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Ginsenoside Rf promotes testosterone synthesis through the cAMP/PKA/CREB signaling pathway to improve obesity-related

Zhang Runqi1, Zheng Xiaoxing1, Chen Yuqing2

  • 1Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China.

Biochemical Pharmacology
|January 30, 2026
PubMed

Insights

Ginsenoside Rf effectively combats obesity-related male hypogonadism by reducing body weight and improving testicular function. This natural compound promotes testosterone synthesis through the cAMP/PKA/CREB pathway.

Area of Science:

  • Endocrinology
  • Metabolic Disorders
  • Natural Product Chemistry

Background:

  • Obesity is a global health crisis linked to male hypogonadism.
  • The role of ginsenoside Rf in this condition is not well understood.

Purpose of the Study:

  • To investigate the effects of ginsenoside Rf on obesity-related male hypogonadism.
  • To explore the underlying mechanisms of ginsenoside Rf action.

Main Methods:

  • Male mice were fed a high-fat diet (HFD) and treated with ginsenoside Rf.
  • Testicular tissues were analyzed for lipid deposition, fibrosis, and protein expression.
  • Network pharmacology and cell-based assays (Leydig cells) were used to elucidate mechanisms.

Main Results:

  • Ginsenoside Rf reduced HFD-induced body weight, testicular lipid deposition, and fibrosis.
  • It increased testosterone levels and upregulated key steroidogenic proteins (Star, Srb1, Cyp11a1, Cyp17a1).
  • Ginsenoside Rf activated the cAMP/PKA/CREB pathway in Leydig cells, promoting testosterone synthesis.

Conclusions:

  • Ginsenoside Rf demonstrates therapeutic potential for obesity-related male hypogonadism.
  • It acts by enhancing testosterone synthesis through the cAMP/PKA/CREB signaling pathway.
Keywords:
Ginsenoside RfLate-Onset HypogonadismMale HypogonadismNetwork Pharmacology AnalysisObesityTestosterone

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