Natural Products and Bioprospecting
·
2025
·Vol. 15
·期 1
·1-17
·
IF 4.9
Zhao Huimin,Wang Yuyang,Liu Zining,Lin Lin,Xiang Jiasi,Zhu Zihao,Yang Xiongli,Fang Yongsheng,Kong Lingmei,Li Yan
Natural product tanshinone I exhibits weak potency and poor drug-like properties, which have restricted its clinical development as an anticancer agent. Herein, twenty novel tanshinone I-pyridinium salt derivatives and a pyridinium salt precursor were designed and synthesized, and their antitumor activities were evaluated. Among these tanshinone I-pyridinium salts, compound a4 , bearing a 4-bromobenzoylmethyl substituent at the N -1 position of the pyridine ring, showed the most potent cytotoxicity against breast cancer (MDA-MB-231), hepatocellular carcinoma (HepG2), and prostate cancer (22RV1) cell lines, with IC 50 values of 1.40–1.63 μM. Preliminary mechanistic studies suggest that a4 targets PI3Kα with the IC 50 of 9.24 ± 0.20 μM and exerts effective inhibition of the phosphorylation of key PI3K/Akt/mTOR signaling proteins. Besides, a4 significantly downregulates the expression of the immune checkpoint protein PD-L1, indicating its potential to activate tumor immunity. These findings demonstrate that tanshinone I-pyridinium salt derivative a4 is a novel PI3Kα inhibitor, providing a solid foundation for further development of antitumor agents. Graphical
研究领域:
药物化学
·
肿瘤学
·
药理学
·
药物设计
·
天然产物研究
✓ 已验证
DOI
PubMed
高影响因子
RARE METALS
·
2025
·
IF 11
Zhu Yi-Bing,Zang Yu-Fan,Yu Jia-Nan,Li Cheng-Yu,Jia Shao-Sheng,Liang Yu-Han,Bai Ling-Chuang,Li Bin,Li Jing-An,Chen Lan
Superior vena cava syndrome (SVCS) caused by lung cancer accounts for 75% of patients with SVCS, which is one of the common complications of tumors. Interventional therapy is currently the most effective approach to relieve obstruction, but existing stents cannot inhibit or eliminate tumors, requiring postoperative radiotherapy and chemotherapy that may lead to secondary obstruction. Based on the characteristics of the tumor microenvironment and the interlayer ion replaceable properties of the layered material-montmorillonite (MMT), the composite coating (MMT/Em/PDA) of emodin (Em)-loaded MMT and dopamine was constructed on the magnesium alloy by liquid phase ion exchange technology and hydrothermal technology. The in vitro and in vivo results showed that the modified samples showed excellent corrosion resistance, the drug loading through adsorption and complexation with Zn 2+ between MMT layers, and the drug-loaded samples possessed good pH and near-infrared response-controlled release drug performances. The MMT/Em/PDA sample exhibited an excellent photothermal conversion performance. Photothermal (PTT) synergistic drug therapy of samples could significantly promote the production of ROS in lung cancer cells damage mitochondria, and further inhibit cell adhesion, proliferation, and invasion by down-regulating PI3K-AKT and EMT signaling pathways, thereby causing tumor cell death. Furthermore, the multimodal therapies of samples promoted the repolarization of tumor-associated macrophages into the M1 phenotype to re-activate tumor immunity through activating the AKT-NF-κB signaling pathway. In normal tissues, they can significantly promote the M2 phenotype polarization to promote vascular tissue repair by inhibiting the AKT-NF-κB signaling pathway. This work helps to provide a new insight into designing the modified magnesium alloy. Graphical abstract
研究领域:
生物材料
·
纳米医学
·
癌症治疗
·
免疫治疗
·
生物医学工程
·
药理学
·
材料科学
✓ 已验证
DOI
高影响因子
NUTRITION RESEARCH
·
2022
·
IF 3.876
Yafang Du,Deming Li,Jingsi Chen,Yun-Hong Li,Zixiang Zhang,Khemayanto Hidayat,Zhongxiao Wan,Jia-Ying Xu,Li-Qiang Qin
Lactoferrin (Lf) is an iron-binding glycoprotein with potentially beneficial biological functions. However, the interaction between Lf and type 2 diabetes mellitus (T2DM) remains unclear. We hypothesized that Lf would improve hepatic insulin resistance and pancreatic dysfunction in diabetic mice. Male C57BL/6J mice were fed a high-fat diet for 15 weeks and injected with streptozotocin (STZ) for 5 consecutive days to establish a T2DM model. One week after STZ injection, mice with ≥11.1 mmol/L fasting blood glucose concentration were considered T2DM mice. These mice received 0.5% or 2% Lf solution for another 12 weeks. Biochemical parameters were measured, and histopathological examination of the pancreas and liver was performed. Hepatic protein expression related to the insulin signalling pathway was also assessed. Diabetic mice showed insulin resistance and abnormal glucolipid metabolism. Lf decreased serum concentrations of glycated serum protein , fasting insulin, cholesterol, and triglyceride and increased liver insulin sensitivity . Hematoxylin-eosin staining showed that Lf reversed the abnormal pancreatic islets of diabetic mice. Lf improved pancreatic dysfunction by reducing oxidative stress and inflammation responses. Furthermore, Lf upregulated the protein expression of insulin receptor , insulin receptor substrate-1, glucose transporter 4 , phosphor phosphatidylinositol 3-kinase/phosphatidylinositol 3-kinase (PI3K), and phosphor protein kinase B/protein kinase B (AKT) in the liver. This study indicated that Lf supplementation improved hepatic insulin resistance and pancreatic dysfunction, possibly by regulating the PI3K/AKT signaling pathway in T2DM mice.
研究领域:
内分泌学
·
糖尿病研究
·
分子生物学
·
营养科学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2026
·
IF 6.8
Lianghui Zhan,Qian Liu,Changjun Zhang,Jinbao Pu,Ligang Ren
Ethnopharmacological relevance Hedysarum polybotrys Hand.-Mazz. (Hongqi, HQ) is a prized Qi-tonifying herb in Traditional Chinese Medicine (TCM), historically employed to enhance the body's resistance and modulate immune function. While its anti-tumor properties are recognized, the specific immunomodulatory mechanisms by which HQ empowers Natural Killer (NK) cells to combat prostate cancer (PCa) remain under-explored. Aim of the study To systematically elucidate the material basis and molecular mechanisms through which the aqueous extract of HQ enhances NK cell-mediated cytotoxicity against PCa cells, utilizing an integrated approach of multi-omics and experimental validation. Methods The chemical profile of HQ aqueous extract was characterized using UHPLC-MS/MS untargeted metabolomics. Network pharmacology and transcriptomic analyses (RNA-seq) were integrated to predict core targets and signaling pathways. Specific interactions were simulated via molecular docking. Validations were performed using an in vitro co-culture model of NK-92 and PC-3 cells. Assays included CCK-8, LDH release, flow cytometry (apoptosis, surface markers), ELISA (cytokines), and Western blot. Results A total of 69 compounds were identified in HQ, with Genistein and Isoliquiritigenin highlighted as key active constituents. HQ treatment significantly enhanced NK-92 cell cytotoxicity against PC-3 cells, evidenced by increased LDH release and PC-3 apoptosis. Mechanistically, HQ upregulated the expression of cytolytic effectors (Perforin, Granzyme B) and pro-inflammatory cytokines (IFN-γ, TNF-α, IL-17A). Crucially, HQ treatment achieved a "dual-effect": it reactivated the PI3K/AKT signaling pathway in NK cells (confirmed by increased p-PI3K and p-AKT levels) while concurrently downregulating the immunosuppressive PD-1/PD-L1 checkpoint axis. Conclusion This study demonstrates that HQ potentiates NK cell anti-tumor immunity against prostate cancer through a dual mechanism involving PI3K/AKT pathway activation and PD-1/PD-L1 axis inhibition. These findings provide modern pharmacological evidence supporting the traditional use of HQ for enhancing immune surveillance in cancer therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Foods
·
2026
·Vol. 15
·期 9
·1535
·
IF 6
Fangling Feng,Shuo Zhang,Chencen Lai,Zhiyu Chen,Jian Zhang,Jiuming He,Min Zhang,Pengjiao Wang,Xiuli Gao
Depression is a common mental disorder that substantially impairs patients’ daily life and work. To identify natural and safe preventive options, we investigated the preventive effect and underlying mechanism of theGanoderma lucidumandRosa roxburghiiTratt formula (GLRRTF) on depression. A total of 72 chemical components in GLRRTF were identified by UHPLC-ESI-Q-Exactive Plus Orbitrap-MS Analysis. GLRRTF (containing 400 mg/kg ofG. lucidumextract and 800 mg/kg ofR. roxburghiiextract per day), administered as a 1-week preventive intervention followed by 4 weeks of co-administration with chronic unpredictable mild stress, prevented the development of depression-like behaviors in male C57BL/6J mice and reduced neuronal damage in the hippocampus. Airflow-assisted desorption electrospray ionization mass spectrometry imaging and enzyme-linked immunosorbent assays showed that GLRRTF corrected abnormalities in neurotransmitter levels. The 16S rRNA sequencing indicated that GLRRTF restored dysbiosis of the gut microbiota. Metabolomic profiling revealed that GLRRTF increased the level of tryptophan and promoted tryptophan metabolism towards the 5-HT and indole pathways in feces and the brain. Western blot demonstrated that GLRRTF increased 5-HT production from tryptophan in the brain by regulating tryptophan hydroxylase 2 and DOPA decarboxylase. GLRRTF activated the PI3K/AKT pathway by regulating brain-derived neurotrophic factor and its receptor tropomyosin receptor kinase B. This research provides a comprehensive mechanistic understanding of GLRRTF’s preventive effect against depression, highlighting its potential as a novel, safe, and preventive functional food formulation.
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2026
·
IF 5.6
Yu Dun,Jinxi Xie,Jian Zhou,Hanbing Hu,Fuli Liu,Yiru Shao,Jie Shen
CD34/CD45-DSCs alleviate phosgene-induced acute lung injury (P-ALI) in rats. • CD34 + CD45 + cells reside in bone marrow, peripheral blood, and BALF with dynamic changes post-injury. • CD34/CD45-DSCs exhibit MSC-like properties with osteogenic, adipogenic, and chondrogenic potential in vitro. • CD34/CD45-DSCs showed prolonged lung retention perivascular engraftment, and PVSC-like phenotype acquisition without exacerbating fibrosis. • CD34/CD45-DSCs restore pulmonary vascular barrier via VEGF-PI3K/AKT/eNOS signaling pathway. Phosgene inhalation causes acute lung injury (ALI) with high mortality and no effective antidote, and stem cell therapy is limited by poor cell survival and low engraftment efficiency. Here, we identified a rare endogenous CD34 + CD45 + cell fraction that reside in bone marrow, peripheral blood, and bronchoalveolar lavage fluid (∼1% baseline), exhibits a “decrease-then-recovery” dynamic after phosgene injury, and displays MSC-like properties with trilineage (osteogenic, adipogenic, and chondrogenic) potential in vitro. Intravenous administration of expanded CD34 + CD45 + -derived stromal cells (CD34/CD45-DSCs) significantly alleviated pulmonary vascular leakage and inflammatory in a rat model of phosgene-induced ALI (P-ALI). In vivo bioluminescence imaging further revealed that CD34/CD45-DSCs exhibited prolonged pulmonary retention compared with BMSCs (11.3 days vs. 48 h), proliferated, engrafted around the pulmonary vasculature, and acquired a perivascular stromal cell (PVSC)-like phenotype expressing late-stage mesenchymal progenitor, pericyte, and fibroblast markers. In a bleomycin-induced pulmonary fibrosis model, CD34/CD45-DSCs did not exacerbate fibrotic changes at day 28. Mechanistically, VEGF knockdown or neutralization abolished the barrier-protective effect, which was rescued by an AKT agonist and blocked by an inhibitor. Moreover, CD34/CD45-DSCs upregulated tight junction proteins ZO-1 and Occludin in injured endothelial cells via VEGF-PI3K/AKT/eNOS signaling. Collectively, our study defines the origin, spatiotemporal dynamics, perivasucular engraftment, PVSC-like fate acquisition, and VEGF-PI3K/AKT/eNOS-dependent mechanism of CD34/CD45-DSCs, supporting their potential as a relatively safe, long-engrafting, and mechanistically transparent cell-based strategy for ALI.
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2017
·
IF 3.671
Wenjie Jiang,Yanna Cheng,Na Zhao,Lian Li,Yikang Shi,Aizhen Zong,Fengshan Wang
Previous studies demonstrated that SIP-SII, a sulfated derivative of SIP that is isolated from the ink of Sepiella maindroni , showed significant inhibition of tumor growth and metastasis. In this study, the effects of SIP-SII on the migration, invasion and molecular mechanism in ovarian cancer cell line, SKOV-3 cells, were investigated. The flow cytometry, confocal microscope observation, western blot and RT-PCR results indicated that SIP-SII located on cell membrane and inhibited the expression and activation of epidermal growth factor receptor (EGFR). Moreover, the binding capacity of SIP-SII with EGFR was confirmed by surface plasmon resonance (SPR) analysis and co-localization of EGFR and SIP-SII. Accordingly, SIP-SII was proved to attenuate the EGF-induced EGFR phosphorylation and migration by western blot and wound healing assay, respectively. Additionally, SIP-SII inhibited p38/MAPK and PI3K/Akt/mTOR signaling pathways in SKOV-3 cells significantly. What is more, SIP-SII showed amplified inhibitory activity on migration, invasion, and MMP-2 expression in combination with p38-specific inhibitor, PI3K-specific inhibitor or mTOR-specific inhibitor in SKOV-3 cells. Therefore, the mechanism that SIP-SII suppressed EGFR-mediated p38/MAPK and PI3K/Akt/mTOR signaling pathways to inhibit migration and invasion of SKOV-3 cells was demonstrated. These findings suggested that SIP-SII might be used as a potential inhibitor against tumor metastasis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2020
·
IF 7.182
Wei Xu,Sijia Fang,Yong Wang,Xiaoqing Chi,Xiaodan Ma,Tao Zhang,Songhua Hu
The present study was to investigate the molecular mechanism underlying lymphocyte activation by total polysaccharides from Atractylodis macrocephalae (RAMPtp). The results showed that RAMPtp significantly promoted the secretions of cytokines (IFN-γ, IL-1α, IL-21, IFN-α, CCL4, CXCL9 and CXCL10), increased the proportions of CD4 + and CD8 + subpopulations, and enhanced the expressions of c-JUN, NFAT4, STAT1 and STAT3. microRNA sequencing identified 67 differentially expressed miRNAs (DEMs) in RAMPtp-stimulated SMLN lymphocytes, including 55 up-regulated and 12 down-regulated. GO and KEGG enrichment analyses of the predicted DEMs-targeted genes indicated that they were associated with immune system pathways, including PI3K-Akt, MAPKs, Jak-STAT and Calcium signaling pathways, which were confirmed by western blot and pathway inhibition assays. RAMPtp was further observed to favor immunostimulatory effect on both T and B lymphocytes via binding to TCR and membrane Ig individually. These findings might explain the immunomodulatory mechanism of RAMPtp in ameliorating the bovine intramammary infection.
研究领域:
免疫学
·
分子生物学
·
兽医学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Ovarian Research
·
2024
·Vol. 17
·期 1
·1-13
·
IF 3.8
Jiang Nan-Xing,Zhao Wei-Jie,Shen Hao-Ran,Du Dan-feng,Li Xue-Lian
Background Investigating the underlying molecular mechanisms responsible for endometrial dysfunction in women with PCOS is essential, particularly focusing on the role of hyperinsulinemia.Methods We explored the role of insulin in the decidualization process using a synthetic decidualization assay. To dissect the effects of PI3K/AKT-NR4A signaling, we employed small interfering RNAs (siRNAs) targeting the NR4A genes and inhibitors of the PI3K/AKT pathway. We also investigated the disruption of AKT-NR4A1 signaling in the endometrium of PCOS female rats induced with dehydroepiandrosterone (DHEA). Quantitative real-time PCR (qRT-PCR) and Western blot (WB) analyses were utilized to evaluate gene expression regulation.Results Insulin was found to suppress the expression of decidualization markers in human endometrial stromal cells (hESC) in a dose-dependent manner, concurrently triggering an inappropriate activation of the PI3K/AKT pathway. Members of the NR4A family, as downstream effectors in the PI3K/AKT pathway, were implicated in the insulin-induced disruptions during the decidualization process. Moreover, the endometrium of PCOS models showed significantly elevated levels of phosphorylated (Ser473) AKT, with a corresponding reduction in Nr4a1 protein.Conclusion sOur research demonstrates that insulin negatively regulates decidualization in hESC via the PI3K/AKT-NR4A pathway. In vivo analysis revealed a significant dysregulation of the AKT-NR4A1 pathway in the endometrium of PCOS rats. These findings offer novel insights into the pathogenesis of infertility and endometrial disorders associated with hyperinsulinemia in PCOS.
研究领域:
内分泌学
·
生殖生物学
·
分子生物学
·
妇科学
✓ 已验证
DOI
PubMed
高影响因子
TISSUE & CELL
·
2022
·
IF 2.586
Jie Pan,Xiaoping Cai,Xiao Zheng,Xiaoyu Zhu,Jihong Feng,Xiaoqiu Wang
Luteolin inhibits tumorigenesis of non-small cell lung cancer (NSCLC), but its mechanism still needs to be clarified. We hereby explored the effects of luteolin in vascular endothelial cells of NSCLC (NSCLC-VECs). After extraction and identification of NSCLC-VECs, cells were treated with luteolin and transfected. The viability, migration, angiogenesis and invasion of the cells were measured. The levels of miR-133a-3p, purine rich element binding protein B (PURB), vascular endothelial growth factor (VEGF), phosphatidylinositol 3-kinase (PI3K), Akt, mitogen-activated protein kinases (MAPK), matrix metalloproteinase (MMP)-2/-9 were determined. The interaction relationship of miR-133a-3p and PURB was identified. Luteolin inhibited the viability, migration, angiogenesis and invasion of NSCLC-VECs yet up-regulated miR-133a-3p level, while miR-133a-3p inhibitor counteracted the repressive effect of luteolin on the viability, migration, angiogenesis, and invasion in NSCLC-VECs. Luteolin inhibited the expressions of migration- and invasion-associated proteins (VEGF, MMP-2 and MMP-9), PI3K/Akt and MAPK signaling pathways-related factors, while miR-133a-3p inhibitor reversed the inhibitory effect of Luteolin on NSCLC-VECs. Luteolin decreased the level of PURB, which was targeted by miR-133a-3p. ShPURB promoted miR-133a-3p level in NSCLC-VECs, while reversing the promoting effects of miR-133a-3p inhibitor on the migration, invasion, and levels of migration- and invasion-associated proteins, PI3K/Akt and MAPK pathways-associated factors in NSCLC-VECs. Collectively speaking, luteolin inhibits the migration and invasion of NSCLC-VECs via miR-133a-3p/PURB- mediated MAPK and PI3K/Akt pathways.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Immunity Inflammation and Disease
·
2024
·Vol. 12
·期 2
·e1177
·
IF 3.1
Nannan Pang,Shabaaiti Tudahong,Yuejie Zhu,Jiang He,Chunxia Han,Gang Chen,Weiguo Wang,Jing Wang,Jianbing Ding
Background Acute graft-versus-host disease (aGVHD) arises from the imbalance of host T cells. Galectin-9 negatively regulates CD4 effector T cell (Th1 and Th17) function by binding to Tim-3. However, the relationship between Galectin-9/Tim-3 and CD4 + T subsets in patients with aGVHD after Haplo-HSCT (haploidentical peripheral blood hematopoietic stem cell transplantation) has not been fully elucidated. Here, we investigated the role of Galectin-9 and CD4 + T subsets in aGVHD after haplo-HSCT. Methods Forty-two patients underwent Haplo-HSCT (26 without aGVHD and 16 with aGVHD), and 20 healthy controls were included. The concentrations of Galectin-9, interferon-gamma (IFN-γ), interleukin (IL)-4, transforming growth factor (TGF)-β, and IL-17 in the serum and culture supernatant were measured using enzyme-linked immunosorbent assay or cytometric bead array. The expression levels of Galectin-9, PI3K, p-PI3K, and p-mTOR protein were detected by western blot analysis. Flow cytometry was used to analyze the proportions of CD4 + T cell subsets. Bioinformatics analysis was performed. Results In patients with aGVHD, regulatory T (Treg) cells and Galectin-9 decreased, and the Th1, Th17, and Treg cells were significantly imbalanced. Moreover, Treg and Galectin-9 were rapidly reconstituted in the early stage of patients without aGVHD after Haplo-HSCT, but Th17 cells were reconstituted slowly. Furthermore, Tim-3 upregulation on Th17 and Th1 cells was associated with excessive activation of the PI3K/AKT pathway in patients with aGVHD. Specifically, in vitro treatment with Galectin-9 reduced IFN-γ and IL-17 production while augmenting TGF-β secretion. Bioinformatics analysis suggested the potential involvement of the PI3K/AKT/mTOR pathway in aGVHD. Mechanistically, exogenous Galectin-9 was found to mitigate aGVHD by restoring the Treg/Teffs (effector T cells) balance and suppressing PI3K. Conclusion Galectin-9 may ameliorate aGVHD after haplo-HSCT by modulating Treg/Teffs balance and regulating the PI3K/AKT/mTOR pathway. Targeting Galectin-9 may hold potential value for the treatment of aGVHD.
研究领域:
免疫学
·
血液学
·
移植学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Antioxidants
·
2025
·Vol. 14
·期 10
·1206
·
IF 6.6
Haoyu Liu,Zhen Yang,Qian Chen,Hongjuan Zhang,Yu Liu,Di Wu,Dan Shao,Shengyi Wang,Baocheng Hao
Chronic inflammatory bowel disease, ulcerative colitis (UC), currently lacks specific drugs for clinical treatment, and screening effective therapeutic agents from natural plants represents a critical research strategy. This study aimed to investigate the therapeutic potential of the flavonoid extract of Polygonum viviparum L. (TFPV) against UC. Liquid chromatography-mass spectrometry (LC-MS) was used to identify the chemical components of TFPV, while cell and animal models were employed to evaluate its anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation. The mechanism of anti-inflammatory action was further investigated using a mouse model of UC induced by dextran sulfate sodium (DSS). The results revealed the identification of 32 bioactive components in TFPV, with major compounds such as kaempferol, luteolin, galangin, and quercetin. TFPV effectively mitigated inflammatory damage induced by LPS in IPEC-J2 cells and C57BL/6 mice. In the UC modeled by DSS, TFPV attenuated intestinal inflammation by reducing pro-inflammatory cytokines IL-1β, IL-6, and TNF-α; increasing the anti-inflammatory cytokine IL-10; up-regulating tight junction protein expression such as Claudin-1, Occludin, and ZO-1; and inhibiting the expression of PI3K, AKT, NF-κB, and IL-17 proteins. Analysis of mice fecal samples through 16S rRNA gene sequencing demonstrated that TFPV adjusted the equilibrium of gut microbiota by boosting the abundance of Dubosiella and diminishing that of Enterococcus , Romboutsia , and Enterobacter . Untargeted metabolomics analysis further revealed that TFPV reduced inosine and ADP levels while increasing dGMP levels by the regulation of purine metabolism, ultimately resulting in decreased uric acid levels and thereby alleviating intestinal inflammation. Additionally, TFPV safeguarded the intestinal mucosal barrier by enhancing the expression of tight junctions. In conclusion, TFPV alleviates UC by blocking the PI3K/AKT/NF-κB and IL-17 signaling pathways, lessening intestinal inflammation and injury, safeguarding intestinal barrier integrity, balancing gut microbiota, and lowering uric acid levels, suggesting its promise as a therapeutic agent for UC.
✓ 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）