Frontiers in Pharmacology
·
2022
·
IF 5.988
Huang Dan,Sun Chaoqun,Chen Min,Bai Shuyou,Zhao Xuanna,Wang Weiming,Geng Kang,Huang Wenbo,Zhao Tingting,Wu Bin,Zhang Guilin,Wu Dong,Xu Youhua
Airway inflammation and remodeling are critical pathological changes in asthma, and macrophage activation plays a vital role in this process. Sirtuin 1 (SIRT1) reduces airway inflammation by affecting macrophages in asthma. This study aimed to investigate the potential benefit and underlying mechanism of the SIRT1 agonist bergenin as a treatment for asthma. We performed in vivo and in vitro experiments by establishing a Sirt1fl/fl-LysMcre mouse asthma model and using the alveolar macrophage-like cell line MH-S, respectively. Our results show that Sirt1fl/fl-LysMcre asthmatic mice exhibited more severe airway inflammation and airway remodeling than wild-type mice. As an activator of SIRT1, bergenin attenuated asthmatic airway pathology and reduced production of interleukins 1β, IL-5, IL-6, and matrix metalloproteinase 9 (MMP-9) in wild-type asthmatic mice. However, the therapeutic effects of bergenin were significantly attenuated in Sirt1fl/fl-LysMcre asthmatic mice or following coadministration with the SIRT1 inhibitor EX-527. Further experiments showed that activation of SIRT1 by bergenin deacetylates nuclear factor κB and hinders its nuclear translocation, thereby affecting IL-1β, IL-5, IL-6, and MMP-9 production by regulating transcriptional activity. Our study suggests that bergenin can improve asthma-induced airway inflammation and remodeling by activating SIRT1 in macrophages.
研究领域:
免疫学
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药理学
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呼吸医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
World Journal of Acupuncture-Moxibustion
·
2025
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IF 1.3
Xiao-lei ZHANG,Meng-ni HU,Ya-nan LI,Yao WANG,Zhen RONG,Jun MA
Objective
To investigate the effects of electroacupuncture (EA) on the blood-brain barrier permeability and the regulation of matrix metalloproteinases (MMPs) in the mice with Parkinson's disease (PD).
Methods
Forty-eight C57BL/6 mice were randomly assigned into the normal control (NC) group, the PD model (PD) group, the EA group and the EA + SB-3CT inhibitor group (EA + SB-3CT), with 12 mice in each group. In this experiment, the PD model was established by intragastric administration (IG) with rotenone for 4 wk in the PD group, EA group and EA+SB-3CT group. In the EA + SB-3CT group, 1 h after IG with rotenone, the mice were intraperitoneally injected with MMP-2/9 inhibitor, SB-3CT (25 mg/kg/d). After successfully modeled, in the EA group and EA + SB-3CT group, EA was conducted at “Fengfu (GV16)” and bilateral “Taichong (LR3)” and “Zusanli (ST36)”, at 1 mA and 2 Hz for 30 min each time, once a day, for consecutive 2 wk. The behavioral changes of the mice were observed in each group using the open field test, the level of tyrosine hydroxylase (TH) in the substantia nigra was determined by immunohistochemistry, the permeability of the blood-brain barrier was detected by Evans blue staining, and the protein expression of ZO-1, ocludin, claudin-1, MMP-2 and MMP-9 in the substantia nigra was detected by Western blotting.
Results
Compared with the NC group, the behavioral scores increased (P < 0.05), while total time of locomotion, total distance and average speed were reduced (P < 0.05) in the PD group. The expression of TH in the substantia nigra decreased (P < 0.05), Evans blue level in the brain tissue increased (P < 0.05), and the protein expression of ZO-1, occludin and claudin-1 was lower (P < 0.05), whereas MMP-2 and MMP-9 expression was higher (P < 0.05) in the PD group. Compared with the PD group, behavioral scores decreased (P < 0.05), while the total time of locomotion, total distance and average speed increased (P < 0.05) in the EA group. Additionally, TH expression in the substantia nigra was elevated (P < 0.05), Evans blue level in the brain tissue was lower (P < 0.05), the protein expression of ZO-1, occludin and claudin-1 was up-regulated (P < 0.05), and MMP-2 and MMP-9 expression was down-regulated (P < 0.05) in the EA group. Compared with the EA group, Evans blue level was reduced (P < 0.05), the protein expression of ZO-1 and occludin was up-regulated (P < 0.05), and MMP-2 and MMP-9 expression was further down-regulated (P < 0.05) in the EA+SB-3CT group.
Conclusion
EA can effectively ameliorate the motor dysfunction of PD mice, reduce the damage of dopaminergic neurons, and play a neuroprotective role. EA can effectively improve the blood–brain barrier permeability in PD mice by up-regulating the expression of tight junction proteins, ZO-1 and occludin, and down-regulating the expression of matrix metalloporteinases, MMP-2 and MMP-9. The neuroprotective role of EA may be obtained by improving the blood-brain barrier permeability mediated by MMP-2/9 pathway.
研究领域:
神经科学
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药理学
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病理生理学
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中医
✓ 已验证
产品关联
DOI
高影响因子
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
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2019
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IF 2.086
Rui-Li Zhu,Ying-Kun Zhi,Lang Yi,Jin-Fang Luo,Jing Li,Sha-Sha Bai,Liang Liu,Pei-Xun Wang,Hua Zhou,Yan Dong
Objective: To investigate the cellular mechanism that sinomenine (SIN) inhibits inflammation in macrophages induced by LPS through α7 nicotinic acetylcholine receptor (α7nAChR).Materials and methods: RAW264.7 cells were stimulated with LPS and treated by SIN or nicotine (Nic). A selective antagonist of α7nAChR, α-bungarotoxin (BTX) was used to block α7nAChR. AG490 was used to inhibit JAK2 activation. ELISA was performed to detect the levels of TNF-α and MCP-1. Western blotting was used to analyze the expression of MIF, MMP-9, CD14, TLR4, STAT3 and p-STAT3. Intracellular-free calcium level was measured by Fluorescent probe fluo-3/AMResults: SIN inhibited the production of TNF-α, MCP-1, MIF, and MMP-9, decreased the expression of CD14 and TLR4, and inhibited the release of intracellular-free calcium from intracellular stores in RAW 264.7 cells stimulated by LPS. JAK-specific inhibitor AG490 attenuated the inhibitory effect of SIN on TNF-α. SIN increased the phosphorylation of STAT3. And the above effects of SIN were attenuated by antagonist of α7nAChR.Conclusions: SIN can decrease the expression of CD14/TLR4 and intracellular free calcium level, activate JAK2/STAT3 pathway to inhibit inflammatory response through α7nAChR in macrophages.
研究领域:
免疫学
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药理学
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细胞生物学
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炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POWDER TECHNOLOGY
·
2018
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IF 3.23
Chao Qin,Xin Yang,Yubing Wu,Yaqi Lv,Li Zhang,Xiaofei Xin,Lei Yang,Wei He,Xiaopeng Han,Lifang Yin,Chunyong Wu
ABSTRACT A matrix metalloproteinases (MMPs) triggered multifunctional micellar system loading traditional chemotherapeutic agent paclitaxel (PTX) and marimastat (MATT), an inhibition of matrix metalloproteinases, was established to prevent tumor growth and metastasis. The micelles were self-assembled by the conjugate synthesized with an MMPs sensitive peptide as the bridge between PTX and poly(ethylene glycol) (PEG). 4T1 cell line derived from a murine breast tumor was selected as the cell model due to its high metastasis. The cytotoxicity assay and cell apoptosis analysis revealed that the sensitive micelles increased the toxicity and cell apoptosis compared with the insensitive micelles. In addition, this system also exhibited high penetration ability in tumor spheroids and significant invasion inhibition with the method of Transwell invasion assay. In the BALB/c mice bearing 4T1 tumors, this system inhibited the growth of the metastatic tumor and prevented the incidence of lung metastasis with low systemic toxicity. And the expression of MMP-2 and MMP-9, which are important in the process of tumor metastasis, was down-regulated. Generally, the data obtained from the in vitro and in vivo studies confirmed that the codelivery of PTX and MATT by the MMPs sensitive micelles achieved not only significant antitumor effect but also obvious inhibition effect of tumor metastasis, which are the leading cause of cancer deaths. This functional particle system may provide a promising strategy for metastatic breast cancer therapy.
研究领域:
肿瘤学
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药学
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生物医学工程
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产品关联
DOI
高影响因子
Molecular Medicine Reports
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2023
·Vol. 29
·期 1
·1-17
·
IF 3.4
Yao Zhao,Mirensha Yakufu,Chong Ma,Baicai Wang,Jianhua Yang,Junping Hu
Nonalcoholic steatohepatitis (NASH) is emerging as the primary driver of liver disease‑induced fibrosis. The imperative need for noninvasive biomarkers to ascertain disease progression stage is evident. The present study elucidated the biological roles of hub genes that could potentially serve as diagnostic markers for NASH. Using an in vivo approach, C57BL/6J mice were subjected to a high‑fat and fructose diet (HFFD) for 6, 10, 14, 18 or 22 weeks. Serological biochemical indices were assessed and liver specimens were obtained to identify potential markers linked to the NASH process, employing a comprehensive strategy that combined transcriptomic and histopathological analyses. The HFFD regimen induced hyperlipidemia, obesity and insulin resistance, progressively culminating in NASH with fibrosis over time. The transcriptomic analyses indicated temporal patterns of pivotal gene sets intricately connected to NASH progression, which encompassed processes such as glucose homeostasis, inflammatory responses, reactive oxygen species‑mediated damage, lipid metabolism disruptions and the formation of fibrotic tissue. Among these genes, Serpine1 and Mmp9 demonstrated promising diagnostic potential for NASH, with their intrahepatic mRNA expression levels serving as robust indicators. Moreover, the levels of PAI‑1 (encoded by the Serpine1 gene) and MMP‑9 in the serum of mice demonstrated a parallel increase with the duration of HFFD intervention. In vitro experiments utilizing HepG2 cells further validated these findings, demonstrating a significant elevation in the protein expression levels of both PAI‑1 and MMP‑9 upon exposure to free fatty acids, in agreement with the results of the animal study. Consequently, PAI‑1 and MMP‑9 are promising noninvasive biomarkers for assessing the progression of NASH.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL LUNG RESEARCH
·
2023
·
IF 1.7
Ting Yang,Chang Xu,Niu Ding,Shujuan Luo,Bichen Wu,Shijie Jin,Yanping Chen
Background To investigate the protective effect of p14ARF in a nitric acid (NA) aerosol inhalation-induced bronchiolitis obliterans (BO) mouse model and its potential regulatory mechanism.Methods A BO mouse model was established by NA aerosol inhalation. The expressions of p14ARF, phosphatidylinositol-3-kinase (PI3K), and protein kinase B (AKT) were detected by quantitative reverse transcription PCR (qRT-PCR) and western blot (WB). Hematoxylin (HE) staining, Masson staining, and periodic acid-Schiff (PAS) staining observed pulmonary histological changes. TdT-mediated dUTP nick end labeling (TUNEL) staining detected pulmonary cell apoptosis, and enzyme-linked immunosorbent assay (ELISA) measured matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), interleukon-6 (IL-6), and transforminh growth factor-β (TGF-β) levels in lung tissue and bronchoalveolar lavage fluid (BALF).Results The expressions of p14ARF, PI3K, and AKT showed a time gradient change, with a decrease trend (*P < 0.05 and **P < 0.01). Severe inflammatory infiltration and tracheal fibrosis were found in lung tissue in the modeling group (BO group) compared with the control group (Con group). The pH, PaO2, and PaO2/FiO2 values significantly reduced, while the PaCO2 value and the number of TUNEL-positive cells increased in BO group (P < 0.05). In addition, MMP-2, MMP-9, IL-6, and TGF-β levels remarkably increased, with an increase in the number of white blood cells, neutrophils, and lymphocytes in BO group (P < 0.05). Furthermore, p14ARF up-regulation reversed the trend of the aforementioned indexes in BO mice.Conclusions p14ARF ameliorated the inflammatory response and airway remodeling in a BO mouse model via the PI3K/AKT pathway.
研究领域:
呼吸医学
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分子生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
·
2024
·
IF 4.6
Zhou Xuebin,Li Jinhua,Quan Shengli,Zhang Xinyue,Gu Lili,Hu Min,Huang Wenhai,Li Qin
The pathological and physiological studies of Alzheimer’s disease (AD) have been in-depth, and apolipoprotein E4 (ApoE4) has been proven to be highly correlated with AD, and clinical and experimental data show that ApoE4 can cause blood–brain barrier (BBB) injury, and the change of BBB permeability is an important factor affecting the development of AD. Andrographolide (Andro), as the active component of the natural plant Andrographis paniculata , has been proven to have anti-inflammatory and antioxidant effects, which have potential neuroprotective effects. To verify the protective effect of Andro on BBB in a short term, our research group used atorvastatin (Atorva)-mediated zebrafish brain injury model and the ApoE4-mediated cell co-culture model of BBB injury to explore the protective effects and mechanisms of Andro on BBB injury. Studies have shown that Andro can inhibit the activation of CypA/NF-κB/MMP-9 signaling pathway and has achieved the effect of antagonizing the inhibition of ApoE4 on intercellular tight junction proteins (occludin, claudin-5, and ZO-1). At the same time, Andro can inhibit the secretion of cell adhesion molecules (VCAM-1 and ICAM-1) in cells, thereby delaying the occurrence and progression of neuroinflammation and playing a protective role in BBB. In conclusion, Andro is a potent natural product which can protect the blood–brain barrier.
研究领域:
神经科学
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药理学
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分子生物学
·
神经退行性疾病
✓ 已验证
DOI
PubMed
高影响因子
Chinese Journal of Natural Medicines
·
2023
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IF 4.6
Chengshan JIN,Xiaotian WU,Yue YOU,Yuing WANG,Jing WU,Along ZUO,Yan ZHENG,Jianpeng GUO
ABSTRACT Diabetic kidney disease (DKD) is the most common complication of diabetes mellitus (DM). Qianjin Wenwu decoction (QWD), a well-known traditional Korean medicine, has been used for the treatment of DKD, with satisfactory therapeutic effects. This study was designed to investigate the active components and mechanisms of action of QWD in the treatment of DKD. The results demonstrated that a total of 13 active components in five types were found in QWD, including flavonoids, flavonoid glycosides, phenylpropionic acids, saponins, coumarins, and lignins. Two key proteins, TGF- β 1 and TIMP-1, were identified as the target proteins through molecular docking. Furthermore, QWD significantly suppressed Scr and BUN levels which increased after unilateral ureteral obstruction (UUO). Hematoxylin & eosin (H&E) and Masson staining results demonstrated that QWD significantly alleviated renal interstitial fibrosis in UUO mice. We also found that QWD promoted ECM degradation by regulating MMP-9/TIMP-1 homeostasis to improve renal tubulointerstitial fibrosis and interfere with the expression and activity of TGF- β 1 in DKD treatment. These findings explain the underlying mechanism of QWD for the treatment of DKD, and also provide methodological reference for investigating the mechanism of traditional medicine in the treatment of DKD.
研究领域:
药理学
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肾病学
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传统医学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Nanoscale
·
2020
·Vol. 12
·期 15
·8546-8562
·
IF 6.895
Na Yin,Xinyi Tan,Hongbing Liu,Fengming He,Ning Ding,Jingxin Gou,Tian Yin,Haibing He,Yu Zhang,Xing Tang
Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammatory cell infiltration, and cartilage and bone disruption, which ultimately leads to loss of joint function. Current treatments for RA only focus on anti-inflammatory activity but neglect to prevent further damage to articular cartilage and bone. Here we attempted to co-deliver indomethacin (IND), methotrexate (MTX) and a small-interfering RNA targeting MMP-9 using an in situ hydrogel loaded with PEI-SS-IND-MTX-MMP-9 siRNA nanoparticles (D/siRNA-NGel) to treat RA synergistically and comprehensively. IND, MTX and MMP-9 siRNA were able to escape from the endosome and down-regulate the expression of MMP-9 and inflammatory cytokines of Raw-264.7 cells. After intra-articular injection in arthritic mice, the D/siRNA-NGel effectively relieved joint swelling and significantly reduced the expression of TNF-α, IL-6 and MMP-9 in the ankle fluid, knee joint fluid and plasma of RA mice without causing any side effects. Most importantly, the co-delivery system restored the morphological parameters of the ankle joints close to normal. The D/siRNA-NGel could achieve good anti-inflammatory activity and reverse cartilage disruption through a synergistic effect between chemical drugs and MMP-9 siRNA. This co-delivery system should have promising applications in the treatment of rheumatoid arthritis and other metabolic bone diseases which cause serious bone erosion.
研究领域:
药理学
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生物医学工程
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风湿病学
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纳米技术
✓ 已验证
DOI
PubMed
高影响因子
Arabian Journal of Chemistry
·
2024
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IF 5.3
Yuanquan Ran,Lanlan Yang,Xiaoyan Jia,Huan Zhao,Qiong Hu,Bing Yang,Dongxin Tang,Minyi Tian
Background Akebia trifoliata is a widely distributed medicine and food homology plant. Its fruit is used to treat tumors and the seed’s weight proportion exceeds 50%. However, the anti-tumor effect of A. trifoliata seed remains poorly studied. Methods UHPLC-Q-Orbitrap-MS was used to identify the chemical components of A. trifoliata seed water extract (WE) and ethanolic extract (EE), and their cytotoxicity was evaluated using MTT assay. Further, colony formation and cell cycle assays examined the anti-proliferative effect of A. trifoliata seed EE. Next, morphology observation, AO/EB staining, Hoechst 33,258 staining, Annexin V-PE/7-AAD staining, and JC-1 assays were employed to detect apoptosis. The influence of A. trifoliata seed EE on A549 cell metastasis was assessed by wound healing and transwell invasion tests. In addition, western blotting and network pharmacology were applied to further analyze its anticancer mechanism. Results Eighty-two components were characterized from the A. trifoliata seed WE and EE. For anticancer activity, A. trifoliata seed EE exhibited high cytotoxicity against cancer cells A549 (IC 50 : 52.38 ± 1.04 μg/mL) and NCI-H1299 (IC 50 : 70.29 ± 0.58 μg/mL) and revealed low cytotoxicity against non-cancer cells MRC-5 (IC 50 : 101.28 ± 2.84 μg/mL) and L929 (IC 50 : 113.44 ± 0.55 μg/mL). A. trifoliata seed EE suppressed A549 cell proliferation by inducing S-phase arrest via down-regulation of CDK2 and p21 as well as up-regulation of cyclin E1 and E2. It increased the Bax/Bcl-2 ratio, reduced mitochondrial membrane potential (ΔΨm), activated caspase-9 and caspase-3, cleaved PARP, and triggered apoptosis through the mitochondrial pathway. Besides, it repressed migratory and invasive ability by reducing MMP-2, MMP-9, and N-cadherin levels. Conclusion A. trifoliata seed EE exhibits outstanding anticancer properties and has the exploitation potential as an anticancer drug in the pharmaceutical industry.
研究领域:
药理学
·
肿瘤学
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植物科学
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细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2021
·Vol. 47
·期 5
·1-11
·
IF 4.101
Yunsheng Liu,Xiangping Xu,Han Tang,Yuchen Pan,Bing Hu,Guodong Huang
There is a growing evidence that Fyn kinase is upregulated in glioblastoma multiforme (GBM), where it plays a key role in tumor proliferation and invasion. In the present study, the antitumor effects of rosmarinic acid (RA), a Fyn inhibitor, were explored in human‑derived U251 and U343 glioma cell lines. These cells were treated with various concentrations of RA to determine its effects on proliferation, migration, invasion, apoptosis, and gene and protein expression levels. The CCK‑8 assay revealed that RA significantly suppressed cell viability of U251 and U343 cells. Furthermore, RA significantly reduced proliferation rates, inhibited migration and invasion, and decreased the expression levels of invasion‑related factors, such as matrix metalloproteinase (MMP)‑2 and MMP‑9. TUNEL staining revealed that RA resulted in a dose‑dependent increase of U251 and U343 cell apoptosis. In line with this finding, the expression of apoptosis suppressor protein Bcl‑2 was downregulated and that of the pro‑apoptotic proteins Bax and cleaved caspase‑3 was increased. In addition, it was revealed that the phosphatidylinositol 3‑kinase (PI3K)/Akt/nuclear factor‑κB (NF‑κB) signaling pathway was involved in RA‑induced cytotoxicity in U251 and U343 cells. Collectively, the present study suggested RA as a drug candidate for the treatment of GBM.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of the Mechanical Behavior of Biomedical Materials
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2020
·
IF 3.372
Jingqiu Xu,Mingxing Li,Wenting Wang,Zhifang Wu,Chaoyang Wang,Xiaoting Jin,Ling Zhang,Wenxiang Jiang,Baiping Fu
Objectives The study investigated the effects of novel prime-&-rinse mode using MDP (10-methacryloyloxydecyl dihydrogenphosphate) and matrix metalloproteinase (MMPs) inhibitors on dentin microtensile bond strengths (MTBS) of self-etch adhesive, resin-dentin interface degradations, and activity of recombinant human (rh) MMP-8, -9. Materials and methods Eight experimental primers were prepared using 5% and 15% of MDP ethanol-aqueous (1:1) solution in combination with/without MMPs inhibitors (1%benzalkonium chloride (BAC), 1000 μm/mL polyvinylphosphonic acid (PVPA) and 15%proanthocyanidin (PA)). Ninety human mid-coronal dentin surfaces were applied with the experimental primers, water-sprayed and gently air-dried (prime-&-rinse mode), or not (control, self-etch mode). The specimens were bonded with self-etch adhesive (Clearfil S3 Bond) and composite resin (Clearfil Majesty). The resin-bonded specimens were prepared into multiple micro-beams for MTBS tests after 24 h and 1 yr of water storage. The resin-dentin interfaces were analyzed with SEM/TEM. The inhibitory effects of eight primers on rhMMP-8, 9 were determined. The data were analyzed using two-way ANOVA and LSD multiple comparisons tests. Results Compared with control, all the primers used in prime-&-rinse mode could significantly improve long-term dentin MTBS ( P < 0.05), while 5%MDP-BAC, 15%MDP and 15%MDP+MMPs inhibitors could significantly increase the short-term dentin MTBS ( P < 0.05). The SEM/TEM findings revealed that the resin-dentin interfaces were stable over time when the prime-&-rinse mode used. Eight primers possessed the high inhibitory ratio of rh MMP-8, 9. Conclusions The novel prime-&-rinse mode using 5%MDP-BAC, 15%MDP and 15%MDP+MMPs inhibitors could significantly increase the short- and long-term dentin MTBS of self-etch adhesive. This might be a supplement to contemporary dentin bonding strategies.
研究领域:
牙科学
·
材料科学
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生物材料
✓ 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）