查找使用阿拉丁产品的科研文献

The mechanism of Shenbing Decoction II against IgA nephropathy renal fibrosis revealed by UPLC-MS/MS, network pharmacology and experimental verification

Huaxi Liu,Weijie Chen,Chunyang Tian,Yijian Deng,Liangwo Xu,Wenkun Ouyang,Renjie Qiu,Yanting You,Pingping Jiang,Lin Zhou,Jingru Cheng,Hiu Yee Kwan,Xiaoshan Zhao,Xiaomin Sun

Background IgA nephropathy (IgAN) is a major and growing public health problem. Renal fibrosis plays a vital role in the progression of IgAN. This study is to investigate the mechanisms of action underlying the therapeutic effects of Shenbing Decoction II (SBDII) in IgAN renal fibrosis treatment based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), network pharmacology and experimental verification. Method We first used UPLC-MS/MS to explore the main compounds of SBDII, and then used network pharmacology to predict the targets and key pathways of SBDII in the treatment of IgAN renal fibrosis. Next, bovine serum albumin (BSA), lipopolysaccharide (LPS), and carbon tetrachloride (CCL4) were used to induce IgAN in rats, and then biochemical indicators, renal tissue pathology, and renal fibrosis-related indicators were examined. At the same time, part of the results predicted by network pharmacology were also verified. Result A total of 105 compounds were identified in SBDII by UPLC-MS/MS. Network pharmacology results showed that the active compounds such as acacetin, eupatilin, and galangin may mediate the therapeutic effects of SBDII in treating IgAN by targeting tumor protein p53 (TP53) and regulating phosphatidylinositol 3-kinase (PI3K)-Akt kinase (Akt) signaling pathway. Animal experiments showed that SBDII not only significantly improved renal function and fibrosis in IgAN rats, but also significantly downregulated the expressions of p53, p-PI3K and p -Akt. Conclusion This UPLC-MS/MS, network pharmacological and experimental study highlights that the TP53 as a target, and PI3K-Akt signaling pathway are the potential mechanism by which SBDII is involved in IgAN renal fibrosis treatment. Acacetin, eupatilin, and galangin are probable active compounds in SBDII, these results might provide valuable guidance for further studies of IgAN renal fibrosis treatment.

Biological characteristics of menstrual blood-derived endometrial stem cell-derived secretome and its therapeutic potential

Yinglei Liu,Guojie Hao,Miaomiao Ma,Haolong Wang,Yu Sun,Wenqiang Zhang,Xingpeng Kang,Haofeng Song,Yilin Lu,Junfang Wu,Wenqiang Fan,Yanli Liu,Juntang Lin

This study aims to systematically characterize the protein and metabolite compositions of the secretome isolated from menstrual blood-derived endometrial stem cell (MenSC-S), elucidate its biological properties, explore potential active components and mechanisms of action as an acellular therapeutic agent, and provide a scientific foundation for advancing its clinical applications. A total of 878 shared proteins were identified in MenSC-S samples from volunteers of varying ages (25, 35, and 45 years), among which 242 were recognized as secretory proteins. The investigation revealed that the key protein heat shock protein family A member 8 (HSPA8) negatively regulates the assembly of the NLRP3 inflammasome complex by activating the PI3K-Akt signaling pathway. Untargeted metabolomic analysis indicated that metabolites present in MenSC-S play significant roles in biological processes such as nitrogen metabolism, amino acid synthesis, and detoxification. Integrated protein-metabolite analysis highlighted the considerable complexity of both proteome and metabolome along with their synergistic effects. Dialysis experiments confirmed that the metabolite fractions within MenSC-S are crucial for enhancing cell viability in both normal cells and those damaged by Cisplatin. This study partially elucidates the biological properties of MenSC-S along with potential molecular mechanisms underlying its therapeutic effects. It not only identifies specific potential active components for developing acellular therapeutic strategies targeting various diseases based on MenSC-S but also establishes a foundation for further exploration into the clinical translation of mesenchymal stem cells (MSCs) and their derivatives.

Green carbon dots derived from Zingiberis Rhizoma Carbonisatum alleviate ovalbumin-induced allergic rhinitis

Long Zhou,Yingxin Yang,Tingjie Li,Yafang Zhao,Jinye Yuan,Chenxin He,Yan Huang,Jinyu Ma,Yue Zhang,Fang Lu,Jiaze Wu,Zijian Li,Hui Kong,Yan Zhao,Huihua Qu

Background: Allergic rhinitis (AR) affects up to 40% of the population, leading to significant healthcare expenditures. Current mainstream treatments, while effective, can lead to side effects and do not address the underlying immunological imbalances. Zingiberis Rhizoma Carbonisatum (ZRC), the partially charred product of Zingiberis Rhizoma (ZR), has been widely used clinically in China since ancient times to treat respiratory disorders.Methods: Inspired by the similarity between high-temperature pyrolysis and carbonization processing of herbal medicine, ZRC derived CDs (ZRC-CDs) were extracted and purified through several procedures. Then, the physicochemical characteristics of CDs were delineated through a suite of characterization methods. Moreover, our investigation zeroed in on elucidating the ameliorative impacts of CDs on ovalbumin-induced rat models alongside their underlying mechanisms.Results: ZRC-CDs with particle sizes ranging from 1.0 to 3.5 nm and rich surface functional groups. Additionally, we observed that ZRC-CDs significantly attenuated nasal symptoms and pathological damage in ovalbumin-induced AR rats, and modulated lipid metabolism and type 2 inflammatory responses. They also inhibit PI3K/AKT and JAK/STAT pathways, which are associated with metabolism and inflammation. Importantly, ZRC-CDs demonstrated high biocompatibility, underscoring their potential as a novel therapeutic agent.Conclusion: ZRC-CDs offer a promising alternative for AR treatment and could help facilitate broader clinical use of the ZRC. In addition, the exploration of the inherent bioactivity of CDs can help to broaden their biological applications.

High-molecular-weight fucosylated glycosaminoglycan induces human platelet aggregation depending on αIIbβ3 and platelet secretion

Lisha Lin,Lian Yang,Jun Chen,Lutan Zhou,Sujuan Li,Na Gao,Jinhua Zhao

Fucosylated glycosaminoglycan (FG) from sea cucumbers has been reported to have anticoagulant effects via targeting intrinsic tenase. However, FG from natural source also potentially poses risks due to its FXIIa activation and platelet aggregating effects. Here, we found that the effect of FG on human platelet aggregation depended on both the sulfation pattern and chain length. FGs with higher content of Fuc2S4S and larger molecular weight (≥14 kD) had stronger activity. Both platelet aggregation and P-selectin expression induced by TaFG (an FG from Thelenota ananas) were decreased as the molecular weight reduced. Ticagrelor, aspirin and wortmannin completely blocked the secretion (ADP) but only partially blocked the aggregation induced by TaFG. Tirofiban an αIIbβ3 antagonist however potently inhibited both the secretion and aggregation, with IC50 of 6.01 ± 1.1.97 nM. Furthermore, TaFG could bind to human αIIbβ3 with high affinity, and the affinities of two FGs were paralleled with their activity in platelet aggregation or activation. These results indicated that αIIbβ3 played an important role in TaFG-induced platelet aggregation which was mediated by PI3K, and that platelet secretion was required for the amplification of aggregation.

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.

A Glutathione Peroxidase-Mimicking Nanozyme Precisely Alleviates Reactive Oxygen Species and Promotes Periodontal Bone Regeneration

Bijun Zhu,Jiangjiexing Wu,Tong Li,Songtao Liu,Junheng Guo,Yijun Yu,Xinyi Qiu,Yue Zhao,Haoran Peng,Jinli Zhang,Leiying Miao,Hui Wei

The use of oxidoreductase nanozymes to regulate reactive oxygen species (ROS) has gradually emerged in periodontology treatments. However, current nanozymes for treating periodontitis eliminate ROS extensively and non-specifically, ignoring the physiological functions of ROS under normal conditions, which may result in uncontrolled side effects. Herein, using the MIL-47(V)-F (MVF) nanozyme, which mimics the function of glutathione peroxidase (GPx), we propose that ROS can be properly regulated by specifically eliminating H 2 O 2 , the most prominent ROS. Through H 2 O 2 elimination, MVF contributes to limiting inflammation, regulating immune microenvironment, and promoting periodontal regeneration. Moreover, MVF stimulates osteogenic differentiation of periodontal stem cells directly, further promoting regeneration due to the vanadium in MVF. Mechanistically, MVF regulates ROS by activating the Nrf2/HO-1 pathway and promotes osteogenic differentiation directly through the PI3K/Akt pathway. We present a promising periodontitis therapy strategy using GPx-mimicking nanozymes through their triple effects of antioxidation, immunomodulation, and bone remodeling regulation, making nanozymes an excellent tool for developing precision medicine. This article is protected by copyright. All rights reserved

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.

Enhancing HepG2 cell apoptosis with a combined nanoparticle delivery of miR-128-3p agomir and Oroxin B: A novel drug delivery approach based on PI3K-AKT and VEGF pathway crosstalk

Hechen Wang,Xudan Shen,Xinlan Zhu,Su Zeng,Sheng Cai

Hepatocellular carcinoma (HCC) shows the highest morbidity among liver cancers and accounts for a major factor inducing cancer-associated mortality globally. It is characterized by genetic mutations in hepatocytes, leading to uncontrolled cell growth and proliferation. Treatment options for HCC include surgery, chemotherapy, and immunotherapy. But chemotherapeutics, which focus on single-targeted drug therapy, are still associated with certain limitations and may affect the treatment outcomes. Compared with chemotherapy drugs, natural products also show the anticancer effect of HCC and hypotoxicity, but overall low activity of natural products limits their further application. MiRNAs can modulate post-transcriptional functions of target genes. An increasing body of evidence has demonstrated that miRNAs are the key regulators in HCC by targeting different molecules in different signaling pathways. However, miRNAs are fragile and liable to catabolism by RNases in serum and other body fluids and small molecules separated from natural products may have limited bio-availability. According to this background, a chitosan based, targeted sustained-release nanoparticle delivery miR-128-3p agomir (NA-miR-128-3p) was developed in this work. This nanoparticle was prepared by pentasodium tripolyphosphate (TPP), chitosan hydrochloride, and miR-128-3p agomir with target aptamer which was loaded into the chitosan nanoparticle by self-assembly. It can intervene in HCC progress by affecting AKT1 expression. Based on this, a novel, efficient, long-acting, multi-mechanism, low-dosage combination drug delivery strategy was proposed in this work and showed a prominent anti-tumor effect. NA-miR-128-3p combined with natural product Oroxin B significantly affected HCC progression by the interference with VEGF and PI3K-AKT pathways, better than using NA-miR-128-3p and Oroxin B alone. Taken together, this nanoparticle and combinative administration compensate for the shortcomings of the fragile RNA drugs and the low activity of natural products, with high prospects in HCC treatment.

Muscle-Targeted Nanocomposite Therapy Alleviates Age-Related Sarcopenia via Antioxidant and Metabolic Reprogramming

Zhang Liu,Zile Shen,Hengli Lu,Bingqiang Lu,Peng Zhang,Wenhao Chen,Guowei Huang,Xinyu Qu,Zhen Yu,Feng Chen,Wangfu Zang

Sarcopenia, a progressive skeletal muscle disorder marked by loss of mass and function, presents growing societal challenges due to limited therapeutic options. Here, we identify mitochondrial dysfunction and oxidative stress as central drivers of sarcopenia through integrated bioinformatics and clinical validation. To address this pathophysiology, we engineer a muscle-targeted nanocomposite (BP-PEG-MOTS-c, BM) combining mitochondrial-derived peptide MOTS-c with antioxidant black phosphorus nanosheets (BP). BM exhibits dual functionality: MOTS-c restores mitochondrial function, while BP synergistically amplifies ROS scavenging capacity. In cellular and murine models with age-related sarcopenia, BM treatment alleviates muscle dysfunction and muscle loss, concurrently normalizing mitochondrial function and reducing lipid peroxidation. Mechanistic profiling via RNA-seq reveals BM’s activation of PI3K/AKT/Nrf2 and suppression of ROS/p38 MAPK signaling pathway, mediating antioxidant responses and maintenance of mitochondrial homeostasis. The nanocomposite demonstrats superior biocompatibility in toxicity assays, outperforming conventional delivery systems. Our findings establish that BM has been established as a promising mitochondrial redox modulator with translational potential for sarcopenia and related age-associated pathologies.