The Effect and Mechanism of Cinnamaldehyde on Testosterone Secretion in Murine Model | [Pakistan Veterinary Journal • 2025]

Author(s):

1. Qingrui Meng: Jinshan College, Fujian Agriculture and Forestry University,Fuzhou, Fujian Province, 350002,PR China

2. Xiaoyu Huang: College of Animal Science, Fujian Agriculture and Forestry University,Fuzhou, Fujian Province, 350002,PR China

3. Congguang Cai: College of Animal Science, Fujian Agriculture and Forestry University,Fuzhou, Fujian Province, 350002,PR China

4. Yuxin Guo: College of Animal Science, Fujian Agriculture and Forestry University,Fuzhou, Fujian Province, 350002,PR China

5. Yang Yang: College of Animal Science, Fujian Agriculture and Forestry University,Fuzhou, Fujian Province, 350002,PR China

6. Zhijian Huang: College of Animal Science, Fujian Agriculture and Forestry University,Fuzhou, Fujian Province, 350002,PR China

7. Dengfeng Wang: College of Animal Science, Fujian Agriculture and Forestry University,Fuzhou, Fujian Province, 350002,PR China

8. Muhammad Mohsin: Fujian University of Traditional Chinese Medicine,Fuzhou, Fujian Province,China

9. Guangwen Yin: College of Animal Science, Fujian Agriculture and Forestry University,Fuzhou, Fujian Province, 350002,PR China

10. Lei Wang: College of Animal Science, Fujian Agriculture and Forestry University,Fuzhou, Fujian Province, 350002,PR China

Abstract:

Cinnamon (Cinnamomum cassia (L.) D. Don) is a commonly used drug in traditional Chinese medicine; it is especially useful for improving the reproductive performance in males and females. Cinnamaldehyde is the main component of cinnamon, which has bactericidal and disinfectant properties, promotes gastrointestinal motility and regulates testosterone secretion in the male. The present study aimed to investigate the mechanisms by which cinnamaldehyde regulates testosterone secretion in male animals. For this purpose, four-month-old male mice (n=25) were randomly divided into five groups (n=5 each) and treated with PBS, DMSO and three doses of cinnamaldehyde (25, 50 and 75mg/kg) by gavage for 2 weeks. Histological (IHC), ELISA and molecular analyses (WB, RTqPCR) were used to assess effects of cinnamaldehyde on murine liver, serum testosterone levels, and testicular enzymes associated with testosterone production. The mechanisms by which cinnamaldehyde affects testosterone secretion in testis Leydig cells were explored using ELISA, flow cytometry, WB, fluorescent quantitative PCR, and dual luciferase reporter systems. The results showed that cinnamaldehyde elevated murine body weight, serum testosterone, testicular interstitial cell density, and steroidogenic enzyme expression (StAR, CYP11A1, 3ßHSD) without altering hepatic tissue and testicular indices. Cinnamaldehyde treatment at 5×10-5M increased the expression of steroid hormone synthase in Leydig cells, increased the proportion of cells in the S phase, significantly increased the promoter activity of the steroid hormone synthesis nuclear receptor steroidogenic factor 1 (SF-1), and up-regulated the expression of the nuclear receptor SF-1. The present study showed that cinnamaldehyde can upregulate the expression of steroid hormone synthase by increasing the activity of the steroid hormone synthesis nuclear receptor promoter, which in turn increases the synthesis and secretion of testosterone from testicular interstitial cells.

Page(s): 683-692

DOI: 10.29261/pakvetj/2025.191

Published: Journal: Pakistan Veterinary Journal, Volume: 45, Issue: 2, Year: 2025

Keywords:

Cinnamaldehyde Leydig cells Nuclear receptors Steroidogenicrelated genes Testosterone

References:

[1] Alvarez-Fernandez M,Malumbres M .2014 .Preparing a cell for nuclear envelope breakdown: Spatio-temporal control of phosphorylation during mitotic entry. Bioessays, 36(8) : 757-765.

[2] Azmahani A,Nakamura Y,Felizola SJ .2014 .Steroidogenic enzymes, their related transcription factors and nuclear receptors in human sebaceous glands under normal and pathological conditions. J Steroid Biochem Mol Biol, : 268-279.

[3] Cao LH,Qiao JY,Huang HY .2019 .PI3K-AKT signaling activation and Icariin:The potential effects on the perimenopausal depressionlike rat model. Molecules, 10(20) : 3700.

[4] Chou ST,Chang WL,Chang CT .2013 .Cinnamomum cassia essential oil inhibits alpha-MSH-induced melanin production and oxidative stress in murine B16 melanoma cells. Int J Mol Sci, 14(9) : 19186-19201.

[5] Di-Luoffo M,Daems C,Bergeron F .2015 .Novel targets for the transcription factors MEF2 in MA-10 Leydig cells. Biol Reprod, 93(1) : .

[6] Dou L,Zheng Y,Li L .2018 .The effect of cinnamon on polycystic ovary syndrome in a mouse model. Reprod Biol Endocrinol, 16(1) : 99.

[7] Doyle AA,Stephens JC .2019 .A review of cinnamaldehyde and its derivatives as antibacterial agents. Fitoterapia, 139 : 104405.

[8] Dube C,Bergeron F,Vaillant MJ .2009 .The nuclear receptors SF1 and LRH1 are expressed in endometrial cancer cells and regulate steroidogenic gene transcription by cooperating with AP-1 factors. Cancer Lett, 275(1) : 127-138.

[9] Gomez-Sanchez CE,Gomez-Sanchez EP,Steroidogenesis Adrenal .2024 .. Endocrinology, 165(4) : bqae032.

[10] Gopalakrishnan S,Dhaware M,Sudharma AA .2023 .Chemopreventive Effect of Cinnamon and Its Bioactive Compounds in a Rat Model of Premalignant Prostate Carcinogenesis. Cancer Prev Res (Phila), 16(3) : 139-151.

[11] Iwaoka Y,Hashimoto R,Koizumi H .2010 .Selective stimulation by cinnamaldehyde of progesterone secretion in human adrenal cells. Life Sci, 86 : 894-898.

[12] Johansson M,Clarke DJ .2022 .Cell cycle checkpoints and cell surface damage. Bioessays, 44(7) : e2200079.

[13] Ka H,Park HJ,Jung HJ .2003 .Cinnamaldehyde induces apoptosis by ROS-mediated mitochondrial permeability transition in human promyelocytic leukemia HL-60 cells. Cancer Lett, 196(2) : 143-152.

[14] Kraemer FB .2007 .Adrenal cholesterol utilization. Mol Cell Endocrinol, 265 : 42-45.

[15] Liu H,Wang G,Sui C .2025 .Woxuanzhongzhou formula improves DHEAS and high-fat diet-induced IR and anovulatory mice via AMPK/PGC1- alpha/Irisin pathway. J Ovarian Res, 18(1) : 7.

[16] Luo Q,Li X,Huang J .2024 .Shenqi Pill alleviates acetaminopheninduced liver injury: a comprehensive strategy of network pharmacology and spectrum-effect relationship reveals mechanisms and active components. Phytomedicine, 135 : 156050.

[17] Martin LJ,Boucher N,Brousseau C .2008 .The orphan nuclear receptor NUR77 regulates hormone-induced StAR transcription in Leydig cells through cooperation with Ca2+/calmodulin-dependent protein kinase I. Mol Endocrinol 22, (9) : 2021-2037.

[18] Mirmosayyeb O,Tanhaei A,Sohrabi HR .2017 .Possible Role of Common Spices as a Preventive and Therapeutic Agent for Alzheimer's Disease. Int J Prev Med, 8 : 5.

[19] Pereira RG,Pires OS,Hoefle CA .2024 .GnRH analogs induce a LH peak and increase pregnancy per timed-AI in ewes. Theriogenology, 215 : 132-137.

[20] Ranasinghe P,Pigera S,Premakumara GAS .2013 .Medicinal properties of 'true' cinnamon (Cinnamomum zeylanicum): a systematic review. BMC Complem Altern, Med13 : 275.

[21] Safaei F,Tamaddonfard E,Nafisi S .2021 .Effects of intraperitoneal and intracerebroventricular injection of cinnamaldehyde and yohimbine on blood glucose and serum insulin concentrations in ketamine-xylazine induced acute hyperglycemia. Vet Res Forum, 12(2) : 149-156.

[22] Taniguchi H,Komiyama J,Viger RS .2009 .The expression of the nuclear receptors NR5A1 and NR5A2 and transcription factor GATA6 correlates with steroidogenic gene expression in the bovine corpus luteum. Mol Reprod Dev, 76(9) : 873-880.

[23] Vigneron S,Sundermann L,Labbe JC .2018 .Cyclin A-cdk1- Dependent Phosphorylation of Bora Is the Triggering Factor Promoting Mitotic Entry. Dev Cell, 05(5) : 637-650.

[24] Wang D,Zhao X,Li J .2025 .Ginkgo biloba extract mediates HT22 cell proliferation and migration after oxygen-glucose deprivation/reoxygenation via regulating RhoA-ROCK2 signalling pathway. Metab Brain Dis, 40(1) : 91.

[25] Wang L,Lu M,Zhang R .2019 .Inhibition of Luman/CREB3 expression leads to the upregulation of testosterone synthesis in mouse Leydig cells. J Cell Physiol, 234(9) : 15257-15269.

[26] Wang L,Meng Q,Yang L .2021 .Luman/CREB3 knock-down inhibit hCG induced MLTC-1 apoptosis. Theriogenology, 161 : 140-150.

[27] Wang L,Meng Q,Wang H .2023 .Luman regulates the activity of the LHCGR promoter. Res Vet Sci, 161 : 132-137.

[28] Wang Z,Ren M,Liu W .1879 .Role of cell division cycle-associated proteins in regulating cell cycle and promoting tumor progression. Biochim Biophys Acta Rev Cancer, 5 : 189147.

[29] Wu L,Lan D,Sun B .2024 .Luoshi Neiyi Prescription inhibits estradiol synthesis and inflammation in endometriosis through the HIF1A/EZH2/SF-1 pathway. J Ethnopharmacol, 335 : 118659.

[30] Xiao Y,Zhao L,Li W .2021 .Circadian clock gene BMAL1 controls testosterone production by regulating steroidogenesis-related gene transcription in goat Leydig cells. J Cell Physiol, 236(9) : 6706-6725.

[31] Xiong Y,Chen H,Lin P .2017 .ATF6 knockdown decreases apoptosis, arrests the S phase of the cell cycle, and increases steroid hormone production in mouse granulosa cells. Am J Physiol Cell Physiol, 312(3) : C341-C353.

[32] Yang R,Muller C,Huynh V .1999 .Functions of cyclin A1 in the cell cycle and its interactions with transcription factor E2F-1 and the Rb family of proteins. Mol Cell Biol, 19(3) : 2400-2407.

[33] Yu Z,Li L,Wang C .2020 .Cantharidin Induces Apoptosis and Promotes Differentiation of AML Cells Through Nuclear Receptor Nur77-Mediated Signaling Pathway. Front Pharmacol, 11 : 1321.

[34] Zhang L,Jiang X,Shi J .2024 .Isoastragaloside I attenuates cholestatic liver diseases by ameliorating liver injury, regulating bile acid metabolism and restoring intestinal barrier. J Ethnopharmacol, 335 : .

[35] Mellon Zhang P,SH Zhang P .1997 .Multiple orphan nuclear receptors converge to regulate rat P450c17 gene transcription: novel mechanisms for orphan nuclear receptor action. Mol Endocrinol 11, (7) : 891-904.

[36] Zhu W,Giangrande PH,Nevins JR .2004 .E2Fs link the control of G1/S and G2/M transcription. EMBO J, 23(23) : 4615-4626.

[37] Zirkin BR,Papadopoulos V .2018 .Leydig cells: formation, function, and regulation. Biol Reprod, 99(1) : 101-111.

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