BIOORGANIC CHEMISTRY
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2023
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IF 5.1
Jiling Song,Zhanwei Wang,Yu Chi,Yong Zhang,Chenyi Fang,Yuting Shu,Jing Cui,Helong Bai,Jing Wang
Xanthine oxidase (XO) plays a critical role in the progression of gout. We showed in a previous study that Sanghuangporus vaninii ( S. vaninii ), a perennial, medicinal, and edible fungus traditionally used to treat various symptoms, contains XO inhibitors. In the current study, we isolated an active component of S. vaninii using high performance countercurrent chromatography and identified it as davallialactone using mass spectrometry with 97.726 % purity. A microplate reader showed that davallialactone had mixed inhibition of XO activity with a half-inhibitory concentration value of 90.07 ± 2.12 μM. In addition, the collision between davallialactone and XO led to fluorescence quenching and conformational changes in XO, which were mainly driven by hydrophobicity and hydrogen bonding. Molecular simulations further showed that davallialactone was located at the center of the molybdopterin (Mo-Pt) of XO and interacted with amino acid residues Phe798, Arg912, Met1038, Ala1078, Ala1079, Gln1194, and Gly1260, suggesting that entering the enzyme-catalyzed reaction was unfavorable for the substrate. We also observed face-to-face π-π interactions between the aryl ring of davallialactone and Phe914. Cell biology experiments indicated that davallialactone reduced the expression of the inflammatory factors, tumor necrosis factor alpha and interleukin-1 beta ( P < 0.05), can effectively alleviate cellular oxidative stress. This study showed that davallialactone significantly inhibits XO and has the potential to be developed into a novel medicine to prevent hyperuricemia and treat gout.
研究领域:
药理学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Journal of Herbal Medicine
·
2024
·
IF 2.2
T.M. Le,C.D.P. Nguyen,A.C. Ha
ABSTRACT Introduction Psidium guajava L. ( P guajava ) and its leaf, one of the most popular plants in traditional medicine and cuisine, were demonstrated to have high flavonoid content with many bioactivities, including antigout activity. However, the correlation between total flavonoid content ( TFC ) and antigout activities and the optimal conditions for extracting P guajava have not been reported. Methods This study established the optimisation of ethanol extracts of P guajava leaves for TFC and antigout activities using the single-factor method and response surface methodology. The antigout activities were determined through the xanthine oxidase inhibition ( XOI ) method. Results The four independent variables (ethanol concentration, plant-solvent ratio, extraction time, and temperature) significantly impacted two response variables (TFC and XOI activity). The optimal extracts for XOI activity reach the maximum TFC of 323.86 ± 2.26 mg quercetin/g and XOI activity of 26.37 ± 0.5 μg/ml. The changes in the chemical structure of extracts were analysed by Fourier transform infrared, which indicated that several flavonoids in P guajava do not have XOI activity. The correlation of TFC and XOI is robust with the Pearson correlation of −0.882 and Spearman Rho test of −0.884. Additionally, the biological activities, such as antioxidant and anti-inflammatory, of optimal extracts for XOI and TFC were determined to extend the application capacity to support the treatment of gout diseases. Conclusions The optimised extraction conditions are critical to isolating flavonoids, which can serve as functional food or medicine for managing gout and its complications.
研究领域:
药用植物学
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天然产物化学
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生物活性研究
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DOI
高影响因子
JOURNAL OF BIOTECHNOLOGY
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2024
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IF 4.1
Hanwei Zheng,Zhiqing Liu,Hao Zheng,Yuman Miao,Chenyu Liu,Minhua Zong,Wenyong Lou
To enhance the activity of Lactiplantibacillus plantarum FS4722 ( L. plantarum FS4722 ) in reducing uric acid, this study optimized the culture medium components and fermentation conditions using response surface methodology. The results indicated that the optimal culture medium comprised glucose at 25.61 g/L, yeast extract powder ( YEP ) at 26.86 g/L, and nucleoside addition at 0.48 g/L. The optimal fermentation conditions were: a fermentation time of 10 h, an initial pH of 6.5, a fermentation temperature of 33 °C, and an inoculum size of 1.0 %. Under these conditions, the nucleoside degradation ability of L. plantarum FS4722 increased by 41.9 times, enhancing its potential applications in reducing uric acid and developing anti-gout foods, health supplements, and pharmaceuticals.
研究领域:
微生物学
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生物技术
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食品科学
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药学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
·
IF 5.7
Zhiren Yao,Tian Li,Meiling Jin,Siyang Fang,Jie Wang,Jiaming Zheng,Ke Pan,Jian Zhang,Guoqing Zhao,Zhiqi Yin,Yaping Huang
Piper sintenense Hatusima (PsH) is a member of the Piper genus used as food and folk medicine in China. However, the detailed chemical ingredients and potential pharmacological effects are still underexploited. In this study, we evaluated the anti-inflammatory and antigouty arthritis effect of the ethanolic extract of P. sintenense. Active compounds were isolated from the petroleum ether fraction resulting in six novel amide alkaloids (1–6) and 13 known analogues (7–19). All of the compounds exhibited excellent anti-inflammatory activities. Bioinformatics analysis and in vitro experiments showed that compound 4 had anti-inflammatory properties (IC50 = 4.86 ± 0.32 μM) and antigouty arthritis activity. Mechanistic studies revealed that compound 4 exerted its favorable efficacy by regulating macrophage polarization by inhibiting P-STAT1/4. These findings provide new insights into the chemical composition and function of P. sintenense and expand its promising application as a functional food in the prevention and treatment of gouty arthritis.
研究领域:
药理学
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生物化学
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药物化学
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传统医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Chen Wu,Zhongyun Zhang,Lijie Bai,Shuhui Lei,Min Zou,Zilu Bao,Zhaoxiang Ren,Kaiqun Liu,Hui-Hong Gong,Wenjun Ma,Lvyi Chen
Ethnopharmacological relevance Gout, a painful joint disease with a prevalence ranging from 0.86% to 2.2% in China over the past decade. Traditional medicine has long utilized the medicinal and edible Piper longum L. (PL) fruit spikes for treating gout and other joint conditions like rheumatoid arthritis. However, the exact mechanisms behind its effectiveness remain unclear. Aim of the study This study aimed to investigate the potential of alcoholic extracts from PL fruit spikes as a safe and effective treatment for gout. We used a combined network pharmacology and experimental validation approach to evaluate the mechanisms behind the anti-gout properties of PL. Materials and methods UPLC-Q/TOF-MS analysis determined the major components of PL. Subsequently, network pharmacology analysis predicted potential molecular targets and related signaling pathways for the anti-gout activity of PL. Molecular docking simulations further explored the interactions between PL compounds and proteins and characterized the properties of potential bioactive secondary metabolites. Mouse models of air pouch inflammation and hyperuricemia were further established, and the anti-gout mechanism of PL was confirmed by examining the expression of proteins related to the MAPK and PI3K-AKT pathways in the tissue. Results Our analysis revealed 220 bioactive secondary metabolites within PL extracts. Network pharmacology and molecular docking results indicated that these metabolites primarily combat gout by modulating the PI3K-AKT and MAPK signaling pathways. In vivo experiments have also proven that PL at a dose of 100 mg/kg can optimally reduce acute inflammation of gout and kidney damage caused by high uric acid. The anti-gout mechanism involves the PI3K-AKT/MAPK signaling pathway and its downstream NF-κB pathway. Conclusion This study provides compelling evidence for PL's therapeutic potential in gout management by modulating key inflammatory pathways. The findings offer a strong foundation for future clinical exploration of PL as a gout treatment option.
研究领域:
药理学
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民族药理学
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分子生物学
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炎症研究
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传统医学
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DOI
PubMed
高影响因子
AAPS PHARMSCITECH
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2023
·Vol. 25
·期 1
·1-18
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IF 3.3
Liao Shiji,Qiu Guirong,Hu Yanping,Guo Bohong,Qiu Yuqin
Colchicine is the first-line option for both the treatment and prophylaxis of gout flares. However, due to potentially severe side effects, the clinical use of colchicine is limited. A well-tolerated and safe delivery system for colchicine is widely desired. For this purpose, colchicine-loaded inseparable microneedles were fabricated using silk fibroin. Additionally, separable microneedles made of silk fibroin as the needle tips and PVP K30 as the base material were developed. Both types of microneedles were evaluated for their mechanical strength, swelling and dissolution characteristics, insertion abilities, degradation properties, in vitro penetration, skin irritation, and in vivo anti-gout effects. The results demonstrated that separable microneedles had greater mechanical strength and insertion ability. Moreover, the separable microneedles separated quickly and caused little skin irritation. In the pharmacodynamic test, mice with acute gouty arthritis responded significantly to treatment with separable microneedles. In conclusion, the separable silk fibroin-based microneedles provide a promising route for colchicine delivery. Graphical Abstract
研究领域:
药剂学
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药物递送系统
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
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2023
·Vol. 46
·期 21
·2300090
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IF 3.1
Qiangqiang Jia,Zufan Yang,Qian Wang,Haishan Yang,Xiaofeng Tang,Hongyang Zhang,Lingling Cao,Gong Zhang
It has been proved that purine metabolites are implicated in various biological syndromes and disorders. Therefore, the realization of panoramic detection of purine metabolites will be of great significance to the pathogenesis of purine metabolic disorders. In the present study, an ultra-high performance liquid chromatography with tandem mass spectrometry method was developed for the comprehensive quantification of purine metabolites in rat plasma. The 17 purine metabolites were separated and quantified in the short running time of 15 min. The proposed method was strictly validated by applying SeraSub solution as a matrix and proved to be linear (R 2 ≥ 0.9944), accurate (the recoveries of all analytes ranged from 85.3% to 103.0%, with relative standard deviation values ≤ 9.3%), and precise (the intra- and inter-day precisions were less than 10.8% and 12.4%, respectively). The method was then successfully applied to the qualification of the endogenous purine metabolites in acute gouty arthritis rats, as well as colchicine and anthocyanin-intervened rats. Results showed that uric acid, xanthine, hypoxanthine, and xanthine were considered the key factors of acute gouty arthritis. The established method and measurement of purines in rat plasma might help the investigation of the action mechanisms between purine disorders and related diseases.
研究领域:
药理学
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分析化学
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生物化学
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医学
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产品关联
DOI
PubMed
高影响因子
Waste and Biomass Valorization
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2024
·Vol. 15
·期 7
·4353-4372
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IF 2.6
Shankaranarayana Sahana Hosanagara,Gajanana Vijayalaxmi Karki,Chavan Mohan,Chavannavar Suvarna V.,Doddanagappa Shobha
Purpose To analyse phytochemical composition, antioxidant potential, antimicrobial activity and α-amylase, α-glucosidase and xanthine oxidase inhibitory potential of corn silk extracts derived from the Syngenta 5414 corn variety. Methods Corn silk sample was lyophilized and extracted using 80% ethanol, methanol, water or acetone. Phytochemicals were qualitatively screened and bioactive compounds were identified through GCMS. Antimicrobial activities were evaluated using the agar well method for bacteria and fungal biomass method for fungi. The extracts were subjected to evaluation for their antidiabetic activity through α-amylase and α-glucosidase inhibitory assays, while their anti-gout potential was assessed through xanthine oxidase inhibitory assay, encompassing all four solvent extracts in the study. Results Phytochemical screening revealed the presence of phenols, flavonoids, tannins, alkaloids, sterols, protein xanthoproteic, and cardiac glycosides in the extracts. The Folin-Ciocalteu and AlCl 3 assays demonstrated higher yields of phenolics and flavonoids in 80% ethanolic extract. Furthermore, the extracts remarkably scavenged reactive oxygen species like DPPH, ABTS and elicited considerable ferric ion reducing antioxidant power. GC–MS analysis identified 21 compounds in the 80% ethanolic extract, with 1,2,3-Propanetriol-1-acetate, n-Hexadecanoic acid, and 4H-Pyran-4-one,2,3-dihydro-3,5-dihydroxy-6-methyl- as major components. Antimicrobial assays demonstrated the ethanolic (80%) and methanolic extract's remarkable ability to inhibit the growth of Gram-positive bacteria and exhibit anti-fungal properties. The ethanolic (80%) extract exhibited an IC 50 value of 0.70 ± 0.02 and 0.71 ± 0.01 mg against α-amylase and α-glucosidase, respectively, and 33.76 ± 0.43 mg against xanthine oxidase. Conclusion Corn silk exhibits potential as a valuable reservoir of natural bioactive compounds endowed with a wide array of health-promoting properties. Graphical
研究领域:
天然产物化学
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药用植物学
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生物化学
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药物代谢
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微生物学
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内分泌药理学
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代谢性疾病
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DOI
高影响因子
TOXICOLOGY IN VITRO
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2024
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IF 2.6
Jia-hong Liang,Xiao-lei Yi,Jia-min Gong,Zuo Du
Gout is an immune-metabolic disease that frequently coexists with multiple comorbidities such as chronic kidney disease, cardiovascular disease and metabolic syndrome, therefore, it is often treated in combination with these complications. The present study aimed to evaluate the inhibitory effect of antigout drugs (allopurinol, febuxostat, topiroxostat, benzbromarone, lesinurad and probenecid) on the activity of the crucial phase I drug-metabolizing enzymes, carboxylesterases (CESs). 2-(2-benzoyl-3-methoxyphenyl) benzothiazole (BMBT) and fluorescein diacetate (FD) were utilized as the probe reactions to determine the activity of CES1 and CES2, respectively, through in vitro culturing with human liver microsomes. Benzbromarone and lesinurad exhibited strong inhibition towards CESs with Ki values of 2.16 and 5.15 μM for benzbromarone towards CES1 and CES2, respectively, and 2.94 μM for lesinurad towards CES2. In vitro-in vivo extrapolation (IVIVE) indicated that benzbromarone and lesinurad might disturb the metabolic hydrolysis of clinical drugs in vivo by inhibiting CESs. In silico docking showed that hydrogen bonds and hydrophobic interactions contributed to the intermolecular interactions of antigout drugs on CESs. Therefore, vigilant monitoring of potential drug-drug interactions (DDIs) is imperative when co-administering antigout drugs in clinical practice.
研究领域:
药理学
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临床药理学
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药物代谢
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产品关联
DOI
PubMed
高影响因子
World Journal of Traditional Chinese Medicine
·
2024
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IF 4.3
Gao Hong-Xue,Liu Zhi-Qiang,Hou Zong,Song Feng-Rui,Xing Jun-Peng,Zheng Zhong,Liu Shu
Objective: This study aimed to elucidate the active components and mechanisms of Plantago asiatica L. (PAL) in the treatment of gout. Materials and Methods: Based on its polarity, PAL was partitioned into three parts, P1, P2, and P3, through gradient elution using AB-8 macroporous resin columns. The primary constituents of these fractions include iridoids, phenylethanoid glucosides, and flavonoids. Subsequently, a comprehensive in vitro and in vivo screening and evaluation model was developed considering the fundamental pathological processes of gout, including the inhibition of uric acid (UA) production, augmentation of UA excretion, and anti-inflammatory effects. This model was used to analyze the anti-gout activity of P1, P2, P3, and the overall extracts derived from PAL. Results: All the PAL parts exhibited specific therapeutic properties as part of gout therapy. Specifically, the P2 part demonstrated the ability to diminish interleukin-1 beta levels, lower UA concentrations, suppress joint inflammation in rats, and restore abnormal parameters associated with gout, such as creatinine and urea nitrogen. These findings highlight the significant effect of P2 on gout treatment. Conclusions: Following a thorough assessment of the outcomes derived from diverse anti-gout experiments, P2 exhibited superior anti-gout properties compared to the remaining parts. P2 demonstrated a restorative effect on the aberrant parameters associated with gout, thereby comprehensively elucidating the therapeutic mechanism of P2 against gout. This study provides substantial evidence and serves as a reference for future investigations regarding the material foundation of PAL in gout treatment.
研究领域:
药理学
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药用植物研究
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生物化学
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炎症研究
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2018
·
IF 3.909
Qiuxuan Yang,Qilong Wang,Wenwen Deng,Congyong Sun,Qiuyu Wei,Michael Adu-Frimpong,Jixiang Shi,Jiangnan Yu,Ximing Xu
In this present study, we investigated the anti-hyperuricemic and anti-gouty arthritis effect of a puried water-soluble polysaccharide (LJP-1) obtained from Lonicera japonica . A series of characterization of the purified polysaccharide were carried out in this paper. Monosaccharide analysis showed that LJP-1 composed of glucuronic acid, glucose, galactose, arabinose, and xylose at the ratio of 2.43:1:2.09:1.95:1.96, respectively. The estimated molecular weight of LJP-1 was 17.5 kDa. LJP-1 belonged to pyranose and possessed α- and β -glycosidic configurations. Congo red test showed that LJP-1 had a spatial triple helix structure. In pharmacodynamic experiments, the anti-hyperuricemic activity of LJP-1 was studied using hyperuricemic SD rat model induced via potassium oxonate and hypoxanthine. The result showed that LJP-1 could obviously decrease the serum uric acid level and suppress xanthine oxidase (XOD) activity. Moreover, in the gouty arthritis model established by sodium urate crystals, the degree of swelling of the ankle joint, IL-1β, IL-6, TNF-α and COX-2-related inflammatory factors levels in murine serum all declined. Taken together, these results demonstrated that LJP-1 has anti-gouty arthritis effect. Therefore, LJP-1 could serve as a promising candidate for developing novel natural anti-gouty agent.
研究领域:
药理学
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生物化学
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免疫学
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中药学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
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IF 5.6
Jirui Lang,Li Li,Yunyun Quan,Ruirong Tan,Jinbiao Zhao,Min Li,Jin Zeng,Shilong Chen,Ting Wang,Yong Li,Junning Zhao,Zhujun Yin
Wuwei Shexiang Pill (WSP) is a Tibetan traditional medicine, which has been demonstrated to exhibit potent anti-inflammatory and anti-gout effects. However, the specific pharmacological mechanism is not elucidated clearly. In the present study, liquid chromatography-mass spectrometry (LC-MS)-based metabolomics was applied to investigate the alteration of serum metabolites induced by WSP treatment in MSU-induced gouty rats. Subsequently, bioinformatics was utilized to analyze the potential metabolic pathway of the anti-gout effect of WSP. The pharmacodynamic data discovered that WSP could ameliorate ankle swelling and inflammatory cell infiltration, as well as downregulate the protein expression of IL-1β, p-NF-κB p65, and NLRP3 in the synovial membrane and surrounding tissues of gouty ankles. LC-MS-based metabolomics revealed that there were 30 differential metabolites in the serum between sham-operated rats and gouty ones, which were mainly involved in the metabolism of fructose and mannose, primary bile acid biosynthesis, and cholesterol metabolism. However, compared to the model group, WSP treatment upregulated 11 metabolic biomarkers and downregulated 31 biomarkers in the serum. KEGG enrichment analysis found that 27 metabolic pathways contributed to the therapeutic action of WSP, including linoleic acid metabolism, phenylalanine metabolism, and pantothenate and CoA biosynthesis. The comprehensive analysis-combined network pharmacology and metabolomics further revealed that the regulatory network of WSP against gout might be attributed to 11 metabolites, 7 metabolic pathways, 39 targets, and 49 active ingredients of WSP. In conclusion, WSP could ameliorate the inflammation of the ankle in MSU-induced gouty rats, and its anti-gout mechanism might be relevant to the modulation of multiple metabolic pathways, such as linoleic acid metabolism, phenylalanine metabolism, and pantothenate and CoA biosynthesis. This study provided data support for the secondary development of Chinese traditional patent medicine.
研究领域:
药理学
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代谢组学
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传统中药
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炎症生物学
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生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）