JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Yi Wu,Yilin Ling,Yuqi Yang,Haoxing Long,Linghao Kong,Peiyang Song,Yujie Lu,Wanqiu Zhao,Wei Wang,Jingrong Zhu,Nan Wang
Obesity is a growing global health concern associated with severe metabolic disorders, necessitating the development of safer and more effective therapeutic strategies. Soybean sprout peptides (SSPs), derived from germinated soybeans, are bioactive compounds with potential antiobesity effects. This study aimed to investigate the molecular mechanisms of SSPs through an integrated approach combining network pharmacology, molecular docking, and in vivo experiments. SSP sequences were identified using UPLC-Orbitrap-MS/MS, and their bioactivity was predicted using PeptideRanker. Network pharmacology identified key SSP targets, including AKT1, SRC, STAT3, ESR1, FOS, and NFKB1, which are implicated in the PI3K-Akt and JAK-STAT pathways. Molecular docking validated strong interactions between SSPs and these targets. In vivo, SSP administration significantly reduced body weight gain, abdominal fat accumulation, and serum lipid abnormalities in high-fat-diet-induced obese mice while modulating gut microbiota composition by restoring the Firmicutes-to-Bacteroidetes ratio and reducing pathogenic taxa. Fecal metabolomics revealed that SSP alleviated oxidative stress and improved amino acid metabolism, contributing to its antiobesity effects. These findings suggest that SSP holds promise as a functional food ingredient or nutraceutical for obesity prevention and management.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Zheng-Meng Jiang,Zhi-Yue Fang,Xing Yang,Xing-Xing Ji,Yuan-Yuan Zhao,Bin-Yan Lin,Ze-Bin Weng,E-Hu Liu
Background Dysbiosis of the gut microbiota is pivotal in the development of gastric mucosa injury (GMI). Glycyrrhetinic acid (GA) is a bioactive triterpenoid compound abundantly present in licorice roots. Although GA's potential in mitigating GMI is recognized, its precise mechanism remains elusive, particularly concerning the role of gut microbiota. Purpose This study aimed to explore the protective effects and mechanisms of GA in preventing HCl/ethanol-induced GMI in rats. Results This study demonstrated the protective effects of GA on gastric mucosa, evidenced by enhanced morphology and structure as revealed through H&E staining. Utilizing fecal microbiota transplantation, GA was found to significantly mitigate oxidative damage, inflammation, and expression of apoptosis-related genes in GMI rats by a gut microbiota-dependent mechanism. 16S rRNA sequencing and metabolomics profiling revealed that GA ameliorated HCl/ethanol-triggered intestinal dysbiosis and imbalances in sphingolipid, arginine, and tryptophan metabolism. By promoting the prevalence of Bifidobacterium longum subsp. infantis ( B. infantis ) in the gut microbiota, GA improved metabolic disturbances linked to injury. Furthermore, its action mechanism was related to the inhibition of the Thbs1/PI3K-Akt/p53 signaling pathway. Conclusion The administration of GA improves GMI by mitigating intestinal dysbiosis and fostering colonization of B. infantis . GA offers therapeutic potential for GMI by modulating the Thbs1/PI3K-Akt/p53 pathway, thus alleviating inflammatory responses associated with gut microbiota imbalance.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Nana Gao,Zongyu Huang,Jianjie Xie,Shuang Gao,Biaobiao Wang,Huicong Feng,Cuifen Bao,He Tian,Xia Liu
Ethnopharmacological relevance The Cryptotanshinone (CT) is a kind of Chinese medicine extracted from salvia miltiorrhiza, which has various pharmacological activities and is widely used in the treatment of diseases. Aim of the study The objective is to delve into the mechanism by which cryptotanshinone (CT) exerts its effects on rats with the middle cerebral artery occlusion/reperfusion (MCAO/R) model. Additionally, it aims to further assess the interplay between inflammation and oxidative stress, along with the underlying mechanism of CT's anti-ferroptosis function. Materials and methods We constructed the middle cerebral artery occlusion/reperfusion (MCAO/R) model in rats. The effects of cryptotanshinone (CT) were evaluated using 2,3,5 - triphenyltetrazolium chloride (TTC) staining, behavioral assays, immunofluorescence, hematoxylin - eosin (HE) staining, and Nissl staining. Additionally, in vitro, cell viability was assessed by the Cell Counting Kit - 8 (CCK - 8) assay following experimental dosing. Oxygen - glucose deprivation/oxidation (OGD/R) models were established in PC12 and BV2 cells. Flow cytometry was employed to detect cellular reactive oxygen species (ROS) expression. The activities of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-px), andMitochondrial Membrane Potential Assay Kit with JC-1(JC-1) were measured using biochemical methods. Inflammatory factor levels were determined using enzyme-linked immunosorbent assay (ELISA) kits. Immunoblotting was used to detect the levels of rat phosphatidylinositol 3 - kinase (PI3K), phosphorylated-PI3K (P-PI3K), protein kinase B (AKT), phosphorylated - AKT (P-AKT), nuclear factor erythroid 2related factor 2 (Nrf2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4). Results In rats with the MCAO/R model, CT demonstrated the ability to decrease ROS levels, enhance the activity of glutathione (GSH), mitigate inflammation, augment the activity of glutathione peroxidase 4 (GPX4), inhibit ferroptosis, safeguard neurons, and facilitate the restoration of nerve function. Results from network pharmacology indicated that the action of CT might be mediated via the PI3K/Akt signaling pathway. Simultaneously, in-vivo investigations revealed that CT curbs ferroptosis through the PI3K/AKT/Nrf2 and SLC7A11/GPX4 signaling pathways. Conclusion CT can inhibit ferroptosis by inhibiting the vicious cycle between oxidative stress and inflammation, protect neurons and promote motor function recovery.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL PROLIFERATION
·
2020
·Vol. 53
·期 8
·e12871
·
IF 5.753
Hongping Yu,Pei Liu,Daoyu Zhu,Junhui Yin,Qianhao Yang,Yigang Huang,Yixuan Chen,Changqing Zhang,Youshui Gao
Objectives Osteonecrosis of the femoral head (ONFH), largely caused by alcohol abuse, is a refractory bone disease characterized by the impaired capacity of osteogenic differentiation of bone mesenchymal stem cells (BMSCs), as well as the disordered adipocyte accumulation. Chrysophanic acid (CPA) is a natural anthraquinone which has lipid regulation and bone protection capacity. The aim of this study was to reveal the potential function of CPA and the underlying mechanisms for the alcohol-induced ONFH. Materials and Methods The effects of alcohol and CPA on BMSCs were investigated by cell proliferation, induced differentiation assays and immunofluorescent staining. Meanwhile, the function of PI3K/AKT and AMPK pathway was investigated in the process of osteogenic and adipogenic differentiation, respectively. Furthermore, we established the rat model of alcohol-induced ONFH to reveal the pharmacotherapeutic effect of CPA in vivo using radiographical and histopathological methods. Results In vitro, alcohol significantly inhibited the proliferation and osteogenic differentiation of BMSCs but stimulated the adipogenic differentiation. However, CPA could counteract the anti-osteogenesis of alcohol partly via PI3K/AKT pathway and retard the promotion of alcohol-induced adipogenesis via AMPK pathway. In vivo, radiographical and histopathological findings showed that CPA could alleviate alcohol-induced ONFH and substantially restore the bone volume. Conclusions We demonstrated that CPA ameliorated alcohol-induced ONFH possibly via regulating the differentiation tendency of BMSCs. Hence, CPA may become a beneficial herb extract to alleviate alcohol-induced ONFH.
研究领域:
药理学
·
骨科
·
干细胞研究
✓ 已验证
DOI
PubMed
高影响因子
TISSUE & CELL
·
2022
·
IF 2.586
Xinyan Huang,Songzhao Zhang,Wenxi Wang
Purpose Artesunate (ART) is recognized for its anticancer activity , but a few studies concentrate on its anti-skin cancer effect. This study emphazied this aspect and preliminarily discussed the impact and mechanism of ART on cutaneous squamous cell carcinoma (CSCC). Methods The viability of HaCaT and CSCC cells treated with ART (0, 30, 60, 90, 120, 150, 180, or 210 μmol/L) for 48 h were assessed utilizing cell counting kit-8. Next, the migration, invasion, proliferation, apoptosis, and cell cycle of CSCC cells treated with ART were evaluated by dint of cell function experiments. Then, cell cycle-, apoptosis-, and phosphatidylinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway-related markers were examined via western blot or quantitative real-time PCR. Moreover, the influences of ART and PI3K/AKT agonist IGF-I on CSCC cell biological behaviors were gauged again. Results The suppressive role of ART (30, 60, 90, 120, 150, 180, or 210 μmol/L) was stronger in viability of CSCC cells than in viability of HaCaT cells. ART evidently attenuated the migration, invasion and proliferation, lessened cell numbers at G2/M phase and triggered apoptosis of CSCC cells. At the molecular level, ART regulated cell cycle-, apoptosis-, and PI3K/AKT pathway-related markers in CSCC cells. Moreover, the suppression of ART on CSCC cell malignant phenotypes was reversed by PI3K/AKT agonist IGF-I. Conclusion ART restrains the malignant progression of CSCC, which may be intensely related to the PI3K/AKT pathway repression.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Xujun You,Yongrong Wu,Qixin Li,Wen Sheng,Qing Zhou,Wei Fu
Objective: Prostate cancer (PCa) is an epithelial malignancy of the prostate that currently lacks effective treatment. Traditional Chinese medicine (TCM) can play an anticancer role through regulating the immune system, anti-tumor angiogenesis, regulating tumor cell apoptosis, autophagy dysfunction, and other mechanisms. This study attempted to explore the active ingredients and potential mechanism of action of the Astragalus–Scorpion (A–S) drug pair in PCa, in order to provide new insights into the treatment of PCa. Methods: Network pharmacology was used to analyze the A–S drug pair and PCa targets. Bioinformatics analysis was used to analyze the LncRNAs with significant differences in PCa. The expression of LC3 protein was detected by immunofluorescence. CCK8 was used to detect cell proliferation. The expressions of GDPD4-2, {"type":"entrez-nucleotide","attrs":{"text":"AC144450.1","term_id":"29893803","term_text":"AC144450.1"}} AC144450.1 , LINC01513, AC004009.2, {"type":"entrez-nucleotide","attrs":{"text":"AL096869.1","term_id":"5565922","term_text":"AL096869.1"}} AL096869.1 , {"type":"entrez-nucleotide","attrs":{"text":"AP005210.1","term_id":"21039028","term_text":"AP005210.1"}} AP005210.1 , and {"type":"entrez-nucleotide","attrs":{"text":"BX119924.1","term_id":"27884222","term_text":"BX119924.1"}} BX119924.1 were detected by RT-qPCR. The expression of the PI3K/AKT/mTOR pathway and autophagy-related proteins were detected by western blot. LC-MS/MS was used to identify the active components of Astragalus and Scorpion. Results: A–S drug pair and PCa have a total of 163 targets, which were mainly related to the prostate cancer and PI3K/AKT pathways. A–S drug pair inhibited the formation of PCa, promoted the expression of LC3Ⅱ and Beclin1 proteins, and inhibited the expression of P62 and PI3K–AKT pathway proteins in PCa mice. Astragaloside IV and polypeptide extract from scorpion venom (PESV) were identified as the main active components of the A–S drug pair. GDPD4-2 was involved in the treatment of PCa by Astragaloside IV-PESV. Silencing GDPD4-2 reversed the therapeutic effects of Astragaloside IV-PESV by regulating the PI3K/AKT/mTOR pathway. Conclusion: Astragaloside IV-PESV is the main active components of A–S drug pair treated PCa by regulating the GDPD4-2/PI3K–AKT/mTOR pathway and autophagy.
研究领域:
肿瘤学
·
药理学
·
中医
·
分子生物学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
Phytochemistry Letters
·
2021
·
IF 1.679
Yan Zhao,Yijia Zheng,Xin Chen,Rui Du,Zhaowei Yan
Malignant tumors are increasing the human mortality rate year by year, so there is an urgent need to develop novel and highly effective drugs. Camptothecin (CPT) is a natural medicinal product with broad-spectrum antitumor activity. In this study, 11 CPT derivatives were synthesized. Their antitumor activities were evaluated by CCK-8, morphological observation, plate cloning, scratching, DAPI staining, cell cycle, and apoptosis. The conformational relationships were also analyzed by molecular docking and 3D-QSAR. The results showed that the CPT derivatives showed significant inhibitory effects on all five tumor cell lines, A549, HepG2, MCF-7, HemECs, and PC-3M, with the best inhibitory ability against PC-3M in prostate cancer. Among all derivatives, compound 5 had the lowest IC50 value of 0.0881 μM. In addition, compound 5 regulated the downstream cascade response by inhibiting the PI3K-Akt signaling pathway, causing cycle arrest and apoptosis. The predicted results of molecular docking and 3D-QSAR were consistent with those of the experimental group. This demonstrates the anti-tumor potential of compound 5.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2019
·
IF 3.17
Dong-Shuai Shen,Ya-Jun Yang,Xiao-Jun Kong,Ning Ma,Xi-Wang Liu,Shi-Hong Li,Zeng-Hua Jiao,Zhe Qin,Mei-Zhou Huang,Jian-Yong Li
Aspirin eugenol ester (AEE) was a promising drug candidate for treating inflammation, pain and fever and preventing cardiovascular diseases with fewer side effects than its precursors. Previous researches indicated that AEE could markedly inhibit agonist-induced platelet aggregation in vitro and ex vivo , however, the anti-platelet aggregation mechanisms of AEE remain to be defined. Here, AEE in vitro effects on agonist-induced granule-secretion, intercellular Ca 2+ mobilization and thromboxane A 2 (TXA 2 ) generation were examined. Vasodilator-stimulated phosphoprotein (VASP), mitogen-activated protein kinase (MAPK), Akt, Sirt 1 and CD40L expressions were also studied. In agonist-activated platelets in vitro , AEE markedly attenuated granule secretion markers (P-selectin expression and ATP release), intercellular Ca 2+ mobilization and thromboxane B 2 (TXB 2 ) formation. AEE also attenuated CD40L activation, suppressed extracellular-signal-regulated protein kinase 2 (ERK2), c-Jun N-terminal kinase 1 (JNK1) and Akt phosphorylation, and recovered Sirt1 expression, but the activation of p38, VASP Ser157 and VASP Ser239 , and the levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were not affected by AEE. Overall, this study demonstrates that AEE inhibits agonist-induced platelet aggregation in vitro by regulating PI3K/Akt, MAPK and Sirt 1/CD40L pathways.
研究领域:
药理学
·
心血管疾病
·
分子生物学
·
炎症研究
✓ 已验证
DOI
PubMed
高影响因子
Odontology
·
2023
·
IF 2.5
Cui Zhao,Xu Yunhe,Wu Peng,Lu Ying,Tao Yongxin,Zhou Chuibing,Cui Ruting,Li Jingying,Han Rongpeng
Periodontal tissue regeneration engineering based on human periodontal ligament stem cells (hPDLSCs) provides a broad prospect for the treatment of periodontal disease. N-Acetyltransferase 10 (NAT10)-catalyzed non-histone acetylation is widely involved in physiological or pathophysiological processes. However, its function in hPDLSCs is still missing. hPDLSCs were isolated, purified, and cultured from extracted teeth. Surface markers were detected by flow cytometry. Osteogenic, adipogenic, and chondrogenic differentiation potential was detected by alizarin red staining (ARS), oil red O staining, and Alcian blue staining. Alkaline phosphatase (ALP) activity was assessed by ALP assay. Quantitative real-time PCR (qRT-PCR) and western blot were used to detect the expression of key molecules, such as NAT10, Vascular endothelial growth factor A (VEGFA), PI3K/AKT pathway, as well as bone markers (RUNX2, OCN, OPN). RNA-Binding Protein Immunoprecipitation PCR (RIP-PCR) was used to detect the N4-acetylcytidine (ac4C) mRNA level. Genes related to VEGFA were identified by bioinformatics analysis. NAT10 was highly expressed in the osteogenic differentiation process with enhanced ALP activity and osteogenic capability, and elevated expression of osteogenesis-related markers. The ac4C level and expression of VEGFA were obviously regulated by NAT10 and overexpression of VEGFA also had similar effects to NAT10. The phosphorylation level of PI3K and AKT was also elevated by overexpression of VEGFA. VEGFA could reverse the effects of NAT10 in hPDLSCs. NAT10 enhances the osteogenic development of hPDLSCs via regulation of the VEGFA-mediated PI3K/AKT signaling pathway by ac4C alteration.
研究领域:
干细胞生物学
·
分子生物学
·
再生医学
·
牙科科学
✓ 已验证
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2022
·
IF 2.65
Si-Mai Shao,Kyung Hye Park,Ye Yuan,Zijuan Zhang,Yanwen You,Zhenqiang Zhang,Li Hao
The main characteristic of Alzheimer’s disease (AD) is the progressive decline of learning and memory ability. Electroacupuncture (EA) may improve AD-related learning and memory ability. However, the underlying molecular mechanism of action remains unclear. The objective of the present study was to assess the effects and the molecular mechanism of EA on learning and memory in an amyloid β25-35 (Aβ25-35) induced AD mouse model. The AD model was established by intracerebroventricular (ICV) administration of Aβ25-35 oligomers. AD mice were electroacupunctured with wisdom three-needle combined with Baihui (GV20) five times per week for three consecutive weeks. The Morris water maze (MWM) and Y maze tests were applied to evaluate spatial learning and memory ability. A transmission electron microscope (TEM) was used to measure mitochondria and autophagy of hippocampal neurons, and western blot was applied to observe molecular changes in the mice hippocampus. The results suggested that EA treatment significantly alleviated learning and memory impairment related to AD, reduced mitochondria damage, improved autophagy, increased mitochondrial protein 2 (Mfn2), Beclin 1, and LC3B, and decreased the expressions of fission protein 1 (Fis1) level. Furthermore, EA further upregulated the protein expression of phosphatidylinositol 3-kinase (PI3K) and the ratio of p-Akt/Akt in the hippocampus of AD mice. This study demonstrates that EA treatment attenuates cognitive deficits, modulates mitochondrial fusion and fission, and enhances autophagy via the PI3K/Akt pathway in a mouse AD model.
研究领域:
神经科学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
European Review for Medical and Pharmacological Sciences
·
2018
·
IF 2.387
X. Lv,C.-Y. Li,P. Han,X.-Y. Xu
OBJECTIVE: MicroRNAs are a class of small non-coding RNAs that be involved in the pathogenesis of non-small cell lung cancer (NSCLC). The purpose of this study was to evaluate the effects of miR-520a-3p in cell growth and metastasis.MATERIALS AND METHODS: The mimics and inhibitor of miR-520a-3p were used to identify the effects of miR-520a-3p on cell proliferation and apoptosis using methylthiazol tetrazolium (MTT) assay and flow-cytometric method, respectively. Transwell assay was used to evaluate the cell migration and invasion. The protein expression levels related PI3K/AKT/mTOR signaling pathways were measured by Western blot.RESULTS: The results showed that miR-520a-3p overexpression could significantly inhibit cell proliferation and induce apoptosis, suppress cell migration and invasion. MiR-520a-3p overexpression could markedly reduce the ratio of p-AKT/AKT, p-PI3K/PI3K and Bcl-2/Bax, the levels of mTOR, matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) compared with control. However, miR-520a-3p overexpression could increase caspase-3 expression compared with control group. After inhibited the expression of miR-520a-3p, the capacity of cell proliferation, migration and invasion were increased, cell apoptosis was inhibited compared with control group. The ratio of p-AKT/AKT, p-PI3K/PI3K and Bcl-2/Bax, the levels of mTOR, MMP-2 and MMP-9 were increased compared with control group.CONCLUSIONS: Our study suggested that miR-520a-3p could suppress the NSCLC proliferation, migration and invasion through PI3K/AKT/mTOR signaling pathway.
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
BIOCHEMICAL PHARMACOLOGY
·
2019
·
IF 4.825
Wensong Yao,Zhen Lin,Peiying Shi,Bing Chen,Gang Wang,Jianyong Huang,Yuxia Sui,Qicai Liu,Shaoguang Li,Xinhua Lin,Qicai Liu,Hong Yao
Colorectal cancer (CRC) is one of the most common malignant tumors worldwide and tends to have drug resistance. Delicaflavone (DLF), a novel anticancer agent of biflavonoid from Selaginella doederleinii Hieron , showed strong anti-CRC activities, which has not yet been reported. In this study, we investigated the effects and possible anti-CRC mechanism of DLF in vitro and in vivo . It was shown that DLF significantly inhibited the cells viability and induced G2/M phase arrest, apoptosis , the loss of mitochondrial membrane potential (Δψm), generation of ROS and increase of intracellular Ca 2+ in HT29 and HCT116 cells by MTT assay, TEM, flow cytometry and inverted fluorescence microscope. Western blot and qPCR assays results further confirmed DLF induced caspase-dependent apoptosis and inhibited PI3K/AKT/mTOR and Ras/MEK/Erk signaling pathways in CRC cells. Meanwhile, DLF significantly suppressed the tumor growth via activation of Caspase-9 and Caspase-3 protein and decrease of ki67 and CD34 protein without apparent side effects in vivo . In summary, these results indicated DLF induced ROS-mediated cell cycle arrest and apoptosis through ER stress and mitochondrial pathway accompanying with the inhibition of PI3K/AKT/mTOR and Ras/MEK/Erk signaling cascade. Thus DLF could be a potential therapeutic agent for CRC.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）