Application of UHPLC/ESI-Q-TOF-MS/MS to Identify Constituents of Erding Granule and Anti-hyperuricemia Effect

Author(s): Haifang Chen, Yun Yao, Yuan Zhan, Hui Jian, Yan Li, Shilin Yang, Yulin Feng*, Wugang Zhang*.

Journal Name: Current Pharmaceutical Analysis

Volume 15 , Issue 5 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Background: Erding granule (EDG) widely used as an agent with the effect of heat-clearing, detoxifying, eliminating dampness, relieving jaundice and upper respiratory tract disease in clinical application, but the systematic chemical information and anti-hyperuricemia effect of EDG was still unclear.

Methods: An ultra-high performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC/ESI-Q-TOF-MS/MS) method was utilized to rapidly identify the chemical constituents of EDG. The anti-hyperuricemia effect of EDG was evaluated based on the effect on xanthine oxidase inhibitory activity (in vitro) and lowering uric acid (in vivo).

Results: 198 compounds were tentatively separated and identified or characterized within 30 min by UHPLC/ESI-Q-TOF MS/MS. These compounds were categorized as 22 coumarins, 38 flavones, 67 alkaloids, 36 organic acids, 16 sesquiterpenes, 14 lignans and 5 the others constituents. Meanwhile, EDG significantly decreases the serum urate level of hyperuricemic mice induced by potassium oxonate, while EDG did not significantly decrease the serum urate level of hyperuricemic mice induced by hypoxanthine and activity of xanthine oxidase in vitro.

Conclusion: The method developed was rapid and sensitive to characterize the chemical constituents of EDG, and provide a systematic view of chemical information for EDG. Furthermore, we first discovered the anti-hyperuricemia effect of EDG and it would further provide the reference for clarifying the mechanism of EDG on lowering uric acid.

Keywords: Traditional Chinese medicine, Erding granule, UHPLC/ESI-Q-TOF-MS/MS, chemical constituent, hyperuricemia, xanthine oxidase.

Kuo, C.C.; Weaver, V.; Fadrowski, J.J.; Lin, Y.S.; Guallar, E.; Navas-Aciena, A. Arsenic exposure, hyperuricemia, and gout in US adults. Environ. Int., 2015, 76, 32-40.
Fenech, G.; Rajzbaum, G.; Mazighi, M.; Blacher, J. Serum uric acid and cardiovascular risk: State of the art and perspectives. Joint Bone Spine, 2014, 81, 392-397.
Lolekha, P.; Wongwan, P.; Kulkantrakorn, K. Association between serum uric acid and motor subtypes of Parkinson’s disease. J. Clin. Neurosci., 2015, 22, 1264-1267.
Van, M.M.; Houtman, P.M.; Stricker, B.H.; Spoelstra, P. Hepatic injury caused by benzbromarone. J. Hepatol., 1994, 20, 376-379.
Felser, A.; Lindinger, P.W.; Schnell, D.; Kratschmar, D.V.; Odermatt, A.; Mies, S.; Jenö, P.; Krähenbühl, S. Hepatocellular toxicity of benzbromarone: Effects on mitochondrial function and structure. Toxicology, 2014, 324, 136-146.
Lin, H.C.; Daimon, M.; Wang, C.H.; Ho, Y.; Uang, Y.S.; Chiang, S.J.; Wang, L.H. Allopurinol, benzbromarone and risk of coronary heart disease in gout patients: A population-based study. Int. J. Cardiol., 2017, 233, 85-90.
Dalbeth, N.; Stamp, L. Allopurinol dosing in renal impairment: walking the tightrope between adequate urate lowering and adverse events. Semin. Dial., 2007, 20, 391-395.
Yan, H.F.; Dai, X.D.; Fan, K.T.; Wang, Y. Research on medication regularity of traditional chinese medicine based on hyperuricemia patents. Chin. Tradit. Herbal Drugs, 2016, 8, 376-381.
Editorial Committee of Pharmacopoeia of Ministry of Health PR China. China Chemical Industry Press, Beijing, 2015.Part1, pp. 435..
Jia, H.H.; Yuan, J.; Gou, J.; Li, D.Y. The bacteriostatic, anti-inflammatory and immunomodulating effects of Erding granule. West China J. Pharm. Sci, 2006, 21, 453-456.
Zhang, G.Y. Efficacy observation of Erding granule on treatment of chronic bronchitis. Hebei J. TCM., 2011, 33, 911-912.
Masoom, R.S.; Zeid, A.A.; Nafisur, R. Analytical techniques in pharmaceutical analysis: a review. Arab. J. Chem., 2017, 10, S1409-S1421.
Zeid, A.A.; Nafisur, R.; Masoom, R.S. Review on pharmaceutical impurities, stability studies and degradation products. Rev. Adv. Sci. Eng., 2013, 2, 155-166.
Nafisur, R.; Syed, N.H.A.; Wu, H.F. The importance of impurity analysis in pharmaceutical products: an integrated approach. Accredit. Qual. Assur., 2006, 11, 69-74.
De Villiers, A.; Venter, P.; Pasch, H. Recent advances and trends in the liquid-chromatography-mass spectrometry analysis of flavonoids. J. Chromatogr. A, 2016, 1430, 16-78.
Zhe, M.; Shi, Z.H.; Su, M.; Sun, H.W. In vitro metabolism analysis of sulfamerazine in mice liver by ultra performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Curr. Pharm. Anal., 2018, 14, 17-22.
Yang, M.; Sun, J.; Lu, Z.; Chen, G.; Guan, S.; Liu, X.; Jiang, B.; Ye, M.; Guo, D.A. Phytochemical analysis of traditional Chinese medicine using liquid chromatography coupled with mass spectrometry. J. Chromatogr. A, 2009, 1216(11), 2045-2062.
Song, H.P.; Zhang, H.; Fu, Y.; Mo, H.Y.; Zhang, M.; Chen, J.; Li, P. Screening for selective inhibitors of xanthine oxidase from Flos Chrysanthemum using ultrafiltration LC-MS combined with enzyme channel blocking. J. Chromatogr. B, 2014, 961, 56-61.
Kong, L.D.; Yang, C.; Ge, F.; Wang, H.D.; Guo, Y.S. A Chinese herbal medicine Ermiao wan reduces serum uric acid level and inhibits liver xanthine dehydrogenase and xanthine oxidase in mice. J. Ethnopharmacol., 2004, 93, 325-330.
Chen, L.Y.; Yin, H.F.; Lan, Z.; Ma, S.W.; Zhang, C.F.; Yang, Z.L.; Li, P.; Lin, B.Q. Anti-hyperuricemic and nephroprotective effects of Smilax China L. J. Ethnopharmacol., 2011, 135, 399-405.
Huang, J.Q.; Wang, J.; Yin, Z.X.; Guo, R.F.; Chen, J.; Liang, H.Y.; Liu, Y. Comparative study of quercetin and allopurinol on serum uric acid levels and function of liver and kidney in hyperuricemic rats. . J. China Pharm. Univ.,, 2015, 46, 458-463.
Chen, H.L.; Dong, X.P.; Zhang, M.; Pei, J.; Tang, P.R.; Zhang, Y. Chemical constituents from Viola yedoensis. Chin. Tradit. Herbal Drugs, 2010, 41, 874-877.
Xu, D.; Hou, F.F.; Wu, L.J.; Kang, Y.G. Chemical constituents of Taraxacum ohwanum Kitag. Chin. J. Chin. Mater. Med., 2004, 29, 278-281.
Shuang, Y.; Tao, S.; Li, J.Z.; Chao, L.; Yao, Z.; Hong, X.L.; Dong, M.R. Chemical constituents of Lobelia chinensis. Fitoterapia, 2014, 93, 168-174.
Shi, S.Y.; Zhou, C.X.; Xu, Y.; Tao, Q.F.; Bai, H.; Lu, F.S.; Lin, W.Y.; Chen, H.Y.; Zheng, W.; Wang, L.W. Chemical constituents of Taraxacum mongolicum Hand. Mazz. Chin. J. Chin. Mater. Med., 2008, 33, 1147-1157.
Shi, S.Y.; Zhang, Y.P.; Huang, K.L.; Zhao, Y.; Liu, S.Q. Flavonoids from Taraxacum mongolicum. Biochem. Syst. Ecol., 2008, 36, 437-440.
Kuo, P.C.; Wang, T.L.; Lin, Y.T.; Kuo, Y.C.; Leu, Y.L. Chemical constituents from Lobelia chinensis and their anti-virus and anti-inflammatory bioactivities. Arch. Pharm. Res., 2011, 34, 715-722.
Zhang, C.E.; Xiong, Y.; Dong, Q.; Gao, D.; Zhang, L.L.; Ma, L.N.; Peng, C.; Dong, X.P.; Yan, D. Comparison of reversed-phase liquid chromatography and hydrophilic interaction chromatography for the fingerprint analysis of Radix isatidis. J. Sep. Sci., 2014, 37, 1141-1147.
Xin, M.T.; Fu, X.T.; Chen, Y.G.; Guo, H.Z. Determination of main free amino acids in Banlangen Keli by UPLC. Chin. J. Chin. Mater. Med, 2011, 36, 3306-3309.
Reng, G.P.; Tian, L.; Li, Z.; Fu, X.D.; Guo, H.Z.; Chen, Y.G. Determination of free amino acids and connected amino acids in Isatidis Radix by HPLC. Chin. New Drug J., 2014, 23, 99-104.
Pan, Y.L.; Chen, H.; Li, J.; Li, X.; Chen, W.J. Chemical constituents from extract of Isatidis Radix. Chin. Tradit. Pat. Med 36, 2014, 780-785.
Yang, S.; Shen, T.; Zhao, L.J.; Li, C.; Zhang, Y.; Lou, H.X.; Ren, D.M. Chemical constituents of Lobelia chinensis. Fitoterapia, 2014, 93, 168-174.
Zhang, M.Z.; Cao, L.W. Chemical constituents of Lobelia hybrid. J. Peking Univ. Acta Sci. Nat., 1991, 27, 205-209.
Yang, S.; Li, C.; Wang, S.Q.; Zhao, L.J.; Hou, Z.; Lou, H.X.; Ren, D.M. Chiral separation of two diastereomeric pairs of enantiomers of novel alkaloid-lignan hybrids from Lobelia chinensis and determination of the tentative absolute configuration. J. Chromatogr. A, 2013, 1311, 134-139.
Zuo, L.; Li, J.; Xu, J.; Yang, J.Z.; Zhang, D.M.; Tong, Y. Studies on chemical constituents in root of Isatis indigotica. Chin. J. Chin. Mater. Med., 2007, 32, 688-691.
Shi, S.Y.; Zhao, Y.; Zhang, Y.P.; Huang, K.L.; Liu, S.Q. Phenylpropanoids from Taraxacum mongolicum. Biochem. Syst. Ecol., 2008, 36, 716-718.
Leu, Y.L.; Wang, Y.L.; Huang, S.C.; Shi, L.S. Chemical constituents from roots of Taraxacum formosanum. Chem. Pharm. Bull., 2005, 53, 853-855.
Michalska, K.; Kisiel, W. Sesquiterpenoids from Taraxacum serotinum. Biochem. Syst. Ecol., 2009, 37, 519-521.
Liu, J.F.; Zhang, N.L.; Liu, M.Q. A new inositol triester from Taraxacum mongolicum. Nat. Prod. Res., 2014, 28, 420-423.
Michalska, K.; Kisiel, W. Sesquiterpene lactones from Taraxacum obovatum. Planta Med., 2003, 69, 181-183.
Shi, S.Y.; Zhou, Q.; Peng, H.; Zhou, C.X.; Hu, M.H.; Tao, Q.F.; Hao, X.J.; Stöckigt, J.; Zhao, Y. Four new constituents from Taraxacum mongolicum. Chin. Chem. Lett., 2007, 18, 1367-1370.
Michalska, K.; Kisiel, W. Sesquiterpene lactones from Taraxacum erythrospermum. Biochem. Syst. Ecol., 2008, 36, 444-446.
Michalska, K.; Żylewski, M.; Marciniuk, J.; Kisiel, W. Structural analysis of 1l-chiro-inositol diester from Taraxacumudum. Carbohydr. Res., 2010, 345, 172-174.
Xiao, P.; Chen, J.W.; Li, X.; Chen, Y.Y. Ultrasound-assisted extraction coupled with SPE-HPLC-DAD for the determination of three bioactive phenylpropanoids from Radix Isatidis. Anal. Methods, 2014, 6, 7547-7553.
Li, B.; Chen, W.S.; Zhang, H.M.; Zhang, W.D.; Yang, G.J.; Qiao, C.Z. A new alkaloids isolated from tetraploidy banlangen. Acta Pharmacol. Sin., 2003, 38, 430-432.
Michalska, K.; Kisiel, W. Taxonomically significant guaianolides from Taraxacum obovatum. Biochem. Syst. Ecol., 2004, 32, 765-768.
Chen, D.; Gong, X.G.; Liu, J.; Wang, D.W.; Yi, K.Y.; Wang, S.F.; Bao, Z.Y. Comparative research on samples of Taraxacum mongolicum Hand. Mazz. extracted by supercritical CO2 fluid extraction and petroleum ether. J. Pharm. Anal., 2010, 30, 619-622.
Zhu, C.S.; Zhang, B.; Lin, Z.J.; Wan, X.J.; Zhou, Y.; Sun, X.X.; Xiao, M.L. Relationship between high-performance liquid chromatography fingerprints and uric acid-lowering activities of Cichorium intybus L. Molecules, 2015, 20, 9455-9467.
Li, J.M.; Zhang, X.; Wang, X.; Xie, Y.C.; Kong, L.D. Protective effects of cortex fraxini coumarines against oxonate-induced hyperuricemia and renal dysfunction in mice. Eur. L. Pharmaco., 2011, 666, 196-204.
Habu, Y.; Yano, I.; Takeuchi, A.; Saito, H.; Okuda, M.; Fukatsu, A.; Inui, K. Decreased activity of basolateral organic ion transports in hyperuricemic rat kidney: roles of organic ion transporters, rOAT1, rOAT3 and rOCT2. Biochem. Pharmacol., 2003, 66, 1107-1114.
Habu, Y.; Yano, I.; Okuda, M.; Fukatsu, A.; Inui, K. Restored expression and activity of organic ion transporters rOAT1, rOAT3 and rOCT2 after hyperuricemia in the rat kidney. Biochem. Pharmacol., 2005, 69, 993-999.
Hua, J.; Huang, P.; Zhu, C.M.; Yuan, X.; Yu, C.H. Anti-hyperuricemic and nephroprotective effects of Modified Simiao Decoction in hyperuricemic mice. J. Ethnopharmacol., 2012, 142, 248-252.
Xu, W.A.; Yin, L.; Pan, H.Y.; Shi, L.; Xu, L.; Zhang, X.; Duan, J.A. Study on the correlation between constituents detected in serum from Rhizoma Smilacis Glabrae and the reduction of uric acid levels in hyperuricemia. J. Ethnopharmacol., 2013, 150, 747-754.
Yang, Y.; Zhang, D.M.; Liu, J.H.; Hu, L.S.; Xue, Q.C.; Ding, X.Q.; Kong, L.D. Wuling San protects kidney dysfunction by inhibiting renal TLR4/MyD88 signaling and NLRP3 inflammasome activation in high fructose-induced hyperuricemic mice. J. Ethnopharmacol., 2015, 169, 49-59.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [465 - 486]
Pages: 22
DOI: 10.2174/1573412914666180612085117
Price: $58

Article Metrics

PDF: 37