Molecular Medicine Reports
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2020
·Vol. 22
·期 4
·3151-3160
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IF 2.1
Bing‑Feng Guan,Xiao‑Feng Dai,Qi‑Bin Huang,Di Zhao,Jin‑Long Shi,Cheng Chen,Yan Zhu,Fen Ai
Icariside II (ICAII) is a bioflavonoid compound which has demonstrated anti‑oxidative, anti‑inflammatory and anti‑apoptotic biological activities. However, to the best of our knowledge, whether ICAII can alleviate myocardial ischemia and reperfusion injury (MIRI) remains unknown. The aim of the present study was to determine whether ICAII exerted a protective effect on MIRI and to investigate the potential underlying mechanism of action. A rat MIRI model was established by ligation of the left anterior descending coronary artery for 30 min, followed by a 24 h reperfusion. Pretreatment with ICAII with or without a PI3K/AKT inhibitor was administered at the beginning of reperfusion. Morphological and histological analyses were detected using hematoxylin and eosin staining; the infarct size was measured using Evans blue and 2,3,5‑triphenyltetrazolium chloride staining; and plasma levels of lactate dehydrogenase (LDH) and creatine kinase‑myocardial band (CK‑MB) were analyzed using commercialized assay kits. In addition, the cardiac function was evaluated by echocardiography and the levels of cardiomyocyte apoptosis were determined using a TUNEL staining. The protein expression levels of Bax, Bcl‑2, cleaved caspase‑3, interleukin‑6, tumor necrosis factor‑α, PI3K, phosphorylated (p)‑PI3K, AKT and p‑AKT were analyzed using western blotting analysis. ICAII significantly reduced the infarct size, decreased the release of LDH and CK‑MB and improved the cardiac function induced by IR injury. Moreover, ICAII pretreatment significantly inhibited myocardial apoptosis and the inflammatory response. ICAII also upregulated the expression levels of p‑PI3K and p‑AKT. However, the protective effects of ICAII were abolished by an inhibitor (LY294002) of the PI3K/AKT signaling pathway. In conclusion, the findings of the present study suggested that ICAII may mitigate MIRI by activating the PI3K/AKT signaling pathway.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
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.
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Communications Biology
·
2024
·Vol. 7
·期 1
·1-15
·
IF 5.2
Zhang Wen,Cai Shuhui,Qin Lihong,Feng Yaru,Ding Menglei,Luo Zichen,Shan Jinjun,Di Liuqing
Aconiti Lateralis Radix Praeparata ( Fuzi in Chinese) is widely used in the clinical treatment of tumors. This study aims to explore the active fractions and underlying mechanisms of Fuzi in the treatment of non-small cell lung cancer (NSCLC). Fuzi alkaloids (FZA) is prepared and found to inhibit the growth of NSCLC both in vitro and in vivo significantly. A total of 53 alkaloids are identified in FZA by UPLC-Q-TOF-MS. Proteomics experiment show that 238 differentially expressed proteins regulated by FZA are involved in amino acid anabolism, pyrimidine metabolism and PI3K/Akt-mTOR signaling pathway. Metabolomics analyses identify 32 significant differential metabolites which are mainly involved in amino acid metabolism, TCA cycle and other pathways. Multi-omics research combined with molecular biological assays suggest that FZA might regulate glycolysis through PI3K/Akt-mTOR pathway to treat NSCLC. The study lays a foundation for the anti-cancer investigation of Fuzi and provides a possible scientific basis for its clinical application.
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JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Yuewei Lin,Qi He,Baihao Chen,Zuang Li,Chuyi Chen,Wei Deng,Haishan Li,Jiamin Yang,Bin Mai,Zhen Zhang,Dongping Wang,Huizhi Guo,Yongchao Tang,Kai Yuan,Guoye Mo,Liangliang Xu,Yongxian Li,Haibin Wang,Shuncong Zhang
Ethnopharmacological relevance Zuogui Pill (ZGP) is a classic herbal formula in Traditional Chinese Medicine, primarily used to tonify the kidney and replenish essence, and is widely applied in treating various kidney deficiency-related conditions. Over time, ZGP has demonstrated significant efficacy in addressing symptoms such as fatigue, weakness, and soreness of the lower back and knees, which are often caused by kidney deficiency. According to Traditional Chinese Medicine theory, the kidneys govern the bones, meaning that sufficient kidney essence is closely related to bone strength. By nourishing the kidneys and replenishing essence, ZGP helps to increase bone density and improve bone microstructure, making it an important therapeutic option for osteoporosis. Aim of the study To investigate the protective effects of ZGP in iron overload-induced osteoporosis and elucidate its molecular mechanisms through the activation of the Phosphoinositide 3-Kinase (PI3K)/Protein Kinase B (AKT) and Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) pathways, which reduce oxidative stress, inhibit osteoblast apoptosis, and promote osteoblast differentiation and mineralization. Materials and methods An in vivo mouse model of iron overload-induced osteoporosis and an in vitro MC3T3-E1 osteoblast model were used. In vitro experiments involved the use of ZGP containing-serum, along with transcriptomic analysis, Western blot, flow cytometry, TUNEL staining, and immunofluorescence, to assess the effects on oxidative stress, mitochondrial function, and apoptosis. In vivo experiments evaluated the effects of ZGP on bone mass, oxidative stress, and apoptosis using Micro-computed tomography (micro-CT), Hematoxylin and eosin staining (H&E), TUNEL staining, and immunohistochemistry. Results The study found that ZGP containing-serum significantly enhanced the viability of osteoblasts induced by iron overload and reduced apoptosis through the reactive oxygen species (ROS)-mediated Phosphoinositide 3-Kinase (PI3K) / Protein Kinase B (AKT) pathway while mitigating mitochondrial damage. In vivo , micro-computed tomography results showed that ZGP improved bone mass, and decreased ROS and apoptosis, consistent with the in vitro findings. Conclusion ZGP demonstrates significant antioxidant and anti-apoptotic effects in iron overload-induced osteoporosis, primarily through the ROS-mediated PI3K/AKT pathway and by reducing mitochondrial damage. These findings suggest that ZGP may be a promising therapeutic agent for treating osteoporosis associated with iron overload.
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PSYCHONEUROENDOCRINOLOGY
·
2025
·
IF 3.6
Zhaoke Ling,Qingqing Kong,Zhiqiang He,Xin Hao,Ruiyao Liu,Jie Liu,Yushi Wang,Jiao Liu,Wenlong Du,Yi Liu
The pathogenesis of depression is associated with synaptic impairment and dysfunction in autophagy processes. Mendelian randomization (MR) analysis revealed that six GWAS IDs revealed a significant association between Beclin-1 levels and depression risk. Besides, all SNPs had a positive effect on depression risk. Analyzing neurons from depressed individuals using single-cell RNA sequencing (scRNA-seq) uncovered decreased expression of AKT, mTOR, and genes linked to synaptic plasticity. The activation of the PI3K/AKT/mTOR signaling has been demonstrated to control autophagy and have a protective effect on the nervous system. Hydrogen sulfide (H 2 S) is an endogenous gasotransmitter that can potentially treat various neurological disorders by improving neuronal synaptic plasticity. However, whether H 2 S regulates autophagy through PI3K/AKT/mTOR signaling, improves neuronal synaptic plasticity damage, and plays an antidepressant role is unclear. Our current research revealed that the reduction in the expression of p-PI3K, p-AKT, and p-mTOR proteins increase in neuronal autophagy activity and decline synaptic plasticity in mice with depression induced by chronic unpredictable mild stress (CUMS). Treatment with the exogenous hydrogen sulfide donor NaHS for one day and continuous treatment for one week improved the depression-like behaviors in the mice. Compared with those after one day of NaHS treatment, the above protein expression levels were restored and maintained, and the antidepressant effect was more significant after one week of continuous treatment with NaHS. Moreover, the PI3K inhibitor LY294002 was used to demonstrate that NaHS suppresses autophagy through activating the PI3K/AKT/mTOR signaling and ameliorates synaptic plasticity impairments. This study provides novel insights into the antidepressant mechanisms of H 2 S, highlighting its antidepressant therapeutic potential.
研究领域:
神经科学
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分子生物学
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药理学
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PHYTOMEDICINE
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2025
·
IF 8.3
Xinyuan Jiang,Zhiyong Xu,Huan Wang,Jiangnan Zhao,Nueraili Maihemuti,Sujing Jiang,Mingshu Xiao,Kaiyue Zhang,Sibei Liang,Yueli Shi,Kai Wang
Background and purpose : As a malignant tumor characterized by a dismal prognosis and a high mortality rate, non-small cell lung cancer (NSCLC) presents significant challenges in contemporary treatment. These challenges include drug resistance and side effects, which severely hamper the effectiveness of current therapeutic strategies. An increasing number of herbal formulas have been utilized in antitumor therapy, owing to their cost-effectiveness, beneficial efficacy, and additional advantages. FuZhengXiaoJi Decoction (FZXJD), a cancer-treating formula, has been successfully applied in NSCLC clinical treatment, but the underlying mechanism remains elusive. Therefore, this paper integrated multiple analytical methods, including network pharmacology, metabolomics, biological approaches, and molecular docking to clarify how FZXJD suppresses NSCLC. Methods : This study assessed the anti-NSCLC efficacy of FZXJD using in vitro assays and lung cancer xenograft models, and the primary components and potential mechanisms of FZXJD inhibition of NSCLC were identified by high-performance liquid chromatography (HPLC) and network pharmacology. Subsequently, inhibitory mechanisms of FZXJD and its principal effector component oleanolic acid (OA) on NSCLC were explored by molecular docking, as well as biological experiments. Finally, effects of FZXJD on critical metabolic pathways in tumors were further investigated by metabolomics and metabolite enrichment analysis. Results : Inhibition of FZXJD on NSCLC cells was confirmed in vitro experiments. Correspondingly, in vivo experiments revealed that FZXJD impeded tumor progression without obvious toxic side effects. Network pharmacology and molecular docking disclosed that target genes involved in FZXJD’s inhibition of NSCLC were significantly enriched in the PI3K/AKT and ERK/MAPK signaling pathways. Additionally, 14 core genes (HSP90AA1, VEGFA, AKT1, JUN, EGFR, CASP3, ESR1, ERBB2, STAT3, MTOR, SRC, MDM2, CCND1, MAPK3) as well as the main component of the antitumor effect of FZXJD, the OA, were also identified. Biological experiments and molecular docking demonstrated that FZXJD and OA exerted antitumor effects by inhibiting two significant pathways, PI3K/AKT and ERK/MAPK. Metabolomics analysis indicated that FZXJD treatment suppressed glutathione metabolism in vivo. Conclusion FZXJD and its main active ingredient, OA, impede NSCLC progression by inhibiting PI3K/AKT and ERK/MAPK signaling pathways. FZXJD treatment also markedly attenuates glutathione metabolism. This research provides a promising strategy for the application of herbal formulas in NSCLC.
研究领域:
肿瘤学
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中药学
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生物信息学
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药理学
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CURRENT PHARMACEUTICAL DESIGN
·
2025
·Vol. 31
·期 42
·3416-3426
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IF 2.8
Chenguang Yao,Ting Tan,Jiangning Yan,Zijia Zhao,Romina Onintsoa Diarimalala,Junjie Wang,William Wang,Hanluo Li,Jingbiao Liu,Yanhong Wei,Kanghong Hu
ObjectiveTo develop new Anderson-type polyoxometalates (POMs) with high efficiency and low cytotoxicity, and investigate the effects and mechanisms against lung (A549), cervical (Hela), and breast cancer (MCF7) cell lines.MethodsCytotoxicity assessments on Hela, A549, and MCF-7 tumor cells were tested by MTT assay. Antitumor activities of B1 (vanadium-centered, methyl-modified) and B7 (vanadium-centered, hydroxyl-modified) were detected by apoptosis, scratch, and colony formation assay. The antitumor molecular mechanisms were explored by Western blotting.ResultsThis study synthesized and evaluated twelve Anderson-type compounds which were centered with vanadium, chromium, iron, cobalt, nickel, and copper heteroatoms, modified with methyl and hydroxyl at the side chains. Cytotoxicity assessments revealed that compounds B1 and B7 exhibited superior efficacy, with IC50 values of approximately 7 μmol/L of three cell lines. B1 and B7 inhibited proliferation and migration in these cell lines and induced apoptosis in MCF7 and A549 cells. Mechanistic investigations indicated that B1 induces apoptosis in MCF7 cells by inhibiting the AKT signaling pathway and downregulating the expression of apoptosis-related proteins Bcl-2 and Caspase-9.ConclusionNovel Anderson-type POMs B1 (vanadium-centered, methyl-modified) and B7 (vanadium-centered, hydroxyl-modified) exhibited superior efficacy against tumor cells and induced apoptosis via PI3K/AKT pathway, which provides new theoretical avenues for developing POM-mediated antitumor chemotherapeutic medications.
研究领域:
肿瘤学
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药理学
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分子生物学
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无机化学
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转化医学
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细胞生物学
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JOURNAL OF ETHNOPHARMACOLOGY
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2025
·
IF 5.4
Zhengwen Zhang,Zhaojun Wang,Yushun Cui,Min Yao,Jiajian Lu,Mingzhen He,Yulin Feng,JunMao Li
Ethnopharmacological relevance Ainsliaea fragrans Champ. (AFC) , a traditional Chinese medicinal herb with a well-documented history in the management of gynecological disorders, serves as the principal component of several Chinese patent medicines that have demonstrated significant clinical efficacy against cervicitis, endometritis, and pelvic inflammatory disease. However, its specific mechanism of action against cervicitis has not been fully elucidated. Purpose This study aims to determine the therapeutic efficacy and underlying mechanisms of AFC in treating cervicitis, and identifying its key active components. Materials and methods First, an in vivo model of cervicitis was established using a phenolic mucilage solution, while an in vitro LPS induced RAW264.7 cell inflammation model was employed. The therapeutic effects of AFC were evaluated through HE staining, uterine index measurements, RT-qPCR and ELISA. The chemical constituents of AFC were identified using ultra-performance liquid chromatography coupled with UPLC-Q-TOF/MS. Subsequently, cellular metabolomics and network pharmacology were utilized to predict the potential targets, mechanisms, and active components of AFC in treating cervicitis. Finally, the underlying mechanisms and active ingredients were validated using methods such as RT-qPCR, Western blot, and molecular docking. Results Both in vivo and in vitro experiments demonstrated that AFC ameliorated phenol mucilage-induced cervicitis in rats and significantly suppressed the expression of inflammatory factors including IL-6, TNF-α, and IL-1β. UPLC-Q-TOF-MS/MS analysis identified 93 chemical constituents in AFC. Cellular metabolomics revealed 79 differential metabolites, including PGE2 and COX-2, among others. Integrated network pharmacology analysis identified potential targets including IDO1 and COX-2, and enriched signaling pathways such as TLR4 and PI3K/AKT-mTOR. Among the nine candidate compounds screened, luteolin, apigenin, and isorhamnetin ranked as the top three by degree value were hypothesized to be the primary active constituents of AFC against cervicitis. Subsequent experimental validation through RT-qPCR, Western blot, and molecular docking demonstrated that AFC treats cervicitis by modulating the PGE2/COX-2/IDO1-FLG in coordination with the TLR4 and PI3K/AKT-mTOR pathways, with luteolin, apigenin, and isorhamnetin confirmed as the key active compounds. Conclusion AFC exerts its therapeutic effects against cervicitis through coordinated regulation of the PGE2/COX-2/IDO1-FLG in conjunction with the TLR4 and PI3K/AKT-mTOR signaling pathways.
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CARBOHYDRATE POLYMERS
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2025
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IF 12.5
Chaoyu Li,Shengjin Zhou,Siyu Chen,Zhen Xu,Qinbing Xue,Hao Wang,Ting Liu,Wei Chen,Jie Feng,Jingjing Chen,Miao Yu,Bing Wang,Zheng Qi
A novel ginseng polysaccharide (GP-A) was investigated for its immune modulation and anti-tumor effects in an S180 sarcoma mouse model. GP-A, with a molecular weight of 1.121 × 10 4 g/mol, primarily consists of a polysaccharide main chain formed by →4)-α-D-Glc p -(1 → sugar residues, along with 1,3,5-Ara f and 1,5-Ara f side chains. In vivo, GP-A improved immune organ recovery and serum cytokine levels, restoring immune balance by downregulating IL-10 and upregulating TNF-α and IL-6. GP-A enhanced IL-6-mediated PI3K/AKT signaling, promoting splenic immune cell proliferation and activation, thereby improving the host's anti-tumor immune response and inhibiting tumor cell proliferation. Oral administration of GP-A (100, 200, 400 mg/kg) for 10 days significantly reduced tumor size, volume, and weight, with the 400 mg/kg group achieving a 66.52 % tumor inhibition rate (96.91 % in the CTX group). Additionally, GP-A improved gut microbiota dysbiosis induced by the tumor, increasing Lactobacillus abundance while decreasing Alloprevotella and Bacteroides . It also elevated short-chain fatty acid (SCFA) levels, particularly propionate and butyrate, maintaining gut microecological balance. GP-A exhibited milder and safer immune modulation, suggesting its potential as a novel immune modulator for cancer therapy.
研究领域:
免疫学
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肿瘤学
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微生物组学
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中药药理学
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分子生物学
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转化医学
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Natural Product Communications
·
2020
·
IF 0.468
Yang Fu,Peipei Yuan,Yingying Ke,Yangang Cao,Qi Zhang,Ying Hou,Yaxin Wei,Liyuan Gao,Xiaoke Zheng,Weisheng feng
The antihypertensive mechanism was studied of the ethyl acetate fraction of the ethanol extract (EAPF) of Gardenia jasminoides var. radicans Makino (GJRM). GJRM is a fake product of Gardenia jasminoides Ellis (G. jasminoides), but in China’s Henan province, the production of GJRM is much more than G. jasminoides’s, but its traditional usage is as a dye. Gardenia jasminoides can be used to reduce blood pressure and blood glucose levels. The chemical compositions of GJRM and G. jasminoides are similar, and we previously confirmed that GJRM can also reduce blood pressure. Here, we report that the EAPF of GJRM could activate the phosphoinositide 3-kinases (PI3K) pathway in the kidneys of spontaneously hypertensive rats, thus increasing the content of nitric oxide and bradykinin in sera and decreasing endothelin-1 content. EAPF can also decrease the levels of with-no-lysine kinase 1 (WNK1) expression, WNK4 and oxidative stress-responsive kinase 1 messenger ribonucleic acid (mRNA), and Na-K-2Cl cotransporter and sodium chloride cotransporters mRNA and phosphorylation. To investigate the antihypertensive effects of the EAPF of GJRM, 5 monoterpenoids isolated from EAPF were studied for their effects on NRK52e and IMCD3 cells. These compounds inhibited the PI3K-WNK signaling pathway to varying degrees under hypotonic conditions; 4-methoxyrehmapicrogenin had the best effect.
研究领域:
药理学
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分子生物学
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心血管研究
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2026
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IF 6.1
Shaoying Gong,Tianju Yang,Ruoyu Wu,Qinghai Sheng,Tangwei Zhang,Ming Xiao,Miao Wang,Yongxin She,Jing Wang,A.M. Abd El-Aty
Nonylphenol (NP) is known to damage the intestinal epithelial barrier (IEB), although its mechanisms remain unclear. Arabinogalactan (AG) is a natural polysaccharide with intestinal protective properties. This study explored the mechanisms of NP-induced IEB damage and evaluated the protective potential of AG in a Caco-2 cell monolayer model. The results revealed that NP induces inflammation and oxidative stress through the PI3K/AKT/mTOR signaling pathway, thereby inhibiting tight junction (TJ) gene and protein expression and ultimately leading to IEB damage. Conversely, AG enhanced TJ expression and suppressed inflammation and oxidative stress by activating the PI3K/AKT/mTOR signaling pathway, thus alleviating NP-induced IEB damage. This research provides new insights into the molecular mechanisms of NP-induced IEB damage and highlights the potential of AG as a functional food ingredient for promoting intestinal health. Moreover, our study provides a theoretical basis for supporting policies aimed at restricting NP residues in food and offers a potential dietary reference for high-risk populations exposed to NP-contaminated environments.
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Natural Products and Bioprospecting
·
2026
·Vol. 16
·期 1
·13
·
IF 4.9
Mei Mei,Sun Huawei,Zhang Kai,Zhang Feng,Sun Shiqing,Zhang Yu
In this study, a diabetic nephropathy (DN) rat model was established using 2% Streptozocin (STZ) solution, and an in vitro DN model was constructed by stimulating HK-2 cells with 30 mM glucose to investigate the mechanism of Phellodendron amurense Rupr. Polysaccharides (PAP) in ameliorating DN. Results demonstrated that PAP, a neutral homogeneous polysaccharide with molecular weight of 1.98 × 105 Da composed of Rha, GalA, Gal, and D-Xyl, exerted renal protective effects through multiple pathways. It enhanced renal antioxidant capacity and alleviated oxidative damage in DN by upregulating PI3K/AKT pathway-related protein expression. Simultaneously, PAP activated the TGF-β/Smad pathway via Nrf2 to mitigate renal fibrosis symptoms in DN, while inhibiting cellular apoptosis. Furthermore, PAP suppressed renal inflammation through gut microbiota reduction, thereby protecting against renal injury in DN rats. This study reveals that PAP alleviates DN symptoms by modulating gut microbiota, enhancing antioxidant and anti-fibrotic capacities, and inhibiting apoptotic pathways, comprehensively elucidating its multifaceted therapeutic mechanisms against DN. Graphical
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