(20S)-Protopanaxatriol is a metabolite derived from ginsenosides, possessing diverse biological activities and pharmacological effects[1]. (20S)-Protopanaxatriol functions by binding to glucocorticoid receptors and estrogen receptors, and can inhibit the activity of liver X receptor alpha[2]. (20S)-Protopanaxatriol is capable of modulating cellular glycolysis levels[3], and exhibits significant anti-cancer properties by effectively suppressing cancer progression[4].
In vitro, treatment of triple-negative breast cancer cell lines SUM-159-PT and MDA-MB-231 with (20S)-Protopanaxatriol (20-60μM) for 24-48 hours significantly inhibited cell proliferation and migration, while inducing non-protective autophagy and apoptosis[5]. When differentiating 3T3-L1 preadipocytes were treated with (20S)-Protopanaxatriol (10μM) for 7 days, (20S)-Protopanaxatriol markedly promoted adipocyte differentiation and lipid accumulation, concurrently activating the transcriptional activity of peroxisome proliferator-activated receptor gamma[6].
In vivo, oral administration of (20S)-Protopanaxatriol (10mg/kg and 20mg/kg) once daily for three consecutive days in TNBS-induced colitis mice significantly suppressed colon shortening and myeloperoxidase activity, while reducing the expression of pro-inflammatory cytokines[7]. In tumor-bearing mice inoculated with H1975-luc cells, daily intraperitoneal injection of (20S)-Protopanaxatriol (1mg/kg/day) in combination with Gefitinib (50mg/kg/day) resulted in significant inhibition of tumor growth and reversal of EGFR-TKI resistance[8].
References:
[1] Sun H, Ye Y, Pan Y. Immunological-adjuvant saponins from the roots of Panax notoginseng. Chem Biodivers. 2005 Apr;2(4):510-5.
[2] Oh GS, Yoon J, Lee GG, et al. 20(S)-protopanaxatriol inhibits liver X receptor α-mediated expression of lipogenic genes in hepatocytes. J Pharmacol Sci. 2015 Jun;128(2):71-7.
[3] Li J, Liu T, Zhao L, et al. Ginsenoside 20(S)‑Rg3 inhibits the Warburg effect through STAT3 pathways in ovarian cancer cells. Int J Oncol. 2015 Feb;46(2):775-81.
[4] Saw CL, Yang AY, Cheng DC, et al. Pharmacodynamics of ginsenosides: antioxidant activities, activation of Nrf2, and potential synergistic effects of combinations. Chem Res Toxicol. 2012 Aug 20;25(8):1574-80.
[5] Li Y, Wang P, Zou Z, et al. Ginsenoside (20S)-protopanaxatriol induces non-protective autophagy and apoptosis by inhibiting Akt/mTOR signaling pathway in triple-negative breast cancer cells. Biochem Biophys Res Commun. 2021 Dec 17;583:184-191.
[6] Liu Y, Guo X, Wu L, et al. Lipid rafts promote liver cancer cell proliferation and migration by up-regulation of TLR7 expression. Oncotarget. 2016 Sep 27;7(39):63856-63869.
[7] Lee SY, Jeong JJ, Eun SH, et al. Anti-inflammatory effects of ginsenoside Rg1 and its metabolites ginsenoside Rh1 and 20(S)-protopanaxatriol in mice with TNBS-induced colitis. Eur J Pharmacol. 2015 Sep 5;762:333-43.
[8] Huang Q, Wang Q, Li D, et al. Co-administration of 20(S)-protopanaxatriol (g-PPT) and EGFR-TKI overcomes EGFR-TKI resistance by decreasing SCD1 induced lipid accumulation in non-small cell lung cancer. J Exp Clin Cancer Res. 2019 Mar 15;38(1):129.
(20S)-Protopanaxatriol是一种来源于人参皂苷的代谢产物，具有多种生物活性和药理作用[1]。(20S)-Protopanaxatriol 可以通过结合糖皮质激素受体和雌激素受体发挥作用，并且能够抑制肝脏X受体α的活性[2]。(20S)-Protopanaxatriol能够调节细胞的糖酵解水平[3]。(20S)-Protopanaxatriol还具有抗良好的抑制癌症发展的作用[4]。
在体外，(20S)-Protopanaxatriol(20-60μM)处理三阴性乳腺癌细胞系SUM-159-PT和MDA-MB-231细胞24-48小时，能够显著抑制细胞增殖和迁移能力，并诱导非保护性自噬和细胞凋亡[5]。(20S)-Protopanaxatriol(10μM) 处理分化中的3T3-L1前脂肪细胞7天，能够显著促进脂肪细胞分化和脂质积累，同时激活过氧化物酶体增殖物激活受体γ的转录活性[6]。
在体内，(20S)-Protopanaxatriol (10mg/kg和20mg/kg) 每日一次口服给药，连续3天处理TNBS诱导的结肠炎小鼠，能够显著抑制结肠缩短和髓过氧化物酶活性，并降低促炎细胞因子的表达[7]。(20S)-Protopanaxatriol(1mg/kg/day) 联合Gefitinib (50mg/kg/day) 每日一次腹腔注射，用于处理接种H1975-luc细胞的荷瘤小鼠，(20S)-Protopanaxatriol能够显著抑制肿瘤生长并逆转EGFR-TKI耐药性[8]。