Journal of Integrative Neuroscience
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2021
·Vol. 20
·期 1
·67-75
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IF 2.117
Dong-Xing Liu,Di Zhang,Wei-Min Hu,Yan-Fang Chang,Xiao-Hui Wang,Lin Li
Overactivation of the PI3-K/Akt/mTOR signaling pathway and inhibition of autophagy in the brain are involved in Alzheimer’s disease. The present paper’s goal was to explore the potential mechanisms of geniposide to protect against Alzheimer’s disease. We treated the human neuroblastoma SH-SY5Y cell line with Aβ1-42 as an Alzheimer’s disease in vitro model to explore the potential mechanisms of geniposide to protect against Alzheimer’s disease. Further, SH-SY5Y cells damaged by Aβ1-42 were treated with geniposide. Akt/mTOR-related proteins and autophagy-associated proteins were measured to reveal the molecular mechanisms by which geniposide protects against Aβ1-42-induced toxicity. Results showed that Akt and mTOR’s geniposide inhibited phosphorylation induced by Aβ1-42, enhanced expression of the LC3II/LC3I ratio, and Atg7 and Beclin1 expression and inhibited expression of p62 induced by Aβ1-42. Our results lead us to hypothesize that inhibition of the Akt/mTOR signaling pathway and autophagy enhancement are fundamental molecular mechanisms for geniposide to protect against Aβ toxicity.
研究领域:
神经科学
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药理学
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细胞生物学
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PubMed
高影响因子
Journal of Functional Foods
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2023
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IF 5.6
Yi Wei,Chao Liu,Lujia Li
Geniposide (Gen) is a natural compound derived from Gardenia jasminoides that has anti-inflammatory, antioxidative stress, antiapoptotic, and antitumour properties. However, its mechanisms of action in idiopathic pulmonary fibrosis (IPF) have not been well studied. Recent studies have found that the progression of IPF is influenced by host metabolism. This study investigated the antifibrotic effects and metabolic modulation of Gen. Gen significantly ameliorated pathological injury in the IPF mouse model. Gen reduced the expression of proinflammatory cytokines and inhibited oxidative stress levels. Gen also inhibited NLRP3 inflammasome activation. Untargeted metabolomics analysis revealed that metabolites were affected in the lung. These metabolites were associated with the regulation of arachidonic acid metabolism, histidine metabolism, and tryptophan metabolism. Gen reduced the inflammatory response and oxidative stress and inhibited NLRP3 inflammasome activation in IPF mice. Mechanistically, Gen-mediated treatment of IPF may be linked to the regulation of host metabolism.
研究领域:
药理学
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免疫学
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代谢组学
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肺科学
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高影响因子
CHEMICAL ENGINEERING JOURNAL
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2026
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IF 12.5
Xiaolan Luo,Cilin Zhao,Feifei Yu,Xiaoyan Dong,Yinju Hao,Huiping Zhang,Bin Liu,Yideng Jiang
Atherosclerosis (AS) is characterized by chronic, persistent inflammation and lipid deposition. Macrophage mitochondrial dysfunction leads to excessive release of reactive oxygen species (ROS), exacerbating inflammatory responses and lipid metabolism dysfunction. This study developed a novel nanodrug system (TM@AG NPs) for restoring macrophage mitochondrial function. The system is based on the co-assembly of astaxanthin (AST) and geniposide (Gen), with macrophage membrane coating and triphenylphosphonium (TPP) modification. In vitro experiments demonstrated that mitochondria-targeted TM@AG NPs promoted the repolarization of macrophages from the M1 to the M2 phenotype and suppressed inflammation by efficiently scavenging mitochondrial ROS (mtROS), restoring mitochondrial respiration and energy supply, thereby ameliorating lipid metabolism disorders. In vivo assay using ApoE −/− mice model demonstrated that TM@AG NPs efficiently accumulated in atherosclerotic plaques, significantly reduced plaque area, cleared the necrotic core, and enhanced plaque stability. In summary, this study presents a sequentially targeted strategy for the precise treatment of AS.
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PHYTOTHERAPY RESEARCH
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2025
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IF 6.3
Yanhong Bu,Hong Wu,Ran Deng,Yan Wang,Peirong Gan,Xintong Dong,Jiangtao Ke
Angiogenesis driven by aerobic glycolysis in endothelial cells sustains rheumatoid arthritis (RA) progression. Geniposide (GE), an iridoid ether extracted from the Rubiaceae plant Gardenia jasminoides J. Ellis, has shown anti-angiogenic potential in experimental arthritis. However, its role in metabolic regulation of angiogenesis remains unclear. The purpose was to explore the roles of GE on metabolism in angiogenesis and potential mechanisms. Adjuvant arthritis (AA) rat models and human umbilical vein endothelial cells (HUVECs) were established. Network pharmacology predicted potential targets of GE, while metabolomics analysis was conducted on RA patient serum and AA rat synovial tissue. The role of PFKFB3, a key glycolytic enzyme, was validated by gene silencing and pharmacological interventions. The signaling axis was further explored using inhibitors, agonists, and protein interaction assays. The role of the key glycolytic enzyme PFKFB3 and the upstream–downstream relationship of the signaling axis were validated through gene silencing and pharmacological intervention. GE improved angiogenesis in vivo and in vitro models, and PFKFB3 may be a potential target. Metabolomics has shown that GE significantly inhibited the elevated levels of glycolysis metabolism in arthritis rats, which may be related to the inhibition of PFKFB3 expression. PFKFB3-siRNA down-regulated angiogenesis in HUVECs, demonstrating that PFKFB3-mediated glycolysis was involved in angiogenesis. SphK1-siRNA indicated that PFKFB3 was regulated and activated by the SphK1-PI3K-AKt signal and induced a high level of glycolytic metabolism phenotype. GE intervention significantly downregulated the levels of glycolysis metabolism in arthritis models by inhibiting the SphK1-PI3K-AKt-PFKFB3 signal. The SphK1-PI3K-Akt-PFKB3 signal is the metabolic mechanism of the natural product active ingredient GE in anti-angiogenesis, revealing the important role of glycolytic metabolism in RA angiogenesis. This provides new insights into metabolic regulation in RA treatment and potential therapeutic strategies for metabolic targeted interventions.
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高影响因子
BIOPROCESS AND BIOSYSTEMS ENGINEERING
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2026
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IF 4.3
Huang Ziling,Yang Rongling,Zhao Xiangjie,Zhu Chun,Tong Yuli,Li Xiaoyan,Luo Hongzhen
A highly efficient and regioselective method for the synthesis of pharmacologically active geniposide 6´-cinnamate is reported herein for the first time, employing Aspergillus oryzae whole cells as biocatalysts in an acetonitrile-ionic liquid co-solvent system. The catalytic performance was markedly enhanced in the presence of ionic liquids compared to the pure acetonitrile system, with catalytic efficiency influenced by the nature of the anion species (e.g., BF₄⁻, PF₆⁻, Tf₂N⁻) and the structure of the cation (including [BMIM]⁺, [OMIM]⁺, [HMIM]⁺). In the optimized acetonitrile-[OMIM][PF₆] (1%, v/v) system, 99% substrate conversion was achieved within 24 h, with an initial reaction rate of 10.88 mmol·L⁻¹·h⁻¹, approximately twice that observed in pure acetonitrile (5.1 mmol·L⁻¹·h⁻¹). Furthermore, the catalyst exhibited excellent 6’-regioselectivity (> 99%) and remarkable operational stability, retaining 42% of its initial activity after six consecutive batches. In conclusion, incorporating ionic liquids as co-solvent effectively promotes catalytic modification of geniposide in whole cells, offering a novel and economically viable strategy for efficiently synthesizing its derivatives.
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Cell Death Discovery
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2026
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IF 10.4
Chen Yu,Wen Yuetao,Xu Diru,Hao Lei,Liu Qinglin,Kuang Jia,Zhao Wang,Yang Zhao
Depression is associated with complex hippocampal pathology, including disrupted signaling and neuronal damage. In this study, we developed a novel targeted nanoplatform using nucleic acid aptamer-modified astrocyte-derived extracellular vesicles loaded with geniposide (Apt-EVs@GP) to investigate its therapeutic mechanism, with a focus on the GATA binding protein 1 (GATA1)/adrenergic receptor beta 2 (ADRB2) axis in a chronic unpredictable mild stress (CUMS) mouse model. Apt-EVs@GP exhibited excellent biocompatibility and targeted accumulation in the hippocampus. Apt-EVs@GP treatment significantly ameliorated depression-like behaviors, as evidenced by enhanced locomotor activity and reduced immobility in standard behavioral assays. Transcriptomic analysis combined with molecular validation identified a key regulatory mechanism: Apt-EVs@GP suppressed stress-induced upregulation of GATA1, thereby relieving its transcriptional repression of ADRB2. This regulatory interaction was confirmed by chromatin immunoprecipitation and dual-luciferase reporter assays. Restoration of ADRB2 expression led to robust activation of the downstream cAMP/PKA/CREB signaling pathway. Functionally, reprogramming of the GATA1/ADRB2/cAMP axis conferred comprehensive hippocampal protection, including attenuation of neuroinflammation, suppression of neuronal apoptosis, and restoration of synaptic integrity. Our findings demonstrate that Apt-EVs@GP alleviates depression by targeting a novel GATA1/ADRB2 mechanism, highlighting its potential as a promising therapeutic strategy against depression-related hippocampal pathology. The alternative text for this image may have been generated using AI.
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高影响因子
Food Bioscience
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2025
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IF 5.9
Haoyang Zou,Shuang Liao,Ruiqi Lu,Yong Pang,Junfeng Li,Jie Zhang
Gardenia ( Gardenia jasminoides Ellis) is a food homologous Chinese herbal medicine, often indicated for its hypolipidemic and anti-inflammatory effects. Geniposide is the main active ingredient in gardenia, which has been shown to improve lipid metabolism disorders. This work aims to debate the hypolipidemic effect of geniposide and resolve whether its hypolipidemic mechanism is mediated by the glucocorticoid receptor (GR). In vitro experiments demonstrated that geniposide was able to alleviate oleic acid (OA) + palmitic acid (PA) - induced lipid accumulation in AML12 cells and down-regulate glucose 6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase 1 (PCK1), fructose-1,6-bisphosphatase 1 (FBP1), stearoyl-CoA desaturase (SCD1), pyruvate carboxylase (PC), sterol regulatory element binding protein-1c (SREBP1-C), CCAAT/enhancer binding protein β (C/EBPβ) gluconeogenesis and lipid metabolism-related genes and proteins expression level. Furthermore, we constructed a hyperlipidaemic zebrafish model to further investigated the alleviating effect of geniposide on hyperlipidaemia in vivo . To explain the mechanism of action of geniposide, a series of experiments revealed that geniposide could bind to GR, inhibit dexamethasone-induced GR nuclear translocation and display GR antagonistic activity. To confirm whether the therapeutic effect of geniposide was mediated by GR, we performed GR knockdown experiments in AML12 cells, and then discovered that GR knockdown abolished the inhibition of G6pase, PCK1, FBP1, SCD1, SREBP1-C expression by geniposide. Since geniposide can ameliorate hyperlipidaemia in zebrafish, it might be used as a potential source in the development of dietary supplements.
研究领域:
药理学
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分子生物学
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营养学
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高影响因子
FUNDAMENTAL & CLINICAL PHARMACOLOGY
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2016
·Vol. 31
·期 1
·54-63
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IF 2.156
Xiaolei Hu,Xiaomei Zhang,Guoxi Jin,Zhaoming Shi,Weihua Sun,Fengling Chen
Renal pathology was a commonly seen complication in patients with diabetes. Geniposide (GPO) was previously demonstrated to modulate glucose metabolism in diabetes. This study was to investigate effects of GPO in streptozotocin-induced diabetic rats and its underlying mechanism. Renal function in diabetic rats was evaluated by levels of serum creatinine (Scr), blood urea nitrogen (BUN), and urinary albumin. Renal inflammation was appraised by inflammatory cells infiltration and pro-inflammatory cytokines production. Renal monocytes, T lymphocytes infiltration, and intercellular adhesion molecule-1 (ICAM-1) expression were quantitated by immunohistochemistry. Moreover, renal nuclear factor-kappa B (NF-κB) was assayed by Western blotting. Diabetic rats showed renal dysfunction as evidenced by increased levels of Scr, BUN, urinary albumin, and elevator renal index. Histological examination revealed significant glomerular basement membrane (GBM) thickening. However, GPO notably improved renal function and diabetes-induced GBM changes. Additionally, diabetic rats showed noteworthy renal inflammation,as reflected by enhancement of monocytes and T lymphocytes infiltration, increased expression of ICAM-1, tumor necrosis factor-α, interleukin-1 (IL-1), and IL-6. Interestingly, the level of monocytes infiltration positively correlated with the severity of GBM. Further study indicated diabetic rats displayed increased activation of NF-κB, indicated by increased expression of NF-κB p65, IKKα, and p-IκBα in renal tissue. However, all the changes in renal inflammation and NF-κB pathway were obviously reversed in GPO-treated diabetic rats. Our works indicate GPO ameliorates structural and functional abnormalities of kidney in diabetic rats, which is associated with its suppression of NF-κB-mediated inflammatory response.
研究领域:
药理学
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糖尿病学
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肾病学
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DOI
PubMed
高影响因子
JOURNAL OF PROTEOME RESEARCH
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2020
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IF 4.074
Xiang Zhan,Huan Wu,Hong Wu
Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is mainly characterized by joint lesions and permanent loss of joint function. To discover the metabolic characteristics of RA and the underlying mechanisms in treatment with geniposide (GE), untargeted metabolomic analysis based on hydrophilic interaction liquid chromatography coupled to high-resolution mass spectrometry (HILIC–HRMS) was performed using the joint synovial fluid samples from adjuvant arthritis (AA) rats. Microdialysis (MD) was utilized to collect the dialysate samples precisely from the articular cavity of AA rats. Multivariate statistical analysis was then conducted to discover the metabolite changes induced by AA and to differentiate GE-related biomarkers. The mass spectrometry data are available on the Chorus website (https://chorusproject.org/pages/index.html) with the data set identifier 1680. The results showed that 20 metabolites differed significantly between AA rats and normal rats. GE treatment recovered the altered levels of the 13 metabolites mentioned above, such as palmitoylethanolamide (PEA), Cer (d18:0/22:0), and PC (18:1(11Z)/16:1(9Z)), and normalized glycerophospholipid metabolism. As evidenced by western blotting, the changes in PEA levels adjusted by GE were associated with the down-regulated expression of N-acylethanolamine-hydrolyzing acid amidase (NAAA) in synovial tissues. Taken together, the elucidation of metabolic changes of joint synovial fluid and how this is influenced by GE will promote future therapeutic interventions of RA.
研究领域:
药理学
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免疫学
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代谢组学
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风湿病学
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PubMed
高影响因子
SHOCK
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2023
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IF 3.1
Zhang Dewen,He Jian,Ding Xian,Wang Rui,Chen Wei
Background We explored the efficacy and main biological mechanism of geniposide intervention in sepsis. Methods A sepsis model was established in male BALB/c mice through cecal ligation and puncture (CLP). Different doses of geniposide (20 or 40 mg/kg) were administered intravenously at 0 and/or 24 h after CLP surgery. The survival rate of different groups was observed. Additionally, the expression levels of CD16 and MHC-II in monocytes were assessed using flow cytometry. The concentration of TNF-α, IL-1β, IL-6, and IL-10 in the serum were measured by ELISA. We also observed the biological effects of geniposide on CD16 and MHC-II expression levels in RAW264.7 cells, as well as the secretion of TNF-α, IL-1β, IL-6, and IL-10, in the LPS-induced RAW264.7 cell model. The PPARγ levels were determined using western blot analysis. Results Intravenous administration of 40 mg/kg of geniposide at 0 h after CLP significantly improved the survival outcomes in the septic mouse model, with no significant benefits from low dosing (20 mg/kg) or delayed administration (24 h). The effective dose of geniposide significantly decreased the serum cytokine TNF-α, IL-1β, IL-6, and IL-10 concentrations in septic mice ( P < 0.05). Notably, in vitro assays showed that geniposide specifically increased the IL-10 level. Geniposide significantly reduced the CD16 expression ( P < 0.05) and increased MHC-II expression in monocytes ( P < 0.05). Additionally, geniposide elevated the PPARγ level in monocytes ( P < 0.05). Conclusions High-dose early-stage geniposide administration significantly improved the survival rate in a CLP mouse sepsis model by modulating the monocyte phenotype and regulating the cytokine network (IL-6/IL-10 levels). The pharmacological mechanism of geniposide action might be exerted primarily through PPARγ upregulation.
研究领域:
免疫学
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药理学
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分子生物学
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PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
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2026
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IF 8.8
Yueqin Qiu,Shilong Liu,Xinmiao Liao,Wenjing Wang,Jiaxi Tang,Li Wang,Xuefen Yang,Zongyong Jiang
Geniposide alleviated intestinal barrier dysfunction. • Geniposide increased Prevotella copri abundance to alleviate intestinal injury. • Geniposide inhibited diquat-induced intestinal ferroptosis in vivo and in vitro . • Geniposide regulated TRPV4/GPX4-mediated ferroptosis to alleviated intestinal injury. Early weaning disrupts intestinal antioxidant capacity and barrier integrity in human infants and young animals. Geniposide, an iridoid glycoside, exhibits anti-inflammatory and antioxidant activities. However, the mechanism by which geniposide ameliorates weaning-associated intestinal oxidative injury remains to be elucidated. Therefore, this study aimed to investigate whether and how geniposide attenuates intestinal injury, using diquat (DQ)-challenged weaned piglets, mice, and IPEC-J2 cells as experimental models. The results showed that geniposide supplementation significantly alleviated DQ-induced growth inhibition by increasing ADG and ADFI in the piglets. Additionally, geniposide significantly alleviated DQ-induced intestinal barrier damage, as evidenced by increased gene and protein expression of occludin and claudin-1 and decreased intestinal permeability in the ileum. Moreover, geniposide significantly attenuated DQ-induced oxidative stress, as shown by reduced levels of MDA, ROS, and 4-HNE, along with increased activities of T-AOC, GSH-Px, and T-SOD, as well as upregulated protein abundance of NRF2 and GCLM. Microbiome analysis showed that geniposide significantly increased Prevotella copri abundance in the ileum of DQ-challenged piglets. Prevotella copri supplementation alleviated DQ-induced intestinal injury in mice. Transcriptomic and non-targeted metabolomic analyses revealed that geniposide inhibited the DQ-induced ferroptosis signaling pathway. Additionally, geniposide significantly alleviated the DQ-induced the increases in the levels of MDA and Fe 2+ , and restored expression of the anti-ferroptotic proteins GPX4, SLC7A11, and FTL. Mechanistically, geniposide inhibited DQ-induced intestinal ferroptosis through modulation of the TRPV4/GPX4 pathway and increasing Prevotella copri abundance. Collectively, this study revealed that geniposide alleviated DQ-induced intestinal injury by modulating the TRPV4/GPX4-mediated ferroptosis pathway and increasing Prevotella copri abundance, suggesting its potential as a therapeutic agent against weaning-associated intestinal oxidative damage. Download: Download high-res image (117KB) Download: Download full-size image
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高影响因子
BIOCHEMICAL PHARMACOLOGY
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2024
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IF 5.3
Jia Xi Ye,Jia Ying Wu,Liang Ai,Min Zhu,Yun Li,Dong Yin,Qihui Huang
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the significant involvement of amyloid-beta (Aβ) peptide in its pathogenesis. Geniposide, derived from the versatile medicinal of Gardenia jasminoides , is one of the active compounds studied extensively. The objective was to explore the impact of geniposide on Aβ 25-35 -induced damage in HT22 cells, specifically focusing on its modulation of PINK1/Parkin-mediated mitophagy. In our investigation, geniposide exhibited remarkable restorative effects by enhancing cell viability and preserving the mitochondrial membrane potential. Moreover, it effectively reduced and mitigated the oxidative stress and apoptosis rates induced by Aβ 25-35 . Notably, geniposide exhibited the capacity to enhance autophagic flux, upregulate LC3II and Beclin-1 expression, and downregulate the expression of p62. Furthermore, geniposide positively influenced the expression of PINK1 and Parkin proteins, with molecular docking substantiating a strong interaction between geniposide and PINK1/Parkin proteins. Intriguingly, the beneficial outcomes of geniposide on alleviating the pronounced apoptosis rates, the overproduction of reactive oxygen species, and diminished the PINK1 and Parkin expression induced by Aβ 25-35 were compromised by the mitophagy inhibitor cyclosporine A (CsA). Collectively, these findings suggested that geniposide potentially shields HT22 cells against neurodegenerative damage triggered by Aβ 25-35 through the activation of mitophagy. The insights contribute valuable references to the defensive consequences against neurological damage of geniposide, thereby highlighting its potential as a therapeutic intervention in AD.
研究领域:
神经科学
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药理学
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细胞生物学
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分子生物学
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神经退行性疾病
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DOI
PubMed
高影响因子
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