Quercetin and Apigenin of Cymbopogon citratus mediate inhibition of HCT-116 and PC-3 cell cycle progression and ameliorate Doxorubicin-induced testicular dysfunction in male rats

Abstract

Introduction: This study aims to elucidate the possible ameliorative effect of Cymbopogon citratus (CC), i.e. lemon grass, in a Doxorubicin (Dox)-induced male testicular damage and infertility model. Moreover, the anticancer role of the main active constituents of CC (Apigenin and Quercetin) was evaluated on prostatic and colon cancer (PC-3 and HCT-116 carcinoma cell lines, respectively).
 Methods: In vitro studies of the cell lines were carried out to determine the IC50 of each active constituent of CC, in order to select the most suitable dose for in vivo studies. For the in vivo studies, 24 rats were divided into 4 groups: Group 1 received saline treatment (negative control), Group 2 received treatment with CC (300 mg/kg body weight (b.w.)), Group 3 received Dox treatment (25 mg/kg b.w. intraperitoneally (i.p.)) on day 9 of the study, and Group 4 received CC treatment followed by Dox treatment on day 9 of the study. All the treatments were administered orally for 10 consecutive days.
 Results: The data revealed that Apigenin and Quercetin (AQ) had greater potency against PC-3 cells than HCT-116 cells. In vivo studies demonstrated that Dox treatment induced testicular damage and increased nitrosative stress, inflammation, and cell death, while decreasing cell energy markers for testes. In contrast, rats treated with CC only, or in parallel with Dox, showed ameliorative responses against Dox; they also showed greater testicular activity than normal, which reflected the ability of CC to significantly improve reproductive health performance.
 Conclusion: In conclusion, CC inhibits the activity and growth of PC-3 and HCT-116 carcinoma cell lines and, moreover, the whole extract of CC ameliorates testicular dysfunction induced by Dox.

Apigenin Isolated from Carduus crispus Protects against H2O2-Induced Oxidative Damage and Spermatogenic Expression Changes in GC-2spd Sperm Cells

“…In relation to male reproductive functions, apigenin exhibited beneficial effects in improving testicular functions in a variety of in vitro and in vivo insults such as heat-, chloroquine-, doxorubicin- and ischemia reperfusion-induced models [ 4 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. However, the effects of apigenin against ROS-induced oxidative damage in sperm cells was not elucidated.…”

Biosynthesis of Diverse Class FlavonoidsviaShikimate and Phenylpropanoid Pathway

“…The diverse type flavonoids show diverse biological function as protection from UV radiation, apoptosis, treatment of psoriasis [7,8]. The diverse class of flavonoids have been isolated from several plant species as quercetin and apigenin from Cymbopogon citratus [9], pinostrobin and cardamonin chalcone from rhizomes of Boesenbergia rotunda [10], 6-aldehydo-isoophiopogonanone A, 6-aldehydo-isoophiopogonanone B, methylophiopogonanone A and methylophiopogonanone B from fibrous roots of Ophiopogon japonicus [11]. The diverse type flavonoids were synthesized in plant species via shikimate and phenylpropanoid pathway.…”

Ovatrine, a compound from plant extracts, used for female infertility treatment and increase the number of ovarian follicles

“…Additionally, the whole extract ameliorates testicular dysfunction and prevent the testicular fail induced by anti-tumor drug such doxorubicin. 7 Concerning the serum sex hormones, the testosterone and follicle stimulating hormone will be changed when diet rich with polyphenols or glycosides or flavonoids can be administrated daily for some time. For example the longterm exposure to tea polyphenols increased the follicle stimulating hormone and this associated with improved reproduction in hens and thus improved egg production.…”