JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Yudi Yao,Yang Chen,Huijian Chen,Xin Pan,Xiaojun Li,Wenqi Liu,Yerlan Bahetjan,Binan Lu,Kejian Pang,Xinzhou Yang,Zongran Pang
Ethnopharmacological relevance Black mulberry ( Morus nigra L.) is an ancient dual-use plant resource for medicine and food. It is widely used in Uyghur folklore for hypoglycemic treatment and is a folkloric plant medicine with regional characteristics. However, the mechanism of Morus nigra L. treatment in diabetes mellitus has not been fully understood, especially from the perspective of hepatic lipid accumulation is less reported. Objective of this study This study was to explore the potential of Morus nigra L. fruit ethyl acetate extract (MNF-EA) to reduce blood sugar levels by preventing the production of hepatic lipogenesis and to provide more evidence for the use of MNF-EA as an adjuvant therapy for type 2 diabetes mellitus (T2DM). Materials and methods In this study, the chemical composition of MNF-EA was first analyzed and characterized using UPLC-Q-TOF-MS technique. A series of in vitro studies were performed with HepG2-IR cells and oleic acid (OA)-induced HepG2 cells, including MTT assay, glucose uptake assay, oil red O staining and Western blot analysis . The STZ-HFD co-induced T2DM mice were employed for in vivo research, including physical indices, biochemical analysis, histopathological examination, and Western blot analysis. Results The 19 compounds in MNF-EA were identified by UPLC-Q-TOF-MS technique. Insulin resistance (IR) and lipid droplet accumulation in HepG2 cells were greatly improved by MNF-EA treatment, which had no appreciable side effects at the dosage used. In T2DM mice, MNF-EA decreased fasting blood glucose (FBG), saved body weight, and significantly improved oral glucose tolerance (OGTT) and IR status. In addition, MNF-EA treatment also improved lipid metabolism disorders and liver function in T2DM mice. Histopathological sections showed that MNF-EA treatment reduced hepatic steatosis . Mechanistic studies suggest that MNF-EA acted through the AMPK/mTOR pathway. Conclusions These results suggest that MNF-EA has great potential to reverse the metabolic abnormalities associated with T2DM by regulating the AMPK/mTOR signaling pathway. Therefore, we believe that MNF is a promising medicinal and food-homologous agent to improve T2DM.
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Journal of Integrative Neuroscience
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2021
·Vol. 20
·期 1
·67-75
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IF 2.117
Dong-Xing Liu,Di Zhang,Wei-Min Hu,Yan-Fang Chang,Xiao-Hui Wang,Lin Li
Overactivation of the PI3-K/Akt/mTOR signaling pathway and inhibition of autophagy in the brain are involved in Alzheimer’s disease. The present paper’s goal was to explore the potential mechanisms of geniposide to protect against Alzheimer’s disease. We treated the human neuroblastoma SH-SY5Y cell line with Aβ1-42 as an Alzheimer’s disease in vitro model to explore the potential mechanisms of geniposide to protect against Alzheimer’s disease. Further, SH-SY5Y cells damaged by Aβ1-42 were treated with geniposide. Akt/mTOR-related proteins and autophagy-associated proteins were measured to reveal the molecular mechanisms by which geniposide protects against Aβ1-42-induced toxicity. Results showed that Akt and mTOR’s geniposide inhibited phosphorylation induced by Aβ1-42, enhanced expression of the LC3II/LC3I ratio, and Atg7 and Beclin1 expression and inhibited expression of p62 induced by Aβ1-42. Our results lead us to hypothesize that inhibition of the Akt/mTOR signaling pathway and autophagy enhancement are fundamental molecular mechanisms for geniposide to protect against Aβ toxicity.
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Frontiers in Pharmacology
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2020
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IF 4.225
Sun Xiaowei,Wang Dongyan,Zhang Tingting,Lu Xuejian,Duan Fangfang,Ju Lili,Zhuang Xiaotong,Jiang Xicheng
Eugenol, as an active compound isolated from Acorus gramineus, has been shown to protect against cerebral ischemia-reperfusion (I/R) injury. Nonetheless, the detailed neuroprotective mechanisms of eugenol in cerebral I/R injury have not been elaborated. In the present study, cerebral I/R injury model was established by middle cerebral artery occlusion (MCAO) in rats. HT22 cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) to mimic cerebral I/R injury in vitro. The results showed that eugenol pre-treatment relieved cerebral I/R injury as evidenced by improving neurological deficits and reducing infarct volume. Autophagy was induced by MCAO, which was further promoted by eugenol administration. Moreover, rapamycin, an activator of autophagy, promoted eugenol-induced decreases in neurological score, infarct volume, brain water content, and apoptosis. However, pretreatment with 3-MA, an inhibitor of autophagy, led to the opposite results. Similarly, eugenol pretreatment increased the viability and restrained apoptosis of OGD/R-challenged HT22 cells. OGD/R-induced autophagy was strengthened by eugenol. Mechanically, eugenol promoted autophagy through regulating AMPK/mTOR/P70S6K signaling pathway in vivo and in vitro. In conclusion, pretreatment with eugenol attenuated cerebral I/R injury by inducing autophagy via AMPK/mTOR/P70S6K signaling pathway.
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CARBOHYDRATE POLYMERS
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2018
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IF 5.158
Chunyan Hou,Hu Bai,Zhaojie Wang,Yuanhao Qiu,Li-Li Kong,Feifei Sun,Dongdong Wang,Hong Yin,Xiaoli Zhang,Haibo Mu,Jinyou Duan
Accompanied by overproduction of oxidants and reduction of pH, inflammation is closely related to many diseases such as cancer, atherosclerosis, and asthma. Besides chemotherapeutic agents, the potential regulative role of autophagy in inflammation is being actively investigated. RNA interference (RNAi)-based gene therapy is widely explored for clinical therapy but seriously restricted by lack of suitable carriers. In this study, we synthesized a hyaluronan-based ROS-sensitive polymer which was expected to release loaded chemical drugs in inflammatory environment and further developed a stable and nontoxic co-delivery nanosystem of siRNA targeting autophagy suppressive gene and chemotherapeutic agents. The in vitro transfection study of this nanosystem revealed improved intracellular accumulation of siRNA and excellent gene silencing efficacy comparable to that of conventional cationic liposome. Moreover, the mRNA expression of inflammatory cytokines was remarkably decreased by our nanosystem. Considering its biocompatibility, transfection efficacy, and anti-inflammatory capability, this co-delivery nanosystem proclaimed to be a promising combined therapeutic strategy for enhanced anti-inflammatory therapy.
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NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
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2024
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IF 3.1
Wang Guanghui,Cheng Jianxiang,Yao Meizhen,Li Jing,Chen Ting,Zhang Jia,Du Wensheng,Chen Youguo
Ovarian cancer stands as the foremost cause of mortality among gynaecological diseases globally, characterized by high morbidity and mortality. Pinocembrin, a flavonoid from natural plant sources, exhibits diverse pharmacological properties. Despite its known pharmacological activities, its specific role in ovarian cancer treatment remains scarcely reported, and its precise molecular mechanism remains elusive. This study integrates network pharmacology and molecular docking techniques to explore pinocembrin’s potential mechanism in ovarian cancer treatment. The targets of pinocembrin were compiled from the several online databases. Ovarian cancer targets were identified using the GeneCards database, with common target genes determined by data aggregation. Protein–protein interactions were analysed using the STRING platform. Subsequent Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed. Molecular docking assessed the binding affinity between potential targets and active compounds. Finally, target validity was verified through in vitro experiments. We identified 163 potential pinocembrin targets for ovarian cancer treatment. GO and KEGG analyses revealed pinocembrin’s involvement in protein kinase activity, protein phosphorylation, protein kinase complexes and cancer pathways in ovarian cancer treatment. Molecular docking demonstrated strong binding affinity between pinocembrin and most potential target active sites. In vitro experiments suggested pinocembrin’s potential to induce apoptosis in ovarian cancer cells through the AKT1-mTOR signalling pathway. This study comprehensively elucidates pinocembrin’s potential targets and mechanisms against ovarian cancer, aiming to provide promising candidates for developing novel and effective alternative and/or complementary nutritional supplements for the clinical treatment of ovarian cancer.
研究领域:
肿瘤学
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药理学
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生物信息学
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Frontiers in Pharmacology
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2025
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IF 4.8
Xiaoli Deng,Chunjie Hu,Lin Li,Guixian Yang,Chikun Li,Wanxun Zhang,Guangyu Cheng
Background Lung cancer is a leading cause of cancer-related deaths, with cisplatin being a cornerstone of treatment. However, resistance to cisplatin presents a significant challenge. β-elemene, a natural compound, has demonstrated potential to reverse cisplatin resistance. LncRNA LINC00511 has been implicated in cisplatin resistance through its role in activating the PI3K/AKT/mTOR pathway, which supports tumor survival and proliferation. Purpose This study aims to investigate the mechanism by which β-elemene overcomes cisplatin resistance in lung cancer by regulating LINC00511. Methods Human lung adenocarcinoma cells (A549 and A549/DDP) were treated with β-elemene and cisplatin. Cell proliferation and apoptosis were assessed using CCK-8, EdU staining, and flow cytometry. LINC00511 expression was measured by qRT-PCR, and protein levels of PI3K, AKT, and mTOR were evaluated via Western blot. A xenograft model was used to confirm in vivo effects. Results β-elemene significantly enhanced cisplatin-induced apoptosis in A549/DDP cells, reduced LINC00511 expression, and inhibited the PI3K/AKT/mTOR pathway. LINC00511 knockdown further potentiated these effects, both in vitro and in vivo . Xenograft models confirmed the enhanced anti-tumor effects of the combination treatment. Conclusion β-elemene overcomes cisplatin resistance in lung cancer by downregulating LINC00511 and inhibiting the PI3K/AKT/mTOR pathway. These findings propose a promising therapeutic strategy for treating cisplatin-resistant lung cancer.
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JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Ranyi Luo,Yinhao Zhang,Hong Wang,Bing Xu,Jiaorong Qu,Shuwen Duan,Runping Liu,Jia Liu,Shuo Li,Xiaojiaoyang Li
Ethnopharmacological relevance Hepatic ischemia/reperfusion injury (HIRI) is a common occurrence during or after liver surgery, representing a major cause for postoperative complications or increased morbidity and mortality in liver diseases. Rehmanniae Radix Praeparata (RRP) is a traditional Chinese medicine frequently used and has garnered extensive attention for its therapeutic potential treating cardiovascular and hepatic ailments. Recent studies have indicated the possibility of RRP in regulating lipid accumulation and apoptosis in hepatocytes. Aim of the study This study aimed to investigate the specific mechanisms by which RRP may impede the progression of HIRI through the regulation of lipid metabolism. Materials and methods High-performance liquid chromatography (HPLC) was used to identify the major components of RRP water extract. C57BL/6J mice were orally given RRP at doses of 2.5 g/kg, 5 g/kg, and 10 g/kg for a duration of 7 days before undergoing HIRI surgery. Furthermore, we established a lipid-loaded in vitro model by exposing hepatocytes to oleic acid and palmitic acid (OAPA). The anti-HIRI effect of RRP was determined through transcriptomics and various molecular biology experiments. Results After identifying active ingredients in RRP, we observed that RRP exerted lipid-lowering and hepatoprotective effects on HIRI mice and OAPA-treated hepatocytes. RRP activated AMP-activated protein kinase (AMPK) and inhibited mammalian target of rapamycin (mTOR), which further on the one hand, inhibited the cleavage and activation of sterol regulatory element binding protein 2 (SREBP2) by limiting the movement of SREBPs cleavage-activating protein (SCAP)-SREBP2 complex with the help of endoplasmic reticulum lipid raft-associated protein 1 (ERLIN1) and insulin-induced gene 1 (INSIG1), and on the other hand, promoted liver X receptor α (LXRα) nuclear transportation and subsequent cholesterol efflux. Meanwhile, the anti-lipotoxic effect of RRP can be partly reversed by an LXRα inhibitor but largely blocked by the application of compound C, an AMPK inhibitor. Conclusion Our study elucidated that RRP served as a potential AMPK activator to alleviate HIRI by blocking SREBP2 activation and cholesterol synthesis, while also activating LXRα to facilitate cholesterol efflux. These findings shed new light on the potential therapeutic use of RRP for improving HIRI.
研究领域:
药理学
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肝病学
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分子生物学
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Asian Pacific Journal of Tropical Medicine
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2015
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IF 1.062
Chong Shi,Guo-Bin Zhang,Shu-Wang Yin
Objective To explore the effect of bortezomib on migration and invasion of cervical carcinoma HeLa cell and specific molecular mechanism. Methods The effect of bortezomib on the viability of HeLa cell was measured by MTT assay. The effect of bortezomib on cell migration and invasion was measured by Transwell assay and invasion experiment respectively. The activation of Akt/mTOR signaling pathway and expression level of MMP2, MMP9 were assayed by western blot. Results MTT assay indicated bortezomib (2.5 μM, 5 μM, 10 μM) could inhibit HeLa cell viability, and the inhibitory rate was highest at 48 h. Transwell assay and invasion experiment results showed that bortezomib inhibited HeLa cell migration and invasion. Western blotting assays presented bortezomib could suppress the phosphorylation of Akt and mTOR, and down-regulate the expression of MMP2 and MMP9. Conclusions These results suggested bortezomib could inhibit migration and invasion in cervical carcinoma HeLa cell, which might be related to Akt/mTOR signal pathway.
研究领域:
肿瘤学
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细胞生物学
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药理学
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TOXICOLOGY LETTERS
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2026
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IF 3.1
Lele Zhou,Lingbin Chen,Cailin Zheng,Jinneng Wu,Meihua Zhong,Zhixiong Huang,Zhiming Xin,Zhou Chen
Tripchlorolide, a low-toxicity derivative of the natural product triptolide, exhibits significant therapeutic potential for inflammatory and autoimmune diseases; however, its profile of male reproductive toxicity remains a major concern for clinical translation. To address this, we first established its median lethal dose at 33.13 mg/kg in mice to guide safe exposure levels. We then systematically evaluated its reproductive toxicity in male rats following 8-week intraperitoneal administration (2.5, 5, and 10 μg/kg/day). Our results demonstrated a clear dose-dependent toxicity, characterized by significant reductions in testicular and epididymal coefficients, impaired sperm count and motility, disrupted testosterone, follicle-stimulating hormone, and luteinizing hormone levels, and evident histopathological damage in the testes and epididymides. Encouragingly, these adverse effects showed signs of reversal after a 4-week recovery period, suggesting that the impairment is reversible. Through an integrated approach combining network pharmacology prediction and molecular docking, we identified the inhibition of the PI3K/Akt/mTOR signaling pathway as the pivotal molecular event. This mechanism was conclusively validated by our in vivo rescue experiment, where co-administration of the Akt activator SC79 markedly attenuated the tripchlorolide-induced reproductive impairments. Our study provides a comprehensive toxicological profile, defining the dose-response, reversibility, and mechanistic basis of tripchlorolide's male reproductive toxicity, thereby offering critical insights for its risk assessment and potential repurposing.
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Cell Death & Disease
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2026
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IF 12.2
Wu Miaomiao,Li Hui,Li Sujun,Xu Qianwen,Liao Yijing,Qu Lili,Cang Chunlei,Wang Xingbing
Refractory disease and relapse continue to impede effective treatment of myeloid leukemia, despite substantial progress in therapeutic approaches. Emerging evidence implicates lysosomal ion channels in the regulation of cell death pathways, highlighting these channels as viable targets for therapeutic intervention. This study identified elevated expression of the lysosomal ion channel CLN7 in myeloid leukemia cells. Suppression of CLN7 triggered apoptosis, inhibited cellular proliferation, and markedly reduced the abundance of oncogenic proteins. Mechanistically, CLN7 inhibition promoted nuclear translocation of TFEB by downregulating mTOR signaling, thereby enhancing lysosomal biogenesis and macroautophagy. Notably, CLN7 suppression selectively accelerated chaperone-mediated autophagic degradation of BCR-ABL through cathepsin B (CTSB) upregulation. In addition, inhibition of CLN7 induced autophagy-mediated apoptosis, which led to significant impairment of leukemogenic potential. Co-treatment with chemotherapeutic agents and CLN7 suppression enhanced therapeutic efficacy in myeloid leukemia cells. Finally, suppression of CLN7 markedly reduced tumor growth in human xenograft models without compromising normal hematopoietic function. These findings establish CLN7 as a critical regulator of leukemic cell survival, representing a promising therapeutic target for myeloid leukemia.
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JOURNAL OF ETHNOPHARMACOLOGY
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2026
·
IF 5.4
Xing-lan Ye,Ling-shuai Zeng,Qiang Liu,Wen-cheng Xu,Hong Liu,Hong Cheng,Wen-xiao Zheng,Xiao-qin Wang,Xue Xue
Ethnopharmacological relevance Huaiqihuang granule (HQH) is a traditional Chinese herbal formula comprising Trametes robiniophila Murr. , Lycii Fructus ., and Polygonatum sibiricum Red. This granule can nourish Qi and Yin, improve blood circulation and remove blood stasis. HQH has been extensively used to improve immune-mediated kidney diseases, such as IgA vasculitis nephritis (IgAVN). However, its renal protective mechanism remains elusive. Aim of the study This study investigated whether HQH ameliorates IgAVN by modulating the AMPK/mTOR-mediated autophagy pathway. Materials and methods The IgAVN mouse model was established using gliadin sensitization and India ink-mediated reticuloendothelial blockade (n = 10/group). The model mice were then treated for 4 weeks with low/high-dose HQH (4/8 g/kg/day) or dexamethasone (2.5 mg/kg/day). For in vitro analyses, human mesangial cells (HMCs) were first stimulated with aggregated IgA1 (aIgA1, 25 μg/mL) and then treated with the optimal concentration of HQH-containing serum (40 %). Furthermore, biochemical indices assays, renal histopathology, and immunofluorescence analysis of IgA deposition were performed. Moreover, autophagy levels were evaluated by assessing the expression of autophagy-related proteins, MDC staining, and mCherry-EGFP-LC3 transfection. Western blot and immunofluorescence were carried out to assess the levels of the AMPK/mTOR pathway proteins and proliferation markers. Results The results showed that HQH treatment significantly reduced 24-h urinary protein and serum IgA levels, but improved renal histopathology in IgAVN mice. Furthermore, HQH activated autophagy by upregulating p-AMPKα, LC3-Ⅱ/LC3-Ⅰ, and Beclin1, while inhibiting p-mTOR/mTOR and p62. Moreover, in HMCs, 40 % HQH-containing serum optimally inhibited aIgA1-induced mesangial proliferation and increased autophagic levels, as evidenced by the quantitative increase in autophagy activity and mean fluorescence intensity of MDC. However, these effects were blocked by AMPK inhibition. Conclusion This study showed that HQH alleviates IgAVN by upregulating AMPK/mTOR-mediated autophagy, inhibiting mesangial cell proliferation, and mitigating renal injury. These findings suggest that HQH has therapeutic potential for IgAVN and link autophagy modulation to IgAVN treatment.
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Nature Communications
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2026
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IF 18.1
Li Ke-ran,Fu Ping-ping,Bai Wen,Bai Chao-wen,Yang Yitian,Liu Le,Chai Jin-long,Yao Yujia,Huang Dan,Zhang Zhi-qing,Jiang Qin,Ma Zhou-rui,Feng Yu,Yao Jin,Cao Cong
Retinal neovascularization (RNV) is a potential vision-threatening process characterized by the abnormal growth of retinal vessels. Despite its clinical prevalence, the precise mechanisms governing RNV initiation and progression remain incompletely defined. Here we identify myeloid-derived growth factor (MYDGF) as a critical regulator of retinal vascular dynamics. Using single-cell RNA sequencing and human patient validation, we show that MYDGF is upregulated in retinal endothelial cells during proliferative diabetic retinopathy and mouse models of pathological neovascularization. In vitro, MYDGF promotes retinal endothelial cell proliferation, migration, and sprouting. In vivo, endothelial-specific MYDGF depletion inhibits both normal vascular development and pathological neovascularization in neonatal mice, and disrupting adult vascular homeostasis in male mice. MYDGF drives angiogenesis by activating the Akt-mTOR cascade through the Gαi1/3-Gab1 signaling complex; genetic depleting or mutation these components suppress MYDGF-induced Akt-mTOR activation and angiogenic responses. Together, MYDGF promotes retinal angiogenesis and maintains vascular homeostasis via the Gαi1/3-Gab1-Akt-mTOR signaling axis.
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