Search JIM Advanced Search

Journal of Integrative Medicine ›› 2019, Vol. 17 ›› Issue (3): 205-212.doi: 10.1016/j.joim.2019.01.011

• Original Experimental Research • Previous Articles     Next Articles

Icariin protects vascular endothelial cells from oxidative stress through inhibiting endoplasmic reticulum stress

Fang-yuan Wang, Jian Jia, Huan-huan Song, Cheng-ming Jia, Chang-bo Chen, Jing Ma   

  1. Department of Traditional Chinese Medicine, Army Medical Center in Traditional Chinese Medicine, Xijing Hospital, Forth Military Medical University, Xi’an 710032, Shaanxi Province, China
  • Received:2018-07-06 Revised:2018-12-05 Accepted:2018-12-05 Online:2019-05-05 Published:2019-05-01

To investigate the protective effect and underlying mechanism(s) of icariin (ICA) in preventing hydrogen peroxide (H2O2)-induced vascular endothelial cell injury via endoplasmic reticulum stress (ERS).
To study the effects of ICA on H2O2-induced damage, we used the cell counting kit-8 assay to detect cell viability and the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay to determine cell adhesion and apoptosis, respectively. Spectrophotometry and enzyme-linked immunosorbent assay were used to measure the expression levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Subsequently, glucose-regulated protein 78 (GRP78), activating transcription factor-4 (ATF4) and eukaryotic initiation factor-2α (eIF2α) were detected using Western blotting.
In human umbilical vein endothelial cells, different concentrations of ICA exhibited multiple effects, including reduced H2O2 damage, improved cell viability and adhesion, reduced cell apoptosis and increased SOD and GSH-Px activity. Among the ICA concentrations used, only the H2O+ 100 μmol/L ICA group had significant differences compared to the H2O2 group. ERS activators H2O2 and dl-dithiothreitol (DTT) significantly increased GRP78, ATF4 and eIF2α expressions, decreased cell activity and reduced SOD and GSH-Px activity. In contrast, the H2O+ 100 μmol/L ICA and H2O2 + 100 μmol/L ICA + DTT groups had significant inhibitory effects on the expressions of GRP78, ATF4 and eIF2α proteins, showing enhanced cell viability and SOD and GSH-Px activity.
The results showed the dose-dependent effects of ICA against H2O2-induced injury in vascular endothelial cells. The inhibition of GRP78, ATF4 and eIF2α protein expressions in the ERS, and the subsequent alleviation of oxidative stress damage, might be the molecular mechanism.

Key words: Icariin, Endoplasmic reticulum stress, Human umbilical vein endothelial cells, Oxidative stress

[1] Gerli E.G. Herr, Fábio Goulart da Silva, Francisco José Cidral-Filho, Fabricia Petronilho, Lucinéia Gainski Danielski, Mariana Pereira de Souza Goldim, Afonso Shiguemi Inoue Salgado, Franciane Bobinski, Daniel Fernandes Martins, Eliane R. Winkelmann. Effects of the use of bioceramic wraps in patients with lower limb venous ulcers: A randomized double-blind placebo-controlled trial. Journal of Integrative Medicine, 2020, 18(1): 27-.
[2] Álisson de Carvalho Gonçalves, Einy Jéssika Siqueira Moreira, Guilherme Vannucchi Portari. Benfotiamine supplementation prevents oxidative stress in anterior tibialis muscle and heart. Journal of Integrative Medicine, 2019, 17(6): 423-429.
[3] Pranay Soni, Rajesh Choudhary, Surendra H. Bodakhe. Effects of a novel isoflavonoid from the stem bark of Alstonia scholaris against fructose-induced experimental cataract. Journal of Integrative Medicine, 2019, 17(5): 374-382.
[4] Lucky Legbosi Nwidu, Yibala Ibor Oboma. Telfairia occidentalis (Cucurbitaceae) pulp extract mitigates rifampicin-isoniazid-induced hepatotoxicity in an in vivo rat model of oxidative stress. Journal of Integrative Medicine, 2019, 17(1): 46-56.
[5] Kayode E. Adewole, Joseph O. Adebayo. Antioxidant defense system induced by cysteine-stabilized peptide fraction of aqueous extract of Morinda lucida leaf in selected tissues of Plasmodium berghei-infected mice. Journal of Integrative Medicine, 2017, 15(5): 388-397.
[6] Uduak Akpan Okon, Idorenyin Udo Umoren. Comparison of antioxidant activity of insulin, Ocimum gratissimum L., and Vernonia amygdalina L. in type 1 diabetic rat model. Journal of Integrative Medicine, 2017, 15(4): 302-309.
[7] Udhaya Lavinya Baskaran, Evan Prince Sabina. Clinical and experimental research in antituberculosis drug-induced hepatotoxicity: A review. Journal of Integrative Medicine, 2017, 15(1): 27-36.
[8] Khanh Nguyen, Jean Sparks, Felix O. Omoruyi. Investigation of the cytotoxicity, antioxidative and immune-modulatory effects of Ligusticum porteri (Osha) root extract on human peripheral blood lymphocytes. Journal of Integrative Medicine, 2016, 14(6): 465-472.
[9] Benjamin Perry, Junzeng Zhang, Tarek Saleh, Yanwen Wang. Liuwei Dihuang, a traditional Chinese herbal formula, suppresses chronic inflammation and oxidative stress in obese rats. Journal of Integrative Medicine, 2014, 12(5): 447-454.
[10] Mukherjee Avinaba, Boujedaini Naoual, Rahman Khuda-Bukhsh Anisur. Homeopathic Thuja 30C ameliorates benzo(a)pyrene-induced DNA damage, stress and viability of perfused lung cells of mice in vitro. Journal of Integrative Medicine, 2013, 11(6): 397-404.
[11] Marjan Nassiri-Asl, Taghi Naserpour Farivar, Esmail Abbasi, Hamid Reza Sadeghnia, Mehdi Sheikhi, Mina Lotfizadeh, Parisa Bazahang. Effects of rutin on oxidative stress in mice with kainic acid-induced seizure. Journal of Integrative Medicine, 2013, 11(5): 337-342.
[12] Hai-yan Song, Li Zhang, Jie-lu Pan, Li-li Yang, Guang Ji. Bioactivity of five components of Chinese herbal formula Jiangzhi granules against hepatocellular steatosis. Journal of Integrative Medicine, 2013, 11(4): 262-268.
[13] Mao Zhi-min, Song Hai-yan, Yang Li-li, Liu Tao, Li Dong-fei, Zheng Pei-yong, Liu Ping, Ji Guang. Effects of the mixture of Swertia pseudochinensis Hara and Silybum marianum Gaertn extracts on CCl4-induced liver injury in rats with non-alcoholic fatty liver disease. Journal of Chinese Integrative Medicine, 2012, 10(2): 193-199.
[14] Kaulaskar Shyam, Bhutada Pravinkumar, Rahigude Anand, Jain Dilpesh, Harle Uday. Effects of naringenin on allodynia and hyperalgesia in rats with chronic constriction injury-induced neuropathic pain. Journal of Chinese Integrative Medicine, 2012, 10(12): 1482-1489.
[15] Xiang-ying Mao , Qin Bian , Zi-yin Shen. Analysis of the osteogenetic effects exerted on mesenchymal stem cell strain C3H10T1/2 by icariin via MAPK signaling pathway in vitro. Journal of Chinese Integrative Medicine, 2012, 10(11): 1272-1278.
Full text



[1] Zhao-guo Li. Discussion on English translation of commonly used sentences in traditional Chinese medicine: part one. Journal of Chinese Integrative Medicine, 2008, 6(1): 107-110
[2] Yi-ting He, Qing-lin Zha, Jian-ping Yu, Yong Tan, Cheng Lu, Ai-ping Lv. Principal factor analysis of symptoms of rheumatoid arthritis and their correlations with efficacy of traditional Chinese medicine and Western medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 32-36
[3] Dong Yang, Yong-ping Du, Qing Shen, Wei Chen, Yan Yu, Guang-lei Chen. Expression of alpha-smooth muscle actin in renal tubulointerstitium in patients with kidney collateral stasis. Journal of Chinese Integrative Medicine, 2008, 6(1): 41-44
[4] Zhi-chun Jin. Problems in establishing clinical guideline for integrated traditional Chinese and Western medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 5-8
[5] Xi Lin, Jian-ping Liu. Tai chi for treating rheumatoid arthritis. Journal of Chinese Integrative Medicine, 2008, 6(1): 82
[6] Guo-hong Yuan, Xiao-jing Pang, He-chao Ma. Synergic effects of Danggui Buxue Decoction in reducing toxicity of cytoxan in tumor-bearing mice. Journal of Chinese Integrative Medicine, 2008, 6(1): 83-88
[7] Li Zhou, Hong-xing Zhang, Ling-guang Liu, Wen-jun Wan. Effect of electro-acupuncture at Fenglong (GV 16) on nitric oxide and endothelin in rats with hyperlipidemia. Journal of Chinese Integrative Medicine, 2008, 6(1): 89-92
[8] Ning-qun Wang, Liang-duo Jiang, Zong-xing Li. Research progress in asthma-related quality of life. Journal of Chinese Integrative Medicine, 2008, 6(1): 93-97
[9] Daniel Weber, Janelle M Wheat, Geoffrey M Currie. Inflammation and cancer: Tumor initiation, progression and metastasis,and Chinese botanical medicines. Journal of Chinese Integrative Medicine, 2010, 8(11): 1006-1013
[10] Xin-jun Wang, Ling-ling Wang . A mechanism of endogenous opioid peptides for rapid onset of acupuncture effect in treatment of depression. Journal of Chinese Integrative Medicine, 2010, 8(11): 1014-1017