Icariin: Infertility, Potency, Immunity and Atherosclerosis
Icariin is the main active ingredient in the traditional herb Epimedium, also known as Horny Goat Weed or Yin Yang Huo. Epimedium is commonly used as a tonic, aphrodisiac, antirheumatic and anti-cancer agent in traditional herbal preparations in Asian countries such as China, Japan, and Korea.
What is Icariin?
Epimedium Icariin is best known for its aphrodisiac properties. Scientific and pharmacological studies show that it has broad therapeutic potential, especially for enhancing reproductive function and osteoprotective, neuroprotective, cardioprotective, anti-inflammatory, and immunoprotective effects.
It has been extensively studied over the past few years and has been shown to have antioxidant, anti-neuro-inflammatory, and anti-apoptotic effects as well as experimental data. It is currently being considered as a potential therapeutic agent for a wide range of diseases ranging from neoplasms (anti-cancer effects) to cardiovascular diseases.
More recent studies have shown that icariin exhibits potential preventive and/or therapeutic effects in the nervous system. For example, Icariin can prevent the production of amyloid [1-42] and inhibit the expression of the amyloid precursor protein (APP) and the β-site cleavage enzyme APP 1 in animal models of Alzheimer’s disease.
Icariin has been shown to mitigate the pro-inflammatory responses of microglia in cell culture and in animal models of cerebral ischemia, depression, Parkinson’s disease, and multiple sclerosis. Icariin also prevents hydrogen peroxide (H2O2) -induced neurotoxicity and endoplasmic reticulum stress [1,2].
Icariin for Women: a Positive Effect on Infertility
Infertile women are patients who suffer from clinical pregnancy failure after 12 months of regular intercourse without conception. This incidence ranges from 8% to 12% among couples of reproductive age worldwide.
Due to the increase in the number of diseases associated with infertility, reproductive medicine has received widespread attention and has become one of the main areas of research.
Primary scores for infertile women are ovulation, uterine cavity, and fallopian tubes. As an important part of the uterine factors of female infertility, the endometrial thickness is one of the most important conditions for embryo implantation.
Numerous studies have shown that there are significant differences in pregnancy rates between patients with thin endometrium and normal patients. Therefore thin endometrium has been considered as an independent negative factor for pregnancy, whether it is with assisted reproductive technologies or natural pregnancy.
The thin endometrium of infertile women is a complex problem in clinical management. Many medications are used to improve the thin endometrium, including icariin.
Thin Endometrium Treatment
It is assumed that the action of Icariin is associated with its movement through blood vessels and nerves, or its regulation to receptors associated with estrogen, or signaling pathways. Some studies have shown that the endometrium can be thickened by exposure to icariin by increasing the expression levels of estrogen receptors, vascular endothelial growth factor, and kinase insert domain receptors in thin endometrial cells .
In addition, icariin significantly promoted cell migration and the formation of capillary tubes, and the favorable modulation of angiogenesis and redox conditions in endothelial progenitor cells of the bone marrow makes icariin a promising pro-angiogenic agent that enhances vasculogenesis and protects against endothelial dysfunction .
On top of that, icariin acts as a nerve growth factor releasing agent and promotes peripheral nerve regeneration .
Effect of Icariin on Bone Metabolism
Osteoporosis is a bone disease characterized by a decrease in bone mass, which leads to an increased risk of bone fractures and poses a significant risk to public health, especially among the elderly. The traditional Chinese herb Epimedium has been used for centuries to treat bone fractures and bone loss.
In 2018, a comprehensive review of research on icariin, the main component of Epimedium, including its structure and function, and its effect on bone metabolism, and potential for clinical use, was published.
Studies show that Icariin promotes bone formation by stimulating the osteogenic differentiation of bone marrow mesenchymal stem cells while inhibiting osteoclastogenic differentiation and bone resorption activity of osteoclasts. In addition, Icariin has been shown to be more effective than other flavonoid compounds in stimulating osteogenic differentiation and osteoblast maturation.
A 24-month, randomized, double-blind, placebo-controlled clinical trial showed that Icariin was effective in preventing postmenopausal osteoporosis with relatively low side effects. In conclusion, it should be noted that Icariin may be a class of bone-active flavonoids that can be used as a potential treatment for postmenopausal osteoporosis .
Effect on Immunity and Its Potential Uses
In recent years, interest has arisen in the pharmacological study of the immunomodulatory effects of Icariin and its derivatives . Data from in vitro and in vivo studies have shown that Icariin influences the regulation of immunocytes, relative cytokines, and multiple targeting mechanisms.
Molecular mechanisms can include many aspects such as involvement in Th1 / Th17 or Th2 balance, Th17 / Treg regulation, natural killer (NK) cell proliferation, anti-inflammatory / inflammatory cytokines, signaling pathways such as NF-kappaß and Erk-p38 -JNK, lymphocyte transcription factors and other targets such as TLRs, STAT and PTEN, etc. Icariin has also demonstrated general immunosuppressive effects in many autoimmune diseases such as rheumatoid arthritis and autoimmune encephalomyelitis and has also presented anti-tumor results .
Potency. How Much Icariin Equals Viagra?
A number of in vitro studies have demonstrated that Icariin exhibits phosphodiesterase type 5 (PDE-5) inhibitory activity [9-11]. The most famous type 5 phosphodiesterase inhibitor is Viagra, a drug designed to enhance potency.
What is the mechanism of action? In the cells of the smooth muscles of the cavernous bodies of the penis, there is an enzyme PDE-5, which regulates the level of cyclic guazine monophosphate (cGMP), reducing its concentration.
During sexual arousal, the level of cGMP in the cells of the penis increases, which leads to increased blood flow and an erection. That is, the enzyme PDE-5, reducing the level of cGMP, also reduces erection. PDE-5 inhibitors inhibit the activity of this enzyme, preventing the utilization of cGMP. As a result, cGMP begins to accumulate. The erection is enhanced and maintained.
Thus, Icariin has a similar effect to Viagra. However, it was revealed only in experiments on animals, which makes it difficult for the optimal dosage of Icariin in humans to achieve pronounced results. Also, it was only in animal studies that Icariin improved the condition of the reproductive organs and increased circulating testosterone levels .
Atherosclerosis is a chronic inflammatory vascular disease. It is characterized by the formation of atherosclerotic plaques, consisting of foam cells, leukocytes, platelets, inflamed smooth muscle cells, and endothelial cells, leading to vasoconstriction. It is generally accepted that vascular endothelial cells play an important role in the initiation and enhancement of atherogenesis.
Endothelial dysfunction, which is most often associated with exposure to oxidized LDL, is considered a key early stage of the atherosclerotic lesion. Early research showed that Icariin has beneficial effects on cardiovascular diseases such as atherosclerosis .
A later study on human umbilical vein endothelial cells demonstrated that Icariin exerts a protective effect on oxidized LDL-induced damage, and the exact mechanism is associated with antiadhesion and inflammation reduction .
Dosage. How Much Icariin to Take?
The dosage used for Icariin in humans varies widely – from 10 to 200 mg, depending on body weight.
More human studies are needed for a more specific dosage depending on other criteria, such as the purpose of use.
At the indicated dosages, Icariin is considered safe to use.
- An outline for the pharmacological effect of icariin in the nervous system. Jin J, Wang H, Hua X, Chen D, Huang C, Chen Z. Eur J Pharmacol. 2019 Jan 5;842:20-32.
- Anti-Cancer Properties of the Naturally Occurring Aphrodisiacs: Icariin and Its Derivatives. Tan HL, Chan KG, Pusparajah P, Saokaew S, Duangjai A, Lee LH, Goh BH. Front Pharmacol. 2016 Jun 29;7:191.
- Effects of icariin on the expression of ER, VEGF, and KDR in the endometrial cells of thin endometrium. Le AW, Shan L, Wang ZH, Dai XY, Xiao TH, Zuo R. Genet Mol Res. 2015 Sep 22; 14(3):11250-8.
- Icariin promotes angiogenic differentiation and prevents oxidative stress-induced autophagy in endothelial progenitor cells. Tang Y, Jacobi A, Vater C, Zou L, Zou X, Stiehler M. Stem Cells. 2015 Jun; 33(6):1863-77.
- Local administration of icariin contributes to peripheral nerve regeneration and functional recovery. Chen B, Niu SP, Wang ZY, Wang ZW, Deng JX, Zhang PX, Yin XF, Han N, Kou YH, Jiang BG Neural Regen Res. 2015 Jan; 10(1):84-9.
- The effect of icariin on bone metabolism and its potential clinical application. Wang Z, Wang D, Yang D, Zhen W, Zhang J, Peng S. Osteoporos Int. 2018 Mar;29(3):535-544.
- Regulation of Th17/Treg function contributes to the attenuation of chronic airway inflammation by icariin in ovalbumin-induced murine asthma model. Wei Y, Liu B, Sun J, Lv Y, Luo Q, Liu F, Dong J Immunobiology. 2015 Jun; 220(6):789-97.
- The effect of icariin on immunity and its potential application. Rong Shen and Ju-Hua Wang. Am J Clin Exp Immunol. 2018; 7(3): 50–56.
- Jiang Z, Hu B, Wang J, et al. (2006). “Effect of icariin on cyclic GMP levels and on the mRNA expression of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in penile cavernosum”. J. Huazhong Univ. Sci. Technol. Med. Sci. 26 (4): 460–2.
- Ning H, Xin ZC, Lin G, Banie L, Lue TF, Lin CS (December 2006). “Effects of icariin on phosphodiesterase-5 activity in vitro and cyclic guanosine monophosphate level in cavernous smooth muscle cells”. Urology 68 (6): 1350–4.
- Dell’Agli M, Galli GV, Dal Cero E, et al. (September 2008). “Potent inhibition of human phosphodiesterase-5 by icariin derivatives”. J. Nat. Prod. 71 (9): 1513–7.
- The testosterone mimetic properties of icariin.Zhang ZB, Yang QT. Asian J Androl. 2006 Sep; 8(5):601-5.
- Vasorelaxant effects of icariin on isolated canine coronary artery. Xu HB, Huang ZQ. J Cardiovasc Pharmacol. 2007 Apr; 49(4):207-13.
- Effects and mechanisms of icariin on atherosclerosis. Yanwu Hu, Kai Liu, Mengtong Yan, Yang Zhang, Yadi Wang, and Liqun Ren. Int J Clin Exp Med. 2015; 8(3): 3585–3589.
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