In Vivo Antihyperuricemic Activities of 3,4,5-Tri-O-caffeoylquinic acid, 4,4',6'-Trihydroxy-2'-Methoxychalcone, and Caffeic Acid from the Aerial Parts of Gnaphalium Affine

Abstract

The extract of Gnaphalium affine has been reported to have antihyperuricemic and renal protective effects in vivo. The plant could alleviate acute hyperuricemia by inhibiting the activity of xanthine oxidase (XOD). 3,4,5-Tri-O-caffeoylquinic acid (3,4,5-triCQA), 4,4',6'-trihydroxy-2'-methoxychalcone (Chal), and caffeic acid (CA) were identified as the main ingredients of the plant attributed to the potential to retard XOD activity. However, whether the compounds were the effective ingredient of the plant exerting antihyperuricemic activity remained largely unknown. In this study, an experimental mouse model of hyperuricemia was induced by potassium oxonate and hypoxanthine, and orally administered with 3,4,5-triCQA (10 and 20 mg/kg/d), Chal (20 and 40 mg/kg/d), and CA (40 and 80 mg/kg/d) for 6 consecutive days, respectively. Then, serum urate levels and liver XOD activities were assessed. The liver- or kidney-to body weight ratio was calculated. Allopurinol (AP, 50 mg/kg/d) and benzbromarone (BBR, 10 mg/kg/d) were used as controls. Our data showed that there were 52.7 to 81.0% inhibitions in XOD activities in mice treated with 3,4,5-TriCQA (10 and 20 mg/kg/d), Chal (20 and 40 mg/kg/d), and CA (80 mg/kg/d), and 38.8 to 72.5% reduction in uric acid levels in mice treated with 3,4,5-TriCQA (20 mg/kg/d), Chal (20 and 40 mg/kg/d), and CA (40 and 80 mg/kg/d). A larger kidney-to-body weight ratio was observed in hyperuricemic mice and further enhanced by AP treatment. However, the increasing trend was significantly reversed by additional treatment of 3,4,5-triCQA (10 and 20 mg/kg/d) and CA (40 mg/kg/d). Given the above fundings, 3,4,5-triCQA, Chal, and CA may be the key component responsible for the in vivo activities of G. affine for urate-lowering therapy and even promising agents for the treatment of hyperuricemia.

Keywords

Gnaphalium affine - 3,4,5-tri-O-caffeoylquinic acid - 4,4',6'-trihydroxy-2'-methoxychalcone - caffeic acid - antihyperuricemia

Ethics Statement

The use of animals in the study was approved by the Animal Ethical Committee of the Shanghai Institute of Pharmaceutical Industry, which conformed to the National Institutes of Health Guidelines on Laboratory Research and Guide for the Care and Use of Laboratory Animals.

^# These authors contributed equally to this work.

Publikationsverlauf

Eingereicht: 08. Dezember 2022

Angenommen: 14. April 2023

Artikel online veröffentlicht:
24. Mai 2023

• References

• 1 Dalbeth N, Gosling AL, Gaffo A, Abhishek A. Gout. Lancet 2021; 397 (10287): 1843-1855
• 2 Chinese Society of Endocrinology, Chinese Medical Association. Guideline for the diagnosis and management of hyperuricemia and gout in China (2019) [in Chinese]. Zhonghua Neifenmi Daixie Zazhi 2020; 36: 1-13
• 3 Zhang W, Fan SY, Wu CZ. Review on chemical constituents and pharmacological activities of Gnaphalium affine D.Don [in Chinese]. Carol J Pharm 2016; 47 (08) 1057-1064
• 4 Zhang HJ, Li LN, Zhou J. et al. Effects of Gnaphalium affine D. Don on hyperuricemia and acute gouty arthritis. J Ethnopharmacol 2017; 203: 304-311
• 5 Liu F, Liu XZ, Yang Q. et al. Enhanced efficacy and reduced hepatotoxicity by combination of Gnaphalium affine extract and benzbromarone in the treatment of rats with Hyperuricemic nephropathy. Pharmaceut Fronts 2021; 3: e129-e137
• 6 Zhang W, Wu CZ, Fan SY. Chemical constituents from Gnaphalium affine and their xanthine oxidase inhibitory activity. Chin J Nat Med 2018; 16 (05) 347-353
• 7 Lin Y, Liu PG, Liang WQ. et al. Luteolin-4′-O-glucoside and its aglycone, two major flavones of Gnaphalium affine D. Don, resist hyperuricemia and acute gouty arthritis activity in animal models. Phytomedicine 2018; 41: 54-61
• 8 Lafay S, Morand C, Manach C, Besson C, Scalbert A. Absorption and metabolism of caffeic acid and chlorogenic acid in the small intestine of rats. Br J Nutr 2006; 96 (01) 39-46
• 9 Xie M, Chen G, Hu B. et al. Hydrolysis of dicaffeoylquinic acids from Ilex kudingcha happens in the colon by intestinal microbiota. J Agric Food Chem 2016; 64 (51) 9624-9630
• 10 Couteau D, McCartney AL, Gibson GR, Williamson G, Faulds CB. Isolation and characterization of human colonic bacteria able to hydrolyse chlorogenic acid. J Appl Microbiol 2001; 90 (06) 873-881
• 11 Monteiro M, Farah A, Perrone D, Trugo LC, Donangelo C. Chlorogenic acid compounds from coffee are differentially absorbed and metabolized in humans. J Nutr 2007; 137 (10) 2196-2201
• 12 Zhang YP, Lin SS, Shi AH. et al. Total Synthesis of (±) - 2,3,2”,3” -Tetrahydroochnaflavone [in Chinese]. Youji Huaxue 2015; 35: 2114-2118
• 13 Vogel S, Ohmayer S, Brunner G, Heilmann J. Natural and non-natural prenylated chalcones: synthesis, cytotoxicity and anti-oxidative activity. Bioorg Med Chem 2008; 16 (08) 4286-4293
• 14 Yong T, Zhang M, Chen D. et al. Actions of water extract from Cordyceps militaris in hyperuricemic mice induced by potassium oxonate combined with hypoxanthine. J Ethnopharmacol 2016; 194: 403-411
• 15 Aponte JC, Castillo D, Estevez Y. et al. In vitro and in vivo anti-Leishmania activity of polysubstituted synthetic chalcones. Bioorg Med Chem Lett 2010; 20 (01) 100-103
• 16 Paget GE, Barnes JM. Toxicity tests in evaluation of drug activities pharmacometries. In: Laurence DR, Bacharach AL. eds. Evaluation of Drug Activities: Pharmacometrics. New York, NY: Academic Press; 1964: 135-166
• 17 Meng ZQ, Tang ZH, Yan YX. et al. Study on the anti-gout activity of chlorogenic acid: improvement on hyperuricemia and gouty inflammation. Am J Chin Med 2014; 42 (06) 1471-1483
• 18 Nguyen MT, Awale S, Tezuka Y. et al. Hypouricemic effects of acacetin and 4,5-o-dicaffeoylquinic acid methyl ester on serum uric acid levels in potassium oxonate-pretreated rats. Biol Pharm Bull 2005; 28 (12) 2231-2234
• 19 Kondo M, Hirano Y, Nishio M, Furuya Y, Nakamura H, Watanabe T. Xanthine oxidase inhibitory activity and hypouricemic effect of aspalathin from unfermented rooibos. J Food Sci 2013; 78 (12) H1935-H1939
• 20 Zhang K, Wang Q, Yang Q. et al. Enhancement of oral bioavailability and anti-hyperuricemic activity of isoliquiritigenin via self-microemulsifying drug delivery system. AAPS PharmSciTech 2019; 20 (05) 218
• 21 Niu Y, Zhu H, Liu J. et al. 3,5,2′,4′-Tetrahydroxychalcone, a new non-purine xanthine oxidase inhibitor. Chem Biol Interact 2011; 189 (03) 161-166
• 22 Sarawek S, Feistel B, Pischel I, Butterweck V. Flavonoids of Cynara scolymus possess potent xanthinoxidase inhibitory activity in vitro but are devoid of hypouricemic effects in rats after oral application. Planta Med 2008; 74 (03) 221-227
• 23 Wan Y, Wang F, Zou B. et al. Molecular mechanism underlying the ability of caffeic acid to decrease uric acid levels in hyperuricemia rats. J Funct Foods 2019; 57: 150-156
• 24 Strilchuk L, Fogacci F, Cicero AF. Safety and tolerability of available urate-lowering drugs: a critical review. Expert Opin Drug Saf 2019; 18 (04) 261-271
• 25 Bilal M, Ahmad S, Rehman T. et al. Anti-hyperuricemic and uricosuric potential of Berberis vulgaris in oxonate-induced hyperuricemic rats. Dose Response 2021;19(3):15593258211040329