Materials Today Bio
·
2024
·
IF 8.7
Linxiao Sun,Shaoyin Wei,Chenglong Wang,Yipiao Zhang,Xingjie Zan,Lianxin Li,Chunwu Zhang
Chronic inflammatory diseases such as diabetic wounds and osteoarthritis are significant threats to human health. Failure to scavenge longstanding excessive reactive oxygen species (ROS) is an important cause of chronic inflammatory diseases, yet existing treatments that provide long-lasting therapeutic effects are limited. Here, procyanidin capsules were synthesized in a simple one-step way using calcium carbonate as a template. The biosafety of procyanidin capsules in vitro and in vivo was monitored by cytotoxicity and pathological sections. The therapeutic effect of procyanidin capsules in diabetic wounds and osteoarthritis was accessed by pathological evaluation combined with the quantification of inflammatory markers. The data showed that procyanidin capsules could long-term scavenge excessive ROS and effectively promote articular cartilage repair in osteoarthritis, accelerating diabetic wound healing. Lastly, transcriptome analysis suggested that procyanidin capsules commonly regulated adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) signaling in diabetic wounds and osteoarthritis. This study provides a straightforward protocol for creating procyanidin capsules, while presenting a promising new therapeutic option for long-term scavenging ROS in chronic inflammatory diseases.
研究领域:
药理学
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炎症
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生物技术
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伤口愈合
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骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AMERICAN JOURNAL OF CHINESE MEDICINE
·
2023
·Vol. 51
·期 07
·1675-1709
·
IF 5.7
Cho Hyun Hwang,Eungyeong Jang,Jang-Hoon Lee
Salvia miltiorrhiza Bunge, called Danshen in Chinese, is the dried root and rhizome of S. miltiorrhiza , which is part of the mint family, Lamiaceae; it has chiefly been used to treat blood stasis and improve blood flow in cerebrovascular and cardiovascular diseases for over 2000 years. Recent preclinical studies have indicated that S. miltiorrhiza has a wide range of pharmacological properties making it useful for the treatment of diverse liver diseases. S. miltiorrhiza protects the liver from harmful hepatotoxins, reduces hepatic oxidative stress, ameliorates steatosis, and alleviates hepatic inflammation, fibrosis, and cancer. Moreover, several key mechanisms, including apoptosis, AMP-activated protein kinase, mitogen-activated protein kinase, and nuclear factor kappa B, may be involved in the benefits of S. miltiorrhiza in hepatic disorders. In particular, salvianolic acid B and cryptotanshinone, both compounds derived from S. miltiorrhiza , possess therapeutic activities similar to those of S. miltiorrhiza , and thus may play a crucial role in the therapeutic activity of S. miltiorrhiza in liver diseases. Because reports on the pharmacological effects of this herb are scattered, this review aimed to consolidate the available literature to allow the re-evaluation and identification of gaps to guide future research. This review focuses on the role of S. miltiorrhiza in improving the molecular pathology of liver diseases, as reported in in vitro and in vivo studies.
研究领域:
药理学
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肝病学
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分子生物学
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中医药
✓ 已验证
DOI
PubMed
高影响因子
AQUACULTURE
·
2022
·
IF 5.135
Yunqiang Zhang,Wencong Lai,Qiuchi Chen,Wei Fang,Kun Cui,Yuliang He,Xueshan Li,Kangsen Mai,Qinghui Ai
Calcium pyruvate (CP), known as an energetic aid, has been shown to enhance lipid utilization and prevent obesity in mammals. However, very few studies were conducted to evaluate the potential implications of CP for aquatic animals. This study examined the role of CP on fat deposition in large yellow croaker by feeding fish with high-fat diets containing four levels of dietary CP (0, 0.375%, 0.75% and 1.5%). After a 70-d feeding trial, fish fed higher doses of CP significantly decreased weight gain (WG) and hepatosomatic index (HSI). Lipid percentages and triglyceride (TG) contents of whole fish, liver and muscle were negatively correlated with dietary CP. Plasma TG, total cholesterol (TC), LDL-cholesterol (LDL-c) and non-esterified fatty acids (NEFAs) levels significantly decreased with increasing dietary CP, whereas plasma HDL-cholesterol (HDL-c) and β -hydroxybutyrate ( β -HB) levels came to a climax in fish fed the 1.5% CP diet. The fish fed CP diets also exhibited smaller hepatic lipid droplet size . The expression of lipogenic genes (fatty acid synthase, fas ; acetyl-CoA carboxylase, acc ; diacylglycerol acyltransferase 2, dgat2 ) were significantly down-regulated in the liver and muscle of the CP-treated fish. Conversely, the expression of lipolytic genes (adipose triglyceride lipase , atgl ; hormone-sensitive lipase, hsl ; carnitine palmitoyltransferase 1, cpt1 ) were markedly elevated. This was accompanied by enhanced tricarboxylic acid (TCA) cycle capacity (citrate content; succinate dehydrogenase , SDH; malate dehydrogenase , MDH). Further Western blot analysis revealed that CP may dose-dependently induce phosphorylations of AMP-activated protein kinase (AMPK) and ACC in the liver and muscle, together with protein expression of CPT1 and fatty acid translocase 36 (CD36). Surprisingly, treatment with CP impaired glucose utilization, as evidenced by raised plasma glucose and weakened glucose metabolism-related enzymatic activities (hexokinase, HK; phosphofructokinase , PFK; pyruvate kinase , PK; pyruvate dehydrogenase, PDH) and gene expression (glucokinase, gk ; hk ; phosphofructokinase-liver type, pfkl ; pyruvate kinase-muscle type, pkma ) in the liver and muscle. Notably, increased plasma liver enzyme activities (alanine aminotransferase, ALT; aspartate aminotransferase , AST) and hepatic inflammation-related gene expression (interleukin-1 beta, il-1β and cyclooxygenase 2, cox-2 ) and reduced hepatic antioxidant capacity (total antioxidative capacity, T-AOC; catalase , CAT) were found in high-dose CP treatment. These findings indicated that dietary CP could attenuate fat deposition by stimulating β -oxidation through the AMPK-ACC-CPT1 cascade and inhibiting lipogenesis and glucose oxidation. Considering both lipid-lowering effect and growth performance, dietary supplementation with 0.375% ∼ 0.75% CP is suitable for alleviating fat deposition of juvenile large yellow croaker.
研究领域:
水产养殖
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营养学
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分子生物学
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生理学
✓ 已验证
产品关联
DOI
高影响因子
CNS Neuroscience & Therapeutics
·
2023
·
IF 5.5
Tao Zhang,Yuan Tian,Xiaoqing Zheng,Ruomeng Li,Li Hu,Xindong Shui,Yingxue Mei,Quling Wang,Mi Zhang,Xiuzhi Zheng,Long Wang,Dongmei Chen,Wucheng Tao,Tae Ho Lee
Aims The autophagy-lysosomal pathway is important for maintaining cellular proteostasis, while dysfunction of this pathway has been suggested to drive the aberrant intraneuronal accumulation of tau protein, leading to synaptic damage and cognitive impairment. Previous studies have demonstrated that the activation of transient receptor potential vanilloid 1 (TRPV1) by capsaicin has a positive impact on cognition and AD-related biomarkers. However, the effect and mechanism of TPRV1 activation on neuronal tau homeostasis remain elusive. Methods A mouse model of tauopathy was established by overexpressing full-length human tau in the CA3 area. Mice were fed capsaicin diet (0.0125%) or normal diet for 9 weeks. The cognitive ability, synaptic function, tau phosphorylation levels, and autophagy markers were detected. In vitro, capsaicin-induced alterations in cellular autophagy and tau degradation were characterized using two cell models. Besides, various inhibitors were applied to validate the role of TRPV1-mediated autophagy enhancement in tau clearance. Results We observed that TRPV1 activation by capsaicin effectively mitigates hippocampal tau accumulation-induced synaptic damages, gliosis, and cognitive impairment in vivo. Capsaicin promotes the degradation of abnormally accumulated tau through enhancing autophagic function in neurons, which is dependent on TRPV1-mediated activation of AMP-activated protein kinase (AMPK) and subsequent inhibition of the mammalian target of rapamycin (mTOR). Blocking AMPK activation abolishes capsaicin-induced autophagy enhancement and tau degradation in neurons. Conclusion Our findings reveal that capsaicin-induced TRPV1 activation confers neuroprotection by restoring neuronal tau homeostasis via modulating cellular autophagy and provides additional evidence to support the potential of TRPV1 as a therapeutic target for tauopathies.
研究领域:
神经科学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Chenyao Nie,Ji Xu,Yuhui Zhao,Ke Nan,Manqi Tan,Zhaobo Liu,Ming Huang,Wenzhi Ren,Bing Wang
Despite that the current anti-hyperuricemia drugs can effectively reduce uric acid (UA) levels, imprecise medication dosage or uncontrolled lowering of UA levels may result in undesired effects. To address this issue, a closed-loop cascade strategy based on a biocompatible network composite, NW-FPNP/uricase (UOX), is proposed for on-demand regulation of UA levels. NW-FPNP/UOX is constructed by encapsulation of UOX) as UA-responsive element and FPNP, a nanoparticle of phenylboronic acid modified xanthine oxidase (XOD) inhibitor febuxostat, as H 2 O 2 -sensitive element with AMP/Gd 3+ network. It interrelates the UA metabolization and generation processes into a closed loop of cascade reactions involving UOX-catalyzed UA metabolization and H 2 O 2 generation, H 2 O 2 -triggered febuxostat regeneration and XOD inhibition, and XOD-catalyzed UA generation. Through UA level-dependent auto-adjustment of XOD activity, specially 6% at 600 × 10 −6 m UA compared to 82% at 100 × 10 −6 m , UA levels can be regulated to an appropriate range through dynamically balancing UA metabolization and generation. This biocompatible on-demand UA regulation system prevents the overdose of UA-lowering medications and avoids hypouricemia in hyperuricemia treatment, demonstrating great potential in intelligent UA level management. This work also introduces a new concept of a closed-loop cascade strategy for on-demand regulation of biochemical indicators within specific thresholds.
研究领域:
生物医学工程
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药学
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纳米技术
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生物化学
✓ 已验证
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Hai-Ying Tian,Dao-Jiang Yu,Teng Xie,Meng-Xia Xu,Yu-Hao Wang,Xi-Lu Sun,Xin-Meng Zhou,Ying-Xuan Han,Qing-Qing Liao,Yu-Jie Zhao,Juan Liao,Mohamed El-Kassas,Xiao-Dong Sun,Yuan-Yuan Zhang
The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) keeps rising with only a few drugs available. The present study aims to investigate the effects and mechanisms of cordycepin on MASLD. Male C57BL/6 mice were induced with a 90-day high-fat diet (HFD) and intraperitoneal administration with streptozotocin to establish MASLD murine model. Then they were randomly divided into the HFD and cordycepin groups (15, 30, 45 mg/kg). Cordycepin was orally given for 30 days. Serum total cholesterol (TC), triacylglyceride (TG), and aspartate aminotransferase (AST) levels were measured. L02 cells were induced by oleate acid (OA) or lipopolysaccharides (LPS), and treated with cordycepin or combined with inhibitors including chloroquine, 3-Methyladenine, and compound C. Atg7 and Parkin were knocked down in L02 cells using siRNA. Oil Red O and Nile Red staining for measuring lipid deposition. Mitochondria were visualized by transfection with mCherry-TOMM20-N10. Quantitative real-time PCR, Western blotting, and immunofluorescence staining were used to determine expressions of key molecules in inflammation, lipid metabolism, mitochondria homeostasis, and oxidative stress. Cordycepin significantly mitigated lipid deposition and ballooning in the livers of MASLD mice. Serum TC, TG, and AST levels were decreased by cordycepin. Cordycepin alleviated OA-induced lipid deposition and LPS-induced inflammation in L02 cells, attenuated oxidative stress, promoted autophagy, and maintained the autophagic flux by activating AMP-activated protein kinase (AMPK). Cordycepin reduced the accumulation of impaired mitochondria by enhancing Parkin-dependent mitophagy and promoting mitochondrial biogenesis. Cordycepin alleviates MASLD by restoring mitochondrial homeostasis and reducing oxidative stress via activating the Parkin-mediated mitophagy.
研究领域:
药理学
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肝病学
·
分子生物学
·
细胞代谢
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2024
·
IF 5.3
Meng Yang,Shengquan Wu,Qihui Dai,Weihong Qin,Yujie Zhang,Yiting Lei,Haochang Song,Tingting Zheng,Min Guan,Gonghua Huang,Xinguang Liu
Excessive lipid accumulation often occurs in the early stage of chronic kidney disease (CKD) which is prone to induce oxidative stress and mitochondrial damage, promoting the progression of kidney fibrosis. Andrographolide (AP), a multifunctional natural terpenoids derived from Andrographis paniculate , has been suggested to play beneficial roles in metabolic disorders-associated disease. Here, we reported that AP effectively counteracts tubule injury and interstitial fibrosis in mice fed with a long-term high-fat diet (HFD). AP treatment decreased HFD-induced lipid accumulation in kidney parenchyma and attenuated lipotoxicity-mediated oxidative stress and mitochondrial dysfunction, resulting in a marked decrease in tubular cell senescence. Importantly, AP inhibited senescence-associated secretory phenotype (SASP) secretion by senescent tubular cells, and in turn suppressed proliferation and activation of fibroblasts in a paracrine effect. Furthermore, we revealed that AP functions as an AMP-activated protein kinase (AMPK) activator to ameliorate renal lipid accumulation through coordinately modulating AMP-activated protein kinase AMPK target genes. By stimulation of AMPK activity, AP protects injured kidney against tubular cell senescence and fibroblast activation. These results suggest the potential therapeutic application of AP in the prevention and treatment of CKD, highlighting the promising drug strategy of targeting the lipotoxicity-mediated premature senescence in tubular cells.
研究领域:
肾病学
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药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2020
·
IF 4.192
Na Deng,Ziqian He,Ruixue Guo,Bisheng Zheng,Tong Li,Rui Hai Liu
The mechanisms of highland barley whole grain (BWG) with rich phenolics on obese db/db mice were investigated in this study. Oral consumption of BWG reduced food intake, body weight, organ/body weight indexes of liver and fat, levels of serum and hepatic lipids, liver injury, and oxidative stress. Furthermore, BWG recovered the disorder of cecal microbiota by augmenting the Bacteroidetes/Firmicutes ratio and Alistipes abundance and decreasing the abundances of Bacteroides and Desulfovibrionaceae to modulate lipid metabolism-related genes. BWG inhibited fatty acid biosynthesis via upregulating the phosphorylation of AMP-activated protein kinase α, while downregulating sterol regulatory element binding protein-1c, fatty acid synthase (FAS), and stearoyl-CoA desaturase 1 levels. BWG also significantly downregulated miRNA-122, miRNA-33, miRNA-34a, and miRNA-206 levels. Accordingly, BWG exhibited hypolipidemic potential through modulating cecal microbiota, AMPK/SREBP-1c/FAS pathway, and related miRNAs, triggering the alleviation of dyslipidemia. These findings suggested BWG as an effective candidate to ameliorate the symptoms of hyperlipidemia.
研究领域:
营养学
·
微生物学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOTECHNOLOGY AND BIOPROCESS ENGINEERING
·
2015
·Vol. 20
·期 1
·157-167
·
IF 1.113
Chaudhary Narendra,Bhardwaj Jyoti,Hwang Jae-Ho,Seo Hyo-Jin,Kim Min-Yong,Shin Tai-Sun,Wee Ji-Hyang,Shin Yu-Lim,Kim Jong-Deog
Camellia sinensis L. O. Kuntze has traditionally been used in Asian countries as a stimulant, a diuretic, and to prevent obesity. Studies in green tea are well-documented in literature, though the potential of fruit from the plant has never been studied in details. In the present study, the anti-adipogenic effect of aqueous extract of green tea seed cake extract (GTE) were analysed in-vitro and the anti-obesity effects were determined in-vivo in murine model fed high-fat and high-carbohydrate diets. We found that GTE inhibited the lipid accumulation in 3T3-L1 adipocyte and significantly lowered body weight, body fat-pad weights, blood lipid, glucose, insulin, and leptin levels in mice fed high-fat and high-carbohydrate diets. GTE suppressed the expression of important adipogenic genes (PPARγ, C/EBPα, SREBP, LPL, aP2 and leptin) and lipid metabolism genes (FAS). Furthermore, GTE induced the levels of adiponectin in serum and adipose tissue, as well as AMP-activated protein kinase (AMPK) in liver tissue. These results suggested that GTE ameliorates its anti-obesity effect through multiple cells signaling pathways in diets induced obesity in mice.
研究领域:
药理学
·
营养学
·
分子生物学
✓ 已验证
DOI
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2019
·
IF 2.931
Yao Tian,Zhipeng Zhang,Nan Gao,Pengcheng Huang,Fang–Ying Wu
In this work, a label-free, selective, and sensitive luminescent sensing platform was established for tyrosinase (TYR) activity monitoring and its inhibitor screening using one kind of lanthanide coordination polymer nanoparticles AMP–Tb/Ag + . By taking advantage of the specific binding and redox properties of Ag + incorporated into the AMP–Tb network and dopamine (DA) as the product of the model substrate tyramine , the enzymatic reaction and the signal change of the sensing platform was effectively linked. The cooperative effect of a weakened energy transfer from AMP to Tb 3+ by altering the electronic structure of Ag + and an efficient photoinduced election transfer (PET) process caused by dopaquinone facilitated the luminescence quenching of Tb 3+ . Thus, this luminescent sensing platform could be employed for quantitative evaluation of TYR activity. There was a good linear range for TYR activity from 0.08 to 0.20 U mL − 1 with a low detection limit of 0.004 U mL − 1 . Furthermore, this assay was successfully applied to accurate determination of TYR activity in human serum samples and efficient screening of TYR inhibitors. Considering unique spectral characteristics of lanthanides along with operation simplicity and superior analytical performance, this sensing platform is very promising in clinical diagnosis and drugs screening for TYR–associated diseases.
研究领域:
分析化学
·
生物医学工程
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材料科学
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生物化学
·
临床诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2020
·Vol. 24
·期 5
·3022-3033
·
IF 4.486
Zheng Li,Haihua Feng,Lu Han,Lu Ding,Bingyu Shen,Ye Tian,Lilei Zhao,Meiyu Jin,Qi Wang,Haiyan Qin,Jiaqi Cheng,Guowen Liu
Chicoric acid is polyphenol of natural plant and has a variety of bioactivity. Caused by various kinds of stimulating factors, acute liver injury has high fatality rate. The effect of chicoric acid in acute liver injury induced by Lipopolysaccharide (LPS) and d -galactosamine ( d -GalN) was investigated in this study. The results showed that CA decreased the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum and reduced the mortality induced by LPS/ d -GalN. CA can restrain mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) to alleviate inflammation. Meanwhile, the results indicated CA can active nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway with increasing the level of AMP-activated protein kinase (AMPK). And with the treatment of CA, protein levels of autophagy genes were obvious improved. The results of experiments indicate that CA has protective effect in liver injury, and the activation of AMPK and autophagy may make sense.
研究领域:
药理学
·
肝病学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2016
·Vol. 41
·期 9
·2311-2323
·
IF 2.472
Liu Jie,Su Hua,Qu Qiu-Min
Beta-amyloid (Aβ), the hallmark protein in Alzheimer’s disease (AD), induces neurotoxicity that involves oxidative stress and mitochondrial dysfunction, leading to cell death. Carnosic acid (CA), a polyphenolic diterpene isolated from the herb rosemary ( Rosemarinus officinalis ), was investigated in our study to assess its neuroprotective effect and underlying mechanism against Aβ-induced injury in human neuroblastoma SH-SY5Y cells. We found that CA pretreatment alleviated the Aβ 25–35 -induced loss of cell viability, inhibited both Aβ 1–42 accumulation and tau hyperphosphorylation, reduced reactive oxygen species generation, and maintained the mitochondrial membrane potential. Moreover, CA increased the microtubule-associated protein light chain 3 (LC3)-II/I ratio and decreased SQSTM1(p62), indicating that CA could induce autophagy. Autophagy inhibitor 3-methyladenine (3-MA) attenuated the neuroprotective effect of CA, suggesting that autophagy was involved in the neuroprotection of CA. It was also observed that CA activated AMP-activated protein kinase (AMPK) but inhibited mammalian target of rapamycin (mTOR). Furthermore, blocking AMPK with si-AMPKα successfully inhibited the upregulation of LC3-II/I, prevented the downregulation of phosphorylation of mTOR and SQSTM1(p62), indicating that CA induced autophagy in SH-SY5Y cells via the activation of AMPK. These results suggested that CA might be a potential agent for preventing AD.
研究领域:
神经科学
·
药理学
·
细胞生物学
✓ 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）