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

2019 ◽  
Vol 15 (5) ◽  
pp. 465-486 ◽  
Author(s):  
Haifang Chen ◽  
Yun Yao ◽  
Yuan Zhan ◽  
Hui Jian ◽  
Yan Li ◽  
...  

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.

Planta Medica ◽  
2017 ◽  
Vol 83 (17) ◽  
pp. 1335-1341 ◽  
Author(s):  
Jin Kim ◽  
Woo Kim ◽  
Jung Hyun ◽  
Jong Lee ◽  
Jin Kwon ◽  
...  

AbstractHyperuricemia is a clinical condition characterized by an elevated level of serum uric acid and is a key risk factor for the development of gout and metabolic disorders. The existing urate-lowering therapies are often impractical for certain patient populations, providing a rationale to explore new agents with improved safety and efficacy. Here, we discovered that Salvia plebeia extract inhibited the enzyme activity of xanthine oxidase, which is a key enzyme generating uric acid in the liver. In an animal model of hyperuricemia, S. plebeia extract reduced serum urate to the levels observed in control animals. The urate-lowering effect of S. plebeia extract in vivo was supported by the identification of compounds that inhibit xanthine oxidase enzyme activity in vitro. Nepetin, scutellarein, and luteolin contributed significantly to S. plebeia bioactivity in vitro. These compounds showed the highest potency against xanthine oxidase with IC50 values of 2.35, 1.74, and 1.90 µM, respectively, and were present at moderate quantities. These observations serve as a basis for further elaboration of the S. plebeia extracts for the development of new therapeutics for hyperuricemia and related diseases.


Scientifica ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Nour Elhouda Daoudi ◽  
Mohamed Bouhrim ◽  
Hayat Ouassou ◽  
Mohamed Bnouham

Background. The gout is a metabolic disease that is associated with a high level of uric acid in the blood. This disease is treated with some medications that aim to reduce serum urate levels. However, the use of various medicines leads to the appearance of some side effects, hence the importance of using other treatments based on natural resources. Objective. This study presents some medical treatments, their side effects, and some plants that are used for gout management in Morocco in the aim to valorize them. Methods. We have been consulting various English publications in PubMed, Web of Science, and ScienceDirect published between 1991 and 2019 using the following keywords “drugs,” “gout,” “Morocco,” “medicinal plants,” “in vitro,” and “in vivo” terms. Then, we have classified the medicines, according to their action mechanisms, and we have cited some species that were reported in Moroccan pharmacopeia as antigout. Results. Three methods of the gout medical management were cited in this work: xanthine oxidase inhibitors, uric acid excretion enhancer, and uricase recombinant. However, it was found that these treatments had various side effects. We have described 23 species, and some of them showed experimentally an antigout effect by blocking the “xanthine oxidase” enzyme. These plants belong to 11 families. Lamiaceae represents the most dominant family with six species followed by Asteraceae with two species. Colchicine isolated from Colchicum autumnale is the most known compound for its efficiency towards gout. Conclusion. This work summarized different treatments particularly medicinal plants that are used in Morocco to treat gout disease by blocking uric acid secretion. However, several studies are needed to valorize these antigout natural sources.


2020 ◽  
Author(s):  
Teng Lit Ng ◽  
Khye Er Loh ◽  
Sheri-Ann Shu Wei Tan ◽  
Hui Yin Tan ◽  
Sze Ping Wee

Abstract Background: Xanthine oxidase (XO) plays an important role in human’s purine degradation. Excessive uric acid formation results in hyperuricemia and gout. The study aimed to determine the XO inhibitory potential of Chrysanthemum morifolium Ramat. dried flower and its effect on XO gene expression in animal models.Methods: In vitro XO inhibitory assay was employed to investigate the XO inhibitory potential of C. morifolium flowers. The bioactive sub-fraction was investigated further to give additional insight on its uric acid lowering potential via animal study and XO gene expression analysis. HPLC-Q-TOF-MS/MS was utilized to identify the putative compounds in the sub-fraction.Results: Among the fractions, EtOAc fraction exhibited the highest in vitro XO inhibitory potency (51.77 ± 0.98%; IC50 = 10.64 ± 0.51 µg/mL) and it was further fractionated into 15 sub-fractions through open column chromatography. EtOAc F7, F8, F9, F10, and F11 possessed >75% XO inhibition. F9 and F10 exhibited high in vitro XO inhibitory activity, cellular pro-proliferative effect and intracellular antioxidant activity among the sub-fractions tested. These two sub-fractions were also non-cytotoxic at the concentration range of 0.1 – 10 µg/mL. F10 was shown to be very effective in both serum and urine uric acid lowering properties in rats model upon oral consumption. It was subjected to further fractionation and a total of 11 sub-fractions were obtained. F10-4, F10-8, F10-9, and F10-10 possessed >90% XO inhibition. These sub-fractions were subjected to HPLC-Q-TOF-MS/MS analysis. A total of nine known compounds have been identified and 26 unknown compounds were detected. Conclusions: The possible mechanisms contributed to the anti-hyperuricemic effect of F10 were suggested to be non-competitive inhibition of XO enzyme, XO gene expression down regulation, and enhancement of uric acid excretion. Structure elucidation of the unknown compounds and the evaluation of the XO inhibitory activity of a single or a mixture of these compounds are recommended to identify possible synergism between them.


2015 ◽  
Vol 10 (6) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Lee-Chuen Cheng ◽  
Vikneswaran Murugaiyah ◽  
Kit-Lam Chan

Lippia nodiflora has been traditionally used for treatment of knee joint pain. Hitherto, no studies have been reported on the effective use of L. nodiflora against hyperuricemia, gout or other metabolic disorders. In this present study, L. nodiflora was examined for its ability to lower uric acid levels using an in vitro xanthine oxidase inhibitory assay. The whole plant methanolic extract was subjected to bioactivity-guided fractionation to yield 4 fractions (F1–F4). F3 displayed the highest potency and was further purified by column chromatography to afford two phenylethanoid glycosides, arenarioside (1) and verbascoside (2), and three flavonoids, 6-hydroxyluteolin (3), 6-hydroxyluteolin-7- O-glycoside (4), and nodifloretin (5). These compounds inhibited xanthine oxidase activity, with IC50 values between 7.52 ± 0.01 and 130.00 ± 2.25 μM, of which 3 was the most potent. In contrast, allopurinol, serving as a positive control, was 0.22 ± 0.00 μM. Thus, L. nodiflora, and its chemical constituents are worthy of further studies as potential anti-hyperuricemic agents.


2016 ◽  
Vol 7 (10) ◽  
pp. 4239-4246 ◽  
Author(s):  
Jhih-Jia Jhang ◽  
Jia-Wei Ong ◽  
Chi-Cheng Lu ◽  
Chin-Lin Hsu ◽  
Jia-Hong Lin ◽  
...  

Uric acid is a metabolite obtained from purine by xanthine oxidase activity (XO) and high levels of serum uric acid leads to hyperuricemia and gout.


Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3254 ◽  
Author(s):  
Heung Yuk ◽  
Young-Sil Lee ◽  
Hyung Ryu ◽  
Seung-Hyung Kim ◽  
Dong-Seon Kim

Toona sinensis leaf is used as a seasonal vegetable in Korea. A 70% ethanol extract of these leaves exhibited potent xanthine oxidase (XO) inhibition, with a 50% inhibitory concentration (IC50) of 78.4 µM. To investigate the compounds responsible for this effect, bioassay-guided purification led to the isolation of five constituents, identified as quercetin-3-O-rutinoside, quercetin-3-O-β-d-glucopyranoside, 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranose (compound 3), quercetin-3-O-α-l-rhamnopyranoside, and kaempferol-3-O-α-l-rhamnopyranoside. Compound 3 showed the most potent inhibition of XO, with an IC50 of 2.8 µM. This was similar to that of allopurinol (IC50 = 2.3 µM), which is used clinically to treat hyperuricemia. Kinetic analyses found that compound 3 was a reversible noncompetitive XO inhibitor. In vivo, the T. sinensis leaf extract (300 mg/kg), or compound 3 (40 mg/kg), significantly decreased serum uric acid levels in rats with potassium oxonate-induced hyperuricemia. Furthermore, ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry analysis identified a high level of compound 3 in the leaf extract. These findings suggest that T. sinensis leaves could be developed to produce nutraceutical preparations.


2012 ◽  
Vol 40 (05) ◽  
pp. 979-991 ◽  
Author(s):  
Chien-Wei Hou ◽  
Ying-Chung Lee ◽  
Hsiao-Fang Hung ◽  
Hua-Wen Fu ◽  
Kee-Ching Jeng

Hyperuricemia causes gouty arthritis, kidney disease, heart disease, and other diseases. Xanthine oxidase (XOD) and urate transporters play important roles in urate homeostasis. Numerous plants have been identified as XOD inhibitors. Longan seeds are known to contain high levels of polyphenols such as corilagin, gallic acid and ellagic acid. We examined the effect of longan seed extract on XOD inhibition and urate transporters GLUT1 and GLUT9 using both in vitro and in vivo assays. The results showed that dried longan seed extract (LSE) and its active components inhibited XOD dose-dependently in vitro. LSE inhibited uric acid production and XOD activity in normal liver cells (clone-9 cells) and was not cytotoxic under the concentration of 200 μg/ml. For the in vivo study, Sprague-Dawley (SD) rats were given intraperitoneally for thirty minutes with or without allopurinol (a XOD inhibitor, 3.5 mg/kg) or LSE (80 mg/kg) and then injected intraperitioneally with 250 mg/kg of oxonic acid and 300 mg/kg of hypoxanthine intragastrically. LSE was able to reduce serum uric acid level and XOD activity in hyperuricemic rats. However, LSE or allopurinol did not inhibit the liver XOD activities. On the other hand, GLUT1 protein was suppressed in kidney and GLUT9 was induced in liver from experimental rats and LSE or allopurinol decreased GLUT9 but increased GLUT1 protein level in the liver and kidney, respectively. These results confirmed the claimed effect of longan seeds on gout and other complications and suggested that its urate reducing effect might be due to modulation of urate transporters and inhibition of circulating xanthine oxidase.


Dose-Response ◽  
2021 ◽  
Vol 19 (3) ◽  
pp. 155932582110403
Author(s):  
Muhammad Bilal ◽  
Saeed Ahmad ◽  
Tayyeba Rehman ◽  
Aymen Owais Ghauri ◽  
Sana Khalid ◽  
...  

Hyperuricemia is a metabolic disorder with characteristic elevated serum uric acid. Recently, several plant-based medicines are being used for the treatment of hyperuricemia. The study aimed to find the hypouricemic potential of Berberis vulgaris in in-vitro and in-vivo study models. In i n-vitro studies, xanthine oxidase inhibition assay was performed to evaluate IC50 value and capsule absorbance of the drug, respectively. For in-vivo experiment, the study comprised 15 groups of rats. In-vitro results revealed that significant xanthine oxidase inhibition was shown by Berberis vulgaris with an IC50 value of 272.73±.3 μg/mL. Similarly, oral administration of Berberis vulgaris with dosages of 250 and 500 mg/kg decreased serum and liver uric acid levels significantly in a dose- and time-dependent manner in oxonate-induced hyperuricemic rats. Furthermore, 3-day and 7-day administration of Berberis vulgaris showed more potential compared to 1-day administrations. The present study indicated marked hypouricemic effects of Berberis vulgaris in rats. Due to caveat of the small sample size, a firm assumption of the hypouricemic effect of Berberis vulgaris cannot be made. However, extensive study is needed to find out the exact molecular mechanism involved and to translate its effects into clinical trials for the further validation of the results.


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