Penthorum chinense Pursh. attenuates hyperuricemia by regulation of uric acid excretion and gut microbiota

Abstract

Objective: Hyperuricemia (HUA) is a metabolic disease that threatens human health. The role of Penthorum chinense Pursh. (PCP) in the treatment of HUA has begun to receive attention in recent years. This study aimed to investigate the effects and potential mechanisms of PCP in HUA treatment.

Methods: A HUA murine model was induced in C57/BL6 mice using potassium oxonate (PO) and adenine (AD). Serum uric acid (SUA) was measured using ultra-performance liquid chromatography (UPLC). Serum creatinine (Scr) was detected using a creatine oxidase assay kit, and serum blood urea nitrogen (BUN) was detected using a urease indophenol blue assay kit. Protein expression levels were detected using western blotting, and gut microbiota were detected using 16S rRNA.

Results: PCP substantially improved the serum contents of SUA, Scr, and BUN and alleviated kidney injury. PCP promotes renal uric acid excretion by downregulating GLUT9 and URAT1 expression and upregulating ABCG2 and OAT1 expression PCP also regulated the NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) pathway and reduced the expression of inflammatory factors, thus attenuating kidney injury in HUA mice. PCP regulated the structure of the gut microbiota, including the relative abundance of beneficial bacteria, such as Lactobacillus and Alistipes, which promoted uric acid metabolism and anti-inflammatory effects.

Conclusions: PCP can reduce uric acid levels by promoting renal uric acid excretion and regulating the gut microbiota. PCP improves kidney injury by inhibiting the activation of the NLRP3 signaling pathway and reducing the levels of inflammatory factors.

Keywords

Gut microbiota / Hyperuricemia / NLRP3 / Penthorum chinense Pursh

Conflict of interest statement

Tao Wang is an editorial board member of this journal. The other authors declare no conflict of interest.

Funding

This research was funded by the National Natural Science Foundation of China (82304870), Innovation Team and Talents Cultivation Program of National Administmiceion of Traditional Chinese Medicine (ZYYCXTD-C-202009), Tianjin Municipal Health Commission Project (2024009), and Tianjin University Students’ Innovation and Entrepreneurship Training Program Project (202410063027).

Author contributions

Yang Wang, Dan Wang, Yi Zhang, and Tao Wang participated in research design. Jing Xie, Siya Yan, Meifang Cheng, Yan Jing, Ke Li, Fengyan Yang, Qian Chen, Jian Li, and Yuzheng Wu participated in the performance of the research and analyzed the data. Yang Wang and Dan Wang were responsible for writing the manuscript. Yi Zhang and Tao Wang checked the manuscript. Tao Wang and Dan Wang provided the funding.

Ethical approval of studies and informed consent

Animal experiments were approved by the Science and Technological Committee and the Animal Use and Care Committee of TJUTCM (TCM-LAEC2022060).

Acknowledgments

None.

Data availability

All data generated or analyzed during this study are included in this published article.

References

[1] Nian YL, You CG. Susceptibility genes of hyperuricemia and gout. Hereditas 2022; 159(1):30.

[2] Zhang XY, Chen J, Yi K, et al. Phlorizin alleviated obesity-associated endotoxemia and insulin resistance in high-fat diet-fed mice by targeting the gut microbiota and intestinal barrier integrity. Gut Microbes 2020; 12(1):1-18.

[3] Zhang ZH, Li RR, Chen Y, et al. Integration of traditional, complementary, and alternative medicine with modern biomedicine: the scientization, evidence, and challenges for integration of traditional Chinese medicine. Acupunct Herb Med. 2024; 4(1):68-78.

[4] Oshima S, Shiiya S, Nakamura Y. Combined supplementation with glycine and tryptophan reduces purine-induced serum uric acid elevation by accelerating urinary uric acid excretion: a randomized, single-blind, placebo-controlled, crossover study. Nutrients 2019; 11(11):2562.

[5] Chang YH, Chiang YF, Chen HY, et al. Anti-inflammatory and anti-hyperuricemic effects of chrysin on a high fructose corn syrup-induced hyperuricemia rat model via the amelioration of urate transporters and inhibition of NLRP 3 inflammasome signaling pathway. Antioxidants (Basel) 2021; 10(4):564.

[6] Sun X, Wen J, Guan B, et al. Folic acid and zinc improve hyperuricemia by altering the gut microbiota of mice with high-purine diet-induced hyperuricemia. Front Microbiol 2022; 13:907952.

[7] Xu Y, Cao X, Zhao H, et al. Impact of Camellia japonica bee pollen polyphenols on hyperuricemia and gut microbiota in potassium oxonate-induced mice. Nutrients 2021; 13(8):2665.

[8] Wang Z, Li Y, Liao W, et al. Gut microbiota remodeling: a promising therapeutic strategy to confront hyperuricemia and gout. Front Cell Infect Microbiol 2022; 12:935723.

[9] Martínez-Nava GA, Méndez-Salazar EO, Vázquez-Mellado J, et al. The impact of short-chain fatty acid-producing bacteria of the gut microbiota in hyperuricemia and gout diagnosis. Clin Rheumatol 2023; 42(1):203-214.

[10] Wei J, Zhang Y, Dalbeth N, et al. Association between gut microbiota and elevated serum uric acid in two independent cohorts. Arthritis Rheumatol 2022; 74(4):682-691.

[11] Wang P, Zhang X, Zheng X, et al. Folic acid protects against hyperuricemia in C57BL/6J mice via ameliorating gut-kidney axis dysfunction. J Agric Food Chem 2022; 70(50):15787-15803.

[12] Manolis AA, Manolis TA, Melita H, et al. Low serum albumin: a neglected predictor in patients with cardiovascular disease. Eur J Intern Med 2022; 102:24-39.

[13] Liu C, Zhao Q, Ma X, et al. Prognostic implication of serum glycated albumin for patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention. Cardiovasc Diabetol 2022; 21(1):11.

[14] Wang A, Li M, Huang H, et al. A review of Penthorum chinense Pursh for hepatoprotection: traditional use, phytochemistry, pharmacology, toxicology and clinical trials. J Ethnopharmacol 2020; 251:112569.

[15] Hu J, Xie H, Lin N, et al. Penthorum chinense Pursh improves type 2 diabetes mellitus via modulating gut microbiota in db/db mice. BMC Complement Med Ther 2023; 23(1):314.

[16] Tao W, Li Z, Nabi F, et al. Penthorum chinense Pursh compound ameliorates AFB1-induced oxidative stress and apoptosis via modulation of mitochondrial pathways in broiler chicken kidneys. Front Vet Sci 2021; 8:750937.

[17] Li X, Zhao W, Xiao M, et al. Penthorum chinense Pursh. extract attenuates non-alcholic fatty liver disease by regulating gut microbiota and bile acid metabolism in mice. J Ethnopharmacol 2022; 294:115333.

[18] Tao W, Zhu W, Nabi F, et al. Penthorum chinense Pursh compound flavonoids supplementation alleviates Aflatoxin B1-induced liver injury via modulation of intestinal barrier and gut microbiota in broiler. Ecotoxicol Environ Saf 2023; 255:114805.

[19] Wang D, Liu L, Li K, et al. Eurycoma longifolia alkaloid components ameliorate hyperuricemic nephropathy via regulating serum uric acid level and relieving inflammatory reaction. J Nat Med 2023; 77(4):867-879.

[20] Wen S, Wang D, Yu H, et al. The time-feature of uric acid excretion in hyperuricemia mice induced by potassium oxonate and adenine. Int J Mol Sci 2020; 21(15):5178-5189.

[21] Becker MA, Jolly M. Hyperuricemia and associated diseases. Rheum Dis Clin North Am 2006; 32(2):275-293.

[22] Chen Y, Li C, Duan S, et al. Curcumin attenuates potassium oxonate-induced hyperuricemia and kidney inflammation in mice. Biomed Pharmacother 2019; 118:109195.

[23] Wang M, Zhao J, Zhang N, et al. Astilbin improves potassium oxonate-induced hyperuricemia and kidney injury through regulating oxidative stress and inflammation response in mice. Biomed Pharmacother 2016; 83:975-988.

[24] Wu M, Ma Y, Chen X, et al. Hyperuricemia causes kidney damage by promoting autophagy and NLRP3-mediated inflammation in mice with urate oxidase deficiency. Dis Model Mech 2021; 14(3):048041-048056.

[25] Li Y, Zhao Z, Luo J, et al. Apigenin ameliorates hyperuricemic nephropathy by inhibiting URAT1 and GLUT9 and relieving renal fibrosis via the Wnt/β-catenin pathway. Phytomedicine 2021; 87:153585.

[26] Taniguchi T, Omura K, Motoki K, et al. Hypouricemic agents reduce indoxyl sulfate excretion by inhibiting the renal transporters OAT1/3 and ABCG2. Sci Rep 2021; 11(1):7232.

[27] Vávra J, Mančíková A, Pavelcová K, et al. Functional characterization of rare variants in OAT1/SLC22A6 and OAT3/SLC22A8 urate transporters identified in a gout and hyperuricemia cohort. Cells 2022; 11(7):1063.

[28] Li H, Liu X, Lee MH, et al. Vitamin C alleviates hyperuricemia nephropathy by reducing inflammation and fibrosis. J Food Sci 2021; 86(7):3265-3276.

[29] Riaz M, Al Kury LT, Atzaz N, et al. Carvacrol alleviates hyperuricemia-induced oxidative stress and inflammation by modulating the NLRP3/NF-κB pathway. Drug Des Devel Ther 2022; 16:1159-1170.

[30] Fu J, Wu H. Structural mechanisms of NLRP3 inflammasome assembly and activation. Annu Rev Immunol 2023; 41:301-316.

[31] Yang L, Xu HH, Hong Q, et al. Crocus sativus L. produces anti-inflammatory effects and regulates NLRP3-NF-κB pathway. Acupunct Herb Med. 2024; 4(3):375-385.

[32] Yao H, Zhang D, Yu H, et al. Gut microbiota regulates chronic ethanol exposure-induced depressive-like behavior through hippocampal NLRP3-mediated neuroinflammation. Mol Psychiatry 2023; 28(2):919-930.

[33] Fathallah-Shaykh SA, Cramer MT. Uric acid and the kidney. Pediatr Nephrol 2014; 29(6):999-1008.

[34] Lu Q, Xu D, Zhang X, et al. Association of hyperuricemia with immune disorders and intestinal barrier dysfunction. Front Physiol 2020; 11:524236.

[35] Song S, Lou Y, Mao Y, et al. Apigenin ameliorates hyperuricemic nephropathy by inhibiting URAT1 and GLUT9 and relieving renal fibrosis via the Wnt/β-catenin pathway. Front Immunol 2022; 13:804306.