查找使用阿拉丁产品的科研文献

Fractional extraction phenolics from C. oleifera seed kernels exhibited anti-inflammatory effect via PI3K/Akt/NF-κB signaling pathway under Caco-2/RAW264.7 co-culture cell model

Chengyu Jin,Chu Chu,Xianghai Zhu,Yuanchao Lu,Ningxiang Yu,Qin Ye,Yuanxiang Jin,Xianghe Meng

Camellia oleifera Abel ( C. oleifera ) is a multifunctional oilseed, which is rich in many biological active substances with health-promoting properties, especially polyphenols. Previous research revealed that camellia oil phenolics exhibited anti-inflammatory effect, which originated from seed. Thus, we aimed to explore the components of camellia seed phenolics and its potential mechanism of anti-inflammation. Initially, fractional extraction was processed to prepare the phenolics from camellia seed kernels, and we compare four different fractions of phenolics under the LPS-induced Caco-2/RAW264.7 coculturing model. Results showed that free phenolics (FP) had best effect on alleviating pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and TNF-α) compared to esterified-bound phenolics (EP), glycosylated-bound phenolics (GP) and insoluble-bound phenolics (IP). Furthermore, FP reduced inflammation by suppressing the PI3K/Akt/NF-κB signaling pathway and effectively inhibited LPS-induced intestinal permeability increase, tight junction related proteins loss (ZO-1, claudin-1). Same results obtained, as the transepithelial electrical resistance (TEER) and alkaline phosphatase (AKP) activity of high-dose FP treated group was high than model group. Finally, molecular docking was used for evaluating the anti-inflammatory effect for phenolic monomer. KGRG (kaempferol −3-O-(2-O-glucopyranosyl-6-O-rhamnopyranosyl)-glucopyranoside), KXR (kaempferol 3-O-(2′’-xylopyranosyl)-rutinoside) and leucoside (kaempferol 3-O-sambubioside) show lower binding energy docking with NF-κB, PI3K and Akt protein, indicating better interactions, which might be effective constituents against inflammation. Subsequently, five major polyphenols were obtained to validate the docking results, especially, indicating the best anti-inflammatory activities of KGRG. Overall, this research sheds insights on the therapy of phenolics from C. oleifera seed towards LPS-induced intestinal inflammation model in vitro and its related mechanism.

Metal-Phenolic Modified Coaxial Electrospun Biomembrane Combined with the Photothermal Effect Enhances Bone Regeneration by Ameliorating Oxidative Stress and Mitochondrial Dysfunction via the PI3K/Akt Signaling Pathway

Shikang Zheng,Xiumei Sun,Kai Chen,Mingjun Zhang,Chentong Zou,Lin Wang,Zhipeng Guo,Zhaoyi Jin,Ziyi Ma,Guanyu Li,Guomin Wu

Critical-sized bone defect regeneration remains a significant clinical challenge due to the complex cascade of biological processes involved. To address this, we developed a sophisticated hierarchical biomembrane (PCS@MPN10) designed to modulate the osteogenic microenvironment. Using coaxial electrospinning, we fabricated a core–shell structure with polylactic acid (PLA) as the membrane base, incorporating simvastatin in the core and chitosan in the shell. The membrane surface was further modified with a tannic acid-iron metal-polyphenol network coating. Our results demonstrated that the biomembrane exhibits excellent biocompatibility, photothermal properties, and significant antibacterial activity. Additionally, the membrane regulates the microenvironment by promoting M1-to-M2 macrophage polarization, showing strong osteogenic potential both in vitro and in vivo. Furthermore, PCS@MPN10+NIR modulates mitochondrial function through the PI3K-AKT pathway, clears mitochondrial reactive oxygen species (ROS), and alleviates cellular oxidative stress, thereby enhancing bone regeneration. Overall, these findings suggest that this biomembrane holds great promise as a strategy for improving bone regeneration in critical-sized defects.

Concerted inhibition of mTORC1/2 and NF-κB by Yuye Jiedu granule via AMPK activation and PI3K/Akt suppression: A novel therapeutic strategy against upper respiratory infections

Xiaolong Feng,Xinru Tao,Penghui Li,Jun Chen,Kaiyi Chen,Jinsheng Jiang,Yuan Cai,Yanmei Peng

Ethnopharmacological relevance Yuye Jiedu Granule (YYJD), a traditional herb preparation developed by Hunan Changde Sanjin Pharmaceutical Co., Ltd., has been used in clinical settings for many years to manage upper respiratory tract infections (URTI) attributed to exogenous wind-heat. Although its effectiveness is well recognized, the active constituents responsible for its effects and the molecular pathways involved are not clear yet. Aim of the study To identify the bioactive constituents of YYJD and elucidate its molecular mechanisms in treating URTI. Materials and methods Initially, the chemical composition of YYJD was analyzed using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) in combination with a molecular networking approach. Anti-inflammatory components within the formula were then identified using a UPLC-based separation system and a dual-luciferase reporter gene screening assay, followed by in vitro validation. Subsequently, an acute pneumonia model was developed using Pseudomonas aeruginosa infection to comprehensively assess the therapeutic efficacy of YYJD through integrated transcriptomic, metabolomic, and network pharmacology analyses. Finally, the underlying molecular mechanisms were experimentally confirmed. Results A total of 145 chemical constituents were identified in YYJD, among which 15 were found to inhibit NF-κB. In vivo studies demonstrated that YYJD notably decreased mortality, lung indices, and serum pro-inflammatory cytokines in P. aeruginosa -infected mice. Integrated multi-omics analysis highlighted adenosine monophosphate (AMP) as a central metabolite, with major bioactive compounds classified as organic acids, flavonoids, iridoid glycosides, and triterpenoid saponins . Nine pivotal targets and the AMPK-mTORC1/2-PI3K/Akt/NF-κB axis were identified as central to YYJD’s anti-URTI effects. Mechanistically, YYJD modulated the phosphorylation of GSK3β, Akt, IκBα, mTOR, and AMPK, along with the p65 expression. Conclusion This study presents the first in-depth analysis of YYJD’s chemical profile and elucidates its multi-target therapeutic mechanisms against URTI through AMPK-centered metabolic-inflammatory interplay. These results offer a stronger scientific foundation for the clinical use of YYJD and introduce a potential new approach for treating respiratory infections.

Butyrate ameliorates DSS-induced ulcerative colitis in mice by facilitating autophagy in intestinal epithelial cells and modulating the gut microbiota through blocking the PI3K-AKT-mTOR pathway

Ruifang Li,Yan Sun,Drolma Kelsang,Mingzhi Feng,Hanhui Cai,Jun Zhang

Background Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disease of the colon that imposes a significant global public health burden due to its recurrent and refractory nature. The therapeutic effects of butyrate on UC have been documented previously, but its specific mechanisms remain unclear. Objective This study aimed to investigate the effects and potential mechanisms of butyrate in dextran sulfate sodium (DSS)-induced UC. Methods A UC mouse model was induced utilizing 3% DSS, followed by interventions of 300 mg/kg, 600 mg/kg, or 1200 mg/kg of butyrate. The fecal condition and colonic pathology of the mice were observed, along with measurements of body weight and colon length. The expression of serum inflammatory factors, autophagy-related proteins, and the PI3K/AKT/mTOR pathway-related proteins were detected. Additionally, the impact of butyrate on the mouse gut microbial communities was evaluated using 16S rRNA sequencing technology. Results It was demonstrated that butyrate effectively alleviated UC symptoms, including bloody stools, weight loss, and colon shortening. Furthermore, butyrate reduced colonic tissue damage, decreased the expression of TNF-α, IL-1β, and IL-6, and significantly upregulated Beclin-1, Atg5, and the LC3II/I ratio, while reducing P62 expression. Butyrate also decreased the relative expression of p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR. 16S rRNA sequencing results revealed that butyrate improved the intestinal microbial community structure by inhibiting harmful bacteria and accelerating the growth of beneficial bacteria. Conclusion This study suggests that butyrate may alleviate DSS-induced UC in mice by blocking the PI3K/AKT/mTOR pathway to facilitating autophagy in intestinal epithelial cells and by modulating the gut microbiota.

Ginsenoside Ro attenuates aging-related cognitive impairment and associated neuroinflammatory changes via multi-target modulation of the PI3K-Akt axis: a convergent network pharmacology and experimental validation study

Hou Jingyi,Yang Kailan,Zhang Dandan,Ba Yi,Wang Yubo,Zhao Changqi,Zhu Naiqiang,Gu Miao

The increasing global burden of aging-related cognitive impairment (ACI) highlights an urgent need for disease-modifying therapeutics, as current pharmacological options provide only temporary symptomatic relief without affecting underlying pathological trajectories. Ginsenoside Ro, an oleanane-type saponin derived from Panax ginseng, displays anti-inflammatory and cytoprotective properties; however, the target network and signaling mechanisms through which it may alleviate ACI remain inadequately defined. This study aims to thoroughly define the therapeutic efficacy and underlying molecular mechanisms of Ginsenoside Ro against ACI utilizing a convergent analytical approach that integrates network pharmacology, in silico molecular simulation, and empirical validation in aging-model mice and senescent PC12 cells. Putative targets of Ginsenoside Ro were sourced from PubChem, SwissTargetPrediction, STITCH, ChEMBL, and SEA databases. ACI-relevant and aging-associated targets were curated from HAGR, OMIM, and GeneCards databases. A protein–protein interaction (PPI) network was constructed using STRING, and hub targets were identified with the cytoHubba algorithm. Functional enrichment analysis, including GO and KEGG analyses, was performed via DAVID. Binding interactions were evaluated using molecular docking and 100 ns molecular dynamics (MD) simulations. In vivo characterization involved the development of a senescence mouse model via intraperitoneal D-galactose (D-Gal) administration (125 mg/kg/d for 10 weeks), followed by oral treatment with Ginsenoside Ro (5 and 10 mg/kg) or melatonin (100 mg/kg) for 6 weeks. Cognitive performance was assessed using the Morris water maze (MWM) and open field test (OFT). Systemic oxidative status was monitored by measuring serum MDA, SOD, and MAO, while neural tissue integrity was examined through H&E and Nissl staining. In vitro, D-Gal-induced senescent PC12 cells were treated with Ginsenoside Ro (3.125–12.5 µM), followed by evaluations of cell viability, SA- β -galactosidase activity, ROS accumulation, SOD function, and expression levels of TNF-α, IL-6, EGFR, and components of the PI3K-Akt cascade using CCK-8, flow cytometry, RT-qPCR, and Western blot. Target intersection analysis identified 30 overlapping nodes between Ginsenoside Ro and ACI, with TNF-α, IL-6, AKT1, and EGFR recognized as core targets. KEGG enrichment analysis highlighted PI3K-Akt signaling as a key mechanistic pathway. Molecular docking yielded binding energies ranging from − 8.8 to − 4.8 kcal/mol, while MD trajectories demonstrated RMSD/RMSF profiles, hydrogen-bond interactions, and distinct deep free-energy minima consistent with sustained complex formation over the simulation period. In the D-Gal mouse model, Ginsenoside Ro reduced escape latency, increased platform crossings and exploratory behavior, decreased serum MDA, restored SOD and MAO levels, and ameliorated neuronal loss and nuclear pyknosis in the hippocampus and cortex. In PC12 cells, Ginsenoside Ro improved viability, diminished SA- β -gal positivity and ROS accumulation, enhanced SOD activity, restored EGFR expression, suppressed IL-6/TNF-α induction, and normalized the elevated p-PI3K/PI3K and p-AKT/AKT ratios. These findings suggest that Ginsenoside Ro is associated with the modulation of TNF-α, IL-6, AKT1, and EGFR, and that the PI3K-Akt pathway may serve as a central axis correlated with its observed neuroprotective effects. Ginsenoside Ro emerges as a promising candidate for ameliorating aging-associated cognitive dysfunction and related pathological changes, providing a preclinical basis for future translational development.

Antioxidative Lignin Materials Attenuate Type 2 Diabetes Mellitus (T2DM) Progression by Preserving Glutathione via Insulin Receptor Substrate 1/Phosphoinositide 3-Kinase/Protein Kinase B (IRS1/PI3K/AKT) Axis

Shuang Qi,Hui Yang,Tian Fang,Tingwei Zhang,Bo Jiang,Sehrish Manan,Chaofeng Zhang,Peng Wang,Caoxing Huang,Wenjuan Wu,Yongcan Jin

Lignin, a natural and renewable aromatic biopolymer, has gained attention in various biomedical applications due to its diverse structure, excellent biocompatibility, and antioxidant activity. However, the effects of lignin with tailored molecular weight on treating type 2 diabetes mellitus (T2DM) remain largely unexplored. In this study, a series of heterogeneous natural phenolic kraft lignin (KL) with tailored molecular weights, derived through an anti-sugar strategy, were prepared by continuous fractionation. The lignin fractions were categorized as F1, F2, and F3, corresponding to high, medium, and low molecular weights, respectively. Their therapeutic effects on T2DM were evaluated using a fractionated lignin culture cell model and intravenous injection into the tail vein of diabetic rats. The results demonstrated that lignin's protective effects in attenuating T2DM progression were molecular weight-dependent. Specifically, F3 reduced fasting blood glucose, reversed insulin resistance, and improved insulin sensitivity by mitigating oxidative stress and inflammatory responses. Mechanistic investigations revealed that F3 positively regulated glucose and lipid metabolism, inhibited hepatic gluconeogenesis, and enhanced hepatic glycogen synthesis by activating the insulin receptor substrate 1/phosphoinositide 3-kinase/protein kinase B (IRS1/PI3K/AKT) signaling pathway. Results revealed that lignin exerts its therapeutic effects on T2DM in a molecular weight-dependent manner, with IRS1/PI3K/AKT signaling as a potential underlying mechanism. This highlights lignin with a defined molecular weight as a promising candidate for T2DM treatment.

Integration of network pharmacology, lipidomics, and transcriptomics analysis to reveal the mechanisms underlying the amelioration of AKT-induced nonalcoholic fatty liver disease by total flavonoids in vine tea

Siyu Du,Xin Chen,Rumeng Ren,Li Li,Baohui Zhang,Qi Wang,Yan Meng,Zhenpeng Qiu,Guihong Wang,Guohua Zheng,Junjie Hu

Nonalcoholic fatty liver disease (NAFLD) is the main reason for chronic liver diseases and malignancies. Currently, there is a lack of approved drugs for the prevention or treatment of NAFLD. Vine tea (Ampelopsis grossedentata) has been used as a traditional Chinese beverage for centuries. Vine tea carries out several biological activities including the regulation of plasma lipids and blood glucose, hepato-protective function, and anti-tumor activity and contains the highest content of flavonoids. However, the underlying mechanisms of total flavonoids from vine tea (TF) in the attenuation of NAFLD remain unclear. Therefore, we investigated the interventions and mechanisms of TF in mice with NAFLD using an integrated analysis of network pharmacology, lipidomics, and transcriptomics. Staining and biochemical tests revealed a significant increase in AKT-overexpression-induced (abbreviated as AKT-induced) NAFLD in mice. Lipid accumulation in hepatic intracellular vacuoles was alleviated after TF treatment. In addition, TF reduced the hepatic and serum triglyceride levels in mice with AKT-induced NAFLD. Lipidomics results showed 32 differential lipids in the liver, mainly including triglycerides (TG), diglycerides (DG), phosphatidylcholine (PC), and phosphatidylethanolamine (PE). Transcriptomic analysis revealed that 314 differentially expressed genes were commonly upregulated in the AKT group and downregulated in the TF group. The differential regulation of lipids by the genes Pparg, Scd1, Chpt1, Dgkz, and Pla2g12b was further revealed by network enrichment analysis and confirmed by RT-qPCR. Furthermore, we used immunohistochemistry (IHC) to detect changes in the protein levels of the key proteins PPARγ and SCD1. In summary, TF can improve hepatic steatosis by targeting the PPAR signaling pathway, thereby reducing de novo fatty acid synthesis and modulating the glycerophospholipid metabolism.

Elucidation of the mechanism of the fruit of Rubus chingii Hu against CCl4-induced liver injury in mice based on met/Tlr2/Tlr4 -mediated PI3K-Akt signaling pathway

Ping Jiang,Yanfei He,Guangpei Xu,Chuanbo Sun

This study aims to evaluate the mechanism of RCH against CCl 4 -induced liver injury in mice. RCH treatment effectively inhibited CCl 4 -induced liver injury and apoptosis in mice, and reduced liver enzyme activities, blood inflammatory cell and serum inflammatory factor levels. Network pharmacology and machine learning predicted that PI3K-Akt pathway and Met proteins play important roles in RCH anti-CCl 4 -induced liver injury. The results of qRT-PCR and Western blot showed that RCH could down-regulate the expression of the receptor proteins Met, Tlr2, and Tlr4, and inhibit the phosphorylation of Pik3ca and Akt1, and prevent the phosphorylation of NF-κB P65, and decrease cleaved Caspase3 expression. These findings suggest that RCH effectively alleviated liver injury in CCl 4 -induced mice by inhibiting the Met/Tlr2/Tlr4-mediated PI3K-Akt signaling pathway.

Paeonia delavayi seed oil rich in oleic acid and linolenic acid alleviates UVB-induced inflammation and oxidative stress in keratinocytes through inhibition of PI3K/Akt and NF-κB pathways

Rencong Wang,Peng Xu,Yindi Zhang,Xiaoli Jin,Ziyan Zhao,Liping Qu,Feifei Wang

Excessive exposure to UVB can induce inflammatory responses and oxidative stress, leading to skin damage. Peony seed oil is rich in unsaturated fatty acids and has been reported to possess anti-inflammatory and antioxidant properties. This study investigated the protective effects and underlying mechanisms of Paeonia delavayi seed oil (PDSO) against UVB-induced damage in human keratinocytes. PDSO at 30–120 μg/mL attenuated UVB-induced inflammation by reducing the mRNA expression of TNF , IL6 , CXCL8 , and PTGS2 and suppressing the secretion of IL-6 and IL-8. PDSO also inhibited UVB-induced activation of NF-κB signaling. Regarding oxidative stress, 120 μg/mL PDSO reduced intracellular ROS production, decreased MDA levels by approximately 29.4%, and increased SOD activity by approximately 122.0% compared with the UVB group. PDSO also increased the mRNA expression of antioxidant-related genes, including NFE2L2, HMOX1, SOD1, CAT, GCLC, and GCLM . In addition, PDSO alleviated the UVB-induced reduction in keratinocyte viability and attenuated photoaging-related changes. Transcriptomic analysis identified PI3K/Akt signaling as a candidate pathway associated with PDSO treatment, and western blotting further showed that PDSO inhibited UVB-induced PI3K/Akt signaling. Pharmacological intervention with the PI3K activator 740Y P partially reversed the anti-inflammatory effects of PDSO, whereas LY294002 exerted anti-inflammatory effects and further enhanced those of PDSO. Moreover, oleic acid and linolenic acid alleviated UVB-induced inflammation and oxidative stress. Collectively, PDSO protects keratinocytes against UVB-induced damage, with PI3K/Akt and NF-κB signaling contributing to its protective effects. Download: Download high-res image (117KB) Download: Download full-size image

The ameliorating effects of Guizhi Fuling Wan combined with rosiglitazone in a rat ovarian model of polycystic ovary syndrome by the PI3K/AKT/NF-κB and Nrf2/HO-1 pathways

Yongju Ye,Weimei Zhou,Yuefang Ren,Jiali Lu,Aixue Chen,Ruiying Jin,Feilan Xuan

MicroRNA miR-106a-5p targets forkhead box transcription factor FOXC1 to suppress the cell proliferation, migration, and invasion of ectopic endometrial stromal cells via the PI3K/Akt/mTOR signaling pathway

Xinyue Zhou,Zhenyu Chen,Lipeng Pei,Jingli Sun

Emerging evidence has exhibited an obvious decreased expression of miR-106a-5p in the ectopic endometrial tissue of endometriosis (EMS) patients. Thus far, the pathophysiological function of miR-106a-5p in EMS is unknown. A previous study showed an increased FOXC1 expression in the ectopic endometrial tissue of patients with EMS. Moreover, we found that there was a binding site of miR-106a-5p on the 3ʹUTR of FOXC1 through bioinformatics predictions. Hence, we speculated that miR-106a-5p might affect the development of EMS via targeting FOXC1. We first showed a decreased level of miR-106a-5p and an increased level of FOXC1 mRNA in ectopic endometrial tissues compared with normal tissues. Functionally, we transfected ectopic endometrial stromal cells (ESCs) with miR-106a-5p mimics or NC mimics and indicated an inhibitory role of miR-106a-5p on ESC proliferation, invasion, and migration. Mechanistically, FOXC1 was found to be a target gene of miR-106a-5p. To confirm whether miR-106a-5p exerted an inhibitory activity in ESCs via targeting FOXC1, miR-106a-5p mimic was co-transfected into ESCs with the FOXC1-plasmid or vector. We found that FOXC1 overexpression evidently reversed the results caused by a miR-106a-5p mimic in ESCs. Additionally, our results demonstrated that miR-106a-5p mimic inhibited the expression of p-Akt and p-PI3K. Collectively, these results revealed that miR-106a-5p inhibited the proliferative, migratory, and invasive ability of ESCs via directly binding to FOXC1, likely through the suppression of the PI3K and its downstream signaling pathway, which offered a potential and novel therapeutic strategy for EMS treatment.

Clostridium butyricum protects intestinal barrier function via upregulation of tight junction proteins and activation of the Akt/mTOR signaling pathway in a mouse model of dextran sodium sulfate‑induced colitis

Miao Liu,Wenjie Xie,Xinyue Wan,Tao Deng

Clostridium butyricum (CB), a probiotic, is a gram-positive obligate anaerobic bacillus with acid and heat resistant properties. Previous studies have reported that CB has beneficial effects in intestinal diseases and regulates intestinal function. The aim of the present study was to investigate the protective effects and mechanisms of CB on the intestinal barrier function. Mice were randomly divided into three experimental groups (n=15 mice/group), including control, dextran sodium sulfate (DSS) and DSS + CB. In the DSS and DSS + CB groups colitis was induced with 3% DSS dissolved in drinking water for 7 days. DSS + CB group mice were co-treated daily with 200 µl (2x108 CFU) CB solution via gavage. The intestinal mucosal barrier function in mice was assessed by measuring FITC-labeled 4-kDa dextran (molecular weight, 4,000 Da) flux and by analyzing the expression of tight junction (TJ)-related proteins using western blot analysis. In addition, the secretion levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-10 and IL-13, and the concentration of malondialdehyde, glutathione and superoxide dismutase were detected using ELISAs to determine inflammation and oxidative stress, respectively. The activation status of the Akt/mTOR signaling pathway was also investigated using western blot analysis. The results demonstrated that, in mice with DSS-induced colitis treatment, co-treatment with CB attenuated colitis symptoms and intestinal permeability, increased the expression levels of TJ-related proteins, decreased TNF-α, IL-1β and IL-13 secretion levels but increased those of IL-10, and reduced oxidative stress. Additionally, CB elevated the phosphorylation of Akt, mTOR and p70 ribosomal protein S6 kinase. Collectively, the present results indicated that CB protected intestinal barrier function and decreased intestinal mucosal permeability via upregulating the expression levels of TJ-related proteins in a mouse model of DSS-induced colitis. Moreover, the results suggested that the effects of CB could be mediated by the Akt/mTOR signaling pathway.