• Modeling Mechanism：

  Adenine, as a purine precursor, increases uric acid production and synergistically raises serum uric acid (UA) levels with potassium oxalate. Persistent hyperuricemia leads to dysfunction of renal uric acid transporters (upregulation of reabsorption transporters and downregulation of secretory transporters), which in turn causes renal tubular damage and inflammatory infiltration, mimicking the pathophysiological process of human hyperuricemia and related kidney damage.

• Modeling Method：

  Experimental Subject：Experimental subjects: SPF-grade male Kunming mice, 7 weeks old, weighing approximately 20-25g after 1 week of environmental acclimatization; housing conditions: temperature 25±2℃, humidity 60±5%, 12-hour light-dark cycle, free access to food and water.

  Dosage and Administration Route：① Core modeling: potassium oxalate (200 mg/kg) + adenine (50 mg/kg) suspended in 5% gum arabic solution, administered by gavage, once daily for 21 consecutive days; ② Control treatment: equal volume of 5% gum arabic solution administered by gavage in the same manner; ③ Intervention verification (optional): benzbromarone (50 mg/kg) suspended in 5% gum arabic solution, administered by gavage, given 1 hour apart from the modeling drug, for 21 consecutive days.

  Dosing Frequency and Duration Model：once daily for 21 consecutive days

• Validation：

  Serum uric acid (UA): Significantly increased on day 3 of modeling (model group 123.45 μmol/L vs control group 42.03 μmol/L, p<0.001), peaking on day 7 (approximately 175.70 μmol/L, 3 times that of the control group), and then remained stable at a high level; Uric acid clearance (Cur): Significantly decreased from day 3 (model group 0.73 vs control group 1.56), and continued to decrease with the extension of modeling time (decreased to 0.19 on day 21); Urine indicators: The 24-hour urine volume of the model group was significantly increased, but the urinary uric acid excretion was reduced; Pathological indicators: - HE staining: Mild renal tubular epithelial cell necrosis and inflammatory infiltration appeared on day 3; the damage worsened from day 10, manifested as renal tubular dilation, blurred cell boundaries, and a large number of inflammatory cell infiltrations, with amyloid bodies visible in some renal tubules; Molecular indicators: - Renal transporters: Western blot detection showed that on day 3 of modeling... From day 7 onwards, the expression of URAT1 and GLUT9 (uric acid reabsorption transporters) proteins was significantly upregulated, while the expression of ABCG2 and OAT1 (uric acid secretion transporters) was significantly downregulated. NPT1 (secretion transporter) was significantly downregulated from day 7, with the most significant change on day 10. General condition: - Mice in the model group were lethargic, had decreased weight, dry fur, increased water intake and decreased food intake, which were significantly different from the normal group.

• Related Products：

  Adenine hydrochloride,Adenine hemisulfate，Potassium oxonate

*Precautions： On days 3, 7, 10, 14, 17, and 21 after blood collection, these mice were subsequently euthanized by carbon dioxide.

*References：Wen S,et,al. The Time-Feature of Uric Acid Excretion in Hyperuricemia Mice Induced by Potassium Oxonate and Adenine. Int J Mol Sci. 2020 Jul 22;21(15):5178.

• Modeling Mechanism：

  ① Adenine, as a purine precursor, increases uric acid production, and excessive uric acid deposition in the kidneys causes crystalline damage; ② Ethambutol hydrochloride inhibits renal uric acid excretion, exacerbating uric acid accumulation in the body and further aggravating kidney damage; ③ The two work together to activate inflammatory pathways, leading to upregulation of pro-inflammatory factors such as IL-6 and TNF, triggering renal tissue inflammation, glomerular sclerosis, and interstitial fibrosis, mimicking the core pathological process of human hyperuricemic nephropathy.

• Modeling Method：

  Experimental Subject：Experimental subjects: SPF-grade male Wistar rats, 7-8 weeks old, weighing 200-220g, acclimatized to the environment for 1 week (SPF-grade animal room, 12-hour light-dark cycle, temperature 20-24℃, humidity 45-65%, free access to food and water).

  Dosage and Administration Route：① Core modeling: Adenine (100 mg/kg) + ethambutol hydrochloride (250 mg/kg) dissolved in deionized water to prepare a 1% adenine + 2.5% ethambutol hydrochloride suspension, administered by gavage once daily for 3 consecutive weeks; ② Control treatment: Equal volume of deionized water administered by gavage in the same manner; ③ Intervention validation (optional): - Allopurinol (50 mg/kg) 0.5% solution administered by gavage, starting from week 2 of modeling, for 2 consecutive weeks; - Chicory formulation (CF) 8.64 g/kg (high dose), 2.16 g/kg (low dose). g/kg • Decoction administered by gavage • Starting from the second week of modeling, continue for 2 weeks.

  Dosing Frequency and Duration Model：

• Validation：

  Key indicators (serum biochemistry): - Serum uric acid (UA): The model group reached 2.40 μMol/L, significantly higher than the control group (2.25 μMol/L). After intervention with allopurinol and high-dose CF, it decreased to 1.57 μMol/L (p<0.05); - Renal function indicators: Serum urea (UREA) increased from 6.75 mMol/L to 15.87 mMol/L, and serum creatinine (CREA) increased from 38.5 μmol/L to 64.83 μMol/L (p<0.001), both significantly decreasing after intervention; Pathological indicators: - HE staining showed disordered kidney structure in the model group, with glomerular sclerosis, renal tubular epithelial cell damage, renal interstitial inflammation, and uric acid crystal deposition. Pathological damage was significantly reduced in the intervention group; Molecular indicators: - Significantly upregulated expression of IL-6, TP53, and TNF mRNA in renal tissue (p<0.05), and VEGFA and CASP3 mRNA expression... The expression was downgraded, and the trend could be reversed after intervention.

• Related Products：

  Adenine hydrochloride,Adenine hemisulfate，Ethambutol dihydrochloride

*Precautions： To alleviate pain, rats were euthanized by intraperitoneal injection of sodium pentobarbital.

*References：Li N,et,al. Integration of network pharmacology and intestinal flora to investigate the mechanism of action of Chinese herbal Cichorium intybus formula in attenuating adenine and ethambutol hydrochloride-induced hyperuricemic nephropathy in rats. Pharm Biol. 2022 Dec;60(1):2338-2354.