JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
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IF 6.2
Xinyuan Wu,Dan Su,Jiaxin Xu,Ge Ge,Yongzhen Zhang,Bingjian Wu,Kun Hu,Jie Ren,Hao Yang
Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder among older adults, significantly impairs behavioral and cognitive functions, posing a severe threat to patients’ health and quality of life. The Tricetin (TRN), a natural flavonoid found in wheat, pomegranate, and eucalyptus honey, has demonstrated anti-inflammatory, antitumor, and neuroprotective properties. However, its role in the context of AD has not been previously explored. This study investigated the antineuroinflammatory and autophagic protective effects of TRN in lipopolysaccharide (LPS)-induced BV2 cells and D-galactose/sodium nitrite/aluminum chloride (D-gal/NaNO2/AlCl3)-induced AD mice. The RNA sequencing examined the underlying mechanisms by which TRN ameliorates AD-related pathologies. Our research findings revealed that TRN significantly improved memory and mobility in AD mice, reduced Aβ deposition, and inhibited Tau protein phosphorylation. Furthermore, TRN regulated enzyme activities and reduced pathological markers associated with AD. Moreover, it modulated inflammatory mediators, inhibited the nuclear translocation of NF-κB in LPS-induced BV2 cells, and exerted anti-inflammatory and autophagic protective effects via the PI3K/Akt/mTOR signaling pathway. In conclusion, TRN demonstrated robust neuroprotective effects in vitro and in vivo AD models by regulating the PI3K/Akt/mTOR signaling pathway. These findings highlight its potential as a promising therapeutic agent for treating AD.
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
CURRENT MEDICINAL CHEMISTRY
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2024
·Vol. 32
·期 33
·7357-7376
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IF 3.5
Jinna Di,Wei Bo,Chun Wang,Chunying Liu
IntroductionThe effectiveness of therapy is strongly impacted by the resistance of lung cancer cells to cisplatin. The objective of this research is to characterize the impact of ailanthone on cisplatin resistance in non-small cell lung cancer (NSCLC) and examine any potential in vivo and in vitro molecular pathways.MethodsFollowing treatment of A549/DDP cells with ailanthone and cisplatin, cell survival and apoptosis were measured using flow cytometry and Cell Counting Kit-8 (CCK8) assays, respectively. mRFP-GFP-LC3 adenovirus transfection was used to track autophagy, and protein expression levels were analyzed by western blotting. Hematoxylin and eosin (H&E) staining was used after the organs of the mice were removed for in vivo investigations. In A549/DDP cells, ailanthone and cisplatin together induced autophagy and apoptosis in a dose and time-dependent manner (p< 0.05). After receiving combined treatment with ailanthone and cisplatin, the expression levels of cleaved caspase-3, Bcl-2, cleaved PARP, Beclin 1, LC3B-II were considerably elevated by inhibiting the PI3K/AKT/mTOR signaling pathway.ResultsOur findings show that ailanthone, without causing adverse effects in vivo, greatly suppressed the growth of A549/DDP-grafted tumors and improved the anti-tumor efficaciousness of cisplatin.ConclusionAccording to this study, ailanthone may increase sensitivity to cisplatin and promote autophagy and death in NSCLC A549/DDP cells through the signaling pathway of PI3K/AKT/mTOR.
研究领域:
肿瘤学
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分子生物学
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药理学
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转化医学
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细胞信号转导
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DOI
高影响因子
Bioengineered
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2021
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IF 3.269
Yingnan Dai,Yeping Chen,Guoqian Wei,Li Zha,Xueqi Li
Ivabradine (Iva), a heart rate reducing agent that specifically inhibits the pacemaker I(f) ionic current, has been demonstrated to be cardioprotective in many cardiovascular diseases. Autophagy is an evolutionarily conserved metabolic process that regulates cardiac homeostasis. This study is aimed to explore whether autophagy is functionally involved in the cardioprotective effect of Iva in a rat model of myocardial infarction (MI). We observed that Iva treatment (po, 10 mg/kg/day) showed significant recovery on the hemodynamics parameters in MI rats, including left ventricular systolic pressure, left ventricular end diastolic pressure, and maximal ascending/descending rate of left ventricular pressure. Also, Iva treatment dramatically decreased infarct size, inhibited myocardial apoptosis, and reduced the levels of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in MI rats. Moreover, Iva treatment enhanced autophagy and inhibited PI3K/AKT/mTOR/p70S6K pathway in MI rats. Simultaneously, we observed that autophagy enhancer rapamycin (ip, 10 mg/kg/day) showed similar cardioprotective effects with Iva. Furthermore, we observed that addition of autophagy inhibitor 3-methyladenine (ip, 10 mg/kg/day) counteracted the therapeutic effect of Iva, addressing that Iva attenuated post-MI cardiac injury by enhancing autophagy. In summary, these findings demonstrated that Iva attenuated MI in rats by enhancing autophagy, and PI3K/AKT/mTOR/p70S6K pathway might be involved in the process. Autophagy activation by Iva may be a potential therapeutic strategy for the treatment of MI.
研究领域:
心脏病学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
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2024
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IF 4.8
Suizhi Cheng,Jin Chen,Qianhui Li,Yuhong Nie,Ting Ni,Caiting Peng,Xi Luo,Yasin Pazilat,Shumin Zhang,Jiancai Tang,Zhenzhong Liu
Recent research has revealed that N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) constitutes a significant risk factor in the development of esophageal cancer. Several investigations have elucidated the beneficial impact of folic acid (FA) in safeguarding esophageal epithelial cells against MNNG-induced damage. Therefore, we hypothesized that FA might prevent MNNG-induced proliferation of esophageal epithelial cells by interfering with the PI3K/AKT/mTOR signaling pathway. In vivo experiments, we found that FA antagonized MNNG-induced proliferation of rat esophageal mucosal epithelial echinocytes and activation of the PI3K/AKT/mTOR signaling pathway. In our in vitro experiments, it was observed that acute exposure to MNNG for 24 h led to a decrease in proliferative capacity and inhibition of the PI3K/AKT/mTOR signaling pathway in an immortalized human normal esophageal epithelial cell line (Het-1A), which was also ameliorated by supplementation with FA. We successfully established a Het-1A-T-cell line by inducing malignant transformation in Het-1A cells through exposure to MNNG. Notably, the PI3K/AKT2/mTOR pathway showed early suppression followed by activation during this transition. Next, we observed that FA inhibited cell proliferation and activation of the PI3K/AKT2/mTOR signaling pathway in Het-1A-T malignantly transformed cells. We further investigated the impact of 740Y-P, a PI3K agonist, and LY294002, a PI3K inhibitor, on Het-1A-T-cell proliferation. Overall, our findings show that FA supplementation may be beneficial in safeguarding normal esophageal epithelial cell proliferation and avoiding the development of esophageal cancer by decreasing the activation of the MNNG-induced PI3K/AKT2/mTOR signaling pathway.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
American Journal of Translational Research
·
2021
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IF 4.06
Lingli Huang,Di Xiao,Tianyu Wu,Xin Hu,Jun Deng,Xinjian Yan,Jingtao Wu,Simeng Xu,Xiaoping Yang,Gaofeng Li
Sorafenib is a first-line drug to treat advanced hepatocellular carcinoma (HCC), which can prolong the median overall survival of patients by approximately 3 months. Phenformin is a biguanide derivative that has been shown to exhibit antitumor activity superior to that of metformin. We herein explored the ability of phenformin to enhance the anti-cancer activity of sorafenib against HCC and the mechanisms underlying such synergy. The Hep-G2 and SMMC-7721 HCC cell lines were treated with sorafenib and/or phenformin, after which the proliferation of these cells was evaluated via MTT and colony formation assays, while invasion and apoptotic cell death were evaluated via Transwell and flow cytometry assays, respectively. In addition, protein levels were assessed by Western blotting, drug synergy was assessed with the CompuSyn software, and xenograft models were established by implanting Hep-G2 cells into nude mice and then assessing drug antitumor efficacy. Sorafenib and phenformin exhibited a synergistic ability to suppress HCC cell proliferation, migration, and survival. Phenformin further bolstered the ability of sorafenib to inhibit the CRAF/ERK and PI3K/AKT/mTOR pathways. Strikingly, the combination of these two drugs achieved better in vivo efficacy in a murine model system, without causing significant weight loss or hepatorenal toxicity. Sorafenib and phenformin can synergistically suppress CRAF/ERK and PI3K/AKT/mTOR pathway activation in HCC cells, and may thus represent a promising approach to treating this deadly cancer.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Heliyon
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2024
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IF 3.4
Yingjie Wu,Mingxiang Fan,Shixiang Tan,Qiucheng Guo,Hegui Xu
Objective To examine and talk about the mechanism of the Huoxue Jiegu compound capsule's effects on osteoblasts and the PI3K/Akt/mTOR signal pathway in rabbits suffering from tibial fractures. Method In vitro, CCK8 was used to assess the survival rates. Alizarinred staining was used to evaluate mineralized nodules. ALP staining was used to observe the osteoblasts. qRT-PCR was used to determine the mRNA expression of the bone formation-related factors BMP-2, bFGF, and TGF-β. In vivo, three groups of nine male rabbits each were randomly assigned to three groups: the Model group, the Huoxue Jiegu compound capsule group (HXJGC group), and the inhibitor group (HXJGC+3-MA), four weeks following the intervention. HE staining was employed to examine the rabbits' bone histology. immunohistochemistry was employed to examine the relative expression of the proteins VEGF and LC3-II. Western Blot was utilized to examine the relative expression of the proteins Beclin-1, LC3-II/Ⅰ, p62, p-PI3K, p-AKT, and p-mTOR. Results Compared to the control group, the medium- and high-dose groups exhibited considerably higher survival rates ( P < 0.05), as well as enhanced cell proliferation and differentiation ( P < 0.05) and more pronounced mineralized nodules. ( P < 0.05), but the low-dose groups showed no appreciable variation. In the low, medium, and high-dose groups, there was a substantial reduction in the expression of bFGF mRNA, whereas the levels of BMP-2 and TGF-β mRNA were considerably higher than in the control group ( P < 0.05). In vivo, after four weeks of treatment, the model control group and inhibito group had a large amount of fibrous hyperplasia accompanied by bleeding and a small amount of inflammatory cell infiltration. But in the HXJGC group, new cartilage appeared, and the surface of the cartilage was smooth and flat. Beclin-1 and LC3-II/I expression in the HXJGC+3 MA group was significantly lower than in the HXJGC and Model groups ( P < 0.05). The HXJGC group showed lower p62 expression than the HXJGC+3 MA and model groups ( P < 0.05). The HXJGC group exhibited significantly reduced levels of p-PI3K, p-AKT, and p-mTOR expression in comparison to HXJGC+3 MA groups ( P < 0.05). Conclusion Rabbits with tibial fractures can be treated with HXJGC, which can control the expression of the PI3K/Akt/mTOR signal pathway. It can promote the differentiation and maturation of osteoblasts at the fracture end of rabbits, accelerate the recovery of fractures, and achieve the purpose of treating the disease.
研究领域:
医学
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生物学
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DOI
PubMed
高影响因子
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
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2024
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IF 1.9
Zheng Delu,Cui Chenli,Ye Chengsong,Shao Chen,Zha Xiujing,Xu Ying,Liu Xu,Wang Can
Coenzyme Q10 (CoQ10) is a potent antioxidant that is implicated in the inhibition of osteoclastogenesis, but the underlying mechanism has not been determined. We explored the underlying molecular mechanisms involved in this process. RAW264.7 cells received receptor activator of NF-κB ligand (RANKL) and CoQ10, after which the differentiation and viability of osteoclasts were assessed. After the cells were treated with CoQ10 and/or H2O2 and RANKL, the levels of reactive oxygen species (ROS) and proteins involved in the PI3K/AKT/mTOR and MAPK pathways and autophagy were tested. Moreover, after the cells were pretreated with or without inhibitors of the two pathways or with the mitophagy agonist, the levels of autophagy-related proteins and osteoclast markers were measured. CoQ10 significantly decreased the number of TRAP-positive cells and the level of ROS but had no significant impact on cell viability. The relative phosphorylation levels of PI3K, AKT, mTOR, ERK, and p38 were significantly reduced, but the levels of FOXO3/LC3/Beclin1 were significantly augmented. Moreover, the levels of FOXO3/LC3/Beclin1 were significantly increased by the inhibitors and mitophagy agonist, while the levels of osteoclast markers showed the opposite results. Our data showed that CoQ10 prevented RANKL-induced osteoclastogenesis by promoting autophagy via inactivation of the PI3K/AKT/mTOR and MAPK pathways in RAW264.7 cells.
研究领域:
细胞生物学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
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2025
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IF 1.7
Sun Jingchi,Zheng Zhousong
Activated microglia are considered to be closely related to brain senescence and the pathogenesis of neurodegenerative diseases. Ginkgo biloba extract (GBE) is widely used to treat cognitive impairment and Alzheimer's disease (AD). This study aims to investigate the active ingredients of GBE and the underlying molecular mechanisms. The active ingredients of GBE in AD treatment were first analyzed by network pharmacology, culminating in the identification of the key ingredient, quercetin, and its targeted protein, NQO1. GO function enriched the oxidative stress pathway, while KEGG enriched the PI3K/Akt/mTOR pathway. Quercetin binding to NQO1 was verified by molecular docking and DARTS analysis. Cytotoxicity assay revealed no significant toxicity of GBE (0–1 mg/mL) and quercetin (0–0.4 μM) over 48 h. Subsequently, we constructed the microglial injury model by H 2 O 2 -induced HMC3 and BV2 cell lines. GBE and quercetin suppressed the senescence characteristics in H 2 O 2 -induced microglia. Further investigation revealed that the expression of NQO1 was downregulated in the injury model, and treatment with GBE and quercetin facilitated the protein expression of NQO1. In addition, silencing NQO1 reduced the promoting effect of quercetin on microglia viability and phosphorylation levels of PI3K, Akt, and mTOR. At the same time, it significantly increased the levels of p53, p21, p16 and β-galactosidase (SA-β-gal). Collectively, GBE mitigated H 2 O 2 -induced microglial injury, which activated the PI3K/Akt/mTOR pathway through the quercetin/NQO1 axis. These findings highlight quercetin/NQO1 signaling as a possible therapeutic target for senescence-related neurodegeneration.
研究领域:
神经生物学
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药理学
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分子医学
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老年医学
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神经退行性疾病
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天然药物化学
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细胞信号转导
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产品关联
DOI
PubMed
高影响因子
BIOLOGICAL & PHARMACEUTICAL BULLETIN
·
2023
·Vol. 46
·期 6
·764-772
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IF 2
Xin Zhang,Zhifang Liang,Ying Zhou,Fang Wang,Shan Wei,Bing Tan,Yujie Guo
Diabetic peripheral neuropathy (DPN) is an early developing complication of diabetes mellitus associated with nerve dysfunction. Artesunate (ART), a natural compound extracted from the herb Artemisia annua L., was reported to benefit neural injury. However, whether ART has a role in preventing DPN is still unknown. In this study, a rat model of DPN with a high fat diet feeding and streptozotocin (STZ) injection was established. The findings indicated that ART treatment significantly ameliorated hyperglycemia-induced hot plate reaction latency (HPRL) decline, cold sensitivity and mechanical allodynia, and nerve injury by inhibiting sciatic nerve apoptosis. Further, ART restored high glucose (HG)-induced elevated apoptosis and deficient survival in rat neuronal Schwann cells, RSC96 cells. We demonstrated that ART promoted protein kinase B (AKT) phosphorylation as well as its downstream factor mammalian target of rapamycin (mTOR) in vivo and in vitro. Of note, the protective effects of ART in RSC96 cells under HG condition could be counteracted by LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor. Taken together, ART mitigated hyperglycemia-induced nerve injury by suppressing apoptosis and promoting the viability of Schwann cells via the PI3K/AKT/mTOR signaling pathway.
研究领域:
神经学
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药理学
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糖尿病
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细胞生物学
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信号传导
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2020
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IF 3.701
Fenfen Li,Danfei Huang,Weiyu Yang,Xiaozhen Liu,Shaoping Nie,Mingyong Xie
The preventive role of polysaccharide from the seeds of Plantago asiatica L. (PLCP) against reproductive system injury induced by nonylphenol (NP) was investigated. Male Sprague-Dawley rats were exposed orally to NP 1 h after PLCP intragastric administration continuously for 45 days. The results showed that NP induced significant decrease in relative weight of testes and epididymis, changed testicular histomorphology, and disrupted hormone secretions. Moreover, oxidative stress occurred after NP exposure by overproduction of Malondialdehyde, lipid peroxidation, inducible nitric oxide synthase, and low activities of superoxide dismutase and catalase. Furthermore, the induction of apoptosis and disturbance of PI3K/Akt/mTOR pathway by NP were also proved. Interestingly, PLCP alleviated NP toxicity by improving antioxidant enzymes, recovering hormone secretions, inhibiting apoptosis and autophagy, which involves PI3K/Akt/mTOR pathway. These findings provide a good direction that PLCP may be a good candidate to help body defend against toxic substance, particularly endocrine disrupting chemicals induced reproductive toxicity.
研究领域:
药理学
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毒理学
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生殖生物学
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产品关联
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2019
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IF 3.17
Jihang Dai,Yu Sun,Duoyun Chen,Yaxin Zhang,Lianqi Yan,Xiaolei Li,Jingcheng Wang
Fibroblasts excessive proliferation was considered as a decisive reason for epidural fibrosis , which was known as a serious complication of lumbar laminectomy. As a traditional Chinese medicine , triptolide (TP) was used to be proved effective in preventing several fibrosis scar formation diseases. However, little is known about the effect of TP on preventing epidural fibrosis and its possible mechanism. Here, we performed in vitro and in vivo experiments to detect the possible mechanism of TP in preventing epidural fibrosis. In vitro, the effect of TP on impacting fibroblasts proliferation activities was detected by CCK-8, cell cycle assay and EdU incorporation assay. Also, the expressions of cell proliferation protein markers and the expressions of p-PI3K, p-AKT, p-mTOR were detect by Western blot . Besides, the effect of TP on inducing fibroblast apoptosis and autophagy was tested by Western blots, flow cytometry, TUNEL staining , Transmission electron microscope (TEM) analysis and LC3 immunofluorescent staining. The results suggested that TP could suppress the activation of PI3K/AKT/mTOR signaling pathway. Meanwhile, TP could inhibit fibroblast proliferation and induce fibroblast apoptosis as well as autophagy, which was known as two cellular self-destructions. Furthermore, we speculated the possible molecular pathway, through which that TP could inhibit fibroblast proliferation, induce fibroblast apoptosis and autophagy. We used PI3-kinase activator (740Y-P) to activate the PI3K/AKT/mTOR signaling. Activation of PI3K/AKT/mTOR signaling pathway increase the proliferation of fibroblasts and suppressed the autophagy and apoptosis induced by TP. In vivo, we built epidural fibrosis models in rats and locally applied TP of various concentrations. Hematoxylin–eosin (HE) and Masson's trichrome were used to detect the effect of TP on reducing epidural fibrosis. And the results showed that TP could significantly reduce the surgery-induced epidural fibrosis. In conclusion, the results above shown that TP could reduce epidural fibrosis formation, and the potential mechanism might through inhibiting fibroblast proliferation and stimulating apoptosis and autophagy via suppressing PI3K/AKT/mTOR signaling pathway. It might provide a novel thought for reducing surgery-induced epidural fibrosis.
研究领域:
药理学
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神经外科
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
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IF 4.8
Ying Ren,Xiangka Hu,Mushuang Qi,Wanjun Zhu,Jin Li,Shuyu Yang,Chunmei Dai
Background Diabetes is a metabolic disease characterized by hyperglycaemia. Tangningtongluo Tablet (TNTL) is an inpatient formula extensively utilized to treat diabetes mellitus (DM), but the protective mechanism is not clear. This study aimed to investigate the relevant mechanisms by which TNTL affects pancreatic damage in diabetic mice and autophagy. Methods The impact of TNTL on pancreatic damage in diabetic mice in vitro and in vivo was investigated via glucose and lipid metabolism analyses, HE staining, CCK-8, TUNEL staining, Annexin V/PI, and Western blotting. Molecular docking and Western blotting were used to verify the results of network pharmacological analysis, which was carried out to explore the mechanism by which TNTL affects DM. The autophagosome levels were visualized via RFP-GFP-LC3 and transmission electron microscopy, and lysosomal function was evaluated via Lysotracker red staining. Western blot, immunohistochemistry and immunofluorescence staining were used to detect the expression of the autophagy proteins LC3, p62 and LAMP2. Results Compared with the model group, TNTL protected pancreas from oxidative stress, decreased the level of MDA, increased the levels of SOD and GSH-px, induced the occurrence of autophagy and decreased the levels of apoptotic factors. Moreover, TNTL inhibited the protein expression of p-PI3K, p-Akt and p-mTOR, increased the levels of LC3 and LAMP2 and decreased the level of p62, and the autophagy inhibitor CQ blocked the protective effect of TNTL on pancreatic damage in diabetic mice. Conclusion These results demonstrated that TNTL ameliorated pancreatic damage in diabetic mice by inhibiting the PI3K/Akt/mTOR signaling and regulating autophagy.
研究领域:
药理学
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糖尿病
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分子生物学
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细胞生物学
✓ 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）