|
Pharmacy Information 2025
复方伸筋胶囊对高尿酸血症小鼠降尿酸作用机制研究
|
Abstract:
目的:探讨贵州民族药复方伸筋胶囊对高尿酸血症小鼠尿酸代谢的调控作用及其潜在机制,为其临床应用提供科学依据并揭示其作用机制的分子基础。方法:采用氧嗪酸钾腹腔注射诱导小鼠建立高尿酸血症模型,随机分为空白对照组、模型组、别嘌醇组、复方伸筋胶囊低、中、高剂量组(每组8只)。复方伸筋胶囊按照低、中、高剂量分别以24.5 mg/kg、49 mg/kg、98 mg/kg灌胃,每日1次,共7天。别嘌醇组予10.5 mg/kg灌胃,空白组和模型组予生理盐水灌胃。检测血清尿酸(UA)、黄嘌呤氧化酶(XO)、肌酐(Scr)、尿素氮(BUN)水平。结果:复方伸筋胶囊各剂量组与模型组相比,小鼠血清尿酸水平显著降低(P < 0.05),其中高剂量组降尿酸作用明显;肝脏及血清中XO浓度明显下降,尤以高剂量组降幅最显著(P < 0.05)。复方伸筋胶囊对肾功能指标(Scr、BUN)无显著影响(P > 0.05)。结论:复方伸筋胶囊能够通过抑制XO活性显著降低高尿酸血症小鼠的血清尿酸水平,同时未见明显肝肾毒性,具有潜在的临床应用价值。
Objective: To investigate the regulatory effects and potential mechanisms of Guizhou ethnic medicine compound Shenjin Capsules on uric acid metabolism in a mouse model of hyperuricemia, providing scientific evidence for its clinical application and elucidating its molecular basis. Methods: A hyperuricemia model was established in mice by intraperitoneal injection of potassium oxonate. The mice were randomly divided into six groups: control group, model group, allopurinol group, and low-, medium-, and high-dose Shenjin Capsule groups (8 mice per group). Shenjin Capsules were administered via gavage at doses of 24.5 mg/kg, 49 mg/kg, and 98 mg/kg, respectively, once daily for 7 days. The allopurinol group received 10.5 mg/kg by gavage, while the control and model groups received physiological saline. Serum uric acid (UA), xanthine oxidase (XO), creatinine (Scr), and blood urea nitrogen (BUN) levels were measured. Results: Compared with the model group, all Shenjin Capsule groups exhibited significantly reduced serum UA levels (P < 0.05), with the high-dose group demonstrating the most pronounced effect. Hepatic and serum XO levels also decreased significantly, particularly in the high-dose group (P < 0.05). No significant effects on renal function markers (Scr and BUN) were observed (P > 0.05). Conclusion: Compound Shenjin Capsules significantly lower serum UA levels in hyperuricemic mice by inhibiting XO activity, with no apparent hepatotoxicity or nephrotoxicity, suggesting potential clinical application value.
[1] | Dalbeth, N., Gosling, A.L., Gaffo, A. and Abhishek, A. (2021) Gout. The Lancet, 397, 1843-1855. https://doi.org/10.1016/s0140-6736(21)00569-9 |
[2] | Bardin, T. and Richette, P. (2017) Impact of Comorbidities on Gout and Hyperuricaemia: An Update on Prevalence and Treatment Options. BMC Medicine, 15, Article No. 123. https://doi.org/10.1186/s12916-017-0890-9 |
[3] | Pascart, T. and Lioté, F. (2018) Gout: State of the Art after a Decade of Developments. Rheumatology, 58, 27-44. https://doi.org/10.1093/rheumatology/key002 |
[4] | Gao, T., Xu, J., Xiao, Y., Li, J., Hu, W., Su, X., et al. (2022) Therapeutic Effects and Mechanisms of N-(9,10-Anthraquinone-2-Ylcarbonyl) Xanthine Oxidase Inhibitors on Hyperuricemia. Frontiers in Pharmacology, 13, Article ID: 950699. https://doi.org/10.3389/fphar.2022.950699 |
[5] | El Ridi, R. and Tallima, H. (2017) Physiological Functions and Pathogenic Potential of Uric Acid: A Review. Journal of Advanced Research, 8, 487-493. https://doi.org/10.1016/j.jare.2017.03.003 |
[6] | White, W.B. (2018) Gout, Xanthine Oxidase Inhibition, and Cardiovascular Outcomes. Circulation, 138, 1127-1129. https://doi.org/10.1161/circulationaha.118.036148 |
[7] | Oh, D., Kim, J.R., Choi, C.Y., Choi, C., Na, C., Kang, B.Y., et al. (2019) Effects of Chondrot on Potassium Oxonate-Induced Hyperuricemic Mice: Downregulation of Xanthine Oxidase and Urate Transporter 1. BMC Complementary and Alternative Medicine, 19, Article No. 10. https://doi.org/10.1186/s12906-018-2415-2 |
[8] | Stamp, L.K. and Dalbeth, N. (2018) Prevention and Treatment of Gout. Nature Reviews Rheumatology, 15, 68-70. https://doi.org/10.1038/s41584-018-0149-7 |
[9] | 方宁远, 吕力为, 吕晓希, 等. 中国高尿酸血症相关疾病诊疗多学科专家共识(2023年版) [J]. 中国实用内科杂志, 2023, 43(6): 461-480. |
[10] | Chen, J., Zheng, Y., Gong, S., Zheng, Z., Hu, J., Ma, L., et al. (2023) Mechanisms of Theaflavins against Gout and Strategies for Improving the Bioavailability. Phytomedicine, 114, Article ID: 154782. https://doi.org/10.1016/j.phymed.2023.154782 |
[11] | Oh, K.K., Adnan, M. and Cho, D.H. (2021) Network Pharmacology Study on Morus alba L. Leaves: Pivotal Functions of Bioactives on RAS Signaling Pathway and Its Associated Target Proteins against Gout. International Journal of Molecular Sciences, 22, Article No. 9372. https://doi.org/10.3390/ijms22179372 |
[12] | Li, S., Li, L., Yan, H., Jiang, X., Hu, W., Han, N., et al. (2019) Anti-Gouty Arthritis and Anti-Hyperuricemia Properties of Celery Seed Extracts in Rodent Models. Molecular Medicine Reports, 20, 4623-4633. https://doi.org/10.3892/mmr.2019.10708 |
[13] | Zhang, Y., Jin, L., Liu, J., Wang, W., Yu, H., Li, J., et al. (2018) Effect and Mechanism of Dioscin from Dioscorea Spongiosa on Uric Acid Excretion in Animal Model of Hyperuricemia. Journal of Ethnopharmacology, 214, 29-36. https://doi.org/10.1016/j.jep.2017.12.004 |
[14] | Jung, S.M., Schumacher, H.R., Kim, H., Kim, M., Lee, S.H. and Pessler, F. (2007) Reduction of Urate Crystal-Induced Inflammation by Root Extracts from Traditional Oriental Medicinal Plants: Elevation of Prostaglandin D2 Levels. Arthritis Research & Therapy, 9, R64. https://doi.org/10.1186/ar2222 |
[15] | Li, N., Chen, S., Deng, W., Gong, Z., Guo, Y., Zeng, S., et al. (2023) Kaempferol Attenuates Gouty Arthritis by Regulating the Balance of Th17/Treg Cells and Secretion of IL-17. Inflammation, 46, 1901-1916. https://doi.org/10.1007/s10753-023-01849-8 |