Rare Ginsenosides: Potential Treatment for Hyperuricemia and Spermatozoa Damage
Introduction
With changes in lifestyles and dietary structure, hyperuricemia shows an increasing prevalence year by year, which may become the second largest metabolic disease after diabetes mellitus, as well as the fourth most common chronic disease after hypertension, hyperglycemia, and hyperlipidemia. Recent research unravels that hyperuricemia is closely related to male infertility and affects semen quality. Long-term hyperuricemia, especially among younger individuals, may threaten the reproductive capacity of men at a reproductive age. Noteworthily, rare ginsenosides (RGs), the main active compounds in ginseng, have been proven to be effective in alleviating hyperuricemia and concomitant spermatozoa damage.
About hyperuricemia
Hyperuricemia is a metabolic disease caused by a purine metabolism disorder or insufficient excretion of uric acid. In traditional Chinese medicine (TCM), hyperuricemia is generally categorized as "gout" and "paralysis", which requires differential diagnosis and treatment. As described in the classic traditional Chinese medical text Shang Han Lun (On Cold Damage), ginseng can be used for hyperuricemia treatment.| TCM Type of Hyperuricemia | Treatment |
| Endoretention of damp heat | Clearing heat and dampness; promoting blood circulation to remove meridian obstruction |
| Liver qi stagnation | Soothing liver and relieving depression; regulating qi and relieving pain |
| Spleen vacuity with damp encumbrance | Invigorating spleen and removing dampness; promoting blood circulation to remove meridian obstruction |
| Renal deficiency and blood stasis | Invigorating kidney to replenish essence; promoting blood circulation to remove meridian obstruction |
Restoration of histopathological changes in the liver, kidney, and testes following treatment of RGs
RGs counteract histopathological changes and alleviate the pathological lesions in the kidney and testes. No significant damage is observed in liver of mice with PO-induced hyperuricemia. Post RGS treatment, the renal tubular vacuolar degeneration, dilatation and swelling in potassium oxonate (PO)-induced hyperuricemia are mitigated. In addition to a slight increase in the thickness of the peritubular membrane, PO group shows a significant reduced trend towards the internal diameter of the seminiferous tubules as well as the number of germ cell layers in the tubular wall and mature spermatozoa. Yet, these trends are reversed. Meanwhile, the number of germ cell layers and sperm density are restored in the RGs group.
Preventive and ameliorative effects of RGs in mice with PO-induced hyperuricemia
RGS containing Rg3, Rk1, Rg6, and Rg5 could repress serum uric acid (UA) level, serum and hepatic xanthine oxidase (XO) activity, renal renal creatinine (CRE) and renal creatinine (CRE) levels, the accumulation of malondialdehyde (MDA) in the kidneys and the production of renal IL-1β, while promoting renal superoxide dismutase (SOD) and glutathione (GSH) activities in mice with PO-induced hyperuricemia.
Moreover, RGs can improve sphingolipid metabolism, pyrimidine metabolism, and other metabolic pathways. RGs could increase gut microbial diversity, restore the Firmicutes/Bacteroidetes (F/B) ratio, and adjust the intestinal microbial balance. Remarkably, there is a correlation between differentially metabolites and the gut microbiota (Lactobacillus and Akkermansia).
Conclusion
RGs may be a candidate for the prevention and amelioration of hyperuricemia and concomitant sperm damage. On the one hand, RGs can alleviate PO-induced hyperuricemia by inhibiting XO activity, restoring renal function and regulating the intestinal flora balance. On the other hand, RGS can ameliorate the sperm damage associated with hyperuricemia by regulating sphingolipid metabolism, ameliorating renal oxidative stress, reducing inflammation, reversing renal injury, and repairing testicular tissue.Reference
Ji X, Yu L, Han C, et al. Investigating the effects of rare ginsenosides on hyperuricemia and associated sperm damage via nontargeted metabolomics and gut microbiota. J Ethnopharmacol. 2024;332:118362. doi:10.1016/j.jep.2024.118362BONTAC Ginsenosides
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