside R2 (20-30 μM; 24 h) downregulates the mRNA and protein expressions of α-SMA and COL-I in HSC-T6 cells^[5].
Notoginsenoside R2 (20 μM; 24 h) downregulates fibrosis markers (α-SMA, COL-I, Desmin, TIMP-1) and upregulates senescence markers (p16, p21, p53) in HSC-T6 cells^[5].
Notoginsenoside R2 (20 μM; 24 h) inhibits the JAK/STAT3 signaling pathway in HSC-T6 cells^[5].
Notoginsenoside R2 (20 μM; 24 h) inhibits the mRNA expression of proinflammatory cytokines in HSC-T6 cells^[5].
Notoginsenoside R2 (20 μM; 24 h) upregulates the mRNA expression of SASP components in HSC-T6 cells^[5].
Notoginsenoside R2 (20 μM; 24 h) reduces intracellular ROS levels in HSC-T6 cells^[5].
Notoginsenoside R2 (20 μM; 24 h) induces senescence in HSC-T6 cells^[5]. In Vivo:Notoginsenoside R2 (250 mg/kg, i.p., once daily for 20 consecutive weeks) improves cognitive function, reduces hippocampal neuronal apoptosis, and regulates the expression of apoptosis- and inflammation-related proteins in SAMP8 mice, a spontaneous Alzheimer's disease model^[2].
Notoginsenoside R2 (250 mg/kg; i.p.; once daily; for 20 consecutive weeks) improves cognitive function in Alzheimer's disease rats induced by Aβ_25-35, reduces hippocampal neuronal apoptosis, and regulates the expression of apoptosis- and inflammation-related proteins^[2].
Notoginsenoside R2 (20-40 mg/kg, oral administration daily for 8 weeks) improves renal dysfunction, histopathological damage, lipid accumulation, oxidative stress, mitochondrial dysfunction and apoptosis in db/db mice, a model of diabetic nephropathy. This effect is partially achieved by inhibiting the activation of c-Src^[3].
Notoginsenoside R2 (6.25-25 μM; administered 72 hours after TAA pretreatment) alleviates TAA (HY-Y0698)-induced liver fibrosis in zebrafish in a dose-dependent manner by reducing oxidative stress, suppressing inflammatory responses, and inducing hepatic stellate cell senescence via a STAT3-dependent pathway^[5].