Heliyon
·
2023
·
IF 4
Xiao-Ping Zhao,Xiao-Li Zheng,Min Huang,Ya-Jia Xie,Xiao-Wen Nie,Ali Adnan Nasim,Xiao-Jun Yao,Xing-Xing Fan
Although some important advances have been achieved in clinical and diagnosis in the past few years, the management of non-small cell lung cancer (NSCLC) is ultimately dissatisfactory due to the low overall cure and survival rates. Epidermal growth factor (EGFR) has been recognized as a carcinogenic driver and is a crucial pharmacological target for NSCLC. DMU-212, an analog of resveratrol, has been reported to have significant inhibitory effects on several types of cancer. However, the effect of DMU-212 on lung cancer remains unclear. Therefore, this study aims to determine the effects and underlying mechanism of DMU-212 on EGFR-mutant NSCLC cells. The data found that the cytotoxicity of DMU-212 on three EGFR-mutant NSCLC cell lines was significantly higher than that of normal lung epithelial cell. Further study showed that DMU-212 can regulate the expression of cell cycle-related proteins including p21 and cyclin B1 to induce G2/M phase arrest in both H1975 and PC9 cells. Moreover, treatment with DMU-212 significantly promoted the activation of AMPK and simultaneously down-regulated the expression of EGFR and the phosphorylation of PI3K, Akt and ERK. In conclusion, our study suggested that DMU-212 inhibited the growth of NSCLCs via targeting of AMPK and EGFR.
研究领域:
肿瘤学
·
分子生物学
·
药理学
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DOI
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Su Zuqing,Zeng Kexue,Feng Bing,Tang Lipeng,Sun Chaoyue,Wang Xieqi,Li Caiyun,Zheng Guangjuan,Zhu Ying
Background: Metabolic syndrome is characterized by central obesity, hyperglycemia and hyperlipidemia. Insulin resistance is the leading risk factor for metabolic syndrome. Kun-Dan decoction (KD), a traditional Chinese medicine, has been applied to treat patients with metabolic syndrome for over ten years. It is increasingly recognized that autophagy deficiency is the key cause of metabolic syndrome. Therefore, we aimed to explore whether KD can activate autophagy to improve metabolic syndrome.Methods: Network pharmacology was used to explore the underlying mechanism of KD in the treatment of metabolic syndrome. The high-fat diet-fed rats and oleic acid-induced LO2 cells were employed in our study. Oral glucose tolerance test and insulin tolerance test, obesity and histological examination, serum cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity in high-fat diet-fed rats were analyzed. Furthermore, the protein expressions of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), phospho-AMPK, mammalian target of rapamycin (mTOR), phospho-mTOR, p62, autophagy related protein (Atg) 5, Atg7, Atg12, Atg13, Atg16L1 and microtubule-associated protein 1A/1B-light chain 3 (LC3)-Ⅱ/Ⅰ were examined in rats and LO2 cells. Moreover, autophagy activator rapamycin and inhibitor 3-methyladenine, and small interfering RNA against Atg7 were utilized to verify the role of autophagy in the treatment of metabolic syndrome by KD in oleic acid-induced LO2 cells.Results: Results from network pharmacology indicated that targeted insulin resistance might be the critical mechanism of KD in the treatment of metabolic syndrome. We found that KD significantly suppressed obesity, serum cholesterol, triglyceride and LDL-C levels and increased serum HDL-C level in high-fat diet-fed rats. Furthermore, KD enhanced insulin sensitivity and attenuated HOMA-IR in high-fat diet-fed rats. Western blot showed that KD could enhance autophagy to increase the insulin sensitivity of high-fat diet-fed rats and oleic acid-induced LO2 cells. Furthermore, 3-methyladenine and small interfering RNA against Atg7 could reverse the protective effect of KD on LO2 cells. However, rapamycin could cooperate with KD to enhance autophagic activation to increase insulin sensitivity in LO2 cells.Conclusion: The induction of autophagy may be the major mechanism for KD to improve insulin resistance and metabolic syndrome.
研究领域:
药理学
·
内分泌学
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产品关联
DOI
PubMed
高影响因子
Cardiovascular Diagnosis and Therapy
·
2024
·Vol. 14
·期 4
·576
·
IF 2.1
Meili Zhu,Jiangbiao Hu,Yifan Pan,Qian Jiang,Chang Shu
Background Heart failure (HF) remains one of the most common events in the progression of hypertension. Magnoflorine (MNF) has been shown beneficial effects on the cardiovascular system. However, the action of MNF on angiotensin (Ang) II-induced cardiac remodeling and its underlying mechanisms have not yet been characterised. Here, we assessed the action of MNF in the development of hypertension-related HF. Methods C57BL/6 male mice were subjected to Ang II through a micro-osmotic pump infusion continuously for 4 weeks to induce hypertensive HF. MNF (10 and 20 mg/kg) was administered in the final 2 weeks. Ang II content was measured by enzyme-linked immunosorbent assay (ELISA) kit. Values of ejection fraction (EF) and fractional shortening (FS) were detected using an ultrasound diagnostic instrument. The mRNA levels of hypertrophic and fibrotic genes were determined by real-time quantitative polymerase chain reaction (RT-qPCR). Haematoxylin and eosin (H&E), wheat germ agglutinin (WGA), Masson trichrome, and Sirius Red staining were used to analyse pathologic changes in heart tissues. The expression levels of phosphorylated AMP-activated protein kinase (AMPK), light chain 3 microtubule associated protein II (LC3 II) to LC3 I, and p62 were detected by western blot assay. Results MNF significantly improved cardiac dysfunction and the content of creatine kinase-MB without altering blood pressure in Ang II-challenged mice. MNF obviously corrected the phenotypes of cardiac hypertrophy and fibrosis, including the high mRNA levels of atrial natriuretic peptide ( Anp ), brain natriuretic peptide ( Bnp ), collagen1a ( Col1a1 ), transforming growth factor beta ( Tgfb1 ), enlarged myocardial areas, and increased positive areas of Masson trichrome and Sirius Red staining. In addition, MNF alleviated oxidative injury, reflected by the upregulation of glutathione and the downregulation of reactive oxygen species and malondialdehyde. The activation of AMPK was elevated accompanied by an increased level of autophagy by MNF in hypertensive heart tissues. The therapeutic action of MNF was confirmed in Ang II-challenged H9c2 cells. Specifically, the AMPK inhibitor could eliminate the autophagy pathway in which MNF is involved. Conclusions MNF has benefits in hypertension-induced cardiac remodeling, which was partially associated with the improvement of oxidative stress via the mediation of the AMPK/autophagy axis.
研究领域:
心脏病学
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药理学
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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 ETHNOPHARMACOLOGY
·
2022
·
IF 5.195
Zuqing Su,Hongxia Li,Zeting Ye,Ying Zhu,Bing Feng,Lipeng Tang,Guangjuan Zheng
Ethnopharmacological relevance Qidan Tiaozhi capsule (QD), a traditional Chinese medicine , has been used to treat metabolic syndrome for over a decade. However, the mechanism of QD in the treatment of metabolic syndrome is still unknown. Aim of the study Growing studies demonstrate that impaired mitophagy is one of the important causes of metabolic syndrome. Thus, this research aims to investigate the mechanism of mitophagy in the QD treatment of metabolic syndrome. Materials and methods Network pharmacology and molecular docking were used to probe the mechanism of QD treatment of metabolic syndrome. In an oleic acid-induced cell model, glucose consumption and uptake capacity, triglyceride (TG), total cholesterol (TC), malonaldehyde (MDA), superoxide dismutase (SOD) and ROS levels, and mitochondrial membrane potential (MMP) were examined. mRFP-GFP-LC3 adenovirus and GFP-LC3 lentivirus were used to examine the effect of QD on mitophagy. The IRS2-PI3K and AMPK/PINK1-Parkin signal pathways were also determined. What's more, the PINK1 gene was silenced to verify the above findings. In a high-fat diet-fed mouse model, body weight, organ indexes, OGTT, ITT, HOMA-IR, insulin sensitivity, serum MDA, SOD, TC, TG, LDL-C and HDL-C, hepatic TC, TG, LDL-C and HDL-C levels, hepatic steatosis , and IRS2-PI3K and AMPK/PINK1-Parkin signal pathways were investigated. Results Results from network pharmacology and molecular docking suggested that QD might suppress oxidative stress to improve metabolic syndrome. In an oleic acid-induced cell model, compared with the model group, enhanced glucose consumption and uptake ability, inhibited intracellular lipid accumulation, TC, TG, MDA and ROS levels, and increased SOD level and MMP were found in QD groups. And mitophagy levels, IRS2-PI3K and AMPK/PINK1-Parkin signal pathways were promoted. Interestingly, PINK1 silencing reversed the therapeutic action of QD on oleic acid-induced cells. In high-fat diet-fed mice, inhibited body weight, abdominal fat indexes, liver indexes, HOMA-IR, serum and hepatic TC, TG and LDL-C, serum MDA and hepatic steatosis, and increased insulin sensitivity, serum and hepatic HDL-C, serum SOD, and activated IRS2-PI3K and AMPK/PINK1-Parkin signal pathways were found in QD groups. Conclusion QD activates AMPK/PINK1-Parkin-mediated mitophagy to suppress oxidative stress to treat metabolic syndrome.
研究领域:
民族药理学
·
代谢生物学
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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 CELLULAR AND MOLECULAR MEDICINE
·
2018
·Vol. 22
·期 7
·3514-3525
·
IF 4.302
Wenhui Cui,Zhihui Zhang,Panpan Zhang,Jiao Qu,Cheng Zheng,Xiaoting Mo,Wencheng Zhou,Liang Xu,Hongwei Yao,Jian Gao
Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and abnormal inflammatory response. Wnt/β-catenin and AMP-activated protein kinase (AMPK) have been shown to modulate lung inflammatory responses and injury. However, it remains elusive whether Wnt/β-catenin and AMPK modulate nuclear factor erythroid-2 related factor-2 (Nrf2)-mediated protective responses during the development of emphysema. Here we showed that treatment with a Wnt pathway activator (LiCl) reduced elastase-induced airspace enlargement and cigarette smoke extract (CSE)-induced lung inflammatory responses in WT mice, which was associated with increased activation of Nrf2 pathway. Interestingly, these effects of LiCl were not observed in Nrf2 −/− mice exposed to elastase. In normal human bronchial epithelial (NHBE) cells, Wnt3a overexpression up-regulated, whereas Wnt3a knockdown further down-regulated the levels of Nrf2 and its target proteins heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) by CSE treatment. In contrast, Nrf2 deficiency did not have any effects on Wnt/β-catenin pathway in mouse lungs and NHBE cells. Both elastase and CSE exposures reduced AMPK phosphorylation. A specific AMPK activator metformin increased Wnt3a, β-catenin, Nrf2 phosphorylation and activation but reduced the levels of IL-6 and IL-8 in NHBE cells and mouse lungs exposed to CSE. Furthermore, Nrf2 deficiency abolished the protection of metformin against CSE-induced increase in IL-6 and IL-8 in NHBE cells. In conclusion, Nrf2 mediates the protective effects of both Wnt3a/β-catenin and AMPK on lung inflammatory responses during the development of COPD/emphysema. These findings provide potential therapeutic targets for the intervention of COPD/emphysema.
研究领域:
医学
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分子生物学
·
药理学
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DOI
PubMed
高影响因子
CELL BIOCHEMISTRY AND BIOPHYSICS
·
2024
·
IF 1.8
Tu Jia,Liu Qiaoling,Sun Huirong,Gan Luzhen
Diabetic cardiomyopathy (DCM) is a prevalent complication of diabetes mellitus characterized by cardiac dysfunction and myocardial remodeling. Farrerol (FA), an active ingredient in Rhododendron with various pharmacological activities, has an unclear specific role in DCM. Therefore, this study aims to investigate the effects of FA on DCM rats and elucidate its mechanism. The type 2 diabetes mellitus (T2DM) model was induced in adult male Sprague-Dawley rats by administering a high-fat diet for 8 weeks along with STZ injection. Subsequent to successful modeling, FA and the positive drug Dapagliflozin (Dapa) were orally administered via gavage for an additional 8-week period. After administration, the rats’ body weight, fasting blood glucose, fasting insulin, and blood lipid profiles were quantified. Cardiac function was assessed through evaluation of cardiac function parameters, histopathological examination and measurement of myocardial enzyme markers were conducted to assess myocardial injury and fibrosis, Oil red O staining was utilized to evaluate myocardial lipid accumulation, wheat germ agglutinin (WGA) staining was used for assessing cardiomyocyte hypertrophy, and Western blot analysis was used to detect the proteins expression level of AMP-activated protein kinase (AMPK) pathway. The rat cardiomyocyte H9c2 were induced with palmitic acid to establish an in vitro cell model of myocardial lipid toxicity. Subsequently, the cells were subjected to treatment with FA and AMPK inhibitor Compound C, followed by assessment of lipid formation and expression levels of proteins related to the AMPK signaling pathway. The findings demonstrated that both FA and Dapa exhibited efficacy in ameliorating diabetic symptoms, cardiac dysfunction, myocardial fibrosis, cardiomyocyte hypertrophy, and lipid accumulation in T2DM rats. Additionally, they were found to enhance AMPK phosphorylation and PPARα expression while down-regulating CD36. Similarly, FA was observed to inhibit lipid formation in H9c2 and activate the AMPK signaling pathway. However, the improved effect of FA on lipotoxic cardiomyocytes induced by palmitic acid was partially reversed by Compound C. Therefore, the activation of the AMPK signaling pathway by FA may enhance cardiac lipid metabolism, thereby improving cardiac dysfunction and myocardial fibrosis in DCM rats.
研究领域:
药理学
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心脏病学
·
内分泌学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2022
·
IF 6.59
Wang Chenlei,Yan Xinlei,Bai Yanping,Sun Lina,Zhao Lihua,Jin Ye,Su Lin
Sunit sheep are famous for their high meat quality, but the meat quality of them has declined due to the change in feeding methods. Lactobacillus has a variety of probiotic effects and is widely used in animal diets to optimize meat quality. This study aimed to investigate the effect of dietary supplementation with different levels of Lactobacillus on meat quality. A total of 24 3-month-old Sunit sheep with an average body weight of 19.03 ± 3.67 kg were randomly divided into control (C), 1% (L1), 2% (L2), and 3% Lactobacillus groups (L3), with 6 sheep in each group. Myofiber characteristics, meat quality, and metabolic enzyme activity were detected. Moreover, the regulatory mechanism of Lactobacillus on meat quality was explored by using Western blotting and real-time Quantitative polymerase chain reaction (RT-qPCR). The results showed that dietary addition of Lactobacillus decreased LDH activity in the Biceps femoris of Sunit sheep (P < 0.05). Compared to the other groups, the 1% Lactobacillus group showed the conversion of myofibers from the glycolytic to the oxidative type, and the increasing b* values (P < 0.05), decreasing shear force and cooking loss of meat (P < 0.05) and the relative gene and protein expression levels of AMPK, PGC-1α, NRF1, TFAM, and COX IV (P < 0.05) in the Biceps femoris were also increased in the 1% Lactobacillus group. Therefore, the addition of Lactobacillus to the diet of Sunit sheep could regulate the AMPK signaling pathway to promote myofiber type conversion, which improves meat quality. This study provided a theoretical and data basis for improving the meat quality of sheep and supplied a novel way of applying Lactobacillus.
研究领域:
动物科学
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营养学
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分子生物学
·
肉类科学
✓ 已验证
DOI
PubMed
高影响因子
World Journal of Diabetes
·
2024
·Vol. 15
·期 12
·2338
·
IF 4.2
Lu-Sha Cen,Yi Cao,Yi-Mai Zhou,Jing Guo,Jing-Wen Xue
BACKGROUND Shikonin is a natural remedy that is effective at treating diabetic wounds. NFAT5 is a potential therapeutic target for diabetes, and mitochondrial function is essential for wound healing. However, the relationship among Shikonin, NFAT5, and mitochondrial function has not been thoroughly studied. Here, we offer new perspectives on the advantages of shikonin for managing diabetes. AIM To assess the therapeutic mechanism of shikonin in diabetic wounds, its relationship with NFAT5, and its protection of mitochondrial function. METHODS Hypertonic cell and diabetic wound mouse models were established. NFAT5 expression was measured through western blotting and immunofluorescence, in vivo and in vitro . Mitochondrial function was evaluated using reactive oxygen species (ROS) detection and JC-1 and Calcein AM dyes. Mitochondrial structures were observed using transmission electron microscopy. The NFAT5/AMPK pathway was analyzed using a transfection vector and an inhibitor. The effect of shikonin on cells under hypertonic conditions via the NFAT5/AMPK pathway was assessed using western blotting. RESULTS Shikonin treatment preserved HaCaT cell viability, while significantly reducing cyclooxygenase-2 expression levels in a high-glucose environment ( P < 0.05). Additionally, shikonin maintained mitochondrial morphology, enhanced membrane potential, reduced membrane permeability, and decreased ROS levels in HaCaT cells under hyperosmolar stress. Furthermore, shikonin promoted wound healing in diabetic mice ( P < 0.05). Shikonin also inhibited NFAT5, in vivo and in vitro ( P < 0.05). Shikonin treatment reduced NFAT5 expression levels, subsequently inhibiting AMPK expression in vitro ( P < 0.05). Finally, shikonin inhibited several key downstream molecules of the NFAT5/AMPK pathway, including mammalian target of rapamycin, protein kinase B, nuclear factor kappa-light-chain-enhancer of activated B cells, and inducible nitric oxide synthase ( P < 0.05). CONCLUSION Shikonin protects mitochondria via the NFAT5/AMPK-related pathway and enhances wound healing in diabetes.
研究领域:
药理学
·
内分泌学
·
细胞生物学
·
分子生物学
·
糖尿病研究
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产品关联
DOI
PubMed
高影响因子
International Journal of Endocrinology
·
2025
·Vol. 2025
·期 1
·4473803
·
IF 2.3
Song Xue,Wei Fan,Qingping Li,Hong Huang,Yibo Tang,Min Wu
Background: This study aimed to investigate the potential mechanisms of puerarin in alleviating diabetic nephropathy (DKD) in mice. Method: The DKD model was induced by multiple low-dose injections of streptozotocin (STZ) and a high-sugar and high-fat diet in male C57BL/6J mice. After confirming the onset of DKD, mice were given irbesartan, distilled water, or different concentrations of puerarin (40 and 80 mg/kg/d) by gavage for 8 weeks. HE staining and PAS staining were adopted to assess the pathological changes in the kidney tissues. Meanwhile, the levels of superoxide dismutase, catalase, creatinine, and cystatin C in the serum and the urine albumin and creatinine were measured, and the renal indices as well as the urinary albumin-to-creatinine ratio (UACR) were calculated. The changes of podocin and protein expression levels associated with AMPK/Nrf2 signaling pathway were evaluated by western blot. Results: Puerarin significantly reduced the level of fasting blood glucose, renal index, glomerular mesangial expansion index, renal function, and oxidative stress induced by STZ ( p < 0.05). The pathological injuries in kidney tissues were also alleviated. Furthermore, we demonstrated that the expression level of podocin and protein related to the AMPK/Nrf2 signaling pathway was also decreased significantly by the treatment of puerarin. At the same time, the efficacy of puerarin in the treatment of DKD was better than that of irbesartan, and the treatment effect of the high-dose group (80 mg/kg/d) was also significantly better than that of the low-dose group (40 mg/kg/d). Conclusion: Puerarin could attenuate the severity of DKD and protect the podocyte in mice in a dose-dependent way. Also, it might be performed by regulating the AMPK/Nrf2 pathway. These findings may provide a theoretical basis for updating the clinical management of DKD.
研究领域:
医学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Xiaohan Li,Yue Zhang,Chunxiao Yu,Xu Guo,Xiangxiang Fu,Shiqi Chen,Yanguo Gao,Yu Zhang,Qin Xiang,Wei Lu,Yonghong Zhang,Qibin Wang,Li Chen,Tao Zheng
Background Scrophularia ningpoensis Hemsl. (SN) is a traditional herbal medicine used for treating diabetes mellitus (DM). Previous studies indicated that the aqueous extract of SN (AESN) improves type 2 DM (T2DM) by activating AMPK, but the active components were unclear. Purpose This study aimed to identify the compound in AESN responsible for AMPK activation and to verify its therapeutic effects on T2DM. Methods Rats were administered AESN intragastrically. The absorbed compounds in serum samples were analyzed using LC-MS/MS and subjected to molecular docking with AMPK. The compound with the highest docking score was further verified using SPR, CETSA, and TR-FRET to confirm its effects on AMPK activation. Primary mouse hepatocytes were used to examine the effects of ANC on AMPK activity, Akt/GSK3β signaling, NLRP3 inflammasome activation, and lipid accumulation. An AMPK inhibitor was used to determine whether the effects were AMPK-dependent. In type 2 diabetic db/db mice, various dosages of ANC were administered intragastrically to observe its therapeutic effects. Results Among the 17 absorbed prototype compounds, ANC exhibited the strongest binding ability to AMPK. SPR, CETSA, and TR-FRET assays confirmed that ANC binds to and activates AMPK. In hepatocytes, ANC activated the Akt/GSK3β signaling, suppressed NLRP3 inflammasome activation, and inhibited lipid accumulation in an AMPK-dependent manner. In db/db mice, ANC intervention improved glucose and lipid metabolic disorders, insulin resistance, and histopathological abnormalities in a dose-dependent manner, while activating AMPK and alleviating lipid metabolic disorders and metabolic inflammatory responses. Conclusion ANC can treat T2DM by directly binding to and activating AMPK.
研究领域:
药理学
·
代谢病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
·
2025
·
IF 4.9
Min Jia,Hao Yue,Xiuxiu Wang,Aizhen Zong,Tongcheng Xu,Yong-Jiang Xu,Yuanfa Liu
Medium-chain triacylglycerol (MCT) is a healthy lipid mainly composed of medium-chain fatty acids (MCFA), which has been proven to have physiological activities in improving metabolic disorders, reducing blood cholesterol, and controlling weight. Brown adipose tissue (BAT) has been regarded as a potential organ to fight obesity due to the function of thermogenesis and energy dissipation. Previous reports found that a diet rich in MCT contributed to the activation of BAT. However, the potential mechanism between MCT and BAT remains unknown. In the current study, MCFA was applied on C3H/10T1/2 cells differentiated brown adipocytes, and MCT was applied on high-fat diet (HFD) induced obese mice. The results showed that MCFA and MCT induced browning of adipocytes and activation of BAT, significantly increased the enrichment of mitochondria, and significantly reduced intracellular lipid accumulation and body weights in vivo and in vitro . Mechanically, MCT significantly increased the level of UCP1, AMPK, and the downstream signaling factors of Pgc1α and Ulk1 , further significantly elevated the brown differentiation factor of Pparγ . Moreover, The AMPK inhibitor dorsomorphin partially impaired the beneficial effects caused by MCT. In conclusion, this study proved that AMPK is the potential target of MCT to induce BAT activation and provided theoretical evidence for the application of MCT in the future.
研究领域:
营养学
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代谢生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
·
2019
·
IF 5.574
Jin Wen,Bin Xu,Yuchao Sun,Mengqiao Lian,Yanli Li,Yuan Lin,Dapeng Chen,Yunpeng Diao,Marwan Almoiliqy,Li Wang
Intestinal ischemia-reperfusion (I/R) injury is a common pathological process with high clinical morbidity and mortality. Paeoniflorin , a monoterpene glucoside, is found to have diverse health beneficial effects including autophagy modulation, anti-inflammatory, anti-apoptotic, and anti-oxidative effects. Based on our pre-experiments, we proposed that paeoniflorin could ameliorate intestinal I/R injury and restore autophagy through activating LKB1/AMPK signal pathway. Our proposal was verified using rat intestinal I/R model in vivo and intestinal epithelial cell line (IEC-6 cells) hypoxia/reoxygenation (H/R) model in vitro. Our results showed that paeoniflorin pretreatment exerted protective effects in rat intestinal I/R injury by reducing intestinal morphological damage, inflammation, oxidative stress, and apoptosis . Paeoniflorin restored H/R-impaired autophagy flux by up-regulating autophagy-related protein p62/SQSTM1 degradation, LC3II and beclin-1 expression, and autophagosomes synthesis without significantly affecting control IEC-6 cells. Paeoniflorin pretreatment significantly activated LKB1/AMPK signaling pathway by reversing the decreased LKB1 and AMPK phosphorylation without affecting total LKB1 both in vivo and in vitro . LKB1 knockdown reduced AMPK phosphorylation, suppressed LC3II and Beclin-1 level, and decreased the degradation of SQSTM/p62, and the knockdown weakened the effects of paeoniflorin in restoring the impaired autophagy flux in H/R injured IEC-6 cells, suggesting that paeoniflorin mitigated the intestinal I/R-impaired autophagy flux by activating LKB1/AMPK signaling pathway. Our study may provide valuable information for further studies.
研究领域:
药理学
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病理生理学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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