Food & Function
·
2022
·Vol. 13
·期 7
·3946-3956
·
IF 6.317
Zhe Wang,Chunhai Li,Xi He,Kang Xu,Zhipeng Xue,Ting Wang,Zhenshang Xu,Xinli Liu
The effect of Platycodon grandiflorum (PG) on colitis and its underlying mechanism were rarely studied. In this study, Lactobacillus rhamnosus 217-1 was used to ferment PG roots, and the concentrations of platycodin-D, flavonoids, and polyphenols and the DPPH free radical scavenging rate were significantly increased. Treatment with a PG root fermentation broth (PGRFB) could reduce dextran sulfate sodium (DSS) induced ulcerative colitis (UC) in mice. Meanwhile, the PGRFB significantly reduced the content of inflammatory factors in mouse serum and the expression of inflammatory factor mRNA in the intestinal tract, regulated the polarization of M1/M2 macrophages, and increased the expression of tight junction protein mRNA in intestinal epithelial cells. In summary, it was proved that the PGRFB could inhibit the nuclear factor kappa B (NF-κB) signaling pathway and the expression of Nod-like receptor protein 3 (NLRP3) inflammasomes by activating AMP-activated protein kinase (AMPK) and lowering the release of pro-inflammatory cytokines.
研究领域:
药理学
·
免疫学
·
微生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2023
·Vol. 103
·期 5
·2367-2377
·
IF 4.1
Shun Chen,HuiJuan Liu,JiaQi Zhang,BinBin Zhou,XiaoFang He,Tian Wang,Chao Wang
BACKGROUND This study was conducted to investigate the effect of dietary rutin on the meat quality, antioxidant status and mitochondrial structure and function in the breast muscle of heat-stressed broilers. A total of 192 male broilers were randomly assigned into three groups and treated with normal control (CON), heat stress (34 °C, HS), and HS with 500 mg kg −1 rutin supplementation (HS + Rutin), respectively. RESULTS Dietary rutin significantly reversed HS-induced decrease in body weight, average daily feed intake, average daily gain, and feed efficiency. Rutin supplementation attenuated HS-induced impaired meat quality by decreasing the lightness, drip loss at 24 and 48 h, the peak time of free water ( T 22 ) and the peak area ratio of free water ( P 22 ), and increasing the pH 24h and peak area ratio of immobilized water ( P 21 ). Rutin supplementation promoted superoxide dismutase, glutathione peroxidase activities and total antioxidant capacity, and decreased malondialdehyde levels compared with the HS group. Moreover, rutin attenuated HS-induced mitochondrial damage by increasing the mitochondrial DNA copy number and improving mitochondrial morphology. Dietary rutin significantly increased mitochondrial biogenesis-related mRNA (proliferator-activated γ receptor coactivator-1α [PGC-1α], nuclear respiratory factor 1 [NRF1], and mitochondrial transcription factor A [TFAM]) expression via the AMP-activated protein kinase (AMPK) signaling pathway. HS significantly increased mitophagy-related genes and proteins (Parkin, PTEN-induced putative kinase 1 [PINK1], microtubule associated protein light chain 3-II [LC3-II]) expression, and dietary rutin significantly reversed these alterations. CONCLUSION Dietary rutin attenuated the HS-induced decline in meat quality and antioxidant capacity of broilers, which may be related to inhibition of the AMPK/PINK1–Parkin signaling pathway to attenuate mitochondrial damage. © 2023 Society of Chemical Industry.
研究领域:
动物科学
·
营养学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2021
·
IF 4.451
Xian Zheng,Xiao-Gai Zhang,Yao Liu,Li-Ping Zhu,Xiao-Shuang Liang,Hui Jiang,Gao-Feng Shi,Yuan-Yuan Zhao,Zhi-Wei Zhao,Yuan Teng,Ke Pan,Jian Zhang,Zhi-Qi Yin
Arjunolic acid (AA), as the most abundant triterpenoid component in Cyclocarya paliurus (Batal) Iljinskaja, previously displayed delipidating effects in free fatty acid (FFA)-induced HepG2 steatosis cells. However, whether AA still possesses the ameliorative effects on nonalcoholic fatty liver disease (NAFLD) in normal hepatocytes and in vivo remains vacant and the detailed mechanisms are not defined. In vitro , AA dose-dependently alleviated lipid accumulation in FFA-challenged primary hepatocytes without cytotoxicity. In vivo , AA showed pleiotropic benefits, including attenuating adiposity, mitigating hepatic steatosis and inflammation, improving lipid disorders and insulin resistance, and restoring the impaired gut barrier. Mechanically, we found that AA indirectly activated Sirt1/AMPK-modulated lipid metabolism through elevating NAMPT-mediated NAD + level, and triggering autophagy, together mediating the lipid-lowering effects. Collectively, our results convey that AA can substantially mitigate NAFLD via indirectly activating Sirt1/AMPK signaling, inducing autophagy and restoring gut barrier, and will be considered as a promising candidate for NAFLD therapy.
研究领域:
药理学
·
肝病学
·
分子生物学
·
营养学
✓ 已验证
产品关联
DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2018
·
IF 3.457
Li Zhang,Hui-Xia Li,Wu-Si Pan,Farhan Ullah Khan,Cheng Qian,Feng-Rong Qi-Li,Xiaojun Xu
Background and aims Non-alcoholic steatohepatitis (NASH) is the hepatic manifestation of metabolic syndrome and is characterized by steatosis, inflammation, and fibrosis. We aim to characterize the hepatoprotective effects of Leonurine hydrochloride (LH) and the possible pathway in a cell and rodent model of diet-induced steatohepatitis (NASH). Methods For in vitro studies, Palmitic acid (PA) and free fatty acid (FFA) induced HepG2 and HL7702 steatosis cell models were used. For in vivo studies, NASH was induced by feeding mice MCD diet. These mice received either placebo or LH at three different doses (50、100、200 mg/kg/day) for 6 weeks. Histological staining’s, and commercially available kits for ALT and AST and hepatic contents of TG, TC, MDA, SOD, and GSH were used to assess NASH. Furthermore, relative liver protein and gene expression levels were determined by Western Blot and qPCR, respectively. Results After establishing NASH models, LH treatment improved lipid accumulation, hepatic contents of TG, TC, and expression levels of ALT and AST in dose-dependent manner. Also, LH improved MDA, SOD, and GSH expression levels. The results of RT-PCR and Western blotting showed that LH upregulated the expression of AMPK phosphorylation and downregulated SREBP-1c and its target genes expression level. Conclusions Our data reveal the promising role of Leonurine hydrochloride in the prevention and treatment of NASH, in vitro and in vivo . This effect may be partially mediated by the AMPK/SREBP1 pathway. These findings provide a novel therapeutic target for the clinical treatment of NASH.
研究领域:
药理学
·
肝病学
·
代谢性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ONCOLOGY REPORTS
·
2022
·Vol. 48
·期 6
·1-11
·
IF 4.136
Haoran Miao,Hongliang Hui,Huaming Li,Yangui Lin,Dan Li,Min Luo,Bo Jiang,Yiqian Zhang
Current investigations suggest that pigment epithelial‑derived factor (PEDF) can mediate the progression of non‑small cell lung cancer (NSCLC) by regulating autophagy. However, the underlying mechanisms associated with autophagy remain poorly elucidated. The aim of the present study was to investigate the association between the PEDF/adenosine 5'‑monophosphate‑activated protein kinase (AMPK)/Unc‑51 like autophagy‑activated kinase 1 (ULK1) pathway and autophagy in NSCLC. Intracellular autophagy was evaluated using indicators such as the expression and activation of microtubule‑associated protein light chain 3‑I (LC3‑I), LC3‑II and p62, as well as the distribution and number of autophagosomes observed by confocal microscopy. In addition, the activity and proliferative capacity of NSCLC cells under PEDF overexpression was also examined using Cell Counting Kit‑8 and lactate dehydrogenase (LDH) assays, and western blotting (WB) of related proteins. The results revealed that PEDF significantly inhibited NSCLC cell proliferation and viability, and increased LDH release and intercellular adhesion. Furthermore, PEDF suppressed the expression and activation of LC‑3 and reduced the number and distribution of autophagosomes. The PEDF‑induced inhibition of autophagy exhibited a direct association with the suppressed proliferation capacity and cell viability of NSCLC cells. The results of WB showed that NSCLC cells regulated autophagy through the AMPK/ULK1 signaling pathway. PEDF downregulated the AMPK/ULK1 signaling pathway, and AMPK or ULK1 overexpression markedly reduced the inhibitory effect of PEDF on autophagy. In conclusion, PEDF overexpression significantly inhibited the proliferative capacity and cell viability of NSCLC cells, as PEDF exerted an inhibitory function by regulating autophagy in NSCLC cells. Finally, it was demonstrated that autophagy may be suppressed by inhibiting the AMPK/ULK1 signaling pathway, thereby revealing a mechanism of lung cancer progression.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Hongyan Li,Yanzhi Zeng,Guangjun Wang,Kai Zhang,Wangbao Gong,Zhifei Li,Jingjing Tian,Yun Xia,Wenping Xie,Jun Xie,Shouqi Xie,Ermeng Yu
Diets with high carbohydrate (HC) was reported to have influence on appetite and intermediary metabolism in fish. To illustrate whether betaine could improve appetite and glucose-lipid metabolism in aquatic animals, mandarin fish ( Siniperca chuatsi ) were fed with the HC diets with or without betaine for 8 weeks. The results suggested that betaine enhanced feed intake by regulating the hypothalamic appetite genes. The HC diet-induced downregulation of AMPK and appetite genes was also positively correlated with the decreased autophagy genes, suggesting a possible mechanism that AMPK/mTOR signaling might regulate appetite through autophagy. The HC diet remarkably elevated transcriptional levels of genes related to lipogenesis, while betaine alleviated the HC-induced hepatic lipid deposition. Additionally, betaine supplementation tended to store the energy storage as hepatic glycogen. Our findings proposed the possible mechanism for appetite regulation through autophagy via AMPK/mTOR, and demonstrated the feasibility of betaine as an aquafeed additive to regulate appetite and intermediary metabolism in fish.
研究领域:
水产养殖学
·
营养学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular Metabolism
·
2024
·
IF 7
Junyong Wang,Yaping Guo,Yunduan He,Yifan Qin,Xiuling Li,Ling Yang,Kangdong Liu,Li Xiao
Objective Nonalcoholic fatty liver disease (NAFLD) is an emerging public health threat as the most common chronic liver disease worldwide. However, there remains no effective medication to improve NAFLD. G protein-coupled receptors (GPCRs) are the most frequently investigated drug targets family. The Regulator of G protein signaling proteins 14 (RGS14), as an essential negative modulator of GPCR signaling, play important regulatory roles in liver damage and inflammatory responses. However, the role of RGS14 in NAFLD remains largely unclear. Methods and Results In this study, we found that RGS14 was decreased in hepatocytes in NAFLD individuals in a public database. We employed genetic engineering technique to explore the function of RGS14 in NAFLD. We demonstrated that RGS14 overexpression ameliorated lipid accumulation, inflammatory response and liver fibrosis in hepatocytes in vivo and in vitro . Whereas, hepatocyte specific Rgs14 -knockout ( Rgs14 -HKO) exacerbated high fat high cholesterol diet (HFHC) induced NASH. Further molecular experiments demonstrated that RGS14 depended on GDI activity to attenuate HFHC-feeding NASH. More importantly, RGS14 interacted with Guanine nucleotide-binding protein (Gi) alpha 1 and 3 (Giα1/3, gene named GNAI1/3 ), promoting the generation of cAMP and then activating the subsequent AMPK pathways. GNAI1/3 knockdown abolished the protective role of RGS14, indicating that RGS14 binding to Giα1/3 was required for prevention against hepatic steatosis. Conclusions RGS14 plays a protective role in the progression of NAFLD. RGS14-Giα1/3 interaction accelerated the production of cAMP and then activated cAMP-AMPK signaling. Targeting RGS14 or modulating the RGS14-Giα1/3 interaction may be a potential strategy for the treatment of NAFLD in the future.
研究领域:
分子生物学
·
药理学
·
肝病学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELLULAR AND MOLECULAR LIFE SCIENCES
·
2024
·Vol. 81
·期 1
·1-24
·
IF 6.2
Hong Ling,Xiao Shan,Diao Lianghui,Lian Ruochun,Chen Cong,Zeng Yong,Liu Su
Polycystic ovary syndrome (PCOS) is a complex common endocrine disorder affecting women of reproductive age. Ovulatory dysfunction is recognized as a primary infertile factor, however, even when ovulation is medically induced and restored, PCOS patients continue to experience reduced cumulative pregnancy rates and a higher spontaneous miscarriage rate. Hyperandrogenism, a hallmark feature of PCOS, affects ovarian folliculogenesis, endometrial receptivity, and the establishment and maintenance of pregnancy. Decidualization denotes the transformation that the stromal compart of the endometrium must undergo to accommodate pregnancy, driven by the rising progesterone levels and local cAMP production. However, studies on the impact of hyperandrogenism on decidualization are limited. In this study, we observed that primary endometrial stromal cells from women with PCOS exhibit abnormal responses to progesterone during in vitro decidualization. A high concentration of testosterone inhibits human endometrial stromal cells (HESCs) decidualization. RNA-Seq analysis demonstrated that pyruvate dehydrogenase kinase 4 (PDK4) expression was significantly lower in the endometrium of PCOS patients with hyperandrogenism compared to those without hyperandrogenism. We also characterized that the expression of PDK4 is elevated in the endometrium stroma at the mid-secretory phase. Artificial decidualization could enhance PDK4 expression, while downregulation of PDK4 leads to abnormal decidualization both in vivo and in vitro. Mechanistically, testosterone excess inhibits IGFBP1 and PRL expression, followed by phosphorylating of AMPK that stimulates PDK4 expression. Based on co-immunoprecipitation analysis, we observed an interaction between SIRT1 and PDK4, promoting glycolysis to facilitate decidualization. Restrain of AR activation resumes the AMPK/SIRT1/PDK4 pathway suppressed by testosterone excess, indicating that testosterone primarily acts on decidualization through AR stimulation. Androgen excess in the endometrium inhibits decidualization by disrupting the AMPK/SIRT1/PDK4 signaling pathway. These data demonstrate the critical roles of endometrial PDK4 in regulating decidualization and provide valuable information for understanding the underlying mechanism during decidualization.
研究领域:
生殖内分泌学
·
分子生物学
·
细胞生物学
·
内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MEDIATORS OF INFLAMMATION
·
2022
·
IF 4.529
Jieru Han,Wenhao Li,Guangyu Shi,Yunlei Huang,Xutao Sun,Na Sun,Deyou Jiang
Ulcerative colitis (UC) is a complex inflammatory bowel disease (IBD) associated with mitochondrial function. Atractylenolide III (AT III) is a natural product with anti-inflammatory effects. The aim of this work is to investigate the protective effect of AT III on UC and its underlying mechanisms. Herein, dextran sulfate sodium- (DSS-) induced mice and lipopolysaccharide- (LPS-) stimulated intestinal epithelial cells (IEC-6) were employed to mimic UC pathologies in vivo and in vitro. The results showed that in DSS-induced mice, AT III significantly reversed the body weight loss, colon length reduction, disease activity index (DAI) increase, and histological damage. The production of proinflammatory factors and reduction of antioxidants in colitis were suppressed by AT III. In addition, we demonstrated that AT III attenuated the intestinal epithelial barrier destruction and mitochondrial dysfunction induced by DSS, which was similar to the in vitro results in LPS-treated IEC-6 cells. The protein levels of p-AMPK, SIRT1, and PGC-1α along with acetylated PGC-1α were also upregulated by AT III in vivo and in vitro. In conclusion, these findings support that AT III may protect against mitochondrial dysfunction by the activation of the AMPK/SIRT1/PGC-1α signaling pathway during UC development.
研究领域:
药理学
·
免疫学
·
胃肠病学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Science and Human Wellness
·
2022
·
IF 8.022
Xiaoyu Cai,Songxue Wang,Huali Wang,Suwen Liu,Guishan Liu,Huibin Chen,Ji Kang,Hao Wang
The aim of this study was to explore the lipid-lowering effect of naringenin and the underlying mechanism in high-fat-diet-fed SD rats and 3T3-L1 cells. In this study, SD rats were divided into the normal chow diet group (NCD), high fat diet group (HFD), three treatment groups feeding high-fat diet with naringenin (100, 200, 400 mg/kg) for 12 weeks. Results indicated that naringenin treatment decreased total cholesterol (TC), triglyceride (TG) and the non-high-density lipoprotein cholesterol (non-HDL-C) levels in serum. Naringenin also alleviated hepatic steatosis and reduced the adipocyte size in the epididymis in high-fat-diet-induced SD rats. In addition, naringenin (25−75 µg/mL) decrease TG and TC levels in 3T3 mature adipocytes. The molecular mechanism of naringenin in the treatment of obesity were predicted by using network pharmacology. Real-time PCR analysis results showed that naringenin regulated the expression of lipid metabolism genes . Meanwhile, naringenin increased the AMPK (AMP-activated protein kinase) activity and the expression of AMPK phosphorylated protein in 3T3 mature adipocytes. And the inhibitory effect of naringenin on lipid accumulation in 3T3 adipocytes was abolished by Compound C. Molecular docking results indicated that naringenin could bind to AMPK protein. These results indicated naringenin reduced lipid accumulation through AMPK pathway.
研究领域:
药理学
·
分子生物学
·
营养学
·
代谢学
✓ 已验证
产品关联
DOI
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Gai Gao,Jie Zhao,Jing Ding,Shuyan Liu,Yanyan Shen,Changxin Liu,Huifen Ma,Yu Fu,Jiangyan Xu,Yiran Sun,Xiaowei Zhang,Zhenqiang Zhang,Zhishen Xie
Background The occurrence of hyperlipidemia is significantly influenced by lipid synthesis, which is regulated by sterol regulatory element binding proteins (SREBPs), thus the development of drugs that inhibit lipid synthesis has become a popular treatment strategy for hyperlipidemia. Alisol B (ALB), a triterpenoid compound extracted from Alisma , has been reported to ameliorate NASH and slow obesity. However, the effect of ALB on hyperlipidemia and mechanism are unclear. Purpose To examine the therapeutic impact of ALB on hyperlipidemia whether it inhibits SREBPs to reduce lipid synthesis. Study Design HepG2, HL7702 cells, and C57BL/6J were used to explore the effect of ALB on hyperlipidemia and the molecular mechanism in vivo and in vitro . Methods Hyperlipidemia models were established using western diet (WD)-fed mice in vivo and oleic acid (OA)-induced hepatocytes in vitro . Western blot, real-time PCR and other biological methods verified that ALB regulated AMPK/mTOR/SREBPs to inhibit lipid synthesis. Cellular thermal shift assay (CETSA), molecular dynamics (MD), and ultrafiltration-LC/MS analysis were used to evaluate the binding of ALB to VDAC1. Results ALB decreased TC, TG, LDL-c, and increased HDL-c in blood, thereby ameliorating liver damage. Gene set enrichment analysis (GSEA) indicated that ALB inhibited the biosynthesis of cholesterol and fatty acids. Consistently, ALB inhibited the protein expression of n-SREBPs and downstream genes. Mechanistically, the impact of ALB on SREBPs was dependent on the regulation of AMPK/mTOR, thereby impeding the transportation of SREBPs from endoplasmic reticulum to Golgi apparatus. Further investigations indicated that the activation of AMPK by ALB was independent on traditional CAMKK2 and LKB1. Instead, ALB resulted in a decrease in ATP levels and an increase in the ratios of ADP/ATP and AMP/ATP. CETSA, MD, and ultrafiltration-LC/MS analysis indicated that ALB interacted with VDAC1. Molecular docking revealed that ALB directly bound to VDAC1 by forming hydrogen bonds at the amino acid sites S196 and H184 in the ATP-binding region. Importantly, the thermal stabilization of ALB on VDAC1 was compromised when VDAC1 was mutated at S196 and H184, suggesting that these amino acids played a crucial role in the interaction. Conclusion Our findings reveal that VDAC1 serves as the target of ALB, leading to the inhibition of lipid synthesis, presents potential target and candidate drugs for hyperlipidemia.
研究领域:
药理学
·
分子生物学
·
生物化学
·
细胞生物学
·
代谢
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2024
·
IF 4.2
Lanxin Li,Yang Zhang,Zhengqian Chen,Can Xu,Zhongqiu Xu,Haitao Pei,Wei Wang,Ruyong Yao,Cui Hao
Parkinson's disease (PD) is a common age-related neurodegenerative disorder, which may be largely due to the mitochondrial dysfunction and impaired mitophagy. Thus, it is of great importance to seek novel therapeutic strategies for PD targeting mitochondrial function and mitophagy. Cytarabine is a marine-derived antimetabolite used in the treatment of acute leukemia, which is also used in the study of the nervous system. In this study, we found that cytarabine pretreatment significantly inhibited the apoptosis and necrosis in the ROT-induced SH-SY5Y cell PD model and reduced the oxidative stress, as evidenced by the reduced MDA levels and the increased levels of SOD, GSH, and total antioxidant capacity. Cytarabine can also enhance mitochondrial vitality, improve mitochondrial respiratory function, and preserve mitochondrial morphology. Cytarabine also enhanced the expression of the mitophagy-related proteins PINK1, Parkin, VDAC1, and DJ-1, and its actions can be reversed by treatment with AMPK inhibitor - Compound C (CC), suggesting that AMPK activation may be involved in cytarabine-enhanced mitophagy. Furthermore, cytarabine can also ameliorate the motor symptoms in the MPTP-induced PD-like mice model, and attenuate the neuropathy in the substantia nigra (SN) of PD mice, while Compound C antagonized cytarabine's beneficial effects. In summary, marine-derived compound cytarabine could resist neurological damage both in vitro and in vivo by activating AMPK to increase PINK1/Parkin-induced mitophagy, serving as a promising disease modulator for treating neurodegenerative disease.
研究领域:
神经科学
·
药理学
·
细胞生物学
·
神经退行性疾病
✓ 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）