Potential Gonado-Protective Effect of Cichorium endivia and Its Major Phenolic Acids against Methotrexate-Induced Testicular Injury in Mice

Enas E Eltamany; Esraa M Mosalam; Eman T Mehanna; Basma M Awad; Sarah M Mosaad; Maged S Abdel-Kader; Amany K Ibrahim; Jihan M Badr; Marwa S Goda

doi:10.3390/biomedicines10081986

Potential Gonado-Protective Effect of Cichorium endivia and Its Major Phenolic Acids against Methotrexate-Induced Testicular Injury in Mice

Biomedicines. 2022 Aug 16;10(8):1986. doi: 10.3390/biomedicines10081986.

Authors

Enas E Eltamany¹, Esraa M Mosalam², Eman T Mehanna³, Basma M Awad⁴, Sarah M Mosaad⁵, Maged S Abdel-Kader^{6

7}, Amany K Ibrahim¹, Jihan M Badr¹, Marwa S Goda¹

Affiliations

¹ Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.
² Department of Biochemistry, Faculty of Pharmacy, Menoufia University, Shebin El-Koum 32511, Egypt.
³ Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.
⁴ Department of Pharmacognosy, Faculty of Pharmacy, Sinai University, El-Arish 45518, Egypt.
⁵ Division of Pharmacology and Therapeutics, Department of Continuous Medical Education, General Authority of Healthcare, Ismailia 41522, Egypt.
⁶ Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
⁷ Department of Pharmacognosy, Faculty of Pharmacy, Alexandria University, Alexandria 21215, Egypt.

Abstract

Cichorium endivia L. (Asteraceae) is a wide edible plant that grows in the Mediterranean region. In this study, a phytochemical investigation of C. endivia L. ethanolic extract led to the isolation of stigmasterol (1), ursolic acid (2), β-amyrin (3), azelaic acid (4), vanillic acid (5), (6S, 7E)-6-hydroxy-4,7-megastigmadien-3,9-dione (S(+)-dehydrovomifoliol) (6), 4-hydroxy phenyl acetic acid (7), vomifoliol (8), ferulic acid (9), protocatechuic acid (10), kaempferol (11), p. coumaric acid (12), and luteolin (13). In addition, the total phenolic content as well as the in vitro antioxidant activity of C. endivia L. extract were estimated. Moreover, we inspected the potential gonado-protective effect of C. endivia crude extract, its phenolic fraction, and the isolated coumaric, vanillic, and ferulic acids against methotrexate (MTX)-induced testicular injury in mice. There were seven groups: normal control, MTX control, MTX + C. endivia crude extract, MTX + C. endivia phenolic fraction, MTX + isolated coumaric acid, MTX + isolated vanillic acid, and MTX + isolated ferulic acid. MTX was given by i.p. injection of a 20 mg/kg single dose. The crude extract and phenolic fraction were given with a dose of 100 mg/kg/day, whereas the compounds were given at a dose of 10 mg/kg/day. A histopathological examination was done. The testosterone level was detected in serum together with the testicular content of malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), interleukin 1β (IL-1β), IL-6, tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (NF-κB), B-cell lymphoma 2 (Bcl-2), Bcl-2 associated x protein (Bax), p53, and miR-29a. C. endivia crude extract, the phenolic fraction, and the isolated compounds showed significant elevation in their levels of testosterone, CAT, SOD, Bcl-2 with a significant decrease in their levels of MDA, TNF-α, IL-1β, IL-6, NF-κB, Bax, P53, and miR-29a compared to those of the MTX control group. In conclusion, C. endivia mitigated MTX-induced germ cell toxicity via anti-inflammatory, antioxidant, and antiapoptotic effects.

Keywords: C. endivia extract; antioxidant; apoptosis; inflammation; methotrexate; miR-29a; phenolic content; testicular injury.

Grants and funding

This research received no external funding.