"Correlation between Ziziphus Secondary Metabolites and Amino Acid Homeostasis: Effects on Growth and Renal Biomarkers in a Rabbit Model"

Abstract: Medicinal plants represent a valuable source of bioactive secondary metabolites with proven physiological and therapeutic effects. Ziziphus spina-christi is widely recognized for its rich phytochemical composition and traditional medicinal applications; however, its relationship with amino acid homeostasis and renal function remains insufficiently explored. This study aimed to investigate the correlation between Ziziphus secondary metabolites and amino acid homeostasis and to evaluate their effects on growth performance and renal biomarkers in a rabbit model. Fresh leaves of Ziziphus spina-christi were collected from the Green Mountain region, Libya, extracted using 70% ethanol, and analyzed for amino acid composition using high-performance liquid chromatography (HPLC). Ten healthy male rabbits were randomly assigned to either a Sidr-treated group, receiving 200 mg/kg body weight of the extract orally every other day for six weeks, or a control group receiving distilled water. Body weight was recorded weekly, and serum renal biomarkers, including urea, creatinine, and uric acid, were measured at the end of the experimental period. HPLC analysis revealed a diverse amino acid profile in Ziziphus leaf extract, with proline being the most abundant amino acid (23.10 mg/mL), followed by glutamine (19.60 mg/mL) and serine (16.02 mg/mL), indicating strong nitrogen metabolism and antioxidant potential. Sidr-treated rabbits showed a significant increase in final body weight compared to controls (P < 0.05). Moreover, serum urea, creatinine, and uric acid levels were significantly reduced in the treated group, reflecting improved renal function and nitrogen metabolism. In conclusion, Ziziphus spina-christi extract enhances growth performance and exerts a nephroprotective effect, likely mediated through its rich secondary metabolite content and its role in maintaining amino acid homeostasis. These findings support the potential application of Ziziphus as a natural therapeutic and nutritional agent for promoting metabolic balance and renal health.