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Monotropein improves late-onset hypogonadism in TM3 Leydig cells and aged rats
Hee-Yeon Kwon1, Hyesung Lee2, Ji-Soo Choi1
1College of Pharmacy, Yonsei University, Songdogwahak-ro, Incheon, Yeonsu-gu 21983, Republic of Korea; R&D Center, NSTbio Co., Ltd., 32 Songdogwahak-ro, Yeonsu-gu, Incheon 21984, Republic of Korea.
Background And Aim:
Late-onset hypogonadism (LOH) is an age-related condition characterized by declining testosterone levels and impaired reproductive and metabolic functions. Fermented Morinda citrifolia extract (FME) has demonstrated therapeutic potential against LOH; however, its active constituents and underlying mechanisms remain unclear. The aim of this study was to identify the key bioactive compounds in FME and evaluate their efficacies and mechanisms of action in alleviating LOH.
Methods:
High-performance liquid chromatography (HPLC) was used to quantify the iridoids and coumarins in FME. Among these four candidates, monotropein (MON) was selected for functional evaluation. In vitro assays using TM3 Leydig cells were used to assess the effects of MON on steroidogenic gene and protein expression under oxidative stress. In vivo studies involved oral administration of MON (40 mg/kg/day) to aged Sprague-Dawley rats for 4 weeks. Hormonal, histological, reproductive, metabolic, and safety parameters were measured.
Results:
MON significantly restored testosterone production and upregulated key steroidogenic enzymes (StAR, 3β-HSD2, 17,20-desmolase, and 17β-HSD3) in vitro and in vivo. It improved serum testosterone levels, spermatogenesis, and sperm motility in aged rats. MON also reduced age-associated increases in total cholesterol and triglyceride levels without altering luteinizing hormone, follicle-stimulating hormone, or estradiol, and without inducing hepatic, renal, or prostate toxicity.
Conclusion:
MON was identified as the principal active compound of FME responsible for its LOH-alleviating effects. MON enhanced testicular steroidogenesis and improved reproductive and metabolic outcomes without causing systemic toxicity, supporting its potential as a targeted phytotherapeutic agent against age-related androgen deficiency.
Insights
Monotropein (MON), a compound from fermented Morinda citrifolia extract (FME), effectively treats late-onset hypogonadism (LOH). It boosts testosterone and improves reproductive health without side effects.
Area of Science:
- Phytochemistry
- Endocrinology
- Gerontology
Background:
- Late-onset hypogonadism (LOH) is an age-related decline in testosterone affecting reproductive and metabolic functions.
- Fermented Morinda citrifolia extract (FME) shows promise for LOH, but its active components and mechanisms are unknown.
Purpose of the Study:
- Identify key bioactive compounds in FME for LOH treatment.
- Evaluate the efficacy and mechanisms of identified compounds in alleviating LOH symptoms.
Main Methods:
- HPLC analysis identified iridoids and coumarins in FME, with monotropein (MON) selected for further study.
- In vitro assays assessed MON's effect on steroidogenesis in Leydig cells under oxidative stress.
- In vivo studies administered MON to aged rats, measuring hormonal, reproductive, metabolic, and safety parameters.
Main Results:
- MON significantly increased testosterone production and steroidogenic enzyme expression in vitro and in vivo.
- Oral MON administration improved serum testosterone, sperm parameters, and reduced cholesterol and triglycerides in aged rats.
- MON did not affect gonadotropins or estradiol and showed no hepatic, renal, or prostate toxicity.
Conclusions:
- Monotropein (MON) is the primary active compound in FME responsible for its LOH-alleviating effects.
- MON enhances testicular steroidogenesis, improving reproductive and metabolic health without systemic toxicity.
- MON shows potential as a targeted phytotherapeutic agent for age-related androgen deficiency.
