PHYTOMEDICINE
·
2024
·
IF 6.7
Majid Manzoor,Danni Chen,Jiahui Lin,Ying Wang,Lan Xiang,Jianhua Qi
Background Hair follicles play a crucial role in hair growth, wound healing, thermoregulation, and sebum production. Hair loss affects millions of people worldwide, yet therapeutic options for managing hair loss and pattern baldness are limited. Isoquercitrin (IQ), a natural small molecule from drinkable Chinese tea, is famous for anti-aging properties. Purpose This study aimed to explore the potential of IQ in treating and preventing hair loss, along with its underlying mechanisms. Methods The adult male and female, as well as middle-aged female sprague dawley (SD) rats were used to conduct hair growth experiments in vivo . Signaling pathways and target protein identification were analyzed through western blotting, drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA) and surface plasmon resonance (SPR) analyses. Further, the targets were confirmed through in vivo inhibition experiments. Results IQ is reported here to stimulate anagen phase initiation and hair regrowth by directly interacting with adenosine 5′-monophosphate-activated protein kinase (AMPK) and insulin-like growth factor 1 receptor (IGF-1R). This process involves the AMPK/mammalian target of rapamycin (mTOR)/ unc-51-like autophagy-activating kinase 1 (ULK1) signalling pathway to trigger autophagy and the IGF-1R/phosphatidylinositol 3-kinase (PI3 K)/protein Kinase B (AKT), vascular endothelial growth factor (VEGF)/ vascular endothelial growth factor receptor (VEGFR)/ angiotensin (ANG) pathways to promote angiogenesis in female rats. Furthermore, the hair regrowth efficacy of IQ in adult male rats and middle-aged female rats was verified and shown. Similarly, our findings indicate that IQ promotes hair regrowth in middle-aged rats through autophagy and angiogenesis, akin to its effects in adult rats. Conclusion AMPK and IGF-1R proteins are identified as the target proteins of IQ and the AMPK/mTOR/ULK1, IGF-1R/PI3K/AKT and VEGF/VEGFR/ANG signalling pathways take important roles in hair growth effect of IQ. Thus, these signaling pathways are crucial for developing future treatments and clinical strategies for hair regeneration.
研究领域:
药理学
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皮肤病学
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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 AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Jing Zhou,Ji Zhang,Jiayi Li,Yiqiu Guan,Ting Shen,Fu Li,Xueqin Li,Xiaojun Yang,Weicheng Hu
Ginsenoside F2 (GF2) is a protopanaxdiol saponin from Panax ginseng leaves and possesses many potential pharmacological properties. GF2 may prevent obesity by directly binding to the peroxisome proliferator-activated receptor-γ (PPARγ) and inhibiting adipocyte differentiation. However, the mechanism by which GF2 alleviates obesity is unknown. We therefore explored the anti-adipogenesis and anti-obesity effects of GF2 in vitro and in vivo. GF2 inhibited differentiation and reduced the triglyceride (TG) content of 3T3-L1 preadipocytes in the early stage of adipogenesis. Administration of GF2 (50 and 100 mg/kg) to obese mice for 4 weeks reduced the body weight gain, weight of adipose tissues, adipocyte size, and total cholesterol, TG, and AST levels in serum. RNA sequencing and real-time quantitative PCR indicated that GF2 decreased the expression levels of adipokines, including PPARγ, fatty acid synthase, and adiponectin. KEGG enrichment and western blot analyses demonstrated that GF2 accelerated the phosphorylation of AMPK and ACC in vitro and in vivo. Moreover, GF2 promoted the biosynthesis of mitochondria in 3T3-L1 adipocytes and increased the expression of antioxidant enzymes such as SOD and GSH-Px in the liver of obese mice. Therefore, GF2 suppressed adipogenesis and obesity by regulating the expression of adipokines and activating the AMPK pathway. Hence, the findings suggest that GF2 may have potential therapeutic implications to treat obesity.
研究领域:
药理学
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分子生物学
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细胞生物学
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代谢
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2021
·
IF 4.451
Jie Gao,Manqian Zhang,Ruixue Niu,Xue Gu,Erwei Hao,Xiaotao Hou,Jiagang Deng,Gang Bai
Nutrients in diets, especially functional foods, are beneficial in metabolism-related diseases, such as diabetes. Cinnamaldehyde (CA), a natural flavorant, inhibits glycolysis while enhancing glucose storage. Kaempferol (KP), a flavonol in edible plants, inhibits amino acid metabolism and gluconeogenesis. Whether the combination of CA and KP exerts stronger effects in diabetes needs further investigation. In this work, nontargeted metabolomics results confirmed the simultaneous obstruction of glucose and amino acid metabolism by CA and KP. The falling status of the energy supply, demonstrated by the increased ratio of adenosine monophosphate (AMP) /adenosine triphosphate (ATP), was sensed by AMP-activated protein kinase (AMPK). The activation of AMPK in turn enhanced lipolysis and inhibited fatty acid synthesis both in vivo and in vitro. In conclusion, this study indicated that the CA and KP combination ameliorated glucose and lipid metabolism disorders by enhancing lipid metabolism via the activation of AMPK.
研究领域:
营养学
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代谢学
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药理学
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产品关联
DOI
高影响因子
ENVIRONMENTAL POLLUTION
·
2022
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IF 9.988
Wenjing Pu,Xuesheng Chu,Huiling Guo,Gang Huang,Ting Cui,Bingyan Huang,Xueyan Dai,Caiying Zhang
Cadmium (Cd) and excess molybdenum (Mo) have multiple organ toxicity, and testis is one of their important target organs, but the reproductive toxicity of Mo and Cd combined treatment is still unclear. To explore the effects of Mo and Cd co-exposure on DNA damage and autophagy from the insight of ATM/AMPK/mTOR axis in duck testes, we randomly assigned 40 healthy 8-day-old ducks to control, Mo (100 mg/kg Mo), Cd (4 mg/kg Cd), and Mo + Cd groups for 16 weeks. Results found that Mo and/or Cd exposure caused trace elements imbalance, oxidative stress with a decrease in the activities of GSH-Px, CAT , T-SOD and GSH content, an increase in the concentrations of H 2 O 2 and MDA and pathological damage. Additionally, Mo and/or Cd markedly raised DNA damage-related factors expression levels and 8-OHdG content, caused G1/S arrest followed by decreasing CDK2 and Cyclin E protein levels and increasing CDK1 and Cyclin B protein levels, and activated ATM/AMPK/mTOR axis by enhancing p-ATM/ATM, p-AMPK/AMPK and reducing p-mTOR/mTOR protein levels, eventually triggered autophagy by elevating LC3A, LC3B, Atg5, Beclin-1 mRNA levels and LC3II/LC3I, Beclin-1 protein levels and reducing P62, Dynein, mTOR mRNA levels and P62 protein level. Moreover, these changes were most apparent in the combined group. Altogether, the results reveal that autophagy caused by Mo and/or Cd may be associated with activating the DNA damage-mediated ATM/AMPK/mTOR axis in duck testes, and Mo and Cd co-exposure exacerbates these changes.
研究领域:
毒理学
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生殖生物学
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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
·
2025
·Vol. 29
·期 8
·e70566
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IF 4.2
Ying‐jie Ren,Tian‐qi Sun,Yu Lu,Dan‐Li Liu,Rui Gao,Ting Li,Min Guo,Qing‐hua Liu,Hai‐long Wang,Min Pang
Chronic obstructive pulmonary disease (COPD) is a widespread lung disease marked by alveolar wall damage, leading to inflammation and fibrosis. Key risk factors include age, smoking, sex, and education, with smoking being the most crucial. These factors are globally consistent and linked with aging. Club cell secretory protein 16 (CC16), primarily secreted by non‐ciliated bronchial epithelial cells, is crucial for pulmonary health, offering anti‐inflammatory and antioxidant benefits. CC16 levels are notably reduced in COPD, suggesting its enhancement as a potential treatment. In this study, cellular senescence of BEAS‐2B cells was stimulated using cigarette smoke extract (CSE) and the function of recombinant human CC16 protein (rhCC16) in cellular senescence was assessed by detecting the levels of β‐galactosidase, p16, p21, ROS and the underlined mechanism was revealed by measuring mitochondrial biogenesis and metabolism. Additionally, COPD mice were prepared, and rhCC16's role on the cellular senescence of lung tissues was examined. Our findings showed that rhCC16 ameliorated cellular senescence in BEAS‐2B cells and lung tissues of COPD mice accompanied by lower levels of β‐galactosidase, p16, p21 and ROS. Mechanically, rhCC16 mitigated senescence via triggering PGC‐1α expression through the AMPK/SIRT1 pathway and fostering mitochondrial biogenesis and metabolism to reduce the levels of ROS. Furthermore, the results also indicated that rhCC16 exerted its effect via both integrin α4β1 and clathrin‐mediated endocytosis. Collectively, rhCC16 suppresses cellular senescence and ameliorates COPD‐like symptoms by activating the AMPK/Sirt1‐PGC‐1‐α‐TFAM pathway to foster mitochondrial function.
研究领域:
医学
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生物学
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呼吸系统疾病
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分子生物学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2020
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IF 4.225
Sun Xiaowei,Wang Dongyan,Zhang Tingting,Lu Xuejian,Duan Fangfang,Ju Lili,Zhuang Xiaotong,Jiang Xicheng
Eugenol, as an active compound isolated from Acorus gramineus, has been shown to protect against cerebral ischemia-reperfusion (I/R) injury. Nonetheless, the detailed neuroprotective mechanisms of eugenol in cerebral I/R injury have not been elaborated. In the present study, cerebral I/R injury model was established by middle cerebral artery occlusion (MCAO) in rats. HT22 cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) to mimic cerebral I/R injury in vitro. The results showed that eugenol pre-treatment relieved cerebral I/R injury as evidenced by improving neurological deficits and reducing infarct volume. Autophagy was induced by MCAO, which was further promoted by eugenol administration. Moreover, rapamycin, an activator of autophagy, promoted eugenol-induced decreases in neurological score, infarct volume, brain water content, and apoptosis. However, pretreatment with 3-MA, an inhibitor of autophagy, led to the opposite results. Similarly, eugenol pretreatment increased the viability and restrained apoptosis of OGD/R-challenged HT22 cells. OGD/R-induced autophagy was strengthened by eugenol. Mechanically, eugenol promoted autophagy through regulating AMPK/mTOR/P70S6K signaling pathway in vivo and in vitro. In conclusion, pretreatment with eugenol attenuated cerebral I/R injury by inducing autophagy via AMPK/mTOR/P70S6K signaling pathway.
研究领域:
神经科学
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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
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
·
2021
·Vol. 85
·期 4
·798-804
·
IF 2.043
Yang Yanfei,Li Yabin,Han Jinli,Wang Yanfen
Gastrodin has shown the potential as an anticonvulsant. Epilepsy is a neurological disease with significant effects in children. In the current study, the therapeutic potential of gastrodin in handling pediatric epilepsy was explored by focusing on the AMPK/PPARα pathway. Three-week-old Sprague–Dawley rats were subjected to lithium-pilocarpine method to induce epileptic symptoms and then administrated with gastrodin. The effects of gastrodin on rats were first assessed using electroencephalogram (EEG) recording, Racine classification, Morris water maze test, and histological staining. The levels of BDNF and NGF, and the activity of AMPK/PPARα were measured. Based on the results of EEG, behavior analyses, and histological staining, epileptic symptoms were significantly alleviated by gastrodin. Moreover, the administration of gastrodin also suppressed the levels of BDNF and NGF, and activated the AMPK/PPARα pathway. In conclusion, our results demonstrated that gastrodin contributed to the alleviation of pediatric epilepsy by activating AMPK/PPARα signaling transduction.
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
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2024
·
IF 3.8
Shuwei Ke,Siyu Zhang,Dongsheng Liu,Tengjiao Zhao,Xiayan Lou,Sunying Cheng,Tingheng Zhu,Hanbing Li
Ectopic olfactory receptors, such as OR1A1, are involved in the regulation of lipid metabolism homeostasis. In this study, we investigated the effects of three monoterpenes, (+)-limonene, (−)-carvone and thymol, upon hepatic lipid deposition. Oral administration of (+)-limonene, (−)-carvone and thymol for 8 weeks in high-fat-diet (HFD)-fed mice significantly lowered the levels of fasting blood glucose, improved glucose intolerance, serum lipid parameters, adiposity, and hepatic steatosis. In LO2 cells, (+)-limonene, (−)-carvone and thymol increased the cyclic adenosine monophosphate (cAMP), induced protein kinase A (PKA) activity and phosphorylation of AMPK, downregulated the expression of SREBP-1 and FASN, and eventually led to a reduction in hepatic lipid deposition. Meanwhile, these beneficial effects in cultured LO2 cells were negated by OR1A1 knockdown and the adenylyl cyclase inhibitor SQ22536, respectively, indicating that they can ameliorate disorders of lipid metabolism through activating OR1A1 and subsequent AMPK/SREBP-1/FASN pathway, indicating OR1A1 as a potential target for counteracting hepatic steatosis.
研究领域:
药理学
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代谢学
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肝病学
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分子生物学
✓ 已验证
DOI
高影响因子
Oxidative Medicine and Cellular Longevity
·
2022
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IF 7.31
Xiaoyu Zhu,Fangze Tao,Li Zhang,Yajie Yu,Yanchao Xu,Gang Yang,Zhifeng Wei,Yidong Cheng,Xuelai Yin,Xinyuan Zhang,Wu Wei,Anxi Wang
Aims. Bladder outlet obstruction (BOO) and the consequent low contractility of detrusor are the leading causes of voiding dysfunction. In this study, we aimed to evaluate the pharmacological activity of astragaloside IV (AS-IV), an antioxidant biomolecule that possess beneficial effect in many organs, on detrusor contractility and bladder wall remodeling process. Methods. Partial BOO (pBOO) was created by urethral occlusion in female rats, followed by oral gavage of different dose of AS-IV or vehicle. Cystometric evaluation and contractility test were performed. Bladder wall sections were used in morphology staining, and bladder tissue lysate was used for ELISA assay. Primary smooth muscle cells (SMCs) derived from detrusor were used for mechanism studies. Results. Seven weeks after pBOO, the bladder compensatory enlarged, and the contractility in response to electrical or chemical stimuli was reduced, while AS-IV treatment reversed this effect dose-dependently. AS-IV also showed beneficial effect on reversing the bladder wall remodeling process, as well as reducing ROS level. In mechanism study, AS-IV activated mitophagy and alleviated oxidative stress via an AMPK-dependent pathway. Conclusion. Out data suggested that AS-IV enhanced the contractility of detrusor and protected the bladder from obstruction induced damage, via enhancing the mitophagy and restoring mitochondria function trough an AMPK-dependent way.
研究领域:
药理学
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泌尿科
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
·
2017
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IF 4.593
Hui Zhou,Baocai Fu,Bo Xu,Xiangquan Mi,Gang Li,Chengjun Ma,Jianxin Xie,Ji Li,Zhenhua Wang
Endothelial dysfunction is the key player in the development and progression of vascular events. Oxidative stress is involved in endothelial injury. Rosmarinic acid (RA) is a natural polyphenol with antioxidative, antiapoptotic, and anti-inflammatory properties. The present study investigates the protective effect of RA on endothelial dysfunction induced by hydrogen peroxide (H2O2). Compared with endothelium-denuded aortic rings, the endothelium significantly alleviated the decrease of vasoconstrictive reactivity to PE and KCl induced by H2O2. H2O2 pretreatment significantly injured the vasodilative reactivity to ACh in endothelium-intact aortic rings in a concentration-dependent manner. RA individual pretreatment had no obvious effect on the vasoconstrictive reaction to PE and KCl, while its cotreatment obviously mitigated the endothelium-dependent relaxation impairments and the oxidative stress induced by H2O2. The RA cotreatment reversed the downregulation of AMPK and eNOS phosphorylation induced by H2O2 in HAEC cells. The pretreatment with the inhibitors of AMPK (compound C) and eNOS (L-NAME) wiped off RA’s beneficial effects. All these results demonstrated that RA attenuated the endothelial dysfunction induced by oxidative stress by activating the AMPK/eNOS pathway.
研究领域:
药理学
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心血管研究
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
·
2020
·Vol. 75
·期 4
·321
·
IF 2.598
Cao Qian,Du Hongjiao,Fu Xi,Duan Na,Liu Changhe,Li Xiaodong
Artemisinin is an endoperoxide sesquiterpene lactone from Artemisia annua L with multiple beneficial effects, including anti-inflammation, antioxidant, and vascular protection. Recent studies have found that inflammation along with autophagy deficiency in macrophages is the possible reason for foam cell accumulation in the intima, which leads to atherosclerotic plaque formation. The primary aims of this study were to explore the inhibiting effect of artemisinin on atherosclerosis in high-fat diet–fed ApoE −/− mice and investigate the probable mechanism. Artemisinin (50 and 100 mg/kg, intragastric administration) treatment effectively inhibited foamy macrophage transformation and decreased atherosclerotic plaque formation in atherosclerotic mice. Moreover, artemisinin promoted AMP-activated protein kinase (AMPK) activation, inhibited mammalian target of rapamycin (mTOR) and uncoordinated-51-like kinase 1 (ULK1) phosphorylation, and increased LC-3II accumulation and P62 degradation, thereby enhancing macrophage autophagy . Besides, the inhibiting effect of artemisinin on mTOR and ULK1 phosphorylation could be abrogated by AMPK knockdown, suggesting AMPK was the essential target of artemisinin on promoting macrophage autophagy . Our study indicated that artemisinin alleviated atherosclerotic lesions by accelerating macrophage autophagy through the AMPK/mTOR/ULK1 pathway.
研究领域:
药理学
·
心血管疾病
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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
·
IF 4.1
Weiliang Guan,Wenqian Nong,Xiaobo Wei,Renchi Chen,Zhihai Huang,Yuting Ding,Xiaoming Qin,Luyun Cai,Linchun Mao
Background Water-free transportation (WFT), as a novel strategy for express delivery of live shrimp ( Litopenaeus vannamei ), was recently developed. However, air exposure during this transportation arouses a series of abiotic stress to the shrimp. In this work, the influences of WFT stress on glycolysis and lipolysis metabolism and meat quality (umami flavor and drip loss) were investigated in comparison with the conventional water transportation (WT). Results Results showed that type II muscle fibers with the feature of anaerobic metabolism were dominated in shrimp flesh. In addition, the increments of intracellular Ca 2+ was detected in WFT and WT, which then activated the AMP-activated protein kinase (AMPK) pathway, and thereby promoted the consumption of glycogen, accumulation of lactate and lipolysis under the enzymolysis of hexokinase (HK), pyruvate kinase (PK), lactate dehydrogenase (LDH), and adipose triglyceride lipase (ATGL). Glycogen glycolyzed to latate. Meanwhile, ATP degraded along with glycolysis resulting in the generation of ATP-related adenosine phosphates such as inosine monophosphate (IMP) with umami flavor and phosphoric acid. More remarkable ( p < 0.05) physiological changes (except LDH and lactate) were observed in WFT compared to WT. Additionally, fatty acid profile also slightly changed. Conclusions The transport stress induced significant energy metabolism changes of shrimp flesh, and therefore effected the flesh quality. The intensifications of freshness (K value) of shrimp flesh were detected due to ATP degradation, which were more pronounced after WFT. However, the drip loss of shrimp flesh was more significantly increased ( p < 0.05) after WFT compared to WT. This article is protected by copyright. All rights reserved.
研究领域:
水产养殖
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生物化学
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代谢
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食品科学
✓ 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）