BIOORGANIC CHEMISTRY
·
2024
·
IF 4.5
Yi Chen,Shasha Song,Yongfang Wang,Lili Wu,Jianbing Wu,Zhengmeng Jiang,Xinyu Li
Psoriasis (PSO) is a common inflammatory skin disease caused by multiple factors. Magnolia officinalis is an important medicinal plant in China, with various values such as ecology, medicine, food, and daily chemicals. However, its diverse application potential has not been fully explored. Magnolol (MGO) is the main active compound of Magnolia officinalis with significant anti-inflammatory effect. To investigate the application potential of MGO in inflammatory skin disease, the effects and underlying mechanisms of topical MGO treating psoriasis were explored in this study. Network pharmacology and molecular docking firstly predicted that topical MGO may treat psoriasis by regulating pyroptosis pathway and acting on caspase-1 (CASP1). In vitro experiments then demonstrated that MGO could inhibit the level of inflammatory cytokines and the key protein expression of NOD-like receptor protein 3 (NLRP3)/Caspase-1 pathway in lipopolysaccharide (LPS)-stimulated phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 cells. Meanwhile, MGO could inhibit CuSO 4 -induced neutrophils migration in Tg (mpx:EGFP) zebrafish by suppressing inflammation and pyroptosis. This study further indicated that topical application of MGO ameliorated imiquimod (IMQ)-induced psoriasis-like dermatitis by reducing the release of inflammatory factors and decreasing the key protein expression of pyroptosis-related NLRP3/Caspase-1 pathway. Metabolomics analysis revealed that topical application of MGO could significantly regulate tryptophan metabolism and affect the level of tryptophan in skin lesions. Tryptophan could also regulate inflammation-related genes and inhibit pyroptosis-related NLRP3/Caspase-1 pathway in LPS-stimulated PMA-differentiated THP-1 cells. In conclusion, this study suggested that topical MGO may ameliorate psoriasis-like dermatitis by inhibiting NLRP3/Caspase-1 pathway and regulating tryptophan metabolism.
研究领域:
药理学
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皮肤科
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分子生物学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
Journal of Inflammation Research
·
2023
·
IF 4.5
Yunbo Yan,Linqian Yu,Binyang Chen,Chang’an Cao,Hairong Zhao,Qiang Wang,De Xie,Yuemei Xi,Chenggui Zhang,Jidong Cheng
Background Gouty arthritis is characterized by the accumulation of monosodium urate crystals (MSU) in the synovial joints and surrounding tissues. Mastoparan M (Mast-M) is a biologically active peptide composed of 14 amino acids, extracted from wasp venom. This study aims to assess the impact of Mast-M on in vitro and in vivo gouty arthritis induced by lipolyaccharide (LPS) plus MSU crystal stimulation.Methods PMA-differentiated THP-1 macrophages were pre-treated with Mast-M or left untreated, followed by stimulation with LPS and MSU crystals. Cell lysates were collected to assess the expression of the NLRP3 inflammasome, inflammatory signaling pathways, and oxidative stress. Furthermore, to evaluate the in vivo anti-inflammatory effect of Mast-M, an experimental acute gouty arthritis mouse model was established through intra-articular injection of MSU crystals.Results Mast-M treatment demonstrated significant inhibition of the phosphorylation of MAPKs/NF-κB signaling pathways and reduction in oxidative stress expression in LPS and MSU-induced THP-1 macrophages. This resulted in the suppression of downstream NLRP3 inflammasome activation and IL-1β release. In vivo, Mast-M effectively attenuated the inflammation induced by MSU in mice with gouty arthritis. Specifically, Mast-M reduced swelling in the paws, inhibited the infiltration of neutrophils and macrophages into periarticular tissue, and decreased the activation of the NLRP3 inflammasome and IL-1β production.Conclusion Mast-M significantly improves gouty arthritis, and its potential mechanism may be achieved by inhibiting the MAPK/NF-κB pathway and alleviating oxidative stress, thus suppressing the activation of NLRP3 inflammasomes.
研究领域:
免疫学
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风湿病学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Biochemistry and Biophysics Reports
·
2024
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IF 2.3
Youyang Liu,Yunlu Zhao,Qi Guo,Pengfei Wang,Peixuan Li,Qingqing Du,Huazhou Xu,Qingyin Yu,Xiaoyi Zhao,Weiya Zhang,Shengjun An,Shuhui Wu
Immune responses, especially NLRP3 signaling in macrophages, play critical roles in rheumatoid arthritis (RA), an autoimmune and inflammatory disease. In this study, we aimed to identify novel therapies for RA. We focused on sophoricoside (SOP), an isoflavone glycoside isolated from Sophora japonica . We predicted the targets of SOP and performed a Gene Ontology analysis to assess its effects. The results suggested that SOP is related to inflammation regulation. We verified these findings by performing in vitro experiments with M1 macrophages differentiated from human peripheral blood monocytes (THP-1 cells). Sophoricoside administration reduced inflammatory activity and NLRP3, Caspase-1, and IL-1β protein levels in macrophages. In addition, SOP and triptolide (TP) was administered intragastrically to male SD rats (n = 40) in a collagen-induced arthritis model. We observed that SOP and TP reduced the inflammatory responses and symptoms of RA. Moreover, unlike TP, SOP showed no liver or kidney toxicity in rats. In conclusion, SOP reduces inflammation in type II collagen-induced arthritis by downregulating NLRP3 signaling and has potential for future clinical applications as an ideal therapy for RA.
研究领域:
免疫学
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药理学
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风湿病学
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炎症
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-16
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IF 10.6
Zhang Li,Li Yujiao,Liu Xing,He Xiaolu,Zhang Jieyu,Zhou Jun,Qiao Youbei,Wu Hong,Sun Fangfang,Zhou Qing
Macrophages are multifunctional innate immune cells that play indispensable roles in homeostasis, tissue repair, and immune regulation. However, dysregulated activation of macrophages is implicated in the pathogenesis of various human disorders, making them a potential target for treatment. Through the expression of pattern recognition and scavenger receptors, macrophages exhibit selective uptake of pathogens and apoptotic cells. Consequently, the utilization of drug carriers that mimic pathogenic or apoptotic signals shows potential for targeted delivery to macrophages. In this study, a series of mannosylated or/and phosphatidylserine (PS) -presenting liposomes were developed to target macrophages via the design of experiment (DoE) strategy and the trial-and-error (TaE) approach. The optimal molar ratio for the liposome formulation was DOPC: DSPS: Chol: PEG-PE = 20:60:20:2 based on the results of cellular uptake and cytotoxicity evaluation on RAW 264.7 and THP-1 in vitro. Results from in vivo distribution showed that, in the DSS-induced colitis model and collagen II-induced rheumatoid arthritis model, PS-presenting liposomes (PS-Lipo) showed the highest accumulation in intestine and paws respectively, which holds promising potential for macrophage target therapy since macrophages are abundant at inflammatory sites and contribute to the progression of corresponding diseases. Organs such as the heart, liver, spleen, lung, and kidney did not exhibit histological alterations such as inflammation or necrosis when exposed to PC-presenting liposomes (PC-Lipo) or PS-Lipo. In addition, liposomes demonstrated hemobiocompatibility and no toxicity to liver or kidney for circulation and did not induce metabolic injury in the animals. Thus, the well-designed PS-Lipo demonstrated the most potential for macrophage target therapy.
研究领域:
药理学
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免疫学
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药物递送系统
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炎症
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2022
·
IF 5.223
Li-Hua Zhu,Ying-Yin Xu,Li-ping Zhu,Xian Zheng,Cui-Hua Jiang,Jian-Jing Liu,Jian Zhang,Zhi-Qi Yin
As a new and safe food resource, Cyclocarya paliurus (CP), rich in flavonoids, exhibits hypouricemic, anti-inflammatory and antioxidative properties. However, whether CP aqueous extract (CPA) still possesses the ameliorative effects on hyperuricemia (HUA) and urate-induced renal inflammation remains vacant. In HUA mice, CPA could significantly reduce serum uric acid (UA), alleviate kidney damage and liver steatosis, inhibit xanthine oxidase (XOD) activity, ameliorate renal urate transporters and renal inflammation by inhibiting NLRP3 inflammasome and interleukin-1β (IL-1β). Moreover, the flavonoids quercetin-3- O-β- D-galactopyranoside, quercetin-3- O-β- D-glucopyranoside, and quercetin-3- O-α -L-rhamnopyranoside from CPA could significantly reduce IL-1β and interleukin-6 (IL-6) in MSU-challenged THP-1 cells. Noticeably, quercetin-3- O-β- D-galactopyranoside could inhibit the intracellular XOD activity, reduce intracellular ROS and the expression of pro-IL-1β, IL-1β, and NLRP3 inflammasome. Collectively, CPA shows appreciable therapeutic effects on HUA and evoked renal inflammation. Quercetin-3- O-β -D-galactopyranoside, quercetin-3- O-β -D-glucopyranoside, and quercetin-3- O-α -L-rhamnopyranoside might be the major active compounds of CPA, which obtain the favorable effects through blocking the activation of ROS/NLRP3/IL-1β pathway.
研究领域:
药理学
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营养学
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免疫学
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分子生物学
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产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
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IF 5.4
Liting Zhu,Linjie Mu,Xiaoqiu Ni,Feng Wang,Xinyi Peng,Yujiu Gao,Tingting Wei,Congcong Zeng,Yongheng Bai,Fangyan Wang,Zhengzhong Yuan,Jinguo Cheng
Ethnopharmacological relevance Xin-Zi-Sheng-Wan Decoction (XZSWD), a formulation rooted in the classic Zi-Sheng Pill first recorded in the Qing-dynasty compendium “ Golden Mirror of Medicine ,” is traditionally employed to resolve turbid pathogenic stagnation and restore metabolic equilibrium. Modern ethnopharmacological studies reveal a marked uric acid–lowering effect, although its precise molecular mechanisms have yet to be fully clarified. Aim of the study This study aimed to evaluate the therapeutic efficacy of XZSWD in hyperuricemia (HUA)-induced kidney injury and to elucidate its molecular mechanisms. Methods UPLC-QTOF/MS was used to identify compounds in XZSWD medicated serum. A HUA mouse model was induced by potassium oxonate and hypoxanthine to evaluate the therapeutic effects of XZSWD on renal injury. RNA-Seq, qRT-PCR, Western blot, immunofluorescence, and flow cytometry were applied to investigate immune infiltration and key signaling pathways. A THP-1/HK-2 co-culture system combined with SPP1 overexpression and knockdown was used to explore the molecular mechanisms. Results 99 compounds were identified in XZSWDS. XZSWD improved renal function, reduced serum uric acid levels, and downregulated macrophage-related inflammatory genes while modulating mixed M1/M2 polarization. XZSWD also inhibited the SPP1-CD44 axis and downstream SRC/FAK/β-Catenin signaling to reduce renal extracellular matrix (ECM) deposition. In vitro, SPP1 was identified as a critical target mediating these effects. Conclusions XZSWD alleviates HUA-induced renal injury by suppressing macrophage-mediated inflammation via regulation of the SPP1–CD44 axis and SRC/FAK/β-Catenin signaling, highlighting its therapeutic potential for HUA-related renal dysfunction.
研究领域:
民族药理学
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肾脏病学
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免疫学
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信号转导
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植物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
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2024
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IF 4.2
Chunmeng Ding,Zhenguo Shen,Ruonan Xu,Yajing Liu,Mengyue Xu,Chenyu Fan,Dongyue Hu,Tian Xing
Aim To investigate the impact of exosomes released by Porphyromonas gingivalis -Lipopolysaccharide activated THP-1 macrophages and human periodontal ligament fibroblasts on hepatocyte fat metabolism. Results The liver of rats with experimental periodontitis showed obvious steatosis and inflammation compared with control rats. The culture supernatant of macrophages and human periodontal ligament fibroblasts (hPDLFs), when stimulated with Pg-LPS, induced lipogenesis in HepG2 cells. Furthermore, the lipid-promoting effect was effectively inhibited by the addition of the exosome inhibitor GW4869. Subsequently, we isolated exosomes from cells associated with periodontitis. Exosomes released by Pg-LPS-stimulated macrophages and hPDLFs are taken up by hepatocytes, causing mRNA expression related to fat synthesis, promoting triglyceride synthesis, and aggravating NAFLD progression. Finally, two sets of exosomes were injected into mice through the tail vein. In vivo experiments have also demonstrated that periodontitis-associated exosomes promote the development of hepatic injury and steatosis, upregulate SCD-1 expression and inhibit the AMPK signaling pathway. Conclusions In conclusion, we found that exosomes associated with periodontitis promote hepatocyte adipogenesis by increasing the expression of SCD-1 and suppressing the AMPK pathway, which indicates that close monitoring of the progression of stomatopathy associated extra-oral disorders is important and establishes a theoretical foundation for the prevention and management of fatty liver disease linked to periodontitis.
研究领域:
分子生物学
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细胞生物学
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病理学
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药理学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Pei Lin,Qiqi Wang,Qi Wang,Jiayun Chen,Liangliang He,Zifei Qin,Shaoping Li,Jingyan Han,Xinsheng Yao,Yang Yu,Zhihong Yao
Allium Macrostemon Bge. (AMB) is a well-known homology of herbal medicine and food that has been extensively used for thousands of years to alleviate cardiovascular diseases. It contains a significant amount of polysaccharides, yet limited research exists on whether these polysaccharides are responsible for its cardiovascular protective effects. In this study, the anti-atherosclerosis effect of the crude polysaccharides of AMB (AMBP) was evaluated using ApoE −/− mice fed a high-fat diet, along with ox-LDL-induced Thp-1 foam cells. Subsequently, guided by the inhibitory activity of foam cells formation, a major homogeneous polysaccharide named AMBP80-1a was isolated and purified, yielding 11.1 % from AMB. The molecular weight of AMBP80-1a was determined to be 10.01 kDa. AMBP80-1a was firstly characterized as an agavin-type fructan with main chains consisting of →1)- β - d -Fru f -(2→ and →1,6)- β - d -Fru f -(2→ linked to an internal glucose moiety, with →6)- β - d -Fru f -(2→ and β - d -Fru f -(2→ serving as side chains. Furthermore, the bio-activity results indicated that AMBP80-1a reduced lipid accumulation and cholesterol contents in ox-LDL-induced Thp-1 foam cell. These findings supported the role of AMBP in alleviating atherosclerosis in vivo/vitro . AMBP80-1a, as the predominant homogeneous polysaccharide in AMB, was expected to be developed as a functional agent to prevent atherosclerosis.
研究领域:
药理学
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心血管疾病
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分子生物学
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营养保健品
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DOI
PubMed
高影响因子
Virulence
·
2021
·
IF 5.882
Xuemeng Ji,Ping Lu,Juan Xue,Ning Zhao,Yan Zhang,Lu Dong,Xuejiao Zhang,Ping Li,Yaozhong Hu,Jin Wang,Bowei Zhang,Jingmin Liu,Huan lv,Shuo Wang
Cronobacter sakazakii, an emerging opportunistic pathogen, is implicated in severe foodborne outbreak infections in premature and full-term infants. Generally, acid tolerance is vital for the pathogenesis of foodborne pathogens; however, its role in C. sakazakii virulence remains largely unknown. To screen out acid-tolerance determinants from transposon mutants, anovel counterselection method using gentamicin and acid was developed. Using the counterselection method and growth assay, we screened several acid-sensitive mutants and found that nlpD encodes an acid-resistance factor in C. sakazakii. Compared to the wild-type strain, the nlpD mutant exhibited attenuated virulence in a rat model. Using macrophage THP-1 cells and a pH probe, we verified that nlpD enables bacteria to resist macrophages by resisting acidification. Finally, we confirmed that nlpD maintains C. sakazakii membrane integrity in acid using propidium iodide permeabilization assays via flow cytometry. Our results confirm that nlpD is a novel virulence factor that permits C. sakazakii to survive under acid stress conditions. Considering that NlpD is a conserved lipoprotein located in the bacterial outer membrane, NlpD could be used as a target for drug development.
研究领域:
微生物学
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病理学
·
传染病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Biomed Research International
·
2019
·
IF 2.197
YiXun Li,Huan Li,Yong Duan,XueMei Cai,DingYun You,Feng Zhou,ChuanQi Yang,XiaoYu Tuo,ZiJie Liu
Background. Xuanwei City in Yunnan province has been one of the towns with highest lung cancer mortality in China. The high content of amorphous silica in the bituminous coal from Xuanwei of Yunnan is mainly present as irregular and spherical silica nanoparticles (SiNPs). It has been reported that silica nanoparticles in bituminous coal correlated with the high incidence of lung cancer in Xuanwei. To explore the role and mechanism of SiNPs in the tumorigenesis of lung cancer in Xuanwei, human mononuclear cells (THP-1) and human bronchial epithelial cells (BEAS-2B) were cocultured in a transwell chamber. Combined with Benzo[a]pyrene-7, 8-dihydrodiol-9, and 10-epoxide (BPDE), SiNPs could significantly promote the proliferation and Epithelial-Mesenchymal Transition (EMT) and inhibit apoptosis of BEAS-2B cells and induce the release of TGF-α from THP-1 cells. After neutralizing TGF-α with antibody, the proliferation and EMT were decreased and enhanced apoptosis of BEAS-2B cells. Furthermore, the results showed that TGF-α in the sera of patients with lung adenocarcinoma in Xuanwei were significantly higher than in patients with benign pulmonary lesions in Xuanwei and those with lung adenocarcinoma in outside of Xuanwei of Yunnan. Taken together, our study found that SiNPs promoted the proliferation and EMT of BEAS-2B cells by inducing the release of TGF-α from THP-1 cells.
研究领域:
癌症研究
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纳米技术
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细胞生物学
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分子生物学
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环境健康
✓ 已验证
DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
·
2019
·
IF 4.868
Chunlan Jiang,Wenyi Yang,Chengyi Wang,Wei Qin,Jiajun Ming,Manman Zhang,Haixin Qian,Ting Jiao
Aim. To investigate whether methylene blue-mediated photodynamic therapy (MB-PDT) can affect the “fate” of macrophages in vitro or in periodontitis tissues and to explore the potential mechanism. Methods. For in vitro treatments, THP-1 macrophages were divided into three experimental groups: C/control, no treatment; MB, methylene blue treatment; and MB-PDT, MB and laser irradiation treatment. Then, apoptosis and apoptosis-related proteins were detected in each group. For in vivo treatments, periodontitis was ligature-induced in the first molars of the bilateral maxilla in 12 Sprague Dawley (SD) rats. After six weeks, the ligatures were removed and all the induced molars underwent scaling and root planning (SRP). Then, the rats were divided into three groups according to the following treatments: SRP, saline solution; MB, phenothiazinium dye; and MB-PDT, MB and laser irradiation. Apoptotic macrophages, inflammation levels, and alveolar bone resorption in the periodontal tissues of rats were analyzed in each group. Results. In vitro, flow cytometry analysis demonstrated that 10 μM MB and 40 J/cm2 laser irradiation maximized the apoptosis rate (34.74%) in macrophages. Fluorescence probe and Western blot analyses showed that MB-PDT induced macrophage apoptosis via reactive oxygen species (ROS) and the mitochondrial-dependent apoptotic pathway. Conversely, the addition of exogenous antioxidant glutathione (GSH) and the pan-caspase inhibitor Z-VAD-FMK markedly reduced the apoptotic response in macrophages. In vivo, immunohistochemistry, histology, radiographic, and molecular biology experiments revealed fewer infiltrated macrophages, less bone loss, and lower IL-1β and TNF-α levels in the MB-PDT group than in the SRP and MB groups (). Immunohistochemistry analysis also detected apoptotic macrophages in the MB-PDT group. Conclusion. MB-PDT could induce macrophage apoptosis in vitro and in rats with periodontitis. This may be another way for MB-PDT to relieve periodontitis in addition to its antimicrobial effect. Meanwhile, MB-PDT induced apoptosis in THP-1 macrophages via the mitochondrial caspase pathway.
研究领域:
牙科学
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免疫学
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Chuyao Liao,Di Wang,Siyuan Qin,Ying Zhang,Jie Chen,Ruijie Xu,Fengguo Xu,Pei Zhang
Irinotecan (CPT-11) in combination with 5-fluorouracil and leucovorin is a first-line chemotherapy regimen for the treatment of colorectal cancer; however, its clinical application is limited by the dose-limiting gastrointestinal toxicity of colitis. In our previous studies, several bile acids (BAs) were found significantly elevated in the colon of the CPT-11-induced rat colitis model. On the other hand, NLRP3 inflammasome has been reported to play important roles in mediating colitis. Interestingly, BA was stated to activate the NLRP3 inflammasome in some studies, while in some other reports, it showed an inhibitory effect. We assumed that the inflammatory status in different circumstances might have contributed to the controversial findings. In this study, we first discovered, under non-inflammatory conditions, that supplementing BA could activate the NLRP3 inflammasome in THP-1-differentiated macrophages and promote inflammation. In lipopolysaccharide (LPS)-induced inflammatory macrophages, however, BA inhibited the NLRP3 inflammasome and reduced inflammation. Further experiments demonstrated that Takeda G protein-coupled receptor 5 (TGR5) is essential in mediating the inhibitory effect of BA, while phospho-SP1 (p-SP1) is key to the activation. Furthermore, we applied the above findings to ameliorate CPT-11-caused colitis in rats by inhibiting SP1 with mithramycin A (MitA) or activating TGR5 using oleanolic acid (OA). Our findings may shed light on the discovery of effective interventions for reducing dose-limiting chemotherapy-induced colitis.
研究领域:
肿瘤学
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胃肠病学
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免疫学
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药理学
✓ 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）