CHINESE JOURNAL OF CHEMICAL ENGINEERING
·
2016
·
IF 1.207
Cunyu Li,Yun Ma,Hongyang Li,Guoping Peng
With the rapid increase of water contamination, membrane separation technology and their corresponding molecular weight cut-off (MWCO) evaluation method become more necessary. In this study, Panax notoginseng saponins was used as a new standard marker to determinate ultrafiltration (UF) membrane MWCOs, series of Millipore membranes were selected as control group to analyze and calculate the relationship between retention rate and MWCOs with exponential or logarithmic equation. A new and convenient method was provided for determining the membrane MWCO by modeling analysis retention rate with MWCOs, and the regression coefficients ≥ 0.990. The feasibility and practicability of established method was verified by different manufactures' membrane and dextrans . In the detection progress, as the main ingredient of Panax notoginseng saponins , Notoginsenoside R 1 , Ginsenoside Rg 1 , Ginsenoside Rb 1 and Ginsenoside Rd with different surface activity, the MWCO range of UF membranes can be divided into two zones mainly due to the retention rate difference among Notoginsenoside R 1 , Ginsenoside Rg 1 , Ginsenoside Rb 1 and Ginsenoside Rd . Zone I, 1000–10000; and Zone II, 10000–100000. Thus, the new method would be helpful to improve the applicability of UF membrane in separation technology.
研究领域:
环境科学
·
药学
✓ 已验证
DOI
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Xue Tian,Xu Chen,Qianqian Jiang,Qianbin Sun,Tiantian Liu,Yiqin Hong,Yawen Zhang,Yanyan Jiang,Mingyan Shao,Ran Yang,Chun Li,Qiyan Wang,Yong Wang
Aims: Cardiac lipotoxicity is the common consequence of lipid metabolism disorders in cardiomyocytes during development of heart failure (HF). Adenosine 5′monophosphate-activated protein kinase (AMPK) acts as an energy sensor and has a beneficial effect in reducing lipotoxicity. Notoginsenoside R1 (NGR1) is extracted from the traditional Chinese medicine Panax notoginseng (Burkill) F.H.Chen (P. notoginseng) and has definite cardioprotective effects. However, whether NGR1 can attenuate HF by mitigating lipotoxicity has not been elucidated yet. This study aimed to explore whether NGR1 plays a protective role against HF by ameliorating cardiac lipotoxicity via the AMPK pathway.
Methods: In this study, HF mice model was established by left anterior descending (LAD) ligation. palmitic acid (PA) stimulated H9C2 cell model was applied to clarify the effects and potential mechanism of NGR1 on lipotoxicity. In vivo, NGR1 (7.14 mg/kg/days) and positive drug (simvastatin: 2.9 mg/kg/days) were orally administered for 14 days. Echocardiography was applied to assess heart functions. Lipid levels were measured by Enzyme-linked immunosorbent assay (ELISA) and key proteins in the AMPK pathway were detected by western blots. In vitro, NGR1 (40 μmol/L) or Compound C (an inhibitor of AMPK, 10 μmol/L) was co-cultured with PA stimulation for 24 h in H9C2 cells. CCK-8 assay was used to detect cell viability. Key lipotoxicity-related proteins were detected by western blots and the LipidTOX™ neutral lipid stains were used to assess lipid accumulation. In addition, Apoptosis was assessed by Hoechst/PI staining.
Results: NGR1 could significantly improve the cardiac function and myocardial injury in mice with HF and up-regulate the expression of p-AMPK. Impressively, NGR1 inhibited the synthesis of diacylglycerol (DAG) and ceramide and promoted fatty acid oxidation (FAO) in vivo. Moreover, NGR1 significantly promoted expression of CPT-1A, the key enzyme in FAO pathway, and down-regulated the expression of GPAT and SPT, which were the key enzymes catalyzing production of DAG and ceramide. In vitro experiments showed that NGR1 could significantly attenuate lipid accumulation in PA-induced H9C2 cells and the Hoechst/PI staining results showed that NGR1 ameliorated lipotoxicity-induced apoptosis in PA-stimulated H9C2 cell model. Furthermore, co-treatment with inhibitor of AMPK abrogated the protective effects of NGR1. The regulative effects of NGR1 on lipid metabolism were also reversed by AMPK inhibitor.
Conclusion: NGR1 could significantly improve the heart function of mice with HF and reduce cardiac lipotoxicity. The cardio-protective effects of NGR1 are mediated by the activation of AMPK pathway.Keywords: heart failure, cardiac lipotoxicity, NGR1, AMPK, apoptosis
研究领域:
心脏病学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
AMERICAN JOURNAL OF CHINESE MEDICINE
·
2026
·Vol. 54
·期 05
·1551-1583
·
IF 7.8
Shuangjiang Li,Zhipeng Liu,Guandong Pan,Shuang Li,Guangyu Lv,Shifu Tang,Jiaguang Li,Qiuyun Li,Min Wu,Guandou Yuan,Shuiping Yu,Guoqing Ouyang
Acetaminophen (APAP) overdose is a leading cause of acute liver injury (ALI), yet effective therapeutic options remain limited. Although notoginsenoside R1 (NGR1) is a major bioactive saponin isolated from Panax notoginseng with established anti-inflammatory and anti-oxidant properties, its hepatoprotective potential and underlying mechanisms in APAP-induced liver injury (AILI) have not been systematically investigated. In this study, we established an AILI mouse model and evaluated the protective effects of NGR1 through biochemical assays, histopathology, Western blotting, and immunofluorescence, complemented by integrative transcriptomic, metabolomic, and gut microbiota analyses. Mechanistic involvement of the MAPK/mTOR–autophagy pathway was further validated using L-leucine as a pharmacological activator of mTOR. NGR1 markedly attenuated AILI, as reflected by reduced serum ALT/AST levels, improved hepatic histology, and increased survival in acute liver failure. NGR1 suppressed inflammatory responses by decreasing IL-1 β , IL-6, and TNF- α levels and alleviated oxidative stress by restoring GSH and SOD while reducing MPO, ROS, and MDA accumulation. Multi-omics analysis revealed significant enrichment of MAPK/mTOR signaling, autophagy, ferroptosis, and glutathione metabolism pathways. Mechanistically, NGR1 promoted autophagic flux (increased LC3-II/I, ATG5, and ATG7 with decreased p62), inhibited ferroptosis (upregulation of GPX4 and SLC7A11 with downregulation of ACSL4), and suppressed APAP-induced activation of the MAPK/mTOR pathway. Pharmacological activation of mTOR by L-leucine partly abolished the protective effects of NGR1, reversing autophagy activation and restoring inflammatory and oxidative injury. These findings collectively demonstrate that NGR1 protects against AILI by inhibiting MAPK/mTOR signaling, restoring autophagy, and suppressing ferroptosis, highlighting NGR1 as a promising therapeutic candidate for APAP-induced hepatotoxicity.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Pharmaceutical Investigation
·
2024
·
IF 5.3
Zhou Limei,Shang Yunxia,Wang Yaru,Wei Xiaohui
Purpose Ulcerative colitis (UC) is a chronic and non-specific inflammatory bowel disease that poses a serious threat to individuals' health and lives. Notoginsenoside R1 (R1) alleviates various symptoms caused by UC effectively. However, the application of R1 is somewhat restricted due to its low bioavailability and nontargeted delivery in vivo. Consequently, it is imperative to develop novel strategies to overcome the aforementioned limitations and enhance the efficacy of this drug. To enhance R1's efficacy and targeting ability, polyethylene glycol poly (lactic-co-glycolic acid) nanoparticles loaded with R1 (R1@PEG–PLGA NPs) modified by transferrin (Tf) were prepared in this study and named R1@Tf–PEG–PLGA NPs. Methods R1@PEG–PLGA NPs and R1@Tf–PEG–PLGA NPs were prepared through nanoprecipitation, and the characterization methods were as follows: First, the surface morphology of the NPs was studied through transmission electron microscopy. Second, particle size, polydispersity index (PDI), and zeta potential were measured with a Malvern particle size analyzer, and the Tf grafting rate on the surface of the NPs was determined by using a bicinchoninic acid protein quantification kit. Third, high-performance liquid chromatography was used in determining the drug load (DL), entrapment efficiency (EE), and in vitro release of the prepared preparation. In addition, the fluorescence intensities of fluorescent-labeled NPs absorbed and ingested in Caco-2 cells were observed through in vitro experiments using fluorescence microscopy; the effects of incubation time, incubation temperature, and endocytosis inhibitors on the uptake of nanoparticles were compared; and the uptake-transport mechanism was explored. Finally, in vivo experiments were performed using the oxazolone (OXZ)-induced UC model in Sprague–Dawley (SD) rats to assess the pharmacodynamic effects and tissue distribution of the prepared NPs. Results The experimentally prepared R1@Tf–PEG–PLGA NPs were round particles with particle size and PDI of 153.50 ± 2.01 and 0.11 ± 0.01, respectively. In addition, the DL of R1@Tf-PEG-PLGA NPs was 24.26% ± 0.18%, and the EE was 50.32% ± 0.86%. Furthermore, R1@Tf–PEG–PLGA NPs had a slower cumulative release rate in vitro than R1 and R1@PEG–PLGA NPs. Fluorescence results showed that under the same conditions, Caco-2 cells took up more Tf-PEG–PLGA NPs than they took up PEG–PLGA NPs. Studies on the cellular uptake mechanism of absorption and uptake determined that the PEG–PLGA NPs entered the cells mainly through fovea-mediated endocytosis, whereas the Tf–PEG–PLGA NPs entered the cells mainly through fovea-mediated and lattice protein-mediated endocytosis. In vivo intestinal tissue distribution results in OXZ-induced SD rats showed that R1@Tf–PEG–PLGA NPs were more enriched in the colon than R1 and R1@PEG–PLGA NPs, and pharmacodynamic evaluation showed that R1@Tf–PEG–PLGA NPs exhibited more pronounced effects in ameliorating colonic injury. Conclusion R1@Tf–PEG–PLGA NPs showed significant colonic targeting and anti-UC effect, showing promising applications.
研究领域:
药学
·
纳米技术
·
炎症性肠病
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Qi Chen,Ziwei Huang,Jing Chen,Xiaoyu Tian,Rong Zhang,Qi Liang,Zhongqiu Liu,Yuanyuan Cheng
β2 adrenergic receptor (β2AR) is a G-protein-coupled receptor involved in cardiac protection. In chronic heart failure (CHF), persistent sympathetic nervous system activation occurs, resulting in prolonged β2AR activation and subsequent receptor desensitization and downregulation. Notoginsenoside R1 (NGR1) has the functions of enhancing myocardial energy metabolism and mitigating myocardial fibrosis. The mechanisms of NGR1 against ischemic heart failure are unclear. A left anterior descending (LAD) artery ligation procedure was performed on C57BL/6 J mice for four weeks. From the 4th week onwards, they were treated with various doses (3, 10, 30 mg/kg/day) of NGR1. Subsequently, the impacts of NGR1 on ischemic heart failure were evaluated by assessing cardiac function, morphological changes in cardiac tissue, and the expression of atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC). H9c2 cells were protected by NGR1 when exposed to OGD/R conditions. H9c2 cells were likewise protected from OGD/R damage by NGR1. Furthermore, NGR1 increased β2AR levels and decreased β2AR ubiquitination. Mechanistic studies revealed that NGR1 enhanced MDM2 protein stability and increased the expression of MDM2 and β-arrestin2 while inhibiting their interaction. Additionally, under conditions produced by OGD/R, the protective benefits of NGR1 on H9c2 cells were attenuated upon administration of the MDM2 inhibitor SP141. According to these findings, NGR1 impedes the interplay between β-arrestin2 and MDM2, thereby preventing the ubiquitination and degradation of β2AR to improve CHF.
研究领域:
心脏病学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC Complementary Medicine and Therapies
·
2026
·Vol. 26
·期 1
·80
·
IF 4.4
Gan Xinyu,Liang Mingzhu,Shadekejiang Halinuer,Hong Huan,Lu Jinyu,Li Xu,Zhang Xueqin,Lu Chen
Background Diabetic nephropathy (DN) is a major diabetes complication and a primary cause of end-stage renal failure. Notoginsenoside R1 (NGR1) is known to reduce proteinuria, exert hypoglycemic effects, and enhance renal function in DN patients. However, the exact mechanisms by which NGR1 affects DN are not well understood. Methods An integrative approach combining multi-omics bioinformatics and experimental validation was employed. We analyzed GEO datasets (GSE30122, GSE96804) to identify differentially expressed genes and performed WGCNA to define key modules. Network pharmacology predicted NGR1 targets, which were refined via machine learning (LASSO and Random Forest). Immune infiltration was assessed by CIBERSORT. Molecular docking and dynamics simulations evaluated binding interactions. In vitro functional validation used high glucose (HG)-injured MPC5 podocytes, with MME -specific inhibitor (Thiorphan), confirming target necessity. Results Bioinformatic analysis identified three core targets, MME , PTGS2 , and S100A9 , within the DN pathological network. Functional enrichment revealed their involvement in oxidative stress detoxification, TGF-β-mediated fibrosis, and AGE-RAGE signaling pathways. Immune infiltration analysis indicated an aberrant increase in M0/M2 macrophages and activated mast cells, alongside a reduction in protective γδ T cells, with core targets showing strong correlations with specific immune subsets. Subsequent molecular docking and dynamics simulations indicated that NGR1 exhibited the strongest binding affinity for MME , among the three targets. Corroborating these findings, in vitro experiments confirmed that NGR1 specifically upregulates MME expression transcriptionally and translationally. Crucially, NGR1 counteracted HG-induced oxidative stress, fibrosis, and inflammation. These protective effects were largely abolished upon MME inhibition, demonstrating MME’s essential role in this process. Conclusion This study suggests that NGR1 may exert renoprotective effects in DN potentially through MME modulation, which appears to mitigate oxidative stress, inflammation, and fibrosis. The findings indicate MME could serve as a promising therapeutic target, providing preliminary mechanistic insights for developing targeted DN therapies.
✓ 已验证
DOI
高影响因子
TISSUE & CELL
·
2026
·
IF 3.1
Xuan He,Dan Liang,Xinyi Zhao,Kaixin Liu,Zicheng Zhang,Meiling Li,Xuemeng Ma,Wenxia Chen,Xiaoyi Zhong
Objective This study investigates the influence of Notoginsenoside R1 (NGR1) on the odontogenic differentiation of human dental pulp stem cells (hDPSCs) and its potential application in direct pulp capping, utilizing both in vitro and in vivo models. The results aim to provide a theoretical basis for expanding the clinical use of NGR1. Methods hDPSCs were isolated, cultured and characterized in vitro. The effects of varying concentrations of NGR1 (0, 50, 100, 200 μg/ml) on cell proliferation and migration were evaluated using the CCK-8 and Transwell assays, respectively. The effect of NGR1 on odontogenic differentiation was evaluated by alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining, as well as RT-PCR to detect the mRNA expression levels of ALP and DSPP. A direct pulp capping model was established in adult dogs. The experimental group was rinsed with 100 μg/ml NGR1 solution before capping, and samples were collected at 1, 4, 8, and 12 weeks. Micro-CT scanning and H&E staining were used to analyze reparative dentin and pulp morphology. Additionally, RNA-Seq of hDPSCs treated with 100 μg/ml NGR1 was conducted, followed by DEG screening, GO/KEGG enrichment, GSEA, and PPI analyses, RT-PCR and IHC were used to verify the DEGs. Results NGR1 promotes hDPSCs proliferation, migration, and odontogenic differentiation. In vitro experiments demonstrated that NGR1 enhanced ALP activity and mineralized nodule formation. Both the 100 μg/ml and 200 μg/ml groups significantly promoted the mineralization of hDPSCs. RT-PCR results showed that mRNA expression levels of ALP and DSPP were significantly upregulated in NGR1-treated groups. Animal experiments revealed the formation of continuous, uniform, and thickened reparative dentin over time in both the Control(0 μg/ml) and NGR1-treated groups. H&E staining showed dentin bridges at 4, 8, and 12 weeks in both Control(0 μg/ml) and NGR1 groups. Histological observations suggested that reparative dentin in the NGR1-treated groups appeared to have numerous, regularly arranged dentinal tubules and a compact architecture, whereas the Control(0 μg/ml) groups showed a relatively less organized structure. RNA-Seq results identified 50 upregulated DEGs, including the dentin-related gene S100A9. These DEGs were enriched in the complement and coagulation cascades, cytokine-cytokine receptor interaction, Staphylococcus aureus infection, and tuberculosis pathways. PPI analysis identified SPRR1A, SPRR1B, and SPRR3 as potential hubs. RT-PCR and IHC confirmed that the expression trends of the differentially expressed genes were consistent with the sequencing results. Conclusion NGR1 promotes the proliferation, migration, and odontogenic differentiation of hDPSCs, with the 100 μg/ml concentration providing an optimal balance between proliferative and pro-differentiation effects. In vivo, NGR1 improves the microstructural quality of reparative dentin. Transcriptomic analysis revealed upregulation of S100A9 and enrichment of repair-related pathways, which may serve as a basis for future mechanistic studies.
✓ 已验证
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2026
·
IF 6.8
Qianqian Du,Zhimei Chen,Xian Ma,Yayu Zhang,Yongqiang Fan
Ethnopharmacological relevance Notoginsenoside R1 (NGR1), a primary bioactive constituent of P. notoginseng , has potent anti-inflammatory and immunomodulatory functions, but its role and mechanism in UC remain incompletely understood and warrant further exploration. The global prevalence of ulcerative colitis (UC) is rising steadily, threatening human health. Despite advances in modern therapies, UC treatments remain limited. Aim of the study This work investigated whether NGR1 alleviates DSS-induced colitis by inhibiting the PGAM5-NEK7 interaction and NLRP3 inflammasome activation in macrophages, providing new mechanistic insights and therapeutic targets for UC. Materials and methods UC model was established via 3% DSS administration to assess the protective efficacy of NGR1. Disease activity index (DAI), body weight and colon length were determined to assess disease severity and intestinal injury. HE staining, ELISA and immunofluorescence assays were employed to assess pathological changes in the colon and liver. Macrophages were depleted via tail vein injection of clodronate liposomes. RT-qPCR, ELISA, immunofluorescence and WB were performed to quantify macrophage markers, pro-inflammatory genes and NLRP3 inflammasome-related proteins. In vitro , LPS/ATP-stimulated bone marrow-derived macrophages (BMDMs) demonstrated that NGR1 exerts a potent inhibitory effect on NLRP3 inflammasome activation. After cell treatment, CCK-8, ELISA, RT-qPCR, and WB assays were performed to detect cell viability, inflammatory cytokine levels, and the expression of related genes and proteins. Meanwhile, molecular docking was utilized to verify the interactions among PGAM5, NEK7 and NLRP3. Co-IP in 293T cells overexpressing PGAM5, NEK7 and NLRP3 further verified their interplay. Results Compared with the Model group, NGR1 intervention markedly reduced the DAI scores, ameliorated body weight loss and colon shortening, alleviated colonic and hepatic pathological damage, upregulated the expression of intestinal barrier tight junction proteins (ZO-1, Occludin and Claudin-1), and decreased LPS levels and the release of TNF-α, IL-1β and IL-6 in serum and tissues. Macrophage depletion was observed to markedly abolish protective effects of NGR1, and reduced PGAM5, NEK7, NLRP3, Caspase-1, C-Caspase-1 levels. In vitro , NGR1 inhibited inflammatory factor secretion and NLRP3 inflammasome activation in LPS/ATP-stimulated BMDMs, these effects were partially blocked after PGAM5 or NEK7 gene silencing. Co-IP assays confirmed endogenous interactions between PGAM5, NEK7 and NLRP3. And the molecular docking showed NGR1 could bind to PGAM5, and NGR1 intervention significantly suppressed the expression of the ternary complex formed by the three proteins. Conclusion This study revealed that NGR1 disrupted the PGAM5-NEK7 interaction, restrained NLRP3 inflammasome assembly in macrophages, and relieved colonic damage triggered by DSS, providing a novel target for UC treatment.
✓ 已验证
DOI
PubMed
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
·
2023
·
IF 5.9
Na Li,Huan Xia,Shiyuan Liu,Junjiang Teng,Yanbin Jiang
In order to improve the activity and reusability of β-xylosidase, the β-xylosidase mutant S160N-R333H (R333H) which could convert notoginsenoside R1 to ginsenoside Rg1 and xylose was immobilized on the metal-organic framework (MOF) UiO-66-NH 2 . The physical and biochemical properties of immobilized β-xylosidase ( [email protected] 2 ) were studied in detail. The results showed improved performances, i.e. the high immobilization yield of 93% and recovery activity of 192.8%, better stability under acidic or trypsin-containing conditions, the higher activity in the reaction containing ions , and the improved catalytic efficiency (was 1.37-fold than that of free R333H). Importantly, the ginsenoside Rg1 yields remained more than 80% after six recycles in McIlvaine buffer and pure water. The UiO-66-NH 2 could catalyze xylose dehydration to produce furfural and the yield reached 69%. Thus this study provides a promising method for production of bioactive or platform chemicals via continuous conversion of xyloylated substrates using nanocatalyst synthesized by β-xylosidase and MOF.
研究领域:
生物技术
·
酶工程
·
化学工程
·
药学
✓ 已验证
产品关联
DOI
高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Kangrui Hu,Changjian Li,Tengjie Yu,Huimin Guo,Hong Sun,Shuying Mao,Zhihao Zhou,Wei Jin,Keanqi Liu,Lin Xie,Guangji Wang,Yan Liang
Background The metabolism study of active components for traditional Chinese medicine (TCM) in target organs is conducive to clarify the authentic active ingredients. Notoginsenoside R1 (NG-R1), one of the bioactive components of Panax notoginsenoside (PNS), is commonly acknowledged as the characteristic marker of PNS. However, the metabolism of NG-R1 in target organs has not been clarified yet due to the lack of robust technique and approach. Purpose The present study aimed to develop a reliable and efficient strategy and technology for revealing the qualitative and quantitative metabolism of active components of TCMs in target organs, and to clarify the biotransformation of NG-R1 in liver-brain-intestinal axis. Methods The metabolic transformation of NG-R1 in the brain gut axis was investigated in the in vitro incubation system of fresh rat brain, liver homogenate , and intestinal flora . To quickly lock the target metabolites, we set the mass defect filter (MDF) in different ranges to screen metabolites with different molecular weight (MW). This strategy was defined as multi-stage MDF (mMDF). In addition, we performed relative quantitative analysis on all metabolites according to the peak area acquired by LC-IT-TOF/MS to overcome the challenge that metabolites are difficult to be quantified due to the lack of standards. Results When MDF was set at 0.50 to 0.65 to screen metabolites with MW of 900 to 1200 Da, 6 novel metabolites were quickly found, and then identified as glucuronic acid binding, oxidation , dehydrogenation , methylation and hydrogenation products according to their LC and MS characteristics. When setting MDF at 0.42 - 0.52, 6 metabolites with MW of 600 to 900 Da were effectively screened and identified as Rg1, NG-R2, Rh1, Rg1+CH 2 +2H and Rg1+CH 2 . To screen the metabolites with MW of 300 to 600 Da, MDF was set at 0.25 - 0.42, and 4 novel metabolites were screened rapidly. The results of quantitative metabolism suggested that intestinal flora was the main metabolic site of NG-R1 in rat, and more than 60% of NG-R1 was converted to Rg1 by deglycosylation in the intestinal flora. Conclusion The mMDF strategy can significantly improve the research efficiency of qualitative metabolism of saponins . Although NG-R1 could be transformed into a variety of metabolites in rat liver and brain homogenate , it still existed mainly in prototype form. In the rat flora, NG-R1 mainly existed in the form of deglycosylated metabolite Rg1.
研究领域:
生药学
·
代谢组学
·
分析化学
·
中医药学
·
药物代谢
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）