Rehmannioside A is an inhibitor of cytochrome P450 enzymes (CYP3A4, 2C9, and 2D6), with IC50 values of 10.08, 12.62, and 16.43μM, respectively[1]. Rehmannioside A is an iridoid glycoside isolated from Rehmanniae radix, possessing various biological activities including anti-inflammatory, antioxidant, anti-apoptotic, and neuroprotective effects[2, 3].
In vitro, treatment of mouse osteoblast cell lines (MC3T3-E1 cells) with Rehmannioside A (10-300µM) for 24h significantly improved the survival rate of dexamethasone-exposed osteoblasts at 50-200µM, and promoted the activation of the PI3K/AKT signaling pathway in MC3T3-E1 cells[4]. Treatment of HK2 cells with Rehmannioside A (20-80µM) for 24h significantly improved the survival rate of high glucose (HG)-induced HK2 cells, inhibited apoptosis and oxidative stress, and suppressed the activation of the intracellular MAPK pathway[5].
In vivo, Rehmannioside A (40, 80mg/kg) administered intraperitoneally to rats with vascular dementia (VD) for 14 days dose-dependently reduced the overexpression of TUNEL-positive cells, active Caspase-3, PARP, and cytochrome c in the hippocampus[6]. Oral administration of Rehmannioside A (5, 15, 45mg/kg) to 5×FAD mice significantly improved learning, memory, and cognitive function, reduced the accumulation of Aβ plaques in the hippocampus, reduced the number of microglia, increased the expression of PSD 95 and synaptophysin-1 proteins, and alleviated oxidative stress and inflammation[7].
References:
[1] Wang C, Zhou N, Li M, et al. Rehmannioside A inhibits the activity of CYP3A4, 2C9 and 2D6 in vitro[J]. Xenobiotica, 2024, 54(4): 195-200.
[2] Zhao K, Zhu H, Zheng L, et al. Harnessing the multi-targeted potential of rehmanniae radix natural products against renal fibrosis: a mechanistic review[J]. Frontiers in Pharmacology, 2025, 16: 1690036.
[3] Zhong H Z, Mo J, Li Y X, et al. Changes in Rehmanniae Radix processing and their impact on ovarian hypofunction: potential mechanisms of action[J]. Frontiers in pharmacology, 2024, 15: 1426972.
[4] Huang H, Ji F, Qi G, et al. Rehmannioside A promotes the osteoblastic differentiation of MC3T3-E1 cells via the PI3K/AKT signaling pathway and inhibits glucocorticoid-induced bone loss in vivo[J]. Journal of Pharmacological Sciences, 2024, 156(4): 247-257.
[5] Huai L, Yang L, Xu Q, et al. Rehmannioside A protects against high glucose-induced apoptosis and oxidative stress of renal tubular epithelial cells by inhibiting the MAPK pathway[J]. Tropical Journal of Pharmaceutical Research, 2021, 20(8): 1553-1558.
[6] Sun M, Shen X, Ma Y. Rehmannioside A attenuates cognitive deficits in rats with vascular dementia (VD) through suppressing oxidative stress, inflammation and apoptosis[J]. Biomedicine & Pharmacotherapy, 2019, 120: 109492.
[7] Lai Y, Zhao H. Therapeutic efficacy of rehmannioside A on 5× FAD mice in Alzheimer’s disease[J]. Scientific Reports, 2025, 15(1): 39825.
Rehmannioside A是细胞色素P450酶（CYP3A4、2C9和2D6）的抑制剂，IC50值分别为10.08、12.62和16.43μM[1]。Rehmannioside A是一种从Rehmanniae radix分离得到的环烯醚萜苷，具有抗炎、抗氧化、抗凋亡和神经保护等多种生物活性[2, 3]。
在体外，Rehmannioside A（10-300µM）处理小鼠成骨细胞系（MC3T3-E1细胞）24h，在50-200µM时显著提升了暴露于地塞米松的成骨细胞存活率，促进了MC3T3-E1细胞中PI3K/AKT信号通路的激活[4]。Rehmannioside A（20-80µM）处理HK2细胞24h，显著提升了高糖（HG）诱导的HK2细胞的存活率，抑制了细胞凋亡和氧化应激，抑制了细胞内MAPK通路的激活[5]。
在体内，Rehmannioside A（40, 80mg/kg）通过腹腔注射给药治疗血管性痴呆（VD）大鼠14天，剂量依赖性地降低了大鼠海马中TUNEL阳性细胞、活性Caspase-3、PARP和细胞色素c的过度表达[6]。Rehmannioside A（5, 15, 45mg/kg）通过口服治疗5×FAD小鼠，显著改善了小鼠的学习、记忆和认知功能，减少了海马体中Aβ斑块的积累，减少了小胶质细胞数量，增加了PSD 95和突触素-1蛋白表达，减轻了氧化应激和炎症[7]。