Frontiers in Pharmacology
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2025
·
IF 4.8
Junxi Liu,Youyun Liu,Feifei Wang,Yonglei Yuan,Hongyu Ma,Liping Qu
Introduction: The root of Paeonia suffruticosa Andrews (P. suffruticosa Andr.), is a traditional Chinese medicine. Numerous studies have shown that it possesses anti-inflammatory, antioxidant, and anti-aging effects due to its rich content of bioactive compounds such as polyphenols and paeonol. Thus, it finds extensively applied in the fields of medicine and cosmetics. However, there are few reports on the photoprotective effects of P. suffruticosa Andr. root bark, this study aims to investigate its research in this area.Methods: This study utilized P. suffruticosa Andr. root bark sourced from Kunming, Yunnan Province, China. The P. suffruticosa Andr. root extract (PSAE) was obtained using AB-8 resin. The photoprotective effect of PSAE was assessed using HaCaT cells, HFF cells, and a 3D Reconstructed Human full T-Skin™ model. Mechanistic investigations were performed using RT-qPCR, WB, IF, H&E staining, Masson’s trichrome staining and IHC staining. Finally, an assessment of the effects on humans was conducted.Results: The total phenolic content in the obtained PSAE was 48.9%. Antioxidant activity studies demonstrated that PSAE effectively inhibits DPPH radicals, superoxide anions, hydroxyl radicals, and ABTS radicals, while also enhancing the inhibition rates of collagenase and hyaluronidase. In vitro studies on photoaging resistance revealed that PSAE significantly reduced the UV-induced increases in reactive oxygen species (ROS) levels and senescence-associated β-galactosidase (SA-β-gal) activity. Mechanistic studies indicated that PSAE suppressed the overexpression of IRS1 and its downstream effectors, including PI3K, AKT, and mTOR induced by UV irradiation. A human efficacy assessment was conducted by evaluating parameters such as transepidermal water loss (TEWL), epidermal moisture content, roughness and elasticity, confirming the efficacy of PSAE in humans.Discussion: In summary, PSAE attenuates UV-induced oxidative damage, genetic damage, and collagen degradation associated with photoaging by modulating the IRS/PI3K/FOXO signaling pathway. This study elucidated the mechanism through which PSAE, thereby providing strong support for its application in cosmetic anti-aging formulations.
研究领域:
医学
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化妆品科学
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细胞生物学
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DOI
PubMed
高影响因子
CELL BIOLOGY INTERNATIONAL
·
2022
·Vol. 46
·期 12
·2220-2231
·
IF 4.473
Maomao Miao,Yang Zhang,Xuping Wang,Shanshan Lei,Xiaowen Huang,Luping Qin,Dan Shou
Diabetic osteoporosis (DOP) is a disorder of bone metabolism induced by multiple mechanisms. Previous studies have revealed that microRNAs (miRNAs) play crucial roles in bone metabolism. MiRNA-144-5p has been proven to participate in the regulation of osteoblast activities; however, its specific mechanism in DOP has not been elucidated. This study investigated whether high glucose (HG) inhibited osteoblasts by regulating miRNA-144-5p. Our results showed that HG inhibited bone formation not only in vivo but also in vitro. We observed that HG severely hindered the migration, proliferation and mineralization of osteoblasts, while miRNA-144-5p was upregulated by way of the cell counting kit-8 assay, wound healing assay, alkaline phosphatase (ALP) activity assay and alizarin red staining. Double luciferase reporter experiments showed that miRNA-144-5p directly targeted insulin receptor substrate 1 (IRS1). The IRS1/AKT signaling pathway is closely related to osteoblasts' migration, proliferation, and mineralization. Silencing miRNA-144-5p promoted the mRNA, and protein expression of IRS1, thereby letting the expression of total AKT down, and then preventing phosphorylation of AKT into the nucleus to regulate migration, proliferation, and mineralization genes of osteoblasts. In conclusion, this study indicated that HG regulated the migration, proliferation, and mineralization of osteoblasts via the miRNA-144-5p/IRS1/AKT axis, which suggested a possible mechanism for DOP pathology.
研究领域:
分子生物学
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内分泌学
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骨代谢
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糖尿病
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Yong-Yu Yang,Jing-Jing Qi,Si-Yi Jiang,Ling Ye
Ethnopharmacological relevance Cortex fraxini (also known as qinpi)—the bark of Fraxinus rhynchophylla Hance (Oleaceae)—is widely used as a Chinese traditional medicinal for its anti-inflammatory and anti-hyperuricemic activities. Aim of the study Obesity-induced insulin resistance (IR) is driving the rising incidence of type 2 diabetes mellitus and is related to pathological adipose tissue remodeling. Esculin, a major active component of Cortex fraxini , has anti-diabetic effects. However, whether esculin improves obesity-induced IR by regulating adipose tissue remodeling is unclear. The aims of the present study were to assess the effects of esculin on obesity-induced IR and to explore the underlying mechanisms. Materials and methods Obese IR C57BL/6J mice were treated with esculin (40 or 80 mg/kg/day) for 4 weeks. Oral glucose tolerance tests were used to assess insulin sensitivity. Histological analyses were performed to analyze the number and size distribution of adipocytes. Glucose uptake was assessed using 2-NBDG. Results Esculin had no effect on body weight gain but reduced fasting blood glucose, improved oral glucose tolerance, and increased insulin sensitivity. Esculin reduced adipocyte size and the expression levels of collagen 4A1 and tumor necrosis factor α and increased the number of adipocytes and the expression of vascular endothelial growth factor A. Esculin promoted the differentiation of 3T3-L1 cells and upregulated the mRNA expression of CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor-γ, activated the insulin receptor substrate 1 (IRS1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, and enhanced the translocation of glucose transporter type 4 (GLUT4) and glucose uptake in adipocytes treated with palmitic acid. Conclusions These data suggest that esculin increases insulin sensitivity by improving adipose tissue remodeling and activating the IRS1/PI3K/AKT/GLUT4 pathway.
研究领域:
药理学
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内分泌学
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代谢
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中药
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DOI
PubMed
高影响因子
Food & Function
·
2017
·Vol. 9
·期 1
·397-406
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IF 3.247
Zhou Yang,Fan Wu,Yanming He,Qiang Zhang,Yuan Zhang,Guangrong Zhou,Hongjie Yang,Ping Zhou
Insulin resistance caused by the overexpression of protein tyrosine phosphatase 1 B (PTP1B) as well as the dephosphorylation of its target is one of the main causes of type 2 diabetes (T2D). A newly discovered proteoglycan, Fudan-Yueyang Ganoderma lucidum (FYGL) extracted from Ganoderma lucidum, was first reported to be capable of competitively inhibiting PTP1B activity in vitro in our previous work. In the present study, we sought to reveal the mechanism of PTP1B inhibition by FYGL at the animal and cellular levels. We found that FYGL can decrease blood glucose, reduce body weight and ameliorate insulin resistance in ob/ob mice. Decrease of PTP1B expression and increase of the phosphorylation of PTP1B targets in the insulin signaling pathway of skeletal muscles were observed. In order to clearly reveal the underlying mechanism of the hypoglycemic effect caused by FYGL, we further investigated the effects of FYGL on the PTP1B-involved insulin signaling pathway in rat myoblast L6 cells. We demonstrated that FYGL had excellent cell permeability by using a confocal laser scanning microscope and a flow cytometer. We found that FYGL had a positive effect on insulin-stimulated glucose uptake by using the 2-deoxyglucose (2-DG) method. FYGL could inhibit PTP1B expression at the mRNA level, phosphorylating insulin receptor substrate-1 (IRS1), as well as activating phosphatidylinositol-3 kinase (PI3K) and protein kinase B (Akt). Finally, FYGL increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and consequently up-regulated the expression of glucose transporter type 4 (GLUT4), promoting GLUT4 transportation to the plasma membrane in PTP1B-transfected L6 cells. Our study provides theoretical evidence for FYGL to be potentially used in T2D management.
研究领域:
药理学
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内分泌学
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分子生物学
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糖尿病研究
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PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2019
·
IF 3.571
Yue Gao,Mingwei Zhang,Ruifen Zhang,Lijun You,Tong Li,Rui Hai Liu
The therapeutic benefits of whole grains on diabetes mellitus have been continuously confirmed by in-depth research. To date, limited studies have investigated the effect of extruded products of whole grains on the insulin signaling pathway in vivo. This study investigated the effects of oral consumption of whole grain extrudate, including 97% brown rice and 3% defatted rice bran (w/w, BRD), on glucose metabolism and the hepatic insulin signaling pathway in C57BL/KsJ-db/db mice. BRD treatment induced a remarkable reduction in blood glucose. Moreover, glucose intolerance and insulin resistance were ameliorated in the BRD-treated group compared with those in the db/db control group. BRD also increased the hepatic glycogen content by reducing the expression and increasing the phosphorylation of glycogen synthase kinase 3β (GSK3β). The activities of glucose-6-phosphatase and phosphoenolpyruvate carboxylase and their respective mRNA expression levels in the liver were simultaneously decreased in the BRD-treated group. BRD also significantly upregulated the expression of phosphatidylinositol 3-kinase (PI3K) and increased the phosphorylation of insulin receptor substrate 1 (IRS1) and protein kinase B (AKT). These results indicate that BRD exhibits antidiabetic potential by activating the IRS1/PI3K/AKT signaling pathway, further regulating the expression of the FOXO1 gene and p-GSK3β protein, thus inhibiting hepatic gluconeogenesis, increasing hepatic glycogen storage, and improving insulin resistance. Therefore, BRD could be used as a functional ingredient to alleviate the symptoms of hyperglycemia.
研究领域:
营养学
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内分泌学
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分子生物学
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PubMed
高影响因子
Journal of Future Foods
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2025
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IF 7.2
Li Zhen,Qian Wang,Huimin Cui,Yifen Wang,Jianxin Cao,Yaping Liu,Hesham R El-Seedi,Guiguang Cheng
Goji ( Lycium barbarum L.) leaves are widely processed as a healthy tea (GT) in China for their multiple biological activities. In this study, different polar segments from GT ethanolic extract were obtained using the liquid-liquid fractionation method. n -Butanol fraction (GN) had the highest antioxidant activity while ethyl acetate fraction (GE) showed the highest inhibitory effect on the α -glucosidase enzyme. The anti-diabetic effect of GE was further investigated in type 2 diabetic mellitus (T2DM) mice. The oral administration of GE (300 or 600 mg/kg) reduced fasting blood glucose (FBG) levels, improved glucose tolerance ability, and ameliorated insulin resistance (IR) in T2DM mice. GE intervention could enhance the cholesterol transportation in the serum in coincidence with decreased total cholesterol, triglyceride levels, and non-esterified fatty acid. Transcriptomic, immunofluorescence and western blotting analysis revealed that GE significantly up-regulated insulin receptor substrate 1 (IRS1), phosphatidylinositol-3-kinase (PI3K), protein kinase B (AKT), glycogen synthesis (GS), and glucose transporter 4 (GLUT4). AMP-activated protein kinases (AMPK)-mediate gluconeogenesis and glycogenolysis, such as phosphoenolpyruvate carboxy kinase (PEPCK) and glucose-6-phosphatase (G6Pase) in the liver and kidney tissues of GE groups were decreased. Thus, GE alleviated the liver, kidney, and pancreatic tissue damage. The phytoconstituents of GE were characterized, and rutin, neochlorogenic acid, and its acylated derivatives have hypoglycemic effects. Furthermore, these findings suggested that Goji tea might be used as a promising hypoglycemic candidate.
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高影响因子
CANCER LETTERS
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2023
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IF 9.7
Xiaosong Wei,Beibei Wang,Zixin Wu,Xiaoming Yang,Yufeng Guo,Yang Yang,Zhiwei Fang,Chengzhi Yi,Liuhui Zhang,Xin Fan,Lirong Zhang,Dongkui Song
One of the most abundant protein-protein interaction domains in the human proteome is the WD40 repeat (WDR) domain. A Gene Expression Omnibus dataset revealed 37 differentially expressed WDR domain genes in bladder cancer (BC). WD repeat domain 54 ( WDR54 ), an upregulated WDR domain gene, was selected for further investigation. Sixty pairs of frozen BC tumor and non-malignant bladder tissues and 83 paraffin-embedded BC tissue specimens were obtained. Loss-/gain-of-function experiments were carried out using BC and xenograft tumor models. WDR54 was overexpressed in BC cells, and its high expression was linked to tumor stage and lymph node metastases in patients. WDR54 contributed to the tumorigenesis and metastasis of BC and impaired its chemosensitivity. WDR54 prevented the degradation and ubiquitination of the mediator of ErbB2-driven cell motility 1 (MEMO1). WDR54 also promoted the interaction between MEMO1 and insulin receptor substrate 1 (IRS1) and activated the IRS1/AKT/β-catenin pathway in BC cells. Particularly, WDR54 depended on MEMO1 to exert its biological functions. Our study demonstrated the relevance of WDR54 in BC and provides insight into the molecular mechanism underlying BC.
研究领域:
癌症生物学
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分子生物学
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细胞生物学
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PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2024
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IF 10.7
Hongliang Li,Yingmeng Hou,Shiyu Jia,Mingqian Tan,Haitao Wang
Fucoxanthin (Fx) has garnered significant interest due to its exceptional biological properties. However, its efficacy in enhancing food quality and human health is contingent upon the solubility of the compound in water and its physicochemical stability. Therefore, nanocarriers must be developed to enhance the stability and biocompatibility of Fx. In this study, oxidized paramylon and Fx self-assembled nanoparticles (Fx-OEP) were prepared via the anti-solvent method, with a loading rate of 82.47 % for Fx. The Fx-OEP exhibited robust storage and photostability. In vitro simulated digestion assays demonstrated that Fx-OEP effectively protected Fx from premature gastric release, while achieving a release efficiency of 72.17 % in the intestinal phase. Fx-OEP has the capacity to scavenge a range of reactive oxygen species (ROS) induced by cellular oxidative stress. Treatment with Fx-OEP resulted in a significant reduction in ROS accumulation in insulin-resistant HepG2 cells, which was attributed to the activation of the nuclear factor E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway. This, in turn, activated insulin receptor substrate 1/glucose transporter type 4 (IRS1/GLUT4), promoting cellular glucose absorption and utilization. These findings indicate the potential of self-assembled nanoparticles based on oxidized paramylon as a new type of nanocarrier for delivering hydrophobic substances.
研究领域:
营养学
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药理学
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分子生物学
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PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2023
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IF 6.1
Mingyuan Cao,Jie Wang,Xueying Jiang,Zhipeng Sun,Liyan Zhao,Guitang Chen
Quinoa is a nutrient-rich pseudocereal with a lower glycemic index and glycemic load. However, its therapeutic potency and underlying mechanism against insulin resistance (IR) have not been fully elucidated. In this work, network pharmacology was applied to screen IR targets and their related pathways. The efficacy and mechanism of black quinoa polyphenols (BQP) on IR improvement were evaluated and uncovered based on the IR model in vitro combined with molecular docking. Ten phenolic constituents of BQP were detected, and the network pharmacology results show that PI3K/Akt pathways are the main pathways in BQP against IR. The in vitro assay proved that BQP increases the glucose consumption and glycogen synthesis via upregulating insulin receptor substrate 1 (IRS1)/PI3K/Akt/glucose transporters (GLUTs) signaling pathways to alleviate IR. Rutin, resveratrol, and catechin show lower binding energy docking with IRS1, PI3K, Akt, and GLUT4 proteins, indicating better interactions. It might be an effective constituent against IR. Hence, BQP could become a potential functional food source for blood glucose management among insulin-resistant people.
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PubMed
高影响因子
JOURNAL OF FOOD SCIENCE
·
2025
·Vol. 90
·期 2
·e70046
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IF 3.4
En-Zhong Chi,Li Wang,Jia-jian Pan,Qiang Zhang,Jiangxiong Zhu,Xin-huai Zhao
This study investigated the structural characteristics and hypoglycemic activity of polysaccharides isolated from Ganpu tea (GPT) in different storage periods. Three polysaccharide fractions (GPTPS1-E2, GPTPS3-E2, and GPTPS5-E2, representing 1, 3, and 5 years of storage, respectively, where GPTPS is Ganpu tea polysaccharides) were extracted and purified from GPT. Chemical composition analysis revealed that all fractions were predominantly acidic polysaccharides with total sugar content exceeding 90%. Monosaccharide composition analysis showed galacturonic acid as the primary component, along with significant amounts of galactose and arabinose. Molecular weight distribution showed that different fractions had distinct distributions, with GPTPS1-E2 and GPTPS3-E2 showing the highest and lowest molecular weights, respectively. Fourier-transform infrared and nuclear magnetic resonance spectroscopy provided insights into the structural characteristics of the polysaccharides. Scanning electron microscopy and X-ray diffraction analyses revealed distinct surface morphologies and crystalline structures. The hypoglycemic activity was evaluated using a Caco-2 cell model, demonstrating potential antidiabetic properties via the IRS1-GLUT2-SGLT1 axis. Comparative analysis revealed that storage time could influence the structural characteristics and hypoglycemic activity of GPTPSs, with a certain storage time generally associated with the transformation of structural characteristics related to hypoglycemic activity and the enhanced hypoglycemic effect. This research contributes to the understanding of GPTPS and their potential applications in functional foods and nutraceuticals.
研究领域:
食品科学
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营养保健品
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生物化学
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药理学
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DOI
PubMed
高影响因子
Foods
·
2025
·Vol. 14
·期 12
·2115
·
IF 5.1
Na Li,Hu Li,Duo Feng,Mengjie Li,Di Han,Tianxin Liu,Jing Wang
The effects of soy protein and whey protein supplementation on glycemic control show inconsistency, and the mechanisms underlying the impact of a high-protein diet on blood glucose regulation remain unclear. This study aimed to explore the impact of a dual-protein (DP) blend comprising soy protein isolate (SPI) and whey protein concentrate (WPC), processed through high-pressure homogenization, on mice with Type 2 diabetes mellitus (T2DM) and its potential mechanisms. In the in vitro experiments, an insulin-resistant (IR) HepG2 cell model was treated with DP, resulting in a significant enhancement of glucose uptake and upregulation of IRS1 and GLUT4 expression. For the in vivo experiments, male C57BL/6J mice were randomly assigned into four groups (n = 6) based on body weight: normal control, T2DM model group, Metformin-treated group, and DP-treated group. Following a 5-week feeding period, Metformin and DP significantly reduced levels of blood sugar, AUC, TC, TG, and LDL-C in T2DM mice. Additionally, TP and ALB levels in the DP group were notably higher in the model group. In the liver and pancreas, DP alleviated histopathological changes and promoted liver glycogen synthesis in T2DM mice. Moreover, the levels of IRS1 and PI3K in the livers of mice in the DP group were significantly higher than those in the model group. Compared with the model groups, DP significantly reduced the expression of CD45 and increased the expression of CD206 in the pancreas of mice. Furthermore, 16S rRNA analysis revealed that DP altered the composition of the gut microbiota in diabetic mice, increasing the relative abundance of Lactobacillus , Parvibacter , and Lactobacillaceae . This suggested that DP could alleviate functional metabolic disorders in the gut and potentially reverse the risk of related complications. In conclusion, soy whey dual-protein may have an effective nutritional therapeutic effect on T2DM mice by regulating lipid metabolism, the INS/IRS1/PI3K signaling pathway, and gut microbiota.
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PubMed
高影响因子
Pharmaceuticals
·
2025
·Vol. 18
·期 6
·817
·
IF 4.8
Luqi Qin,Yixia Zhou,Bei Fan,Jiahuan Zheng,Rao Diao,Jiameng Liu,Fengzhong Wang
Background/Objectives: Endophytes can produce bioactive metabolites similar to their host plants. CM-YJ44 ( Pseudomonas protegens CHA0, 99.24% similarity), an endophyte from Dendrobium officinale , has not yet validated hypoglycemic potential. This study aimed to evaluate its anti-insulin resistance (IR) activity and metabolite profile. Methods: The fermentation broth of CM-YJ44 was separated into three fractions (CM-YJ44-1, -2, and -3) using semi-preparative high-performance liquid chromatography (pre-HPLC). An IR HepG2 cell model was constructed to evaluate their glucose uptake capacity. CM-YJ44-3 was further tested for oxidative stress, inflammatory, and insulin signaling pathway activation. Metabolites in CM-YJ44-3 were preliminarily identified using the Q Exactive Focus LC-MS system (QE), and the dendrobine content was quantified by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Molecular docking was performed to predict the binding affinities between dendrobine and target proteins. Results: Among the three fractions, CM-YJ44-3 significantly reduced nitric oxide (NO) and reactive oxygen species (ROS) levels in IR cells, enhanced glycogen synthesis, upregulated the activities of pyruvate kinase (PK) and hexokinase (HK), and suppressed the expression of inflammatory factors. Its mechanism of action was mainly through activation of the IRS1/PI3K/Akt/GSK3β/GLUT4 signaling pathway. QE analysis preliminarily identified 24 metabolites in CM-YJ44-3. Quantitative analysis by UPLC-MS/MS showed that the dendrobine content was 78.73 ± 4.29 ng/mL. Molecular docking results indicated that dendrobine exhibited binding energies below −5 kcal/mol with multiple target proteins involved in this signaling pathway, suggesting it may be a key bioactive component responsible for the anti-IR effect. Conclusions: This study provides the first evidence of hypoglycemic bioactive metabolite production by strain CM-YJ44, indicating its potential as a novel microbial candidate for alleviating IR.
研究领域:
微生物学
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药理学
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植物学
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生物化学
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PubMed
高影响因子
危险品化学品经营许可证（带存储）