The Effect of Hydro‑alcoholic Extract of Rheum Turkestanicum Roots against Oxidative Stress in Endothelial Cells

Azar Hosseini, Sahar Sheikh, Mohammad Soukhtanloo, Bizhan Malaekeh- Nikouei, Arezoo Rajabian


Introduction: Cardiovascular disorders (CVD) are a common cause of mortality worldwide. Oxidative
stress is thought to be a major factor leading to CVD. Anti‑oxidants such as medicinal plants may
have a role in the mitigation of vascular problems through free radicals scavenging. In this study, we
evaluated the protective effects of Rheum turkestanicum against hydrogen peroxide (H2O2)‑induced
toxicity in endothelial cells (BAE‑1). Methods: To evaluate the protective effect of R. turkestanicum
against H2O2 toxicity, four groups comprised of control group (the cells without any treatment),
H2O2 group (the cells incubated with H2O2 (200 μM)), and treatment groups (the cells treated with
R. turkestanicum (12200 μg/ml) alone or 24h before exposure to H2O2). Quercetin (30.23 μg/ml)
was used as a bioactive ingredient of the extract. Then the cell viability, reactive oxygen species,
lipid peroxidation, and apoptosis were evaluated. Results: H 2O2 exposure reduced cell viability to
13.6 ± 1.6%, enhanced ROS generation to 1445 ± 80.7%, lipid peroxidation (LPO, 290 ± 13% of
control), and apoptotic cells (P < 0.001). In contrast, compared with H2O2 group, R. turkestanicum
and quercetin significantly restored the cell viability to 80.3 ± 1.6 and 87.2 ± 2.1%, ROS
formation to 186 ± 10 and 129 ± 1%, as well as LPO to 130.7 ± 7.7 and 116 ± 2.5 of control,
respectively (P < 0.001). Therefore, the extract reduced H2O2‑induced toxicity in BAE‑1 cells by
scavenging of free radicals. Conclusion: Our findings demonstrated that the extract might reduce
toxicity of endothelial cells by attenuation of oxidative stress, which can be related to the presence
of active ingredients including quercetin.


Apoptosis,; endothelial cells; oxidative stress; quercetin; Rheum turkestanicum

Full Text:



Grover‑Páez F, Zavalza‑Gómez AB. Endothelial dysfunction

and cardiovascular risk factors. Diabetes Res Clin Pract


Martin BJ, Anderson TJ. Risk prediction in cardiovascular

disease: The prognostic significance of endothelial dysfunction.

Can J Cardiol 2009;25:15A‑20A.

Siti HN, Kamisah Y, Kamsiah J. The role of oxidative stress,

antioxidants and vascular inflammation in cardiovascular

disease (a review). Vascul. Pharmacol 2015;71:40‑56.

Sifuentes‑Franco S, Padilla‑Tejeda DE, Carrillo‑Ibarra S,

Miranda‑Díaz AG.Oxidative stress, apoptosis, and mitochondrial

function in Diabetic Nephropathy. Int J Endocrinol


Savini I, Catani MV, Evangelista D, Gasperi V, Avigliano L.

Obesity‑associated oxidative Stress: Strategies finalized to

improve redox state.Int J Mol Sci 2013;14:10497‑538.

Cai H. Hydrogen peroxide regulation of endothelial function:

Origins, mechanisms, and consequences. Cardiovasc Res


Rahiman N, Akaberi M, Sahebkar A, Emami SA,

Tayarani‑Najaran Z. Protective effects of saffron and its active

components against oxidative stress and apoptosis in endothelial

cells. Microvasc Res 2018;118:82‑9.

Wongpradabchai S, Chularojmontri L, Phornchirasilp S,Wattanapitayakul SK. Protective effect of phyllanthus emblica

fruit extract against hydrogen peroxide‑induced endothelial cell

death. J Med Assoc Thai 2013;96(Suppl 1):40‑8.

Safaeian L, Sajjadi SE, Javanmard SH, Montazeri H, Samani F.

Protective effect of Melissa officinalis extract against

H2O2‑induced oxidative stress in human vascularendothelial

cells. Res Pharm Sci 2016;11:383‑9.

Bihamta M, Hosseini A, Ghorbani A, Boroushaki MT.

Protective effect of pomegranate seed oil against

H2O2‑induced oxidative stress in cardiomyocytes. Avicenna J

Phytomed 2017;7:46‑53.

Shiezadeh F, Mousavi SH, Amiri MS, Iranshahi M,

Tayarani‑Najaran Z, Karimi G. Cytotoxic and apoptotic potential

of Rheum turkestanicum Janisch root extract on human cancer

and normal cells. Iran J Pharm Res 2013;12:811‑9.

Hosseini A, Rajabian A. Protective effect of Rheum turkestanikum

root against doxorubicin‑induced toxicity in H9c2 cells. Rev

Bras Farmacogn 2016;26:347‑51.

Hosseini A, Fanoudi S, Mollazadeh H, Aghaei A, Boroushaki MT.

Protective effect of Rheum turkestanicum against cisplatin by

reducing oxidative stress in kidney tissue. J Pharm Bioallied Sci


Boroushaki MT, Fanoudi S, Mollazadeh H,

Boroumand‑Noughabi S, Hosseini A. Reno‑protective effect of

Rheum turkestanicum against gentamicin‑induced nephrotoxicity.

Iran J Basic Med Sci 2019;22:328‑33.

Hosseini A, Rajabian A, Fanoudi S, Farzadnia M,

Boroushaki MT. Protective effect of Rheum turkestanicum root

against mercuric chloride‑induced hepatorenal toxicity in rats.

Avicenna J Phytomed 2018;8:488‑97.

Boroushaki MT, Fanoudi S, Rajabian A, Boroumand S,

Aghaee A, Hosseini A. Evaluation of Rheum turkestanicum in

hexachlorobutadien‑induced renal toxicity. Drug Res (Stuttg)


Fei Y, Wang J, Peng B, Peng J, Hu JH, Zeng ZP. Phenolic

constituents from Rheum nobile and their antioxidant activity.

Nat Prod Res 2017;31:2842‑9.

Rajabian A, Sadeghnia HR, Moradzadeh M, Hosseini A. Rheum

turkestanicum reduces glutamate toxicity in PC12 and N2a cell

lines. Folia Neuropathol 2018;56:354‑61.

Hosseini A, Mollazadeh H, Amiri MS, Sadeghnia HR,

Ghorbani A. Effects of a standardized extract of Rheum

turkestanicum Janischew root on diabetic changes in the kidney,

liver and heart of streptozotocin‑induced diabetic rats. Biomed

Pharmacother 2017;86:605‑11.

Singh P, Rawat M. Phytochemistry and biological activity

perspectives of Rheum species. Natural Products J 2016;6:84‑93.

Zhong XF, Huang GD, Luo T, Deng ZY, Hu JN. Protective

effect of rhein against oxidative stress‑related endothelial cell

injury. Mol Med Rep 2012;5:1261‑16.

Hosseini A, Shafiee‑Nick R, Mousavi SH. Combination of

Nigella sativa with Glycyrrhiza glabra and Zingiber officinale

augments their protective effects on doxorubicin‑induced toxicity

in h9c2 cells. Iran J Basic Med Sci 2014;17:993‑1000.

Buege JA, Aust SD. Microsomal lipid peroxidation. Methods

Enzymol 1978;53:302‑10.

Moradzadeh M, Rajabian A, Aghaei A, Hosseini A,

Sadeghnia HR. Rheum turkestanicuminduced apoptosis through

ROS without a differential effect on human leukemic cells.

Jundishapur J Nat Pharm Prod 2019;14:e12198.

Dorsey J F, Kao GD. Aloe (‑emodin) for cancer? More than just

a comforting salve. Cancer Biol Ther 2007;6:89‑90.

Alam MM, Javed K and Jafri MA. Effect of Rheum

emodi (Revand Hindi) on renal functions in rats.

J Ethnopharmacol 2005;96:121‑5.

WuY, Tu X, Lin G, Xia H, Huang H, Wan J, et al.

Emodin‑mediated protection from acute myocardial infarction

via inhibition of inflammation and apoptosis in local ischemic

myocardium. Life Sci 2007;81:1332‑8.

Zhang Y, Lin C, Yang X, Wang Y, Fang Y, Wang F. Effect of

emodin on the expression of TLR4 and P38MAPK in mouse

cardiac tissues with viral myocarditis. Int J Clin Exp Pathol


Chen YW, Chou HC, Lin ST, Chen YH, Chang YJ, Chen L,

et al. Cardioprotective effects of quercetin in cardiomyocyte

under ischemia/reperfusion injury. Evid Based Complement

Alternat Med 2013;2013:364519.

Wang Y, Zhang Z, Wu Y, Ke J, He X, Wang Y. Quercetin

postconditioning attenuates myocardial ischemia/reperfusion

injury in rats through the PI3K/Akt pathway. Braz J Med Biol

Res 2013;46:861‑7.

Dong Q, Chen L, Lu Q, Sharma S, Li L, Morimoto S, et al.

Quercetin attenuates doxorubicin cardiotoxicity by modulating B

mi‑1 expression. Br J Pharmacol 2014;171:4440‑54.

Tatlidede E, Şehirli Ö, Velioğlu‑Öğünç A, Çetinel Ş,

Yeğen BÇ, Yarat A, et al. Resveratrol treatment protects against

doxorubicin‑induced cardiotoxicity by alleviating oxidative

damage. Free Radic Res 2009;43:195‑205.

Danz EDB, Skramsted J, Henry N, Bennett JA, Keller RS.

Resveratrol prevents doxorubicin cardiotoxicity through

mitochondrial stabilization and the Sirt1 pathway. Free Radic

Biol Med 2009;46:1589‑97.

Sin TK, Tam BT, Yung BY, Yip SP, Chan LW, Wong CS, et al.

Resveratrol protects against doxorubicin‑induced cardiotoxicity

in aged hearts through the SIRT1‑USP7 axis. J Physiol


Jeong SO, Son Y, Lee JH, CheongYK, Park SH, Chung HT,

et al. Resveratrol analog piceatannol restores the palmitic

acid‑induced impairment of insulin signaling and production of

endothelial nitric oxide via activation of anti‑inflammatory and

antioxidative heme oxygenase‑1 in human endothelial cells. Mol

Med Rep 2015;12:937‑44.