Brain and testicular metabonomics revealed the protective effects of Guilingji on senile sexual dysfunction rats

Guilingji (GLJ), which has been used to treat male diseases in China for centuries, contains 28 Chinese herbs and was previously established as an effective treatment for male sexual dysfunction . However, its mechanism of action remains unclear. To explore the efficacy and mechanism of action of GLJ in improving senile sexual dysfunction (SSD) in aging rats. An aging rat model of SSD was induced by the subcutaneous injection of d -galactose (300 mg⋅kg -1 ) and used to analyse the effects of GLJ (different concentrations of 37.5, 75, and 150 mg⋅kg -1 ) on the mating of aging rats. At the end of the 8th week, histopathological analysis of testicular tissues, assessment of the hypothalamic-pituitary-gonadal (HPG) axis hormone levels in serum or brain, and metabonomics analysis of the brain and testicular tissue with liquid chromatography–mass spectrometry was performed to explore the mechanism of action of GLJ. After treatment with GLJ, the mount and ejaculation latency levels were increased in the treatment group than those in model group (P < 0.05), moreover, the testicular morphology was improved. Gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) levels in rats were also improved significant (P < 0.05) compared with those in the model group. Furthermore, the metabonomics results in the testicular and brain tissue showed that GLJ improved SSD by adjusting amino acid and lipid metabolism. This study integrated the complementary metabolic profiles of the target tissues. GLJ might affect SSD rats by regulating amino acid and lipid metabolism and may modulate sensitivity to the signaling pathway in the HPG axis. This study provides an essential basis for the broad clinical application of GLJ. • Guilingji improved the sexual ability of aging rats. • The study illustrated the mechanisms of the effects of Guilingji on Senile Sexual Dysfunction rats by metabonomics. • 12 metabolites in brain tissues and 14 in testicular tissues were significantly restored by Guilingji. • Amino acid metabolism and lipid metabolism might be the most important metabolic pathways regulated by Guilingji.