Icariin (Ieariline)

Icariin is a PDE5 inhibitor specific to cGMP. Icariin's inhibitory effects on PDE5 and PDE4 activities are examined using a two-step radioisotope method using 3H-cGMP and 3H-cAMP. Icariin has 167.67 times the efficacy of selectivity on PDE5 (PDE4/PDE5 of IC50)[1]. In this work, cell viability is assessed to determine whether Icariin shields endothelium HUVECs from damage caused by oxidized low-density lipoprotein (ox-LDL). When compared to the control group, the cells' viability is considerably decreased (P<0.05) after being exposed to ox-LDL for 24 hours. On the other hand, Icariin has the ability to significantly (P<0.05) reduce cell harm caused by ox-LDL in a concentration-dependent manner as compared to the ox-LDL-simulated group[3]. Icariin inhibits ERs-mediated (ER Stress) autophagy via the MAPK signaling pathway, thereby shielding BMSCs from OGD-induced apoptosis[4].

Icariin is a PPARα activator that also promotes Cyp4a10 and Cyp4a14. It also regulates the mRNA levels of proteins and enzymes involved in lipid metabolism, such as fatty acid binding protein and fatty acid oxidation in peroxisomes and mitochondria. Icariin is a useful medication for treating hyperlipidemia. Investigating Icariin's effects on PPARα and its target genes helps to understand how it affects lipid metabolism. For five days, mice are given oral dosages of either clofibrate (500 mg/kg) or icicariin (100, 200, 400, and mg/kg). The expressions of the genes involved in lipid metabolism and PPARα are analyzed after liver total RNA is extracted. Icariin and Clofibrate induce PPARα and its marker genes Cyp4a10 and Cyp4a14 2-4 fold and 4-8 fold, respectively. There is a two-fold increase in the fatty acid (FA) binding and co-activator proteins Fabp1, Fabp4, and Acsl1. There is a 2-3 fold increase in the mRNAs of the mitochondrial FA β-oxidation enzymes (Cpt1a, Acat1, Acad1, and Hmgcs2). Icariin and Clofibrate also raise the mRNAs of the proximal β-oxidation enzymes (Acox1, Ech1, and Ehhadh). Icariin has no effect on the mRNA expression of FA synthetase (Fasn) or sterol regulatory element-binding factor-1 (Srebf1). Icariin and Clofibrate stimulate the lipid lysis genes Lipe and Pnpla2[2]. Icariin is administered orally to adult rats for 35 straight days at doses of 0 (control), 50, 100, or 200 mg/kg body weight. The findings demonstrate that Icariin essentially has no effect on the testes' or epididymides' body weight or organ coefficients. On the other hand, epididymal sperm counts are dramatically increased by 100 mg/kg Icariin. Furthermore, Icariin at doses of 50 and 100 mg/kg dramatically raises testosterone levels. Moreover, follicle stimulating hormone receptor (FSHR) and claudin-11 mRNA expression in Sertoli cells are impacted by 100 mg/kg Icariin administration. The tests evaluate malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity; treatment with 50 and 100 mg/kg Icariin increases antioxidant capacity, but treatment with 200 mg/kg Icariin increases oxidative stress[4].

[1]. Xin ZC, et al. Effects of icariin on cGMP-specific PDE5 and cAMP-specific PDE4 activities. Asian J Androl. 2003 Mar;5(1):15-8.
[2]. Lu YF, et al. Icariin is a PPARα activator inducing lipid metabolic gene expression in mice. Molecules. 2014 Nov 6;19(11):18179-91.
[3]. Hu Y, et al. Effects and mechanisms of icariin on atherosclerosis. Int J Clin Exp Med. 2015 Mar 15;8(3):3585-9.
[4]. Chen M, et al. Effects of icariin on reproductive functions in male rats. Molecules. 2014 Jul 3;19(7):9502-14.
[5]. Liu D, et al. Icariin protects rabbit BMSCs against OGD-induced apoptosis by inhibiting ERs-mediated autophagy via MAPK signaling pathway. Life Sci. 2020 Apr 26:117730

C33H40O15

676.66

489-32-7

O1[C@]([H])([C@@]([H])([C@]([H])([C@@]([H])([C@@]1([H])C([H])([H])O[H])O[H])O[H])O[H])OC1C([H])=C(C2C(C(=C(C3C([H])=C([H])C(=C([H])C=3[H])OC([H])([H])[H])OC=2C=1C([H])([H])/C(/[H])=C(\C([H])([H])[H])/C([H])([H])[H])O[C@@]1([H])[C@@]([H])([C@@]([H])([C@]([H])([C@]([H])(C([H])([H])[H])O1)O[H])O[H])O[H])=O)O[H]

TZJALUIVHRYQQB-XLRXWWTNSA-N

InChI=1S/C33H40O15/c1-13(2)5-10-17-19(45-33-28(42)26(40)23(37)20(12-34)46-33)11-18(35)21-24(38)31(48-32-27(41)25(39)22(36)14(3)44-32)29(47-30(17)21)15-6-8-16(43-4)9-7-15/h5-9,11,14,20,22-23,25-28,32-37,39-42H,10,12H2,1-4H3/t14-,20+,22-,23+,25+,26-,27+,28+,32-,33+/m0/s1

5-hydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-en-1-yl)-7-(((2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-3-(((2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-4H-chromen-4-one

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (3.69 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (3.07 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 3: 2.08 mg/mL (3.07 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 4: 10 mg/mL (14.78 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 5: 10 mg/mL (14.78 mM) in 0.5% CMC/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)