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JOURNAL OF ETHNOPHARMACOLOGY · 2021 · IF 4.36

Study on the compatibility effect and active constituents of Atractylodis Rhizoma in Ermiao Wan against Acute Gouty Arthritis

Xiao-Ling Fu,Jie Zhou,Wei-Wei Tang,Yang Liu,Zi-Lu Li,Ping Li,Jun Chen

Ethnopharmacological relevance Ermiao Wan (EMW), composed of Atractylodis Rhizoma (AR) and Phellodendri Chinensis Cortex (PC), is a classical traditional Chinese medicine prescription having been used to treat the disease named “Tong Feng”, which is described as “ache in bones and joints” with the same symptom of modern disease named acute gouty arthritis for many years in TCM clinical practice. Besides, both PC and AR were considered to be effective in anti-inflammatory according to modern pharmacological research. Aim of the study Present study was undertaken to probe the compatibility rationality between the two herbs PC and AR in EMW and the active constituents of AR against acute gouty arthritis (AGA). Materials and methods Rat model of AGA was induced by intra-articular injection of monosodium urate (MSU) crystal suspension, and PC combined with or without different AR extracts were used for AGA treatment. Ankle joint swelling, proinflammatory cytokines in serum and pathological changes of synovium were investigated. Using the developed UHPLC-QQQ-MS method, the plasma concentrations of the primary alkaloids in PC, such as berberine , phellodendrine, magnoflorine , jatrorrhizine , berberrubine , palmatine , and tetrahydropalmatine , in AGA rat were determined, and pharmacokinetics properties were compared following oral administration of PC, PC combined with or without different AR extracts. Results PC, PC combined with AR volatile oil (VO) extract or PC combined with whole AR extract significantly attenuated the ankle joint swelling of AGA rats. Besides, the combination of PC and VO extract of AR showed superior efficacy than other groups in ameliorating ankle joint swelling, reducing the IL-6 expression in serum and improving tissue lesions of ankle joints. Furthermore, it turned out that the VO extract of AR increased the blood exposure level of PC related alkaloids than non-volatile oil (NVO) extract of AR, by comparing the pharmacokinetic results of each group. Conclusions The VO components of AR were the key compatible materials to combine with PC in EMW for AGA treatment. Moreover, the enhanced anti-AGA activity of PC after combining with VO extract of AR may attribute to the influence of VO on the pharmacokinetics of PC. This study may provide useful information for elucidating the compatibility effects of AR in EMW against AGA.

CAS / MDL: 64-86-8
研究领域: 民族药理学 · 中医药 · 药理学 · 炎症研究
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Bioengineered · 2022 · IF 6.832

Cynarin suppresses gouty arthritis induced by monosodium urate crystals

Changgui Wu,Shaohua Chen,Yang Liu,Bo Kong,Wei Yan,Tao Jiang,Hao Tian,Zhaoyi Liu,Qi Shi,Yongjun Wang,Qianqian Liang,Xiaobing Xi,Hao Xu

The study is aimed to determine the effects of cynarin (Cyn) on mice with gouty arthritis (GA) induced by monosodium urate (MSU). We measured swelling in the hind paws of mice in vivo using Vernier calipers and ultrasound. The liver, kidney, and hind paws were stained with hematoxylin-eosin, and M1 type macrophages were detected in the hind paws using anti-F4/80 and anti-iNOS antibodies. The mRNA expression of inflammatory factors in bone marrow-derived macrophages (BMDMs) and in the hind paws was detected via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasomes and the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways were analyzed via western blotting. Cyn was detected in vitro using Cell Counting Kit-8 (CCK-8). Cyn treatment reduced hind paw swelling and M1 macrophage infiltration, suppressed the mRNA expression of inflammatory factors, and inhibited NLRP3 inflammasome activation in vivo, in addition to inhibiting the phosphorylation of IKKa/β, p65, and c-Jun NH 2-terminal kinase (JNK). Furthermore, Cyn exerted anti-inflammatory and anti-swelling effects in mice with GA by regulating the NF-κB and JNK pathways and NLRP3 inflammasomes.

研究领域: 药理学 · 免疫学 · 风湿病学
✓ 已验证 DOI PubMed 高影响因子
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Journal of Natural Medicines · 2020 ·Vol. 75 ·期 1 ·37-47 · IF 2.055

Preventive effect of dioscin against monosodium urate-mediated gouty arthritis through inhibiting inflammasome NLRP3 and TLR4/NF-κB signaling pathway activation: an in vivo and in vitro study

Han Jieru,Shi Guangyu,Li Wenhao,Xie Ying,Li Fuzhen,Jiang Deyou

Monosodium urate (MSU)-mediated inflammation is closely related to gouty arthritis (GA). Dioscin, an active ingredient, has been reported to possess anti-inflammatory property. Nevertheless, the role of dioscin in GA and the underlying mechanism have not been fully understood. In the present study, we investigated the anti-inflammatory effect of dioscin on MSU-induced GA through in vivo and in vitro experiments. Histopathological analysis showed that dioscin alleviated the severity of GA concomitant with the lowered uric acid and creatinine levels. Moreover, the increasing IL-1β, IL-6, and TNF-α levels induced by MSU were decreased via administration of dioscin in mice and human synoviocytes. Western blotting results suggested that dioscin inhibited the activation of NLRP3 through down-regulating the protein expressions of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cleaved-caspase-1, as well as IL-1β. In addition, TLR4, myeloid differentiation primary response gene 88 (MyD88), p-IKKβ, p-p65, and NF-κB p65 in nuclei levels were significantly reduced by dioscin. Importantly, dioscin remarkably lowered the NF-κB p65-DNA activity in MSU-treated mice utilizing electrophoretic mobility shift assay (EMSA) analysis. Taken together, dioscin had a protective effect against MSU-initiated inflammatory response via repressing the production of inflammatory cytokines and the activation of inflammasome NLRP3 and TLR4/NF-κB signaling pathway. The above findings revealed that dioscin could be a potential drug for the treatment of GA.

CAS / MDL: 28718-90-3
研究领域: 药理学 · 免疫学 · 风湿病学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Chemical Biology & Drug Design · 2024 ·Vol. 103 ·期 4 ·e14522 · IF 3.2

Baicalin inhibits monosodium urate crystal-induced pyroptosis in renal tubular epithelial cell line through Panx-1/P2X7 pathways: Molecular docking, molecular dynamics, and in vitro experiments

Wanting Fu,Ziyuan Liu,Yingzhou Wang,Xindi Li,Xiang Yu,Yang Li,Zejun Yu,Yinsheng Qiu,Zhinan Mei,Lingyun Xu

Pyroptosis is a programmed cell death process that frequently occurs in many diseases, including hyperuricemic nephropathy (HN). In HN, a range of stimuli mediates inflammation, leading to the activation of inflammasomes and the production of gasdermin D (GSDMD). Baicalin (BA), a natural flavonoid renowned for its antioxidant and anti-inflammatory properties, was investigated for its role in HN in this study. Initially, HN-like inflammation and pyroptosis were induced in HK-2 cells with treatment of monosodium urate (MSU), followed by the BA treatment. The expression of pyroptosis-associated genes, Panx-1 and P2X7, at both mRNA and protein levels was assessed through real-time polymerase chain reaction (RT-qPCR) and Western blotting (WB) without or with BA treatment. The results showed that expression of Panx-1 and P2X7 at mRNA and protein levels was increased in MSU-treated HK-2 cells, which subsequently decreased upon the BA treatment. Further experiments showed that BA could combine NLRP3 inflammasome and GSDMD, destabilizing GSDMD protein. Moreover, BA protected the cell membrane from MSU-induced damage, as evidenced by Hoechst 33342 and PI double staining, lactate dehydrogenase (LDH) assays, and electron microscopy observations. These results suggest that BA is involved in the regulating Panx-1/P2X7 pathways and thus inhibits pyroptosis, highlighting its potential therapeutic effect for HN.

CAS / MDL: 50-02-2
研究领域: 药理学 · 细胞生物学 · 分子生物学 · 肾病学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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WATER RESEARCH · 2023 · IF 12.8

Disinfectant sodium dichloroisocyanurate synergistically strengthened sludge acidogenic process and pathogens inactivation: Targeted upregulation of functional microorganisms and metabolic traits via self-adaptation

Wenxuan Huang,Yi Li,Feng Wang,Leiyu Feng,Dongbo Wang,Yingqun Ma,Yang Wu,Jingyang Luo

Harmless and resourceful treatment of waste activated sludge (WAS) have been the crucial goal for building environmental-friendly and sustainable society, while the synergistic realization approach is currently limited. This work skillfully utilized the disinfectant sodium dichloroisocyanurate (NaDCC) to simultaneously achieve the pathogenic potential inactivation (decreased by 60.1 %) and efficient volatile fatty acids (VFAs) recovery (increased by 221.9 %) during WAS anaerobic fermentation in rather cost-effective way (Chemicals costs:0.4 USD/kg VFAs versus products benefits: 2.68 USD/kg chemical). Mechanistic analysis revealed that the C=O and N Cl bonds in NaDCC could spontaneously absorb sludge (binding energy -4.9 kJ/mol), and then caused the sludge disintegration and organic substrates release for microbial utilization due to the oxidizability of NaDCC. The disruption of sludge structure along with the increase of bioavailable fermentation substrates contributed to the selectively regulation of microbial community via enriching VFAs-forming microorganisms (e.g., Pseudomonas and Streptomyces ) and reducing VFAs-consuming microorganisms, especially aceticlastic methanogens (e.g., Methanothrix and Methanospirillum ). Correspondingly, the metabolic functions of membrane transport, substrate metabolism, pyruvate metabolism, and fatty acid biosynthesis locating in the central pathway of VFAs production were all upregulated while the methanogenic step was inhibited (especially acetate-type methanogenic pathway). Further exploration unveiled that for those enriched functional anaerobes were capable to activate the self-adaptive systems of DNA replication, SOS response, oxidative stress defense, efflux pump, and energy metabolism to counteract the unfavorable NaDCC stress and maintain high microbial activities for efficient VFAs yields. This study would provide a novel strategy for synergistic realization of harmless and resourceful treatment of WAS, and identify the interrelations between microbial metabolic regulations and adaptive responses.

CAS / MDL: 2893-78-9
研究领域: 环境工程 · 微生物学 · 废物管理 · 生物技术
✓ 已验证 产品关联 DOI PubMed 高影响因子
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SEPARATION AND PURIFICATION TECHNOLOGY · 2025 · IF 9

Unravelling molecular transformation of dissolved organic matter in UV/Dichloroisocyanurate, UV/Chlorine, and UV/Chloramine processes using high Resolution mass spectrometry

Quanfa Zhong,Wangbao Gong,Guangjun Wang,Jun Xie,Jianshu Zhao,Qinghai Jin,Xiaoming Ma,Zhangxin Wang,Di He

This study utilized Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) to investigate the molecular-level transformation of dissolved organic matter (DOM) during treatment with the novel UV/dichloroisocyanurate (NaDCC) process. Comparisons were made with conventional UV/hypochlorite (NaClO) and UV/monochloramine (NH 2 Cl) processes to assess the feasibility and environmental risks of UV/NaDCC. Results showed that UV/NaDCC and UV/NaClO had comparable and stronger DOM mineralization effects than UV/NH 2 Cl. Notably, UV/NaDCC treatment more effectively reduced DOM aromaticity, fluorescence, and apparent molecular weight, producing more oxidized and saturated molecules. Kendrick mass defect (KMD) analysis indicated that demethylation and carboxylation reactions played key roles in UV/NaDCC treatment, supported by a greater number of precursor-product pairs. The UV/NaDCC system produced substantial chlorinated and N-containing byproducts (Cl-BPs and N-BPs). Among the Cl-BPs, species formed via + 2Cl reaction ( e. g. , +H 2 Cl 2 O 2 , +Cl 2 O) were dominant, similar to the UV/NaClO system. The N-BPs with higher nitrogen content ( e. g. , N3 and N4) were more abundant than in UV/NH 2 Cl. The UV/NaDCC system produced the highest concentrations of TCM and DCAN, whereas the UV/NaClO system yielded the highest concentration of DCAA. Toxicity tests revealed that UV/NaDCC effluent displayed the highest toxicity. To the best of our knowledge, this study provides the first molecular-level insight into DOM transformation in UV/NaDCC treatment, offering theoretical and practical guidance for its application.

研究领域: 环境化学 · 水处理技术 · 质谱分析 · 有机物分析 · 副产物生成 · 毒理学
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Frontiers in Pharmacology · 2021 · IF 5.811

A Purified Biflavonoid Extract From Selaginella moellendorffii Alleviates Gout Arthritis via NLRP3/ASC/Caspase-1 Axis Suppression

Zhang Xueyan,Liu Yingbo,Deng Guangrui,Huang Bisheng,Kai Guoyin,chen Keli,Li Juan

Background: Activation of nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in gout. Selaginella moellendorffii has been confirmed effective for the treatment of gout in hospital preparations. Flavonoids, such as amentoflavone (AM), are the main active components of this medicine.Purpose: We aimed to investigate the flavonoid extract (TF) and AM's effects on NLRP3 inflammasome in vitro and their preventive effects on gout in vivo.Methods: LC-MS method was employed to investigate the chemical profile of TF. The cellular inflammation model was established by lipopolysaccharide (LPS) or monosodium urate (MSU) stimulation. The cell membrane integrality and morphological characteristics were determined by using Lactate dehydrogenase (LDH) assay kits, propidium iodide (PI) stain, and scanning electron microscopy (SEM). The inflammatory cytokines and NLRP3 inflammasome activation were determined using enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (RT-PCR), immunofluorescence staining, and western blotting. The acute gout mouse model was induced by MSU injection into footpads, and then the paw edema, inflammatory mediators, and histological examination (HE) were analyzed.Results: The main constituents in TF are AM and robustaflavone. In the cellular inflammation model, TF down-regulated the levels of nitric oxide (NO), TNF-α, and LDH, suppressed NLRP3 inflammasome-derived interleukin-1β (IL-1β) secretion, decreased caspase-1 activation, repressed mature IL-1β expression, inhibited ASC speck formation and NLRP3 protein expression. In an acute gout mouse model, oral administration of TF to mice effectively alleviated paw edema, reduced inflammatory features, and decreased the levels of IL-1β in mouse foot tissue. Similarly, the characteristic constituent AM was also able to down-regulated the levels of NO, TNF-α, and LDH, down-regulate the mRNA expression of IL-1β, TNF-α, caspase-1, and NLRP3. Besides, the foot thickness, lymphocyte infiltration, and IL-1β level were also prevented by AM.Conclusion: The results indicated that TF and its main constituent AM alleviate gout arthritis via NLRP3/ASC/Caspase-1 axis suppression.

CAS / MDL: 64-86-8
研究领域: 药理学 · 免疫学 · 生物化学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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NEPHROLOGY · 2023 · IF 2.5

Baicalin and baicalein attenuate hyperuricemic nephropathy via inhibiting PI3K/AKT/NF-κB signalling pathway

Ziyuan Liu,Huilong Xiang,Qin Deng,Wanting Fu,Yang Li,Zejun Yu,Yinsheng Qiu,Zhinan Mei,Lingyun Xu

Aim Inflammation and apoptosis are main pathological processes that lead to the development of hyperuricemic nephropathy (HN). This study aims to explore whether baicalin (BA) and baicalein (BAI) can relieve the damage through PI3K/AKT/NF-κB signal pathway and provide more reliable and precise evidence for the treatment of HN. Methods HN mice were induced by yeast extract with potassium oxonate (PO), and HK-2 cells were induced by monosodium urate (MSU). Molecular docking, western blot, q-PCR, and other methods were used to explore the changes of various indicators in HN mice and HK-2 cells. Results Molecular docking results showed that BA and BAI had good binding ability with PI3K, AKT, p65 and IκBα. BA and BAI significantly ameliorated the levels of renal function, decreased the p-PI3K, p-AKT and p-p65 expression, down-regulated the BAX/BCL2 and CASP3, and blunted the mRNA levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-18 in both renal tissue of HN mice and HK-2 cells induced by MSU. BA and BAI also decreased the oxidative stress level of MSU-induced HK-2 cells. Conclusion BA and BAI were confirmed to attenuate HN through alleviating renal inflammatory and apoptosis in cells and tissues by inhibiting PI3K/AKT/NF-κB pathway. BA and BAI were expected to be developed as new anti-HN drugs.

CAS / MDL: 50-02-2 2207-75-2
研究领域: 药理学 · 肾病学 · 分子生物学 · 细胞生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2018 · IF 3.909

Anti-hyperuricemic and anti-gouty arthritis activities of polysaccharide purified from Lonicera japonica in model rats

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 · 生物化学 · 免疫学 · 中药学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF ETHNOPHARMACOLOGY · 2021 · IF 4.36

Leojaponin inhibits NLRP3 inflammasome activation through restoration of autophagy via upregulating RAPTOR phosphorylation

Xing-Jie Zhang,Kun Shang,Yu-Kun Pu,Qi Wang,Ting-Ting Wang,Yan Zou,Yong-Mei Wang,Yao-Jun Xu,Xiao-Li Li,Rui-Han Zhang,Wei-Lie Xiao

Ethnopharmacological relevance Duan Teng Yimu decoction is a Chinese herbal medicine compound with proven therapeutic effects on inflammasome-related diseases, such as rheumatoid arthritis . This decoction consists of three Chinese herbal medicines, including Leonurus japonicus ( L. japonicus ), which promotes the blood circulation and exhibits detumescence activity, traditionally curing gynecologic and inflammasome diseases. Aim of the study To explore the anti-inflammasome activity and the underlying mechanisms of action of the compounds from L. japonicus . Materials and methods A series of compounds were isolated from L. japonicus . Their anti-inflammasome activities were evaluated in macrophages that were co-stimulated by lipopolysaccharide (LPS) and NLRP3 inflammasome inducers. NLRP3 inflammasome formation and apoptosis speck like containing a CARD (ASC) oligomerization were evaluated by immunofluorescent microscopy and Western blot analysis . The regulation of autophagy after treatment of this compound was also evaluated. Lastly, in vivo activity of Leojaponin was analyzed in a mouse acute gouty arthritis model. Results Here we show that Leojaponin, a diterpenoid compound from L. japonicus , suppressed lactate dehydrogenase and IL-1β release in Nigericin-stimulated macrophages in a pyroptosis model. Leojaponin inhibits NLRP3 inflammasome activation in both J774A.1 cells and bone marrow-derived macrophages in a dose dependent manner. Moreover, Leojaponin suppressed NLRP3-mediated ASC specks formation and ASC oligomerization. These activities of Leojaponin depend on restoration of autophagy via promoting RAPTOR phosphorylation. Furthermore, Leojaponin ameliorated monosodium urate (MSU)-induced acute gouty arthritis in vivo . Conclusion Our findings suggest that Leojaponin inhibits NLRP3 inflammasome activation through enhancing autophagy via RAPTOR phosphorylation, thereby highlighting Leojaponin as a potent drug for inflammasome-related diseases.

CAS / MDL: 23491-52-3 25535-16-4
研究领域: 药理学 · 免疫学 · 传统中药 · 分子生物学 · 炎症
✓ 已验证 产品关联 DOI PubMed 高影响因子
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