PHARMACOLOGICAL RESEARCH
·
2017
·
IF 4.48
Yuchao Sun,Mengqiao Lian,Yuan Lin,Bin Xu,Yanli Li,Jin Wen,Dapeng Chen,Ming Xu,Marwan Almoiliqy,Li Wang
Intestinal ischemia reperfusion (I/R) may cause inflammation-, oxidative stress-, and apoptosis-related tissue injuries and facilitate bacterial infection, leading to multiple organ failure. Myricetin , a flavonoid , is found to have diverse biological effects including anti-inflammatory, anti-oxidative, and anti-bacterial effects. Based on our pre-experiment, we proposed that myricetin pretreatment (25, 50 mg/kg) could ameliorate intestinal I/R injury and myricetin-induced modulation on MKK7/JNK signal pathway might play a key role in the amelioration. The present study was designed to verify the proposal by using both rat intestinal I/R model in vivo and hypoxia/reoxygenation (H/R)-injured intestinal epithelial cell line (IEC-6 cells) model in vitro. The results confirmed our proposal. Myricetin selectively ameliorated I/R- and H/R-induced injuries in vivo and in vitro respectively without significantly affecting the corresponding normal controls. Myricetin significantly alleviated I/R-induced rat intestinal injury by reducing the generation of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6 and by reducing MPO activity. Myricetin significantly reduced oxidative stress through decreasing MDA level and increasing the levels of SOD and GSH in the intestinal tissues compared with I/R control rats. Myricetin significantly decreased apoptosis by selectively down-regulating the expression of p-MKK7 and p-JNK without affecting MKK7 and JNK, inhibiting Bax, caspase-3 protein expression, and up-regulating Bcl-2 protein expression in I/R-injured jejunum of rats. In vitro study indicated that MKK7 siRNA transfection significantly decreased both MKK7 and p-MKK7 and other apoptosis-related proteins, partially simulating myricetin-induced anti-apoptotic effects. MKK7 siRNA transfection + myricetin could not further decrease MKK7, p-MKK7, and other apoptosis-related proteins, suggesting that inhibition of MKK7/JNK pathway plays a key role in myricetin-induced protection against intestinal I/R. MKK7 overexpression by cDNA transfection abrogated myricetin-reduced apoptosis-related protein expression, confirming that the MKK7/JNK signal pathway is the key target for myricetin-induced amelioration. The present study indicated that pretreatment of myricetin induced selective protection against intestinal I/R injury without significantly affecting corresponding normal controls and p-MKK7 was the key target, suggesting that myricetin is worth further translational studies.
研究领域:
药理学
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分子生物学
·
病理生理学
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL ANIMALS
·
2023
·
IF 2.4
Ce XU,Jiahui HAN,Di JIA,Jimin CAI,Jianming YUAN,Xin GE
Increasing studies have suggested that oxidative stress and inflammation play momentous roles in acute pulmonary embolism (APE). Honokiol, a bioactive biphenolic phytochemical substance, is known for its strong anti-oxidative and anti-inflammatory effects and here serves as an activator of sirtuin3 (SIRT3). The purposes of the study are to explore the effects of Honokiol on APE rats, and investigate whether the function of Honokiol is mediated by SIRT3 activation. In this study, the rats received a right femoral vein injection with dextran gel G-50 particles (12 mg/kg) to establish the APE model, which were administrated with Honokiol and/or selective SIRT3 inhibitor 3- (1H-1, 2, 3-triazol-4-yl) pyridine (3-TYP; 5 mg/kg) intraperitoneally. The data showed that SIRT3 activation by Honokiol attenuated the loss in lung function, ameliorated inflammatory response and oxidative damage as well as inhibited apoptosis in lung tissues of the rats with APE, which was reversed by 3-TYP. In addition, we found AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway might be activated by Honokiol but restrained by 3-TYP. These results indicated that Honokiol was capable of suppressing APE’s adverse effects, which was diminished by SIRT3 suppression, implying that activation of SIRT3 might serve as a therapeutic method for APE.
研究领域:
药理学
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肺科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Anatomical Record-Advances in Integrative Anatomy and Evolutionary Biology
·
2021
·Vol. 305
·期 7
·1672-1681
·
IF 2.064
Yongdui Ruan,Yaohua Fan,Yanfeng Xie,Chunling Ma,Bingquan Mo,Yanni Lai,Geng Li,Xiaohong Liu,Weihong Kuang
Effective therapeutics are not available for acute lung injury (ALI) and acute respiratory distress syndrome. Modified Xiaoqinglong decoction (M-XQL) is reported to effectively treat pneumonia, but the underlying mechanisms are unclear. In this study, the therapeutic effect and mechanism of M-XQL were examined using a lipopolysaccharide (LPS)-induced ALI mouse model. The effects of M-XQL on lung injury, inflammatory responses, and cell apoptosis were analyzed. Additionally, high-throughput sequencing was performed to evaluate the therapeutic mechanism of M-XQL. Pretreatment with M-XQL significantly and dose-dependently mitigated the pathological changes and upregulation of pulmonary, nitric oxide content and cell apoptosis and serum tumor necrosis factor-alpha contents in the LPS-induced ALI mouse model. RNA sequencing analysis revealed that the expression of several arachidonic acid metabolism-associated genes in the LPS + high-dose M-XQL group differed from that in the LPS group. In particular, the Cbr2 , Cyp4f18 , and Cyp2e1 levels were upregulated, whereas the Alox12 , Ptges , and Ptges2 levels were downregulated in the LPS + high-dose M-XQL group. These results suggest that M-XQL exerts therapeutic effects in ALI mice by regulating arachidonic acid metabolism and exerting anti-apoptotic and anti-inflammatory effects. Thus, M-XQL is a potential agent for the clinical treatment of ALI.
研究领域:
药理学
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呼吸病学
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分子生物学
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DOI
PubMed
高影响因子
Oncotarget
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2017
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IF 5.168
Chen Zhu,Yi Wang,Hua Liu,Haiman Mu,Yue Lu,Jiayi Zhang,Jianhua Huang
Although Ginsenoside Rg1 has been reported to have protective cardiac effects, its effects on cardiac toxicity induced by doxorubicin needs to be studied. The present study investigated the effects of oral administration of Rg1 on the heart in mice treated with doxorubicin and found improved fractional shortening and ejection fraction of the heart and decreased cardiac apoptosis in mice treated with doxorubicin. The underlying mechanisms include increased phosphorylation of Akt and Erk by Rg1, increased ratio of Bcl-2 and Bax, and decreased release of cytochrome c from mitochondria, thereby protecting the heart from doxorubicin-induced apoptosis. This phenotype suggested that the oral administration of Rg1 may be a potential method preventing the cardiac toxicity caused by doxorubicin in clinical practice.
研究领域:
药理学
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心脏病学
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肿瘤学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2022
·
IF 5.714
Haihua Zhang,Jing Wang,Wuying Lang,Hongli Liu,Zhiqiang Zhang,Tonglei Wu,Hongqiang Li,Liya Bai,Qiumei Shi
Methotrexate (MTX) treats various diseases but also damages intestinal barrier and leads to enteritis. Albiflorin (ALB) has a variety of pharmacological effects, including antioxidant, anti-inflammation and anti-apoptosis. In the present study, we evaluated the therapeutic effect of ALB on MTX-induced enteritis and investigated the possible mechanisms involved. Male SD rats were intraperitoneally injected with 7 mg/kg MTX for three consecutive days to establish the enteritis model. ALB (20 or 40 mg/kg/day) was intragastrically administrated since two days prior MTX treatment and lasted for six days. We found that ALB treatment increased body weight and intestinal weight of rats with MTX injection. The disease activity index (DAI) score was also decreased after ALB administration. In histological examination, ALB treatment attenuated inflammatory cells infiltration and promoted survival of goblet cells. In detection of inflammatory-associated factors, ALB treatment decreased CD68 + cells infiltration, inhibited myeloperoxidase activity, and suppressed intercellular cell adhesion molecule-1 and cyclooxygenase-2 expression. Additionally, ALB reduced malondialdehyde, glutathione levels, inhibited superoxide dismutase activity and suppressed reactive oxygen species production. Moreover, ALB treatment effectively inhibited NLRP3, as well as caspase 1 p20 and interleukin (IL)-1β and 18 expression. Finally, nuclear factor-κB (NF-κB) p65 phosphorylation and nuclear translocation were also demonstrated to be blocked upon ALB treatment. In conclusion, our findings indicated that ALB alleviated MTX-induced enteritis via inhibiting the NF-κB/NLRP3 pathway.
研究领域:
药理学
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免疫学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
Biochemistry and Cell Biology
·
2021
·Vol. 99
·期 2
·
IF 3.626
Guangwei Liu,Wenxia Zhao,Jiameng Bai,Jianjiao Cui,Haowei Liang,Baoping Lu
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that seriously threatens the health of humans globally. Formononetin (FMN) is a natural herb extract with multiple biological functions. In this study, an experimental model of AIH was established in mice through the use of concanavalin A (ConA). To investigate the effects of FMN on ConA-induced hepatitis, the mice were pretreated with 50 or 100 mg/kg body mass of FMN. The results show that FMN alleviated ConA-induced liver injury of mice in a dose-dependent manner. Moreover, pretreatment with FMN inhibited the apoptosis of hepatocytes in the ConA-treated mice through downregulating the expression of pro-apoptotic proteins (Bax, cleaved caspase 9, and cleaved caspase 3) and upregulating the expression of anti-apoptotic protein (Bcl-2). It was also found that the levels of proinflammatory cytokines were greatly reduced in the serum and liver tissues of mice pretreated with FMN. Further studies showed that FMN reduced the level of phosphorylated nuclear factor kappa B (p-NF-κB) p65 and enhanced the level of IκBα (inhibitor of NF-κB), suggesting that FMN inhibits the activation of the NF-κB signaling pathway. In addition, FMN inhibited activation of the NOD-like receptor protein 3 (NLRP3) inflammasome. Therefore, FMN could be a promising agent for the treatment of AIH.
研究领域:
免疫学
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药理学
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肝病学
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DOI
PubMed
高影响因子
MOLECULES
·
2019
·Vol. 24
·期 6
·1090
·
IF 3.06
Zhenhuang Shen,Qianqian Geng,Haibo Huang,Hong Yao,Tianyu Du,Lifu Chen,Zhenhong Wu,Xiaoqing Miao,Peiying Shi
Oxidative stress plays an important role in the pathogenesis of myocardial infarction (MI).Schisandra chinensisbee pollen extract (SCBPE) possesses powerful antioxidant capacity. This study aimed to further explore the antioxidative and cardioprotective effects of SCBPE on acute MI induced by isoprenaline (ISO) in rats. The rats were intragastrically administrated with SCBPE (600, 1200, or 1800 mg/kg/day) and Compound Danshen dropping pills (270 mg/kg/day) for 30 days, then subcutaneously injected with ISO (65 mg/kg/day) on the 29th and 30th day. Compared with the model group, pretreatment with middle and high doses of SCBPE significantly reduced serum aspartate transaminase, lactate dehydrogenase, and creatine kinase activities and increased myocardial superoxide dismutase, glutathione peroxidase, and catalase activities. The histopathologic aspects showed that pathological heart change was found in the model group and reduced to varying degrees in the SCBPE groups. Moreover, the protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1), and Bcl2 in the heart increased in the SCBPE groups, while that of Bax decreased compared to the model group. Besides this, uridine was isolated fromS. chinensisbee pollen for the first time. This study could provide a scientific basis for usingSchisandra chinensisbee pollen as a functional food for the prevention of MI.Keywords:Schisandra chinensisbee pollen extract;myocardial infarction;cardioprotective effect;antioxidative effect;anti-apoptotic effect
研究领域:
药理学
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心脏病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Traditional Chinese Medicine
·
2023
·Vol. 44
·期 4
·722
·
IF 2.6
Jing YAN,Huimin FENG,Fang QIU,Haijun WANG,Luyun YIN,Xiaofei JIN,Jiyu ZHAO,Hongyang WANG,Xiaoqin YAN
OBJECTIVE: To analyze the serum metabolic targets of the "Zhibian (BL54) through Shuidao (ST28)" acupuncture technique in cyclophosphamide (CTX)-induced premature ovarian insufficiency (POI) model rats and to elucidate the potential molecular mechanism of acupuncture in improving POI. METHODS: We used an intraperitoneal injection of CTX to establish the POI rat model (POI group) and compared serum hormone levels and ovarian histopathological changes to evaluate the effect of the Zhibian (BL54) through Shuidao (ST28) technique (ZS + POI group) on ovarian function. Then, nontargeted metabolomics was performed using rat serum by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). RESULTS: After acupuncture intervention, the serum hormone levels and ovarian pathological morphology of POI rats were effectively improved. Moreover, UPLC-Q-TOF/MS results showed that the ZS + POI group showed a significant reversal of the levels of 6 differential metabolites. Among them, the levels of four serum metabolic markers, divanillyltetrahydrofuran ferulate, trans-ferulic acid, tryptamine, and neuraminic acid, increased significantly. Further analysis of biological effects showed that all metabolites were involved in the regulation of reproductive hormone levels and antioxidant and antiapoptotic effects. CONCLUSIONS: The "Zhibian (BL54) through Shuidao (ST28)" acupuncture method may improve the ovarian function of POI rats by regulating serum metabolite markers to exert antioxidant and antiapoptotic effects, which provides a theoretical basis for the clinical application of acupuncture in the treatment of POI.
研究领域:
生殖医学
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代谢组学
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针灸学
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妇科学
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分子生物学
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药理学
·
转化医学
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DOI
PubMed
高影响因子
BIOMATERIALS
·
2018
·
IF 8.806
Yonglin Yu,Xinkun Shen,Zhong Luo,Yan Hu,Menghuan Li,Pingping Ma,Qichun Ran,Liangliang Dai,Ye He,Kaiyong Cai
Oxidative stress is commonly existed in bone degenerative disease (osteoarthritis, osteoporosis etc .) and some antioxidants had great potential to enhance osteogenesis. In this study, we aim to investigate the anti-oxidative properties of various TiO 2 nanotubes (TNTs) so to screen the desirable size for improved osteogenesis and reveal the underlying molecular mechanism in vitro . Comparing cellular behaviors under normal and oxidative stress conditions, an interesting conclusion was obtained. In normal microenvironment , small TNTs were beneficial for adhesion and proliferation of osteoblasts, but large TNTs greatly increased osteogenic differentiation . However, after H 2 O 2 (300 μM) treatment (mimicking oxidative stress), only large TNTs samples demonstrated superior cellular behaviors of increased osteoblasts' adhesion, survival and differentiation when comparing with those of native titanium (control). Molecular results revealed that oxidative stress resistance of large nanotubes was closely related to the high expression of integrin α5β1 (ITG α5β1), which further up-regulated the production of anti-apoptotic proteins (p-FAK, p-Akt, p-FoxO3a and Bcl2) and down-regulated the expression of pro-apoptotic protein (Bax). Moreover, we found that Wnt signals (Wnt3a, Wnt5a, Lrp5, Lrp6 and β-catenin) played an important role in promoting osteogenic differentiation of osteoblasts under oxidative condition.
研究领域:
材料科学
·
生物材料
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细胞生物学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
Nanoscale Research Letters
·
2021
·Vol. 16
·期 1
·1-16
·
IF 4.703
Zhou Lin,Huang Zhi,Yang Shanyi,Wei Jiarui,Xu Yan,Hu Lin,Guo Xinrong,Yuan Limin,Yuan Zexuan,Yang Xiaoping,Tao Xiaojun,Zhang Qiufang
Hydrophilic polyethylene glycol monomethyl ether (mPEG) was grafted onto Icariin (ICA) by succinic anhydride to form a polyethylene glycol-Icariin (mPEG-ICA) polymer. The structure of the polymer was characterized by Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). mPEG-ICA nanoparticles loaded with ICA were prepared by physical embedding of ICA by dialysis. The particle size was determined to be (220 ± 13.7) nm, and the ζ potential was (2.30 ± 1.33) mV by dynamic light scattering (DLS). Under a transmission electron microscope (TEM), the nanoparticles were spherical, and the morphology was regular. In the medium with pH 7.4, the drug release rate of mPEG-ICA nanoparticles reached (52.80 ± 1.70)% within 72 h. At pH 6.8, the cumulative drug release of nanoparticles reached (75.66 ± 0.17)% within 48 h. Treatment of the nanoparticles with LPS-treated H9c2 cells maintained cell viability, reduced LDH release and exerted antiapoptotic effects. Moreover, ICA-loaded mPEG-ICA nanoparticles significantly decreased the mRNA expression of the myocardial inflammatory cytokines TNF-α, IL-1β and IL-6M. In conclusion, ICA-loaded mPEG-ICA nanoparticles protected against LPS-induced H9c2 cell injury.
研究领域:
药学
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纳米技术
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细胞生物学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2024
·
IF 3.9
Jiewei Zheng,Xin Yang,Cong Zhang,Weipeng Zhang,Yue Hu,Lihai Zeng,Lili Liu,Guoliang Li
Icariin (ICA), an active ingredient found in Epimedium , possesses antioxidant and anti-inflammatory properties and has garnered widespread attention in recent years. This study investigated the protective effects of ICA against cadmium (Cd)-induced kidney injury in rats. Healthy male specific pathogen-free Sprague–Dawley rats were randomly divided into a control group, Cd group, a low-dose ICA group, a middle-dose ICA group, and a high-dose ICA group using a random number table. Tissue and blood samples were analyzed for renal function markers, histopathology, and gene expression. We found that ICA intervention ameliorates Cd-induced nephrotoxicity by enhancing glomerular filtration, mitigating renal tubular epithelial cell damage, reducing cellular degeneration and edema, and decreasing oxidative stress. ICA demonstrated anti-apoptotic activity through the regulation of pro- and anti-apoptotic gene transcription and by inhibiting apoptosis, thus protecting the kidneys. ICA also exhibited anti-inflammatory effects by reducing the transcription of Cd-induced pro-inflammatory genes, inhibiting nucleotide oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasome formation, and preventing pyroptosis. ICA potentially regulated the Toll-like receptor 4/ P2rx7 /nuclear factor kappa B signaling pathway, which modulated the activation of the NLRP3 inflammasome and contributed to its anti-inflammatory action. ICA reduced Cd-induced renal injury in rats, likely through a mechanism involving antioxidant, anti-apoptotic, and anti-inflammatory effects.
研究领域:
药理学
·
毒理学
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分子生物学
·
肾脏生理学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Zihao He,Siyuan Deng,Zhijing Wu,Zheng Cui,Hao Mei,Jinglin Wang,Kaiping Wang,Yu Zhang
Ethnopharmacological relevance Dysfunction of the intestinal barrier was an important trigger for alcoholic liver damage and alcohol had brought about intestinal damage before causing liver damage. The root of Angelica sinensis (Oliv.) Diels, crucial traditional medicinal material, was widely utilized for its blood-invigorating, intestinal-lubricating and gynecological benefits. Angelica sinensis polysaccharide (ASP) was an essential natural active ingredient of Angelica sinensis and exhibited considerable potential for gastrointestinal protection. Nevertheless, the systematic research of ASP on the gastrointestinal tract remained insufficient. Aim of this study To systematically explore the protective effect and underlying mechanisms of ASP against alcohol-induced gastrointestinal injury, including the stomach, ileum and colon. Materials and methods The AFLD mice model was established via the intragastric administration of alcohol twice a day for one week. The protective effect of ASP on the representative segments of the gastrointestinal tract (stomach, ileum and colon) was subsequently studied after confirming its hepatoprotective activity. The impact of ASP on gastrointestinal alcohol metabolism was examined to explain its antioxidant and antiapoptotic activities. Furthermore, the effect of ASP on short-chain fatty acids (SCFA) in the colon and colonic contents was investigated to further enhance the understanding of the underlying mechanisms. Results ASP could reduce oxidative stress and apoptosis in the gastrointestinal tract via regulating CYP2E1-mediated alcohol metabolism. Additionally, ASP could significantly increase the levels of FFAR2, FFAR3 and HCAR2 in colon, thereby promoting the utilization of SCFA. Conclusion ASP was proven for the first time to improve gastrointestinal damage caused by alcohol, indicating its enormous potential as a candidate medicine for the treatment of alcohol related gastrointestinal injury.
研究领域:
药理学
·
胃肠病学
·
肝病学
·
营养保健品
·
民族药理学
✓ 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）