(S)-Equol is an isoflavone compound produced by the gut microbiota of some individuals, primarily derived from the metabolism of daidzein in soybeans by specific gut bacteria[1]. (S)-Equol exhibits significant estrogenic activity and antioxidant properties, binding to estrogen receptors with an affinity for ERβ of Ki=0.73±0.2nM and for ERα of Ki=6.41±1nM[2]. (S)-Equol also has antioxidant effects, scavenging free radicals in the body to reduce oxidative stress and prevent the development of cardiovascular diseases and certain chronic conditions[3]. (S)-Equol has demonstrated antitumor activity by regulating the cell cycle and inducing apoptosis, inhibiting tumor cell growth and spread, and providing new insights for cancer prevention and adjuvant therapy[4].
In vitro, 30μM (S)-Equol pre-treatment of rat primary chondrocytes for 24h, followed by stimulation with 0.8mM Sodium nitroprusside (SNP; 50μM) for 24h, significantly activated the PI3K/Akt signaling pathway, reducing SNP-induced cell death, oxidative stress, apoptosis, and proteoglycan loss, while inhibiting the expression of matrix metalloproteinases (MMPs) and p53[5]. 0.1-10μM (S)-Equol pre-treatment of rat insulinoma beta cell line INS-1 cells, followed by stimulation with high glucose (26.2mM) for 48h, significantly enhanced insulin secretion, decreased cell apoptosis, and inhibited the Chrebp/Txnip signaling pathway, activating PKA/PP2A activity[6].
In vivo, (S)-Equol (20, 40, 80mg/kg) administered daily via gavage for 12 weeks in a diabetic osteoporosis (DOP) rat model significantly increased bone density, improved bone microstructure, and enhanced bone formation markers while reducing bone resorption markers, ameliorating DOP[7]. (S)-Equol (2mg/kg/d) administered orally daily for 8 weeks in a Sprague–Dawley (SD) rat model of varying degrees of menopausal osteoarthritis (OA) significantly reduced OA pathological damage, oxidative stress, and cartilage matrix degradation[8].
References:
[1] Chen LR, Chen KH. Utilization of Isoflavones in Soybeans for Women with Menopausal Syndrome: An Overview. Int J Mol Sci. 2021 Mar 22;22(6):3212.
[2] Setchell KD, Clerici C, Lephart ED, et al. S-equol, a potent ligand for estrogen receptor beta, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora. Am J Clin Nutr. 2005 May;81(5):1072-9.
[3] Sekikawa A, Wharton W, Butts B, et al. Potential Protective Mechanisms of S-equol, a Metabolite of Soy Isoflavone by the Gut Microbiome, on Cognitive Decline and Dementia. Int J Mol Sci. 2022 Oct 7;23(19):11921.
[4] Zhang J, Ren L, Yu M, et al. S-equol inhibits proliferation and promotes apoptosis of human breast cancer MCF-7 cells via regulating miR-10a-5p and PI3K/AKT pathway. Arch Biochem Biophys. 2019 Sep 15;672:108064.
[5] Huang LW, Huang TC, Hu YC, et al. S-Equol Protects Chondrocytes against Sodium Nitroprusside-Caused Matrix Loss and Apoptosis through Activating PI3K/Akt Pathway. Int J Mol Sci. 2021 Jun 30;22(13):7054.
[6] Chen K, Lang H, Wang L, et al. S-Equol ameliorates insulin secretion failure through Chrebp/Txnip signaling via modulating PKA/PP2A activities. Nutr Metab (Lond). 2020 Jan 14;17:7.
[7] Xu Z, Xu J, Li S, et al. S-Equol enhances osteoblastic bone formation and prevents bone loss through OPG/RANKL via the PI3K/Akt pathway in streptozotocin-induced diabetic rats. Front Nutr. 2022 Oct 21;9:986192.
[8] Hu YC, Huang TC, Huang LW, et al. S-Equol Ameliorates Menopausal Osteoarthritis in Rats through Reducing Oxidative Stress and Cartilage Degradation. Nutrients. 2024 Jul 21;16(14):2364.
(S)-Equol是一种由部分人群肠道微生物产生的异黄烷类化合物，主要来源于大豆中的大豆素在特定肠道菌群的作用下生成[1]。(S)-Equol具有显著的雌激素样活性和抗氧化特性，能够与雌激素受体结合，对ERβ的亲和力为Ki=0.73±0.2nM，对ERα的亲和力为Ki=6.41±1nM[2]。(S)-Equol还具有抗氧化作用，可以清除体内自由基，减少氧化应激损伤，对心血管疾病和某些慢性疾病的发生发展具有一定的预防作用[3]。(S)-Equol还表现出一定的抗肿瘤活性，能够通过调节细胞周期和诱导细胞凋亡等方式，抑制肿瘤细胞的生长和扩散，为癌症的预防和辅助治疗提供了新的思路[4]。
在体外，30μM (S)-Equol预处理大鼠原代软骨细胞24h，随后以0.8mM Sodium nitroprusside（SNP；50μM）刺激24h，(S)-Equol显著激活PI3K/Akt信号通路，减轻SNP诱导的细胞死亡、氧化应激、凋亡以及蛋白多糖丢失，同时抑制基质金属蛋白酶（MMPs）及p53的表达[5]。0.1-10μM (S)-Equol预处理大鼠胰岛β细胞系INS-1细胞，随后以高葡萄糖（26.2mM）刺激48h，(S)-Equol显著增强胰岛素分泌，降低细胞凋亡，同时抑制Chrebp/Txnip信号通路，激活PKA/PP2A活性[6]。
在体内，(S)-Equol（20、40、80mg/kg）每日一次灌胃处理，用于干预糖尿病性骨质疏松症（DOP）大鼠模型12周。(S)-Equol显著提高了大鼠的骨密度，改善了骨微结构，增加了骨形成标志物水平，降低了骨吸收标志物水平，改善DOP[7]。S-Equol（2mg/kg/d）每日一次口服给药，用于干预不同程度绝经后骨关节炎（OA）Sprague–Dawley（SD）大鼠模型8周。S-Equol显著减轻了大鼠模型的骨关节炎病理损伤、氧化应激和软骨基质降解[8]。