Icaritin (Anhydroicaritin)

Icaritin (Anhydroicaritin) is a natural flavonoid compound extracted from the traditional Chinese medicine Epimedium. Icaritin (Anhydroicaritin) is often used in research in the fields of anti-cancer, bone protection, anti-inflammation, neuroprotection, cardiovascular protection, and antiviral^[1-9].

Icaritin (Anhydroicaritin)(0-40μM; 24h) induced mitophagy and apoptosis to provoke immunogenic cell death (ICD) both in mouse Hepa1–6 and human Huh7 HCC cells^[1]. Icaritin (Anhydroicaritin) (10μM; 24h) reduces the levels of mature SREBP2 and its target genes in RANKL-induced osteoclasts in RAW264.7 cells^[2]. Icaritin (Anhydroicaritin) (2-3μM; 24h) inhibits cell cycle arrest at the G2/M phase, accompanied by down-regulation of the expression levels of G2/M regulatory proteins (such as cyclin B, cdc2, and cdc25C), and strongly inhibits the growth of breast cancer MDA-MB-453 and MCF7 cells^[3]. Icaritin (Anhydroicaritin) (5-50µM; 24h) increased the Bax/Bcl-2 ratio and caspase-3 activation in HepG2 cells, while Icaritin (Anhydroicaritin) stimulated c-Jun N-terminal kinase 1 (JNK1) but not JNK2, ERK1/2, and p38 subgroups of the mitogen-activated protein kinase (MAPK) family^[4].

In a high-fat diet (HFD)-induced transgenic prostate adenocarcinoma mouse model, Icaritin (Anhydroicaritin) (30mg/kg; ip; 30 weeks) can inhibit the progression of prostate cancer in TRAMP mice by suppressing proinflammatory cytokines^[5]. In the cyclophosphamide-induced bone marrow hematopoietic suppression mouse model, Icaritin (Anhydroicaritin) (10mg/kg; po; 5d) can improve bone marrow suppression by improving the bone marrow hematopoietic microenvironment, promoting the proliferation and differentiation of HSCs, inhibiting the apoptosis of HSCs, and stimulating the expression of G-CSF and TPO^[6]. In the mouse B16F10 melanoma model and MC38 colorectal cancer model, Icaritin (Anhydroicaritin) (35mg/kg; po; 25d) inhibited the reduction of MDSCs frequency at tumor sites and enhanced T cell-mediated anti-tumor immunity^[7]. In the senescence accelerated mouse 8 (SAMP8) mouse model, Icaritin (Anhydroicaritin) (75mg/kg; po; 22d) reduced Aβ production by decreasing BACE1 expression in the hippocampus of SAMP8 mice, thereby improving the memory and learning abilities of mice^[8]. In a cerebral ischemia-reperfusion mouse model, Icaritin (Anhydroicaritin) (60mg/kg; ip; Pre-treatment 1h prior) treatment ameliorates acute cerebral ischemia-reperfusion injury by ameliorating apoptotic neuronal cell death, ROS/RNS-induced lipid peroxidation, ECM accumulation, and EndMT-related fibrosis in the mouse brain^[9].

References:
[1]. Yu Z, Guo J, Hu M, et al. Icaritin exacerbates mitophagy and synergizes with doxorubicin to induce immunogenic cell death in hepatocellular carcinoma[J]. ACS nano, 2020, 14(4): 4816-4828.
[2]. Zheng Z G, Zhang X, Zhou Y P, et al. Anhydroicaritin, a SREBPs inhibitor, inhibits RANKL-induced osteoclastic differentiation and improves diabetic osteoporosis in STZ-induced mice[J]. European Journal of Pharmacology, 2017, 809: 156-162.
[3]. Guo Y M, Zhang X T, Meng J, et al. An anticancer agent icaritin induces sustained activation of the extracellular signal-regulated kinase (ERK) pathway and inhibits growth of breast cancer cells[J]. European journal of pharmacology, 2011, 658(2-3): 114-122.
[4]. He J, Wang Y, Duan F, et al. Icaritin induces apoptosis of HepG2 cells via the JNK1 signaling pathway independent of the estrogen receptor[J]. Planta medica, 2010, 76(16): 1834-1839.
[5]. Hu J, Yang T, Xu H, et al. A novel anticancer agent icaritin inhibited proinflammatory cytokines in TRAMP mice[J]. International urology and nephrology, 2016, 48: 1649-1655.
[6]. Sun C, Yang J, Pan L, et al. Improvement of icaritin on hematopoietic function in cyclophosphamide-induced myelosuppression mice[J]. Immunopharmacology and Immunotoxicology, 2018, 40(1): 25-34.
[7]. Hao H, Zhang Q, Zhu H, et al. Icaritin promotes tumor T‐cell infiltration and induces antitumor immunity in mice[J]. European Journal of Immunology, 2019, 49(12): 2235-2244.
[8]. Li Y Y, Huang N Q, Feng F, et al. Icaritin improves memory and learning ability by decreasing BACE‐1 expression and the Bax/Bcl‐2 ratio in senescence‐accelerated mouse prone 8 (SAMP8) mice[J]. Evidence‐Based Complementary and Alternative Medicine, 2020, 2020(1): 8963845.
[9]. Wu C T, Chen M C, Liu S H, et al. Bioactive flavonoids icaritin and icariin protect against cerebral ischemia–reperfusion-associated apoptosis and extracellular matrix accumulation in an ischemic stroke mouse model[J]. Biomedicines, 2021, 9(11): 1719.

Icaritin (Anhydroicaritin)是从中药淫羊藿中提取的天然黄酮类化合物。Icaritin (Anhydroicaritin)常用于抗癌、骨骼保护、抗炎、神经保护、心血管保护和抗病毒等领域的研究^[1-9]。

Icaritin (Anhydroicaritin)（0-40μM；24h）可诱导线粒体自噬和细胞凋亡，从而引发小鼠Hepa1-6和人类Huh7 HCC细胞中的免疫原性细胞死亡^[1]。Icaritin (Anhydroicaritin)（10μM；24h）降低了RAW264.7细胞中RANKL诱导的破骨细胞中成熟SREBP2及其靶基因的水平^[2]。Icaritin (Anhydroicaritin)（2-3μM；24h）可抑制细胞周期在G2/M期停滞，同时下调G2/M调节蛋白（如细胞周期蛋白B、cdc2和cdc25C）的表达水平，并强烈抑制乳腺癌MDA-MB-453和MCF7细胞的生长^[3]。Icaritin (Anhydroicaritin)（5-50µM；24h）可增加HepG2细胞中的Bax/Bcl-2比率和caspase-3活化，且Icaritin (Anhydroicaritin)可刺激c-Jun N末端激酶1（JNK1），但不刺激丝裂原活化蛋白激酶（MAPK）家族的JNK2、ERK1/2和p38亚群^[4]。

在高脂饮食(HFD)诱导的转基因前列腺癌小鼠模型中，Icaritin (Anhydroicaritin)（30mg/kg；ip；30weeks）可通过抑制促炎细胞因子来抑制TRAMP小鼠前列腺癌的进展^[5]。在环磷酰胺诱导的骨髓造血抑制小鼠模型中，Icaritin (Anhydroicaritin) (10mg/kg；po；5d)可通过改善骨髓造血微环境、促进造血干细胞增殖分化、抑制造血干细胞凋亡、刺激G-CSF和TPO的表达来改善骨髓抑制^[6]。在小鼠B16F10黑色素瘤模型和MC38结直肠癌模型中，Icaritin (Anhydroicaritin)（35mg/kg；po；25d）抑制了肿瘤部位MDSC频率的降低，增强了T细胞介导的抗肿瘤免疫力^[7]。在加速衰老小鼠8（SAMP8）小鼠模型中，Icaritin (Anhydroicaritin)（75mg/kg；po；22d）通过降低SAMP8小鼠海马中BACE1的表达来减少Aβ的产生，从而改善小鼠的记忆力和学习能力^[8]。在小鼠脑缺血再灌注模型中，Icaritin (Anhydroicaritin)（60mg/kg；ip；术前1h给药）可改善小鼠脑内的神经元细胞凋亡、ROS/RNS诱导的脂质过氧化、ECM积聚和EndMT相关的纤维化，从而改善急性脑缺血再灌注损伤^[9]。