PHYTOMEDICINE
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2022
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IF 6.656
Siyuan Shen,Gaojun Wu,Wu Luo,Weixin Li,Xiaobo Li,Chengyi Dai,Weijian Huang,Guang Liang
Background Hypertension is a common risk factor for heart failure, and excessive angiotensin II (Ang II) leads to hypertensive cardiac alterations such as hypertrophy, cardiac fibrosis, remodeling, and dysfunction. Leonurine is the major active alkaloid compound obtained from the traditional Chinese herbal medicine, Leonurus japonicus Houtt. The effects of leonurine on Ang II-induced hypertensive cardiac injury remain unknown. Hypothesis/Purpose In the present study, we investigated the cardioprotective effects of leonurine in Ang II-infused mice and explored the underlying mechanisms in cardiomyocytes. Methods Cardiac injury was induced by Ang II infusion in experimental mice with or without leonurine (at 10 or 20 mg/kg) treatment. H9c2 cells and neonatal rat primary cardiomyocytes were used to investigate the mechanisms through which leonurine exerts its protection effects. Results The results showed that leonurine significantly alleviated Ang II-induced cardiac hypertrophy, fibrosis, and inflammation in both mice and cultured cardiomyocytes. Echocardiography revealed that leonurine preserved cardiac function in mice. Further investigations revealed that leonurine inhibited the activation of the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways to reduce inflammatory response and injuries in Ang II-challenged cardiomyocytes. Inhibition of MAPKs and NF-κB in cardiomyocytes abolished the anti-inflammatory effects of leonurine. Conclusions Our study provides evidence that leonurine exerts protective effects against Ang II-induced hypertensive cardiac remodeling and dysfunction by inhibiting the MAPK and NF-κB pathways. Leonurine may be a promising agent for treating hypertensive heart failure.
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高影响因子
NEUROCHEMICAL RESEARCH
·
2022
·Vol. 48
·期 5
·1424-1437
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IF 4.414
Zhao Yanling,Yan Han,Liang Xue,Zhang Zhenyu,Wang Xuan,Shi Nianwei,Bian Weihong,Di Qing,Huang He
Astrocyte activation is key in neurodegenerative diseases. Hydrogen sulfide (H 2 S) exhibits neuroprotective effects on astrocytes, although the underlying molecular mechanism remains unclear. Here, we explored the effects of H 2 S on lipopolysaccharide (LPS)-induced astrocyte activation and astrocyte-mediated neuroinflammation. After inducing primary astrocytes via LPS exposure, H 2 S levels were altered. The generation and secretion of inflammatory mediators by astrocytes and their interrelation with P-glycoprotein (P-gp), an important transporter belonging to the ABC transporter family, were assessed. Activated astrocytes showed upregulated glial fibrillary acidic protein ( GFAP ) mRNA expression, and significantly increased proinflammatory factor mRNA/protein expression and release. The secretory capacity of astrocytes was reduced, with significantly decreased proinflammatory factor levels in culture supernatant after P-gp inhibitor verapamil pretreatment. The increase in the intracellular H 2 S level inhibited LPS-induced GFAP expression and P65 nuclear entry in astrocytes. mRNA expression and release of proinflammatory factors were reduced significantly, with no significant changes in cytoplasmic protein expression. S-sulfhydration levels increased significantly with the increased concentration of sodium hydrosulfide or S-adenosyl- l -methionine addition, with only moderate changes in astrocyte P-gp expression. H 2 S regulates NF-κB activation, leads to S-sulfhydration of P-gp, and inhibits the biosynthesis and secretion of proinflammatory factors by astrocytes. The regulatory effects of H 2 S on astrocytes may have clinical value for exploring new therapeutic strategies against neurodegenerative diseases.
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2022
·Vol. 23
·期 22
·14024
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IF 6.208
Ping Zhou,Jia Lai,Yueyue Li,Junzhu Deng,Chunling Zhao,Qianqian Huang,Fei Yang,Shuo Yang,Yuesong Wu,Xiaoqin Tang,Feihong Huang,Long Wang,Xinwu Huang,Wenjun Zou,Jianming Wu
Ulcerative colitis (UC) is a complex immune-mediated inflammatory disease. In recent years, the incidence of UC has increased rapidly, however, its exact etiology and mechanism are still unclear. Based on the definite anti-inflammatory and antibacterial activities ofSanguisorba officinalisL., we studied its monomer, methyl gallate (MG). In this study, we employed flow cytometry and detected nitric oxide production, finding MG regulated macrophage polarization and inhibited the expression of proinflammatory cytokines in vitro. MG also exhibited anti-inflammatory activity accompanying with ameliorating body weight loss, improving colon length and histological damage in dextran sulfate sodium-induced UC mice. Meanwhile, transcription sequencing and 16S rRNA sequencing analyzed the key signaling pathways and changes in the gut microbiota of MG for UC treatment, proving that MG could alleviate inflammation by regulating the TLR4/NF-κB pathway in vivo and in vitro. Additionally, MG altered the diversity and composition of the gut microbiota and changed the abundance of metabolic products. In conclusion, our results are the first to demonstrate that MG has obvious therapeutic effects against acute UC, which is related to macrophage polarization, improved intestinal flora dysbiosis and inhibition of TLR4/NF-κB signaling pathway, and MG may be a promising therapeutic agent for UC treatment.Keywords:ulcerative colitis;methyl gallate;gut microbiota;gut immunity;TLR4/NF-κB
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2022
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IF 3.322
Tiantian Wang,Ruihe Zheng,Song Sun
Acute lung injury (ALI) is a significant cause of morbidity and mortality worldwide. To search for a new treatment for acute lung injury, we investigated the effect of escitalopram on lipopolysaccharide (LPS)-induced ALI. Our results showed that escitalopram inhibited salt-inducible kinase 2 (SIK2) activity (IC 50 = 6.36 ± 0.93 μM) and triggered histone deacetylase 4 (HDAC4) dephosphorylation . Following its dephosphorylation, HDAC4 translocated into the nucleus, promoted deacetylation and cytoplasmic shuttling of p65, thus inhibited LPS-induced pro-inflammatory cytokine production. Moreover, escitalopram markedly ameliorated the inflammatory responses, reduced neutrophils infiltration and attenuated LPS-induced pulmonary injury in mice. Taken together, we identified a previously unexplored role for escitalopram in SIK2/HDAC4/NF-κB pathway, therefore escitalopram may be considered as a new treatment for ALI.
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高影响因子
Small
·
2022
·Vol. 18
·期 43
·2106904
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IF 15.153
Zhong Wu,Yanhui Feng,Zhenbo Qin,Xiaopeng Han,Xuerong Zheng,Yida Deng,Wenbin Hu
Development of efficient non-noble metal catalysts for water splitting is of great significance but challenging due to the sluggish kinetics of the hydrogen evolution reaction (HER) in alkaline medium. Herein, a bimetallic multi-level layered catalytic electrode composed of Ni 3 S 2 nanosheets with secondary Co-NiOOH layer of 3D porous and free-standing cathode in alkaline medium is reported. This integrated synergistic catalytic electrode exhibits excellent HER electrocatalytic performance. The resultant Ni 0.67 Co 0.33 /Ni 3 S 2 @NF electrode displays the highest HER activity with only overpotentials of 87 and 203 mV to afford current densities of 10 and 100 mA·cm −2 , respectively, and its Tafel slope is 80 mV·dec −1 . The chronopotentiometry operated at high current density of 50 mA·cm −2 shows negligible deterioration, indicating better stability of Ni 0.67 Co 0.33 /Ni 3 S 2 @NF electrode than Pt/C (20 wt.%). Such a desirable catalytic performance is attributed to the modification of physical and electronic structure that exposes abundant active sites and improves the intrinsic catalytic activity toward HER, which is also confirmed by electrochemically active surface area and X-ray photoelectron spectroscopy analysis. This work provides a strong support for the rational design of high-performance bimetallic electrodes for industrial water splitting.
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BIOMEDICINE & PHARMACOTHERAPY
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2022
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IF 7.419
Mengyang Wang,Wu Luo,Tianxiang Yu,Shiqi Liang,Jinfeng Sun,Yi Zhang,Xue Han,Xiaohong Long,Guang Liang,Gao Li
Heart failure is a fairly common outcome of hypertension. Recent studies have highlighted the key role of the non-hemodynamic activity of angiotensin II (Ang II) in hypertensive heart failure via inducing cardiac inflammation. Drugs that disrupt Ang II-induced cardiac inflammation may have clinical utility in the treatment of hypertensive heart failure. A naturally occurring compound, corynoline, exhibit anti-inflammatory activities in other systems. C57BL/6 mice were injected with Ang II via a micro-osmotic pump for four weeks to develop hypertensive heart failure. The mice were treated with corynoline by gavage for two weeks. RNA-sequencing analysis was performed to explore the potential mechanism of corynoline. We found that corynoline could inhibit inflammation, myocardial fibrosis, and hypertrophy to prevent heart dysfunction, without the alteration of blood pressure. RNA-sequencing analysis indicates that the PPARα pathway is involved Ang II-induced cardiac fibrosis and cardiac remodeling. Corynoline reversed Ang II-induced PPARα inhibition both in vitro and in vivo. We further found that corynoline increases the interaction between PPARα and P65 to inhibit the NF-κB pro-inflammatory pathway in H9c2 cells. Our studies show that corynoline relieves Ang II-induced hypertensive heart failure by increasing the interaction between PPARα and P65 to inhibit the NF-κB pathway.
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MOLECULAR NEUROBIOLOGY
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2022
·Vol. 59
·期 11
·6903-6917
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IF 5.682
Zhao Maofang,Cheng Yuan,Wang Xiaoxuan,Cui Xiaoying,Cheng Xiaojing,Fu Qian,Song Yilin,Yu Peiquan,Liu Yi,Yu Yinghua
Obesity has become a public health epidemic worldwide and is associated with many diseases with high mortality including hypertension, diabetes, and heart disease. High-fat diet (HFD)-induced energy imbalance is one of the primary causes of obesity, but the underlying mechanisms are not fully elucidated. Our study showed that HFD reduced the level of hydrogen sulfide (H 2 S) and its catalytic enzyme cystathionine β-synthase (CBS) in mouse hypothalamus and plasma. We found that HFD activated mTOR, IKK/NF-κB, the main pathway regulating inflammation. Activation of inflammatory pathway promoted the production of pro-inflammatory cytokines including IL-6, IL-1β, and TNF-α, which caused cell damage and loss in the hypothalamus. The disturbance of the hypothalamic neuron circuits resulted in body weight gain in HFD-induced mice. Importantly, we also showed that restoration of H 2 S level with NaHS or activation of CBS with SAMe attenuated HFD-induced activation of mTOR, IKK/NF-κB signaling, which reduced the inflammation and the neuronal cell loss in the hypothalamus, and also inhibited body weight gain in mice. The same effects were obtained by inhibiting mTOR or NF-κB, which suggested that mTOR and NF-κB were the critical molecular factors involved in hypothalamic inflammation. Taken together, this study identified that HFD-induced hypothalamus inflammation plays a critical role in the development of obesity. Moreover, the inhibition of hypothalamic inflammation by regaining H 2 S level could be a potential therapeutic to prevent the development of obesity. Graphical abstract
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ACS Applied Energy Materials
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2021
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IF 6.024
Xiaoying Xiong,Qilong Zhang,Hui Yang
Composites composed of a polymer matrix and inorganic fillers have attracted tremendous attention owing to their promising application in flexible dielectric film capacitors. However, boosting the energy density while ensuring a high charging-discharging efficiency is still a huge challenge. In this work, Ba0.6Sr0.4TiO3 nanofibers (BST NFs) doped with different contents of ultra-fine Au nanoparticles are precisely prepared by one-step electrospinning, and P(VDF-TrFE-CFE) (PVTC)-based composites incorporated with various nanofibers are further prepared via a solution-casting process. A superior discharged energy density of 14.2 J/cm3 and an excellent energy storage efficiency of 71.3% have been achieved in such monolayer composites by optimizing the doping content and distribution of ultra-fine Au nanoparticles in BST NFs, which are induced by enhanced electric displacement and ensure suppressed energy loss and improved electric breakdown strength. Hence, doping moderate ultra-fine metal nanoparticles in one-dimensional inorganic nanofillers is a feasible strategy for designing polymer-based composites with outstanding performance.
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LIFE SCIENCES
·
2021
·
IF 5.037
Mengyuan Fang,Wencui Wan,Qiuming Li,Weiwei Wan,Yang Long,Hongzhuo Liu,Xin Yang
Aim This study aimed to evaluate the effects of Asiatic acid (AA), a naturally occurring compound of pentacyclic triterpenoid, on the pathological processes of diabetic retinopathy (DR). Methods SD rats were induced to develop early DR by intraperitoneal injection of STZ (60 mg/kg). Four weeks after injection, the diabetic rats were orally administrated with 37.5 mg/kg or 75 mg/kg AA every day for four weeks. The integrity of blood-retinal barrier (BRB) was measured by Evans blue staining. The polarization of microglia was determined by real-time PCR, western blot, and ELISA assays. The inner BRB (iBRB) or outer BRB (oBRB) breakdown was induced in human retinal endothelial cells or APRE19 cells through co-culture with high glucose and LPS-stimulated microglia BV2 cells. The damage to the iBRB and oBRB was measured using transendothelial/transepithelial electrical resistance (TEER/TER) and FITC-conjugated dextran cell permeability assays. Key findings Results demonstrated that AA alleviated BRB breakdown, as evidenced by decreased protein expression of occludin, claudin-5, and ZO-1. Furthermore, AA treatment suppressed inflammation and M1 polarization, while it increased M2 polarization in the retina of DR rats. In vitro , the iBRB or oBRB breakdown was alleviated by AA. LPS-induced M1-polarization of BV2 cells under high glucose condition was also repressed through AA administration. Finally, we demonstrated that AA weakened the TLR4/MyD88/NF-κB p65 signaling pathway both in vivo and in vitro . Significance AA ameliorated early DR by regulating microglia polarization via the TLR4/MyD88/NF-κB p65 pathway. These data indicate that AA is a potential candidate for DR treatment.
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Bioengineered
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2020
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IF 2.205
Aimin Liu,Buxin Zhang,Wei Zhao,Yuanhui Tu,Qingxing Wang,Jing Li
Psoriasis is a chronic inflammatory skin disease that affects approximately 2% of worldwide population, and causing long-term troubles to the patients. Therefore, it is urgent to develop safe and effective therapeutic drugs. Catalpol is a natural iridoid glucoside, that has several remarkable pharmacological effects, however, whether catalpol can alleviated psoriasis has not been explored. The goal of the present work is to study the role of catalpol in psoriasis in vivo and in vitro. Imiquimod-induced psoriasis-like mice were applied with different concentrations of catalpol for 8 consecutive days. The severity degree of psoriasis was estimated and the skin pathological changes were detected by H&E staining. Also, TNF-α-stimulated keratinocytes were treated with different concentrations of catalpol, then the oxidative stress and inflammation factors, as well as the expression of SIRT1 and activation of NF-kB and MAPK pathways were measured. The results showed that catalpol reduced the erythema, scaling, ear thickness, and changed pathological phenotypes in the lesioned skin region in mice. Treatment with catalpol significantly suppressed the oxidative stress and inflammatory reactions in vivo and in vitro, as reflected by the decreased secretion or expression of oxidative stress indicators and proinflammatory factors. Furthermore, the SIRT1 was up-regulated and the NF-κB and MAPKs signaling pathways were suppressed by the treatment of catalpol in vivo and in vitro. In summary, our data suggested that catalpol may have a therapeutic property of psoriasis by ameliorating oxidative stress and inflammation partly through SIRT1 mediated suppression of NF-κB and MAPKs pathways.Abbreviation: CAT: catalase; ELISA: enzyme-linked immunosorbent assay; GSH: glutathione; HRP: horseradish peroxidase; IMQ: imiquimod; JNK: c-Jun NH 2-terminal kinases; MAPKs: mitogen-activated protein kinases; MDA: malondialdehyde; NC: negative control group; NF-kB: nuclear factor kappa B; PASI: psoriasis area and severity index; PVDF: polyvinylidene difluoride membranes; qRT-PCR: quantitative real time polymerase chain reaction; ROS: reactive oxygen species; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel; SIRT1: silent information regulator 1; SOD: Cu/Zn superoxide dismutase
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MEDIATORS OF INFLAMMATION
·
2020
·
IF 3.758
Yushi Ding,Suyun Yu,Zhonghong Wei,Rui Deng,Peng Chen,Yifan Sun,Qi Jia,Xiaoman Li,Yuanyuan Wu,Wenxing Chen,Kurt S. Zanker,Aiyun Wang,Yin Lu
Relieving Sore Throat Formula (RSTF) is a formula approved by the China Food and Drug Administration and has been used for the treatment of pharyngitis in clinic for many years. However, the potential pharmacological mechanism still remains unknown. We combined multiple methods including bioinformatics data digging, network pharmacology analysis, and pathway analysis to predict the potential target of RSTF. We verified our in silico prediction results with an in vivo/vitro antibacterial effect test, mouse phagocytic index test, proliferation, transformation, and migration of mouse spleen lymphocytes. Alteration of NF-κB pathway was determined by Western blotting, immunofluorescence, and PCR. The in vivo experiments demonstrated that the RSTF could significantly relieve the symptoms of pharyngitis. A rat saliva secretion test showed that RSTF can effectively relieve the xerostomia symptom. A phenol red excretion test showed that RSTF has an eliminating phlegm effect. A hot plate method and granuloma experiment proved that RSTF also have analgesic and anti-inflammatory effects. In silico prediction demonstrates that 70 active compounds of RSTF were filtered out through ADME screening and 84 putative targets correlated with different diseases. Pathway enrichment analysis showed that the candidate targets were mostly related to the response to bacteria and immunity signalling pathways, which are known contributors to pharyngitis. Experimental results confirmed that RSTF exerted therapeutic effects on pharyngitis mainly by antibacterial effect and downregulation of NF-κB activities. It is demonstrated both in silico and in vivo/vitro that RSTF exerted therapeutic effects on pharyngitis mainly through an antibiotic effect and downregulation of NF-κB signalling pathway.
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高影响因子
DESALINATION
·
2020
·
IF 7.098
Qin Li,Zhipeng Liao,Xiaofeng Fang,Jia Xie,Linhan Ni,Dapeng Wang,Junwen Qi,Xiuyun Sun,Lianjun Wang,Jiansheng Li
In this work, a novel tannic acid assisted interfacial polymerization (TAIP) method was developed for preparing loose nanofiltration membranes (LNMs). Piperazine (PIP) and tannic acid (TA), two kinds of common monomer for interfacial polymerization (IP), were employed to deposit on substrate for the TAIP process. The TAIP process resulted in enlarged pores in the skin layer due to the longer monomers, thus achieved considerable permselectivity in separating salts from dye/salt mixture solution. The optimal TAIP membrane (M4) exhibited high permeability (32.57 LMH·bar − 1 to Congo Red solution), reasonable rejection to dyes (99.40% and 99.19% for Congo Red and Rose Bengal, respectively) and satisfactory transport to salts (90.59% to Na 2 SO 4 and 97.75% to NaCl). Meanwhile, this membrane retained high performance in dye/salt separation (7.16 LMH·bar − 1 of permeability, 97.47% of CR rejection and 2.55% of NaCl retention) under even as high as 6 wt% of salt concentration . Moreover, TAIP LNM showed high stability throughout a 30-hour-long running test to separate salts from dye/salt mixture solution. We anticipated the TAIP methodology, together with the consequential LNM, to provide a potential candidate for dye/salt separation application.
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