Introduction of Icariin

Icariin is the main bioactive pharmaceutical ingredient isolated from the traditional Chinese medicine plant Epimedium, which has powerful cardiovascular protective functions and protective effects against neurological diseases. It can treat a wide range of cardiovascular (atherosclerosis) and neurological diseases, including Alzheimer's disease, Parkinson's disease, ischaemic stroke, depression, multiple sclerosis, glioblastoma and hereditary spastic paraplegia. In addition, it has osteoprotective properties.

Osteoprotective effect

Icariin, as a phytoestrogen, exerts rapid estrogenic and thus osteoprotective effects by crosstalking estrogen receptors in osteoblasts. This study aimed to investigate role ER-α66, ER-α36, GPER in bone metabolism in osteoblasts following treatment with icariin. Human osteoblastic MG-63 cells osteoblast-specific ER-α66 knockout mice were employed. The ERs crosstalk in estrogenic action icariin was evaluated in ER-α66-negative human embryonic kidney HEK293 cells. Icariin, like E2, regulated ER-α36 GPER protein expression in osteoblasts by downregulating them upregulating ER-α66. ER-α36 GPER suppressed actions icariin E2 in bone metabolism. However, in vivo administration E2 (2?mg/kg/day) or icariin (300?mg/kg/day) restored bone conditions in KO osteoblasts. ER-α36 GPER expression increased significantly rapidly activated translocated in KO osteoblasts after treatment with E2 or icariin. ER-α36 overexpression in KO osteoblasts further promoted OPG/RANKL ratio induced by E2 or icariin treatment. This study showed icariin E2 elicit rapid estrogenic responses in bone through recruiting ER-α66, ER-α36, GPER. Notably, in osteoblasts lacking ER-α66, ER-α36, GPER mediate estrogenic effects icariin E2, while in intact osteoblasts, ER-α36 GPER act as negative regulators ER-α66.

Anti-Atherosclerosis

Icariin is a major bioactive pharmaceutical ingredient isolated from Epimedium, which has potent cardiovascular protective properties. Emerging evidence over the past decade suggests that epimedoside possesses multiple atheroprotective functions against atherosclerosis through a variety of mechanisms, including attenuation of DNA damage, correction of endothelial dysfunction, inhibition of smooth muscle cell proliferation and migration, inhibition of macrophage-derived foam cell formation and inflammatory responses, and prevention of platelet activation. All of these protective effects, together with its lipid-modulating effects, contribute to the broad atheroprotective effects of epimedium glycosides.

Anti-Nervous System Diseases

Icariin was reported to be a modulator of adaptive immunity in 1995, and subsequent studies have shown anti-hepatotoxicity and antioxidant activity as well as the ability to stimulate corticosterone production and promote neurite growth. Icariin has pharmacological effects on immunity and the skeletal reproduction system.

Icariin protected PC-12 cells from Aβ-induced apoptosis and showed dose-dependent protective effects on ischaemia/reperfusion-injured neurons at low concentrations, while in vivo it improved learning and memory, possibly through some antioxidant effects. Another in vivo study using 5xFAD mice, considered a better model for AD, showed significantly less axonal and dendritic damage caused by Aβ in the group treated with Icariin. The related compound Icariin II has recently been shown to improve cognitive performance in rats treated with streptozotocin, which has deleterious effects on the hippocampus. A possible additional contributing factor to the usefulness of Epimedium species in the treatment of AD symptoms is the AChE-inhibitory activity of the aporphine alkaloid epimediin, present in E. koreanum.

References:

[1] KA-YING WONG. Icariin, a phytoestrogen, exerts rapid estrogenic actions through crosstalk of estrogen receptors in osteoblasts.[J]. Phytotherapy Research, 2023: 4706-4721. DOI:10.1002/ptr.7939.

[2] SHUANGQIU WANG. Icariin, an Up-and-Coming Bioactive Compound Against Neurological Diseases: Network Pharmacology-Based Study and Literature Review.[J]. Drug Design, Development and Therapy, 2021: 3619-3641. DOI:10.2147/DDDT.S310686.

[3] JIAN FANG Yongjun Z. Icariin, an Anti-atherosclerotic Drug from Chinese Medicinal Herb Horny Goat Weed.[J]. Frontiers in Pharmacology, 2017: 734. DOI:10.3389/fphar.2017.00734.