Volume 31, Issue 145 (March & April 2023)                   J Adv Med Biomed Res 2023, 31(145): 177-183 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Hosseini A, Alavi M S, Mohammadi S, Tayarani Najjaran Z, Rajabian A. Portulaca oleracea Protects H9c2 Cardiomyocytes Against Doxorubicin-Induced Toxicity by Inhibition of Oxidative Stress and Apoptosis. J Adv Med Biomed Res 2023; 31 (145) :177-183
URL: http://journal.zums.ac.ir/article-1-6698-en.html
Portulaca oleracea Protects H9c2 Cardiomyocytes Against Doxorubicin-Induced Toxicity by Inhibition of Oxidative Stress and Apoptosis
Azar Hosseini1 , Mohaddeseh Sadat Alavi1 , Soroush Mohammadi2 , Zahra Tayarani Najjaran3 , Arezoo Rajabian *4
1- Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran
2- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
3- Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
4- Dept. of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran , Rajabianar@mums.ac.ir
Keywords: Cardioprotective agents, Doxorubicin, Cardiomyocytes, Portulaca oleracea
Full-Text [PDF 648 kb]   (7947 Downloads)     |   Abstract (HTML)  (11340 Views)

✅In conclusion, we witnessed that P. oleracea has protective effect against doxorubicin-caused cardiomyocytes damage.


Full-Text:   (902 Views)
Introduction
 

Doxorubicin (DOX), is a member of the anthracycline family, which is frequently used as a chemotherapeutic agent in the treatment of solid and hematologic cancers (1). Despite therapeutic utilization, the clinical administration of DOX is limited due to its adverse effects, especially cardiotoxicity; change in the function, or structure of cardiomyocytes (2, 3). Different mechanisms play role in DOX-induced cardiotoxicity, however, the production of reactive oxygen species (ROS) is more important. Increasing free radicals leads to lipid peroxidation, reduction of anti-oxidant enzymes, and apoptosis (4). Nevertheless, anti-oxidant compounds may decrease doxorubicin toxicity via the scavenging of free radicals. The studies have reported that dexrazoxane decrease DOX-induced cardiotoxicity but attenuates the chemotherapeutic effects of DOX (5, 6). Today, medicinal herbs are applied in different diseases as supplementary or replacement for chemical drugs due to their various properties and their active ingredients (7). In vivo and in vitro studies have shown some medicinal herbs or active ingredients reduce DOX toxicity (8, 9). In in vitro models, the H9c2 cell line is considered as an appropriate in vitro model for studying DOX-induced cardiotoxicity because of its ability to differentiate into skeletal or cardiac muscle phenotypes (8).
Portulaca oleracea (P. oleracea) belongs to the Portulacaceae family which has various names in different regions such as qurfeh (Persia), purslane (the USA and Australia), pigweed (England), rigla (Egypt), pourpier (France), and Ma-Chi-Xian (China) (10). It grows in tropical Asian countries, the United States, and the Mediterranean (10). In folk medicine, P. oleracea is used for febrifuge, antiseptic, and anthelmintic properties (11). Other pharmacological properties are including muscle relaxant activity (12), decreasing locomotor activity (13), anti-convulsant (14), anti-oxidant (15), and anti-inflammatory (16). The anti-oxidant activity of P. oleracea is related to the presence of compounds such as gallotannins, omega-3 fatty acids, ascorbic acid, α-tocopherols, kaempferol, quercetin, and apigenin (17, 18). Various studies have reported cardioprotective effects of the active ingredient of P. oleracea such as quercetin (19, 20), α-linoleic acid (21), kaempferol (22), and apigenin (23, 24) against doxorubicin. In this research, we evaluated the protective effect of the methanolic extract of P. oleracea against DOX-induced toxicity in H9c2 cells. Resveratrol as a phenol compound is found in plants such as grapes, peanuts, and berries. Some studies have shown cardioprotective effects of resveratrol against doxorubicin toxicity (25, 26).
In the current study, we demonstrated that P. oleracea extract significantly decreased DOX-induced cardiomyocyte death, which depended on its ability to attenuate oxidative stress and apoptosis.
 

 

Materials and Methods

Reagents

The H9c2 cell line was obtained from the Pasteur Institute, Tehran, Iran. Glucose-high Dulbecco’s modified Eagle’s medium (DMEM), fetal bovine serum (FBS), and penicillin-streptomycin were purchased from Gibco (Grand Island, NY). Dimethyl sulfoxide (DMSO) was purchased from Merck (Darmstadt, Germany). Propidium iodide (PI), sodium citrate, Triton X-100, Dulbecco’s Phosphate-buffered saline (PBS), resveratrol,  dichlorodihydrofluorescein diacetate (H2DCF-DA), doxorubicin (DOX), and 4,5-Dimethylthiazol-2-yl,2,5-diphenyl tetrazolium (MTT) were obtained from Sigma (St Louis, MO, USA). The study was approved by the Animal Ethics Committee of the Mashhad University of Medical Sciences (IR.MUMS.MEDICAL.REC.1397.070).

Preparation of the extract

The plant material was powdered by a blender. To prepare the methanolic extract of P. oleracea, 50 g of the powder was percolated with 95% methanol at room temperature for 24. The solvent was removed using a rotary evaporator and the extract was dissolved in DMSO and stored at -20°C (27).

Cell culture and treatment

The H9c2 cells were maintained in high glucose DMEM with 10% FBS, and 1% of antibiotics (penicillin-streptomycin, 100 U/ml) at 37 °C in a 5% CO2 atmosphere. After achieving about 70–80% confluency, the cells were seeded (104 cells per well) in 96-well plates for measuring viability, and 106 cells/well in 6-well plates for other tests. Then, the monolayer cells were incubated with the fresh media containing P. oleracea extract (12-400 µg/ml) or resveratrol (50 µM) for 2h before exposure to DOX (5 Μm) for 24h.

Determination of cell survival by MTT assay

After the treatments, MTT solution (10 µl) was added to each well (final concentration of 0.5 mg/ml). After a 3h incubation at 37oC, the supernatant was discarded and the formazan crystals were dissolved by DMSO (100 µl). The absorbance was measured at 490 and 650 nm using a microplate reader. The absorbance of each group was normalized to that of the control group (28).

Measurement of ROS generation

To detect intracellular ROS level in the treated cells, 10 μl of dye 2′,7′dichlorodihydrofluorescein diacetate (10 μM, DCFH-DA) was added to each well. After incubation in dark for 30 min at 37°C, the flouresence intensity was recorded by fluorescence multi-well plate reader (excitation/emission: 485 nm and 530 nm) (29).

Determination of lipid peroxidation

The lipid peroxidation level was measured by calculating the concentration of malondialdehyde (MDA), which is the key product of lipid peroxidation and reacts with TBA to generate fluorescence
adduct following the method of previous studies (30). At the end of the incubation time of the cultured cell with P. oleracea extract, resveratrol, and DOX, a homogenate of cell lysate in trichloroacetic solution (1 ml, 2.5%) was prepared. The supernatant of the samples was separated and then thiobarbituric acid (0.67% w/v, 0.8 ml) and trichloroacetic acid (15% w/v, 0.4 ml) were added. Thereafter, the tubes were placed in boiling water. The mixture was cooled and the absorbance of the upper solution was then read using spectroflourimeter at 532 nm. The data were presented as percentages of the control (untreated group).

Flow cytometry detection of apoptotic cell death

Briefly, DNA staining was performed with PI (5 mg/100 ml, 30 min) in the cells treated with or without P. oleracea extract or resveratrol. Flow cytometer (FACS Calibur flow cytometer; BD Biosciences, USA) measured the cell cycle in each sample (A minimum of 10,000 cells). Finally, DNA histograms were analyzed using Flow Jo 7.6.1 software (31).

Statistical analyses

Comparisons between groups were carried out using one-way ANOVA analysis and Tukey, respectively. The data were statistically analyzed using Prism 8 and reported as mean ± SEM or percentage. P value less than 0.05 statistically indicated significance.

 
 
Results

Effect of P. oleracea on H9c2 cell viability

The H9c2 cells were incubated with increasing concentrations of P. oleracea extract for 24h. The findings showed that the extract at the concentration range of (12-400 µg/ml) did not have cytotoxic effect on cells, as compared with the control group (p > 0.05, Figure1).


Figure 1. Effect of P. oleracea on H9c2 cell viability. Cells were incubated with different concentrations of extract for 24 h. Cell viability was determined by MTT assay. Data are mean±SEM of three separate experiments. 
Figure 1. Effect of P. oleracea on H9c2 cell viability. Cells were incubated with different concentrations of extract for 24 h. Cell viability was determined by MTT assay. Data are mean±SEM of three separate experiments.

 

Protective effect of P. oleracea against doxorubicin-induced toxicity in H9c2 cell

In this experiment, DOX exposure with a concentration of 5 μM for 24h could significantly reduce cell viability (p<0.001). Cells pre-treatment with extract at 12-400 µg/ml concentrations for 2h could attenuate DOX toxicity at concentration of 50, 100 and 200 µg/ml (p<0.01, p<0.001, p<0.001, respectively). Also, resveratrol with a concentration of 50 µM decreased DOX-induced toxicity (p<0.001, Figure 2).
 

Figure 2. Effect of P. oleracea and resveratrol on doxorubicin-induced toxicity in H9c2 cell. The cells were pretreated (for 2 h) with different concentrations of extract and resveratrol before to exposure to doxorubicin. Data are expressed as mean ± SEM of three separate experiments. ### p<0.001 vs control, ** p<0.001 and *** p<0.001 versus doxorubicin. 
Figure 2. Effect of P. oleracea and resveratrol on doxorubicin-induced toxicity in H9c2 cell. The cells were pretreated (for 2 h) with different concentrations of extract and resveratrol before to exposure to doxorubicin. Data are expressed as mean ± SEM of three separate experiments. ### p<0.001 vs control, ** p<0.001 and *** p<0.001 versus doxorubicin.

 

The P. oleracea extract decreased doxorubicin-induced ROS production in H9c2 cell

Results showed that DOX significantly increased the generation of ROS compared to the control group (283 ± 1.68% vs 100 ± 1.5 %, p<0.001). The cells were pre-treated with extract for 2h and then doxorubicin was added. After 24h, P. oleracea extract concentrations of 50, 100, and 200 µg/ml attenuated ROS production following DOX-induced toxicity (p<0.01, p<0.001, p<0.001, respectively, Figure3). Moreover, resveratrol 50 µM decreased DOX-induced toxicity (p<0.001).
 

Figure 3. Effect of P. oleracea and resveratrol on doxorubicin-induced reactive oxygen species (ROS) generation in H9c2 cells. The cells were pretreated (for 2 h) with different concentrations of extract and resveratrol before to exposure to doxorubicin. Data are expressed as mean ± SEM of three separate experiments. ### p<0.001 vs control, ** p<0.001 and *** p<0.001 versus doxorubicin. 
Figure 3. Effect of P. oleracea and resveratrol on doxorubicin-induced reactive oxygen species (ROS) generation in H9c2 cells. The cells were pretreated (for 2 h) with different concentrations of extract and resveratrol before to exposure to doxorubicin. Data are expressed as mean ± SEM of three separate experiments. ### p<0.001 vs control, ** p<0.001 and *** p<0.001 versus doxorubicin.

 

The P. oleracea extract decreased doxorubicin-induced MDA production in H9c2 cell

Increasing ROS production leads to lipid peroxidation and elevation of MDA. As shown in Figure4, DOX significantly increased the amount of MDA in comparison with the control group (p<0.001), while pre-treatment cells with extract reduced the level of MDA at 50, 100, and 200 µg/ml concentrations. (respectively: p<0.01, p<0.01, p<0.001) (Figure.4). Also MDA level reduction was observed by resveratrol (50 µM, p<0.001).
 

Figure 4. Effect of P. oleracea and resveratrol on doxorubicin-induced MDA production in H9c2 cells. The cells were pretreated (for 2 h) with different concentrations of extract and resveratrol before to exposure to doxorubicin. Data are expressed as mean ± SEM of three separate experiments. ### p<0.001 vs control, ** p<0.001 and *** p<0.001 versus doxorubicin. 
Figure 4. Effect of P. oleracea and resveratrol on doxorubicin-induced MDA production in H9c2 cells.  The cells were pretreated (for 2 h) with different concentrations of extract and resveratrol before to exposure to doxorubicin. Data are expressed as mean ± SEM of three separate experiments. ### p<0.001 vs control, ** p<0.001 and *** p<0.001 versus doxorubicin.

 

The P. oleracea extract attenuated doxorubicin-induced apoptosis in H9c2 cell

As shown in Figure 5, DOX increased apoptotic cells while the P. oleracea extract and resveratrol treatment could suppress apoptotic cells following DOX toxicity. (7.5% in control cells vs. 52.2% in DOX-treated cells, and in resveratrol group 12.4%). However, when H9c2 cells were pre-treated with extract (50, 100, and 200 µg/ml), the apoptosis rate was reduced to 41%, 35% and 21%, respectively compared to DOX-injured cells.


Figure 5. Effect of P. oleracea and resveratrol on the percent of H9c2 cells in sub-G1 stage.

Figure 5. Effect of P. oleracea and resveratrol on the percent of H9c2 cells in sub-G1 stage.

 

 

Discussion

In the present study, we evaluated the protective effect of P. oleracea and resveratrol against DOX-induced cardiotoxicity in H9c2 cells. Our findings showed that DOX-induced cell death and apoptosis, and also increased the production of ROS and MDA. Moreover, we showed that P. oleracea extract at the concentration range of 50-200 µg/ml, effectively reduced DOX-caused toxicity via attenuation of intracellular free radicals, lipid peroxidation, and apoptotic cells which were similar to resveratrol.
DOX, as a chemotherapy drug, is applied in the treatment of different cancers including lung, breast, bladder, and leukemia (1). This drug led to acute adverse effects such as arrhythmia and chronic effects like cardiomyopathy (32). The studies have revealed that DOX causes cardiotoxicity via induction of apoptosis, generation of free radicals, and depletion of antioxidant enzymes (33). However, anti-oxidant compounds may reduce DOX-induced cardiotoxicity (34).
Nowadays, phytotherapy is considered as supplementary or alternative drug for the treatment of diseases such as cancer, Alzheimer and cardiovascular because they are composed of various active ingredients (35). P. oleracea is composed of various ingredients such as acid ascorbic, kaempferol, quercetin, apigenin, and β-carotene (36). The in vitro or in vivo studies have revealed quercetin, kaempferol, and apigenin decreased doxorubicin-induced cardiotoxicity. Kaempferol reduced doxorubicin toxicity in H9c2 cells via inhibition of p53 signaling and ERK-dependent MAPK pathways (22). Quercetin protected H9c2 cells against doxorubicin toxicity by attenuation of mitochondrial dysfunction, ROS generation, apoptosis, and DNA double-strand breaks while increasing the expression of Bcl-2 and Bmi-1 (19, 20). Also, in vivo study showed that quercetin reduced the cardiotoxicity of doxorubicin in mice by reduction of oxidative stress (20). α-Linolenic acid (ALA) reduced doxorubicin toxicity in rats by activating Keap1/Nrf2 pathway and anti-apoptosis through activating protein kinase B/extracellular signal-regulated kinase pathway (21). Researchers in the in vivo study showed that apigenin decreased doxorubicin toxicity in cardiac by decreasing apoptotic proteins (caspase3 and Bax), increasing anti-apoptotic protein (Bcl-2) and anti-oxidant enzyme such as SOD (21). It seems that the protective effect of P. oleracea extract in our study is linked to the presence of these ingredients in the herb. Qiao and coworkers examined that P. oleracea has protective effect against acute alcoholic liver injury in rats by decreasing of MDA level and elevation of anti-oxidant enzymes (37). Also, P. oleracea could attenuate rotenone-induced neurotoxicity (38). The extract decreased lipid peroxidation and oxidative stress in thyrotoxic rats (39). The extract showed cardio-protective effects in hyperthyroidism rats (40). Resveratrol as positive control which is found in various medicinal herbs has anti-oxidant activity and attenuated DOX-induced cardiotoxicity in vivo and in vitro studies (25). Interestingly, the supportive effect of P. oleracea extract was similar to resveratrol and may be a good choice in the reduction of DOX toxicity.

 

Conclusion

The study has shown that P. oleracea extract decreased the cardiotoxicity of DOX in H9c2 cells via decreasing oxidative stress and apoptosis. More investigation is needed to perceive the accuracy of mechanisms.

 

Acknowledgements

This paper was financially supported by Vice Chancellor for Research and Technology, Mashhad University of Medical Sciences, Mashhad, Iran.

 

Conflicts of Interest

The Authors declare no conflicts of interests.
 
 

Type of Study: Original Research Article | Subject: Pharmacology
Received: 2022/02/4 | Accepted: 2022/08/6 | Published: 2023/03/13
References
1. Damiani RM, Moura DJ, Viau CM, Caceres RA, Henriques JAP, Saffi J. Pathways of cardiac toxicity: comparison between chemotherapeutic drugs doxorubicin and mitoxantrone. Arch Toxicol. 2016;90(9):2063-76. [DOI:10.1007/s00204-016-1759-y] [PMID]
2. Raj S, Franco VI, Lipshultz SE. Anthracycline-induced cardiotoxicity: a review of pathophysiology, diagnosis, and treatment. Curr Treat Option Cardiovasc Med. 2014;16(6):315. [DOI:10.1007/s11936-014-0315-4] [PMID]
3. Csapo M, Lazar L. Chemotherapy induced cardiotoxicity: Pathophysiology and prevention. Clujul Med. 2014;87(3):135-42. [DOI:10.15386/cjmed-339] [PMID] [PMCID]
4. Zhao L, Zhang B. Doxorubicin induces cardiotoxicity through upregulation of death receptors mediated apoptosis in cardiomyocytes. Sci Rep. 2017;7:44735. [DOI:10.1038/srep44735] [PMID] [PMCID]
5. QuanJun Y, GenJin Y, LiLi W, et al. Protective effects of dexrazoxane against doxorubicin-induced cardiotoxicity: A metabolomic study. PloS one. 2017;12(1):e0169567. [DOI:10.1371/journal.pone.0169567] [PMID] [PMCID]
6. Dallons M, Schepkens C, Dupuis A, Tagliatti V, Colet JM. New insights about doxorubicin-induced toxicity to cardiomyoblast-derived H9C2 cells and dexrazoxane cytoprotective effect: contribution of in vitro (1)H-NMR metabonomics. Front Pharmacol. 2020;11:79. [DOI:10.3389/fphar.2020.00079] [PMID] [PMCID]
7. Hosseini A, Ghorbani A. Cancer therapy with phytochemicals: evidence from clinical studies. Avicenna J Phytomed. 2015;5(2):84.
8. Hosseini A, Sahebkar A. Reversal of doxorubicin-induced cardiotoxicity by using phytotherapy: a review. J Pharmacopuncture. 2017;20(4):243.
9. Sangweni NF, Moremane M, Riedel S, et al. The prophylactic effect of pinocembrin against doxorubicin-induced cardiotoxicity in an in vitro H9c2 cell model. Front Pharmacol. 2020;11:1172. [DOI:10.3389/fphar.2020.01172] [PMID] [PMCID]
10. Elkhayat ES, Ibrahim SR, Aziz MA. Portulene, a new diterpene from Portulaca oleracea L. J Asian Nat Product Res. 2008;10(11):1039-43. [DOI:10.1080/10286020802320590] [PMID]
11. Iranshahy M, Javadi B, Iranshahi M, et al. A review of traditional uses, phytochemistry and pharmacology of Portulaca oleracea L. J Ethnopharmacol. 2017;205:158-72. [DOI:10.1016/j.jep.2017.05.004] [PMID]
12. Khazdair MR, Saadat S, Aslani MR, Shakeri F, Boskabady MH. Experimental and clinical studies on the effects of Portulaca oleracea L. and its constituents on respiratory, allergic, and immunologic disorders, a review. Phytother Res. 2021;35(12):6813-42. [DOI:10.1002/ptr.7268] [PMID]
13. Shafi S, Tabassum N. Acute oral toxicity and hypoglycaemic study of ethanolic extract of portulaca oleracea (whole plant) in swiss albino mice. Int J Pharm Pharm Sci. 2013; 5(4):389-93.
14. Radhakrishnan R, Zakaria M, Islam M, et al. Neuropharmacological actions of Portulaca oleraceae L v. sativa (Hawk). J Ethnopharmacol. 2001;76(2):171-6. [DOI:10.1016/S0378-8741(01)00230-6] [PMID]
15. Lim YY, Quah EP. Antioxidant properties of different cultivars of Portulaca oleracea. Food Chem. 2007;103(3):734-40. [DOI:10.1016/j.foodchem.2006.09.025]
16. Baradaran Rahimi V, Rakhshandeh H, Raucci F, et al. Anti-inflammatory and anti-oxidant activity of Portulaca oleracea extract on LPS-induced rat lung injury. Molecules. 2019;24(1):139. [DOI:10.3390/molecules24010139] [PMID] [PMCID]
17. Zhu H, Wang Y, Liu Y, Xia Y, Tang T. Analysis of flavonoids in Portulaca oleracea L. by UV-vis spectrophotometry with comparative study on different extraction technologies. Food Analyt Method. 2010;3(2):90-7. [DOI:10.1007/s12161-009-9091-2]
18. Subpiramaniyam S. Portulaca oleracea L. for phytoremediation and biomonitoring in metal-contaminated environments. Chemosphere. 2021;280:130784. [DOI:10.1016/j.chemosphere.2021.130784] [PMID]
19. Chen JY, Hu RY, Chou HC. Quercetin-induced cardioprotection against doxorubicin cytotoxicity. J Biomed Sci. 2013;20(1):95. [DOI:10.1186/1423-0127-20-95] [PMID] [PMCID]
20. Dong Q, Chen L, Lu Q, et al. Quercetin attenuates doxorubicin cardiotoxicity by modulating B mi‐1 expression. Br J Pharmacol. 2014;171(19):4440-54. [DOI:10.1111/bph.12795] [PMID] [PMCID]
21. Yu X, Cui L, Zhang Z, Zhao Q, Li S. α-Linolenic acid attenuates doxorubicin-induced cardiotoxicity in rats through suppression of oxidative stress and apoptosis. Acta Biochim Biophys Sin. 2013;45(10):817-26. [DOI:10.1093/abbs/gmt082] [PMID]
22. Xiao J, Sun GB, Sun B, et al. Kaempferol protects against doxorubicin-induced cardiotoxicity in vivo and in vitro. Toxicol. 2012;292(1):53-62. [DOI:10.1016/j.tox.2011.11.018] [PMID]
23. Zare MFR, Rakhshan K, Aboutaleb N, et al. Apigenin attenuates doxorubicin induced cardiotoxicity via reducing oxidative stress and apoptosis in male rats. Life Sci. 2019;232:116623. [DOI:10.1016/j.lfs.2019.116623] [PMID]
24. Yu W, Sun H, Zha W, et al. Apigenin attenuates adriamycin-induced cardiomyocyte apoptosis via the PI3K/AKT/mTOR pathway. Evid Based Complement Alternat Med. 2017;2017. [DOI:10.1155/2017/2590676] [PMID] [PMCID]
25. Arafa MH, Mohammad NS, Atteia HH, Abd-Elaziz HR. Protective effect of resveratrol against doxorubicin-induced cardiac toxicity and fibrosis in male experimental rats. J Physiol Biochem. 2014;70(3):701-11. [DOI:10.1007/s13105-014-0339-y] [PMID]
26. Lou Y, Wang Z, Xu Y, et al. Resveratrol prevents doxorubicin-induced cardiotoxicity in H9c2 cells through the inhibition of endoplasmic reticulum stress and the activation of the Sirt1 pathway. Int J Molec Med. 2015;36(3):873-80. [DOI:10.3892/ijmm.2015.2291] [PMID]
27. Shojaee S, Parhiz H, Eshaghi A, et al. In vitro protective effects of Scutellaria litwinowii root extract against H2O2-induced DNA damage and cytotoxicity. J Complement Integrat Med. 2014;11(2):121-7. [DOI:10.1515/jcim-2014-0009] [PMID]
28. Hosseini A, Rajabian A. Protective effect of Rheum turkestanikum root against doxorubicin-induced toxicity in H9c2 cells. Revista Brasileira de Farmacognosia. 2016;26(3):347-51. [DOI:10.1016/j.bjp.2016.02.004]
29. Mousavi SH, Hosseini A, Bakhtiari E, Rakhshandeh H. Capparis spinosa reduces Doxorubicin-induced cardio-toxicity in cardiomyoblast cells. Avicenna J Phytomed. 2016;6(5):488.
30. Sadeghnia HR, Rajabian A, Ghorbani A, Moradzadeh M, Hosseini A. Effects of standardized extract of Ferula gummosa root on glutamate-induced neurotoxicity. Folia neuropathologica. 2017;55(4):340-6. [DOI:10.5114/fn.2017.72399] [PMID]
31. Rajabian A, Sadeghnia HR, Moradzadeh M, Hosseini A. Rheum turkestanicum reduces glutamate toxicity in PC12 and N2a cell lines. Folia neuropathologica. 2018;56(4):354-61. [DOI:10.5114/fn.2018.80869] [PMID]
32. Sun S, Wang K, Lei H, et al. Inhibition of organic cation transporter 2 and 3 may be involved in the mechanism of the antidepressant-like action of berberine. Progress Neuro Psychopharmacol Biol Psychiatr. 2014;49:1-6. [DOI:10.1016/j.pnpbp.2013.11.005] [PMID]
33. Renu K, Abilash V, PB TP, Arunachalam S. Molecular mechanism of doxorubicin-induced cardiomyopathy-An update. Europ J Pharmacol. 2018;818:241-53. [DOI:10.1016/j.ejphar.2017.10.043] [PMID]
34. Deres P, Halmosi R, Toth A, et al. Prevention of doxorubicin-induced acute cardiotoxicity by an experimental antioxidant compound. J Cardiovasc Pharmacol. 2005;45(1):36-43. [DOI:10.1097/00005344-200501000-00007] [PMID]
35. Liu J, Pei M, Zheng C, et al. A systems-pharmacology analysis of herbal medicines used in health improvement treatment: predicting potential new drugs and targets. Evid Based Complement Alternat Med. 2013;2013. [DOI:10.1155/2013/938764] [PMID] [PMCID]
36. Farkhondeh T, Samarghandian S, Azimi-Nezhad M, Hozeifi S. The hepato-protective effects of Portulaca oleracea L. extract: Review. Curr Drug Discover Technol. 2019;16(2):122-6. [DOI:10.2174/1570163815666180330142724] [PMID]
37. Qiao JY, Li HW, Liu FG, et al. Effects of Portulaca Oleracea extract on acute alcoholic liver injury of rats. Molecules. 2019;24(16):2887. [DOI:10.3390/molecules24162887] [PMID] [PMCID]
38. E Abdel Moneim A. The neuroprotective effects of purslane (Portulaca oleracea) on rotenone-induced biochemical changes and apoptosis in brain of rat. CNS Neurol Disord Drug Targets. 2013;12(6):830-41. [DOI:10.2174/18715273113129990081] [PMID]
39. Pakdel R, Vatanchian M, Niazmand S, et al. Comparing the effects of Portulaca oleracea seed hydro-alcoholic extract, valsartan, and vitamin E on hemodynamic changes, oxidative stress parameters and cardiac hypertrophy in thyrotoxic rats. Drug Chem Toxicol. 2019:1-8. [DOI:10.1080/01480545.2019.1651330] [PMID]
40. Khodadadi H, Pakdel R, Khazaei M, Niazmand S, Bavarsad K, Hadjzadeh MA-R. A comparison of the effects of Portulaca oleracea seeds hydro-alcoholic extract and Vitamin C on biochemical, hemodynamic and functional parameters in cardiac tissue of rats with subclinical hyperthyroidism. Avicenna J Phytomed. 2018;8(2):161.
Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2025 CC BY-NC 4.0 | Journal of Advances in Medical and Biomedical Research

Designed & Developed by : Yektaweb