Ginsenoside Rk3

Ginsenoside Rk3 is a rare saponin component extracted from ginseng or Panax notoginseng. Ginsenoside Rk3 possesses diverse biological activities, such as inhibiting TNF-α-induced NF-κB transcriptional activity (IC₅₀=14.24±1.30µM)^[1-2]. Ginsenoside Rk3 is applicable to research related to Alzheimer's disease, cardiovascular diseases, non-alcoholic steatohepatitis, and cancer^[3-4].

In vitro, Ginsenoside Rk3 (5-60µM) was used to treat human liver cancer cells HepG2 and HCC-LM3 for 24 hours. Ginsenoside Rk3 significantly inhibited cell proliferation, induced G1 phase cell cycle arrest, and promoted both autophagy and apoptosis. This action was mediated by the regulation of the PI3K/AKT signaling pathway^[5]. Ginsenoside Rk3 (50-250µM) was used to treat human esophageal cancer cells Eca109 and KYSE150 for 24 or 48 hours. Ginsenoside Rk3 significantly inhibited cell proliferation, induced G1 phase cell cycle arrest, and promoted both apoptosis and autophagy^[6].

In vivo, in a mouse model of Alzheimer's disease (APP/PS1 double transgenic), Ginsenoside Rk3 (1 or 10mg/kg/day; intraperitoneal injection; for one consecutive month) improved spatial learning and memory abilities, reduced Aβ plaque deposition and tau hyperphosphorylation in the brain, inhibited neuronal apoptosis and glial cell activation, and alleviated oxidative stress by activating the AMPK/Nrf2 signaling pathway^[7]. In an obesity-induced colitis model (C57BL/6 mice), Ginsenoside Rk3 (30 or 60mg/kg/day; oral gavage; for 8 consecutive weeks) reduced oxidative stress levels and lipid accumulation in colon tissues, improved colonic mucosal barrier function, and alleviated colon inflammation by regulating intestinal lipid metabolism, downregulated pro-inflammatory metabolic pathways of n-6 polyunsaturated fatty acids (such as the COX and LOX pathways), and upregulated anti-inflammatory metabolic pathways (such as the CYP pathway)^[8].

References:
[1] Cho K, Song SB, Tung NH, et al. Inhibition of TNF-α-Mediated NF-κB Transcriptional Activity by Dammarane-Type Ginsenosides from Steamed Flower Buds of Panax ginseng in HepG2 and SK-Hep1 Cells. Biomol Ther (Seoul). 2014 Jan;22(1):55-61.
[2] Duan Z, Deng J, Dong Y, et al. Anticancer effects of ginsenoside Rk3 on non-small cell lung cancer cells: in vitro and in vivo. Food Funct. 2017 Oct 18;8(10):3723-3736.
[3] Qu L, Ma X, Fan D. Ginsenoside Rk3 Suppresses Hepatocellular Carcinoma Development through Targeting the Gut-Liver Axis. J Agric Food Chem. 2021 Sep 8;69(35):10121-10137.
[4] Guo M, Zhu C, Fu R, et al. Ginsenoside Rk3 Regulates Nonalcoholic Steatohepatitis by Modulation of Intestinal Flora and the PI3K/AKT Signaling Pathway in C57BL/6 Mice. J Agric Food Chem. 2023 Jun 21;71(24):9370-9380.
[5] Qu L, Liu Y, Deng J, et al. Ginsenoside Rk3 is a novel PI3K/AKT-targeting therapeutics agent that regulates autophagy and apoptosis in hepatocellular carcinoma. J Pharm Anal. 2023 May;13(5):463-482.
[6] Liu H, Zhao J, Fu R, et al. The ginsenoside Rk3 exerts anti-esophageal cancer activity in vitro and in vivo by mediating apoptosis and autophagy through regulation of the PI3K/Akt/mTOR pathway. PLoS One. 2019 May 15;14(5):e0216759.
[7] She L, Xiong L, Li L, et al. Ginsenoside Rk3 ameliorates Aβ-induced neurotoxicity in APP/PS1 model mice via AMPK signaling pathway. Biomed Pharmacother. 2023 Feb;158:114192.
[8] Wang W, Chen H, Zhang W, et al. Ginsenoside Rk3 Ameliorates Obesity-Induced Colitis by Modulating Lipid Metabolism in C57BL/6 Mice. J Agric Food Chem. 2024 Feb 14;72(6):2997-3007.

Ginsenoside Rk3是从人参或三七中提取的稀有皂苷成分，具有多种生物学功能，可抑制抑制 TNF-α诱导的NF-κB转录活性（IC₅₀=14.24±1.30µM）^[1-2]。Ginsenoside Rk3可用于阿尔茨海默病、心血管疾病、非酒精性脂肪性肝炎和癌症的相关研究^[3-4]。

在体外，Ginsenoside Rk3（5-60μM）处理人肝癌细胞HepG2和HCC-LM3 24小时，Ginsenoside Rk3通过调节PI3K/AKT信号通路，显著抑制细胞增殖，并将细胞周期阻滞在G1期，同时诱导细胞自噬和凋亡^[5]。Ginsenoside Rk3（50-250μM）处理人食管癌细胞Eca109和KYSE150 24或48小时，Ginsenoside Rk3显著抑制细胞增殖，并诱导G1期细胞周期阻滞、细胞凋亡和自噬^[6]。

在体内，在阿尔茨海默病小鼠（APP/PS1双转基因）模型中，Ginsenoside Rk3（1或10mg/kg/day；腹腔注射；连续1个月）可改善小鼠的空间学习和记忆能力，减少大脑中Aβ斑块沉积和tau蛋白过度磷酸化，抑制神经元凋亡和神经胶质细胞活化，并激活AMPK/Nrf2信号通路以减轻氧化应激^[7]。在肥胖诱导的结肠炎模型（C57BL/6小鼠）中，Ginsenoside Rk3（30或60mg/kg/day；口服灌胃；连续8周）可降低结肠组织的氧化应激水平和脂质积累，改善结肠黏膜屏障功能，并通过调节肠道脂质代谢，下调n-6多不饱和脂肪酸的促炎代谢通路（如COX、LOX途径）和上调抗炎代谢通路（如CYP途径）来减轻结肠炎症^[8]。