JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
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
·
2023
·Vol. 25
·期 1
·1-18
·
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 MOLECULAR STRUCTURE
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2016
·
IF 1.78
Yanlei Kang,Jianming Gu,Xiurong Hu
Febuxostat was investigated due to its significant effect in the treatment of gout. However, its poor water solubility hinder its potential applications. In recent years, cocrystals have increasingly being applied to enhance the drug solubility . To improve the solubility, two cocrystals of Febuxostat were synthesized through the method of cooling crystallization. The prepared cocrystals febuxostat-isonicotinamide(FEB-INA) and febuxostat-arginine(FEB-Arg) were studied by microscopical observation, Powder X-Ray Diffraction(PXRD), Single Crystal X-ray Diffraction, Differential Scanning Calorimetry(DSC), and infrared spectrometry . At the same time, the cocrystals' solubility and dissolution rate were explored. Both the cocrystals showed higher solubility compared to the pure drug. The FEB-Arg cocrystal enhanced about 900 times of solubility compared to the pure drug. The current study proved that cocrystallization can be a better way to enhance the solubility of the poorly water-soluble drug.
研究领域:
药物化学
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材料科学
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药剂学
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产品关联
DOI
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2023
·Vol. 46
·期 21
·2300090
·
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
JOURNAL OF NANOPARTICLE RESEARCH
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2021
·Vol. 23
·期 6
·1-16
·
IF 2.253
Wang Qilong,Liu Jing,Liu Jian,Thant Yaminn,Weng Wen,Wei Chunmei,Bao Rui,Adu-Frimpong Michael,Yu Qingtong,Deng Wenwen,Cao Xia,Toreniyazov Elmurat,Ji Hao,Xu Ximing,Yu Jiangnan
Recently, bisdemethoxycurcumin (BDMC), a constituent of turmeric, has been studied widely in view of their various therapeutic effects, namely anti-oxidant, anti-cancer, anti-diabetic, and anti-inflammatory. Since ancient times, turmeric has been extensively used as a naturally occurring traditional Chinese medicine (TCM) and as a crucial home remedy for treatment of many health problems such as inflammation and pain. However, the action of anti-gouty arthritis and analgesic activity of its constituents, especially BDMC, have not been scientifically reported yet. Despite the various bioactivities of BDMC, its utilization in clinics has been restricted owing to poor solubility and bioavailability. This research aimed at enhancing oral bioavailability and pharmacokinetic of BDMC via liposome formulation which was modified with d -α-tocopherol polyethylene glycol 1000 succinate (TPGS or vitamin E TPGS) and was characterized using various parameters both in vitro and in vivo. Also, the analgesic and anti-gouty activities of BDMC-loaded TPGS-modified liposomes were investigated by assessing pain threshold and serum uric acid level in potassium oxonate–induced hyperuricemic rats. As the result, BDMC-loaded TPGS-modified liposomes were formulated successfully with optimal physiochemical properties such as 75.98 ± 5.46 nm (particle size), 0.246 ± 0.011 (polydispersity index), − 38.21 ± 0.29 mV (zeta potential), 96.98 ± 0.17 (encapsulation efficiency (EE%)), and 4.84 ± 0.0089 (drug loading capacity (DL%)). Moreover, the oral bioavailability of liposomized BDMC was approximately 10-fold greater than free BDMC in vivo and in vitro cumulative release rates in pH 1.2 (78%) and pH 7 (68%) respectively. This significantly improved the sustaining drug effect of BDMC compared with free form. In addition, BDMC-TPGS liposome acted as a xanthine oxidase inhibitor to evidently reduce uric acid level in potassium oxonate–induced hyperuricemic rats and remarkably increase pain threshold capacity and reaction time in hot plate test at a dose-dependent manner. Altogether, BDMC-conjugated TPGS liposome could act as favorable nanocarriers against gouty arthritis and intense pain with prospect of overcoming the limitation of BDMC application.
研究领域:
药剂学
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生物医学
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中药学
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DOI
高影响因子
Food Analytical Methods
·
2024
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IF 2.6
Hu Rui,Wu Yijun,He Haoliang,Chen Wentao,Xiang Leiwen,Huang Dihui
A reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed to quantify nine gout-related compounds: uric acid, guanine, hypoxanthine, adenine, xanthine, inosine, guanosine, xanthosine, and adenosine. Separation was achieved using a Supersil AQ-C18 column with mobile phase solution A (water:triethylamine:phosphoric acid, 950:11:5, pH 3.93) and solution B (water:acetonitrile, 90:10). The method demonstrated good linearity with linear ranges for nucleosides (1.06–17.00 μg mL −1 ), purines (3.13–50.00 μg mL −1 ), and uric acid (12.50–200.00 μg mL −1 ). The recoveries of analytes in spiked samples ranged from 99.97 to 103.30%. The limit of detection was 1.45 μg mL −1 . This method is characterized by high precision and accuracy, a wide linear range, good reproducibility, and effective quantification of the nine gout-related compounds. The method has been successfully applied to the detection and evaluation of the representative Min cuisine dish, “Buddha Jumps Over the Wall.”
研究领域:
食品科学
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分析化学
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产品关联
DOI
高影响因子
DRUG DELIVERY
·
2019
·
IF 3.829
Yujia Zhang,Nan Zhang,Hui Song,He Li,Jin Wen,Xiaochuan Tan,Wensheng Zheng
Gout is a kind of joint disease characterized by the accumulation of monosodium urate (MSU) crystals in the joint and its surrounding tissue, causing persistent hyperuricemia. Colchicine is the first choice of treatment for acute gout attacks. Due to strong toxicity of colchicines oral tablets, there are high fluctuations of blood drug concentration and serious irritation of gastrointestinal tract, and hence a transdermal preparation can help to slow down the blood drug concentration, reduce the frequency of drug taking, and improve the patients' compliance of the drug. The ethosome is a lipid carrier with high concentration of ethanol and has been proved to promote the penetration of drugs into the skin. Borneol (BO) is an excellent penetration enhancer in Chinese medicine, which can promote the entry of drugs into the skin. This paper prepared the borneol-physically-modified colchicine ethosome (COL-bpES) and used the prepared borneol-dioleoyl phosphoethanloamine (BO-DOPE) to prepare borneol-chemically-modified colchicine ethosome (COL-bcES). Compared to the free colchicine aqueous solution (free COL) and normal colchicine ethosome (COL-ES), the borneol-modified colchicine ethosome (COL-bES) demonstrated better drug penetration effect, while the particle size of the COL-bcES was lower than that of the COL-bpES. Toxicity, in vitro diffusion, pharmacokinetics and pharmacodynamics are superior to those of COL-bpES, providing a better delivery system for the treatment of small molecule inflammatory drugs.
研究领域:
药剂学
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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
TOXICOLOGY IN VITRO
·
2024
·
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
Frontiers in Pharmacology
·
2021
·
IF 5.811
Yang Wenning,Jiang Xiaoquan,Liu Jingtong,Qi Dongying,Luo Zhiqiang,Yu Guohua,Li Xueyan,Sen Muli,Chen Hongjiao,Liu Wei,Liu Yang,Wang Guopeng
The study of screening active constituents from traditional Chinese medicine (TCM) is important for explicating the mechanism of action of TCM and further evaluating the safety and efficacy effectively. However, detecting and identifying the active constituents from complicated biological samples still remain a challenge. Here, a practical, quick, and novel integrated strategy from in vitro, in situ, in vivo to in silico for rapidly screening the active constituents was developed. Firstly, the chemical profile of TCM in vitro was identified using UPLC-Q Exactive-Orbitrap HRMS. Secondly, the in situ intestinal perfusion with venous sampling (IPVS) method was used to investigate the intestinal absorption components. Thirdly, after intragastric administration of the TCM extract, the in vivo absorbed prototype components were detected and identified. Finally, the target network pharmacology approach was applied to explore the potential targets and possible mechanisms of the absorbed components from TCM. The reliability and availability of this approach was demonstrated using Tongfengding capsule (TFDC) as an example of herbal medicine. A total of 141 compounds were detected and identified in TFDC, and among them, 64 components were absorbed into the plasma. Then, a total of 35 absorbed bioactive components and 50 related targets shared commonly by compounds and gout were integrated via target network pharmacology analysis. Ultimately, the effects of the absorbed components on metabolism pathways were verified by experiments. These results demonstrated that this original method may provide a practical tool for screening bioactive compounds from TCM treating particular diseases. Furthermore, it also can clarify the potential mechanism of action of TCM and rationalize the application of TFDC as an effective herbal therapy for gout.
研究领域:
中药学
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药理学
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生物信息学
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药学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2025
·
IF 5.6
Yao-Yao Wei,Yang Zhang,Xue Lu,Jie Zhou,Huang-Wei Cheng,Yuan-Yuan Liu,Hua Zhang,Wen Chen
Gout is a disease caused by the deposition of sodium urate (MSU) crystals in the joints and tissues. Colchicine (COL) has become the first-line drug for the treatment of acute gout due to its low price and efficacy. However, colchicine is highly cytotoxic and oral administration is prone to cause severe adverse effects on the gastrointestinal tract, liver and kidney. Therefore, this study aimed to develop a novel dermal delivery formulation for addressing the safety concerns of this drug. The researchers used ethosomes encapsulation technology to improve the skin permeability of COL. In addition, in order to improve the performance of the ethosomes, it was screened and determined that the addition of 1.0–1.5 mg of ceramide III (Cer3) per mL of ethosomes as a modifier could significantly enhance the stability of the ethosomes, Cer3/COL-ethosomes (CCE) were successfully constructed. The CCE was then mixed with a cataplasm matrix to produce a colchicine-carrying CCE cataplasm, which demonstrated the superimposed effect of the advantages of the two dosage forms, the ethosomes and the cataplasm. Compared with the traditional delivery method of COL, this topical formulation is an attractive alternative for the treatment of gout as it can achieve effective blood levels without causing fluctuations in blood levels, and has good efficacy and higher safety profile.
研究领域:
药剂学
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生物医学
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皮肤病学
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产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2019
·Vol. 2019
·期 1
·2969364
·
IF 1.984
Zi-cong Wu,Qiang Xue,Zhen-ling Zhao,Peng-jun Zhou,Qun Zhou,Zhen Zhang,Jian-ping Deng,Ke Yang,Hua Fan,Yi-fei Wang,Zhi-ping Wang
Background . Huzhentongfeng (HZTF) is an extract from four Chinese medical herbs for treating gout. This study aims to evaluate its antigout activity and preliminary explore its mechanism in vivo and in vitro . Methods . The rats were intragastrically administered with HZTF for 5 days and then injected 0.1 ml (10 mg) of MSU crystals to their joints for generating a gout model to analyze the paw volume and histopathology of joint synovial tissues of rats with different doses. We also investigated the antioxidant capacity of HZTF in vitro using indication including lipid peroxidation, DPPH · , and ABTS + radical-scavenging capacity; besides, we used qRT-PCR to measure the effect of HZTF on interleukin (IL)-1 β , caspase-1, NLRP3, and NQO1 expression in hydrogen peroxide-stimulated RAW264.7 macrophages and IL-1 β , IL-6, and tumor necrosis factor (TNF)- α in MSU crystal-induced THP-1 monocytes. Confocal microscopy analysis was used to observe the dimerization of ASC adapter proteins. In addition, we also established quality standard of HZTF by using the high-performance liquid chromatography (HPLC) method. Results . HZTF could significantly suppress the paw swelling and neutrophil infiltration induced by MSU intra-articular injection in rats compared with the control group. HZTF also showed inhibition effects of inflammatory cytokines (IL-1 β , IL-6, and TNF- α ) secretion at 25.00 and 50.00 μ g/ml in MSU-induced THP-1 cells but showed no effects of IL-1 β , IL-6, and TNF- α mRNA expression in MSU-induced THP-1 cells. Furthermore, confocal microscopy analysis showed that HZTF could prevent the oligomerization of ASC. Moreover, HZTF also showed effects in cell-free and cell-base tests of antioxidant capacity. Conclusion . The results prove that HZTF possessed the potential preventive effect against gout arthritis, and the effect may be attributed to its preventing effect on neutrophil infiltration and proinflammatory cytokines secretion such as IL-1 β , IL-6, and TNF- α which were caused by the activation of inflammasome.
研究领域:
药理学
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免疫学
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风湿病学
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中医药学
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DOI
高影响因子
Foods
·
2022
·Vol. 11
·期 7
·968
·
IF 5.561
Qian Zhou,Xiaoyan Li,Xiaohui Wang,Dongdong Shi,Shengao Zhang,Yuqi Yin,Hanlin Zhang,Bohao Liu,Nannan Song,Yinghua Zhang
Gout is an oxidative stress-related disease. Food-derived vanillic acid, a promising xanthine oxidase inhibitor, could potentially be used as a safe, supportive, and therapeutic product for gout. The extraction of vanillic acid from a classic Chinese herbal plantAmomum villosumwith ethanol was investigated in the study. The optimum conditions were determined as extraction time of 74 min, extraction temperature of 48.36 °C, and a solid-to-liquid ratio of 1:35 g·mL−1using the Box–Behnken design (BBD) of response surface methodology (RSM). The experimental extraction yield of 9.276 mg·g−1matched with the theoretical value of 9.272 ± 0.011 mg·g−1predicted by the model. The vanillic acid inAmomum villosumwas determined to be 0.5450 mg·g−1by high-performance liquid chromatography–diode array detection (HPLC–DAD) under the optimum extraction conditions and exhibited xanthine oxidase (XO) inhibitory activity, with the half-maximal inhibitory concentration (IC50) of 1.762 mg·mL−1. The nanoemulsion ofAmomum villosumextract consists of 49.97% distilled water, 35.09%Smix(mixture of tween 80 and 95% ethanol with 2:1 ratio), and 14.94% n-octanol, with a particle size of 110.3 ± 1.9 nm. The nanoemulsion ofAmomum villosumextract exhibited markable XO inhibitory activity, with an inhibition rate of 58.71%. The result demonstrated the potential benefit ofAmomum villosumas an important dietary source of xanthine oxidase inhibitors for gout.Keywords:gout;oxidative stress;Amomum villosum;vanillic acid;response surface methodology;nanoemulsion
研究领域:
药理学
·
食品科学
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植物化学
✓ 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）