PHYTOMEDICINE
·
2025
·
IF 8.3
Bao-xin Zheng,Yan Yi,Xing-wen Wang,Chun-ying Li,Yong Zhao,Jing-zhuo Tian,Lian-mei Wang,Jia-yin Han,Chen Pan,Su-yan Liu,Chen-yue Liu,Sha-sha Qin,Xuan Tang,Mei-ting Liu,Ai-hua Liang
Background Geniposide (GE) has potential efficacy in treating ulcerative colitis (UC). However, its reactivity can be affected by rapid degradation after oral administration. Furthermore, increasing oral doses may lead to hepatotoxicity. Thus, We used enema administration, characterized by smaller dose and higher localized concentration in the lesion, to improve the above situation. Purpose We aimed to confirm that enema administration is a better modality than oral administration for GE against UC and to explore its mechanism. Study design/Method We established UC mouse model, monitoring Disease Activity Index (DAI), inflammatory cytokines levels, and histopathology. Macrogenomics and bile acid (BAs) metabolomics analysed the major intestinal flora and BAs. Simultaneouslly, we conducted quantitative proteomics analysis and screened core proteins and pathway. In vitro validation was taken by qPCR, immunofluorescence and immunoblotting experiments. Results GE via enema alleviate UC by inhibiting inflammatory factor production through downregulating S100A8/S100A9/NF-κB pathway. Analysis of the intestinal flora and BAs revealed that the enhanced abundance of Lachnospiraceae , which improves the ratio of primary to secondary BAs, and the reduced abundance of Provocaceae , which increases intestinal permeability and promotes inflammation, favored the restoration of the intestinal barrier. In addition, in vitro experiments confirmed that the key BA metabolites (mainly UDCA, DCA, and LCA) stimulated TGR5 signal to inhibit the assembly of the NLRP3 inflammasome and alleviated inflammation. Conclusion We firstly confirmed that GE alleviates UC via the enema route in a better manner than the oral route, through enhancing the intestinal barrier, restoring intestinal flora and BAs homeostasis, and inhibiting inflammatory injury. This study initially revealed that GE can alleviate UC through elevating UDCA, DCA, and LCA levels at the colonic site to activate TGR5 receptor for inhibiting the NLRP3 inflammasome, in addition to downregulating the S100A8/S100A9/-TLR4-NF-κB pathway related inflammatory response directly. The evidences offer a promising strategy and profround meaning for UC treatment.
研究领域:
药理学
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免疫学
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微生物学
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代谢组学
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DOI
PubMed
高影响因子
AMERICAN JOURNAL OF CHINESE MEDICINE
·
2025
·
IF 5.5
Mei Luo,Yuelian Wang,Xiaodong Liu,Lin Liu,Li Zhu,Guo Chen,Qing Ye,Chengshi He,Xujue Xiao,Jike Li
Among the spectrum of digestive system cancers, hepatocellular carcinoma (HCC) poses a particularly formidable challenge due to its poor prognosis. Geniposide, an iridoid glucoside extracted from the fruit of Gardenia jasminoides Ellis, exhibits a diverse array of biological activities. The goal of this study is to delineate the specific roles and underlying mechanisms of geniposide on the progression of HCC. Cell viability, apoptosis and migration of Huh7 and HepG2 cells were, respectively, assessed via CCK-8, flow cytometry and trans-well assays. The level of reactive oxygen species (ROS) was assessed with a dihydroethidium (DHE) probe. The measurement of mitochondrial membrane potential (MMP) was conducted using JC-1 staining. Ferroptosis-related markers were evaluated by Western Blot assay. Transcriptome sequencing was performed in HCC cells both treated and untreated with geniposide. In vivo experiments were applied with the subcutaneous xenograft tumor model. In vitro experiments revealed that geniposide exerted a concentration-dependent suppression on cell viability and migration, concurrently eliciting apoptosis in HCC cells. Ferroptosis was identified as the main form of geniposide-induced cell death in HCC. Geniposide promoted the iron ions levels, ROS accumulation, and the expression of ferroptosis markers, which were partially reversed by the addition of deferoxamine (DFO, ferroptosis inhibitor). Intersection analysis was applied between upregulated genes of HCC cells and ferroptosis-related genes. DUOX1 was proven to be involved in geniposide-mediated roles in HCC. In vivo experiments further clarified the suppressive effects of geniposide on tumors. Geniposide treatment increased intracellular iron ions and induced ferroptosis in HCC. Geniposide attenuated tumor progression and oxidative stress via DUOX1-mediated ferroptosis.
研究领域:
生物医学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2026
·
IF 5.7
Bing Li,Pei-rong Gan,Jing Pang,Jian-jian Li,Hong Wu
Glycolytic reprogramming-driven aberrant proliferation of FLSs is a major cause of synovial hyperplasia in rheumatoid arthritis (RA). Geniposide (GE), an iridoid glycoside extracted from the plant Gardenia jasminoides J. Ellis, has been confirmed to inhibit the proliferative activity of RA-FLSs. However, whether this effect involves the regulation of glycolytic metabolism remains unclear. In this study, collagen-induced arthritis (CIA) rat models and TNF-α-induced MH7A cell models were established to investigate the specific mechanism by which GE regulates glycolytic reprogramming. The results showed that GE not only ameliorated synovial hyperplasia and suppressed glycolysis in CIA rats, but reduced the abnormal proliferation and glycolytic levels of TNF-α-induced MH7A cells. Increased lactylation of PKM2 was observed in the synovium of CIA rats and in TNF-α-induced MH7A cells, accompanied by the transition of PKM2 from tetramer to dimer and enhanced nuclear translocation. GE was found to inhibit the lactylation of PKM2. The SphK1/p300 signaling axis was activated both in vivo and in vitro . Investigations revealed that PF543, an inhibitor of SphK1, and A-485, an inhibitor of p300, inhibited the lactylation of PKM2. Moreover, GE suppressed the SphK1/p300 axis and prevented the interaction between PKM2 and p300. The inhibitory effect of GE on glycolysis was attenuated by lactate and the p300 agonist Cholera Toxin B (CTB). It was also found the suppression of glycolysis by GE was counteracted by both lactate and CTB. These results suggested GE suppressed the abnormal proliferation of FLSs by inhibiting the SphK1/p300-mediated lactylation of PKM2, highlighting a novel treatment strategy for RA.
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PubMed
高影响因子
MOLECULES
·
2016
·Vol. 21
·期 5
·540
·
IF 2.465
Wenhao Xu,Jingbo Yu,Wen Feng,Weike Su
A novel method for the selective extraction of gardenia yellow and geniposide fromGardenia Jasminoides, based on a mechanochemical method is described. Without the need of complex separation techniques, gardenia yellow compliant with the national standard could be extracted in a simple fashion. The optimal ball-milling conditions determined were as follows: 30% g/g. active carbon milling at 200 rpm in a planetary mill for 5 min. The extraction conditions of the milled mixtures were as follows: the milled mixtures were extracted with water (liquid-solid ratio 10:1) at 20 °C for 5 min with yields 85% of total geniposide, followed by extraction with 80% ethanol solution (liquid-solid ratio 5:1) and 1% g/g. Tween 20 at 75 °C for 5 min to yield 1.45% ± 0.108% g/g of gardenia yellow. The mechanism of this selective extraction was demonstrated to follow a microstructure change of activated carbon, which occurred during milling and lead to alteration of the corresponding desorption capacities. Compared with traditional extraction methods, this novel extraction technique greatly simplifies the separation process, and proves to be advantageous in terms of low organic solvent consumption, easy operation, rapid process and high efficiency.Keywords:Gardenia jasminoides;gardenia yellow;geniposide;mechanochemistry;selective extraction
研究领域:
植物化学
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药用植物学
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分离技术
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PubMed
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 65
·37117-37128
·
IF 2.936
Guixin Wu,Min Wen,Lin Sun,Huitao Li,Yubei Liu,Rui Li,Feihua Wu,Rong Yang,Yining Lin
Geniposide (GE) is a major component isolated from Gardenia jasminoides Ellis, which has been used to treat cholestasis liver diseases. Our previous study has shown that GE could notably increase mRNA and protein expressions of BSEP in cholestatic rats. BSEP plays a critical role in maintenance of the enterohepatic circulation of bile acids. BSEP could be regulated by the transactivation pathway of farnesoid X receptor (FXR) and nuclear factor erythroid 2-related factor (Nrf2). Here the mechanisms for BSEP regulation by GE were investigated. GE induced the mRNA levels of BSEP in HepG2 cells and cholestatic mice, and knockdown of FXR and Nrf2 reduced the mRNA expression of BSEP at varying degrees after treatment of GE. FXR acts as the major regulator of BSEP transcription. The involvement of FXR regulated BSEP expression by GE was further investigated. An enhancement was observed in FXR-dependent BSEP promoter activation using luciferase assay. ChIP assay further confirmed the interaction between FXR and BSEP after GE treatment. Using siRNA and ChIP assays, we demonstrated that peroxisome-proliferator-activated receptor γ co-activator-1α (PGC-1α) and co-activator-associated arginine methyltransferase 1 (CARM1) were predominantly recruited to the BSEP promoter upon FXR activation by GE. In conclusion, GE regulated the expression of BSEP through FXR and Nrf2 signaling pathway. The FXR transactivation pathway was enhanced by increasing recruitment of coactivators PGC-1α and CARM1 upon GE treatment, coupled with an increased binding of FXR to the BSEP promoter.
研究领域:
药理学
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分子生物学
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肝病学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Jinhai Lin,Xiaolong Wang,Mingyang Gu,Yuanyuan Chen,Jiongbo Xu,Nhi Van Chau,Junlong Li,Xiaodong Ji,Qingmin Chu,Lijin Qing,Wei Wu
Background Atherosclerosis (AS) is the leading cause of global death, which manifests as arterial lipid stack and plaque formation. Geniposide is an iridoid glycoside extract from Gardenia jasminoides J.Ellis that ameliorates AS by mediating autophagy. However, how Geniposide regulates autophagy and treats AS remains unclear. Purpose To evaluate the efficacy and mechanism of Geniposide in treating AS. Study design and methods: Geniposide was administered to high-fat diet-fed ApoE −/− mice and oxidized low-density lipoprotein-incubated primary vascular smooth muscle cells (VSMCs). AS was evaluated with arterial lipid stack, plaque progression, and collagen loss in the artery. Foam cell formation was detected by lipid accumulation, inflammation, apoptosis, and the expression of foam cell markers. The mechanism of Geniposide in treating AS was assessed using network pharmacology. Lipophagy was measured by lysosomal activity, expression of lipophagy markers, and the co-localization of lipids and lipophagy markers. The effects of lipophagy were blocked using Chloroquine. The role of PARP1 was assessed by Olaparib (a PARP1 inhibitor) intervention and PARP1 overexpression. Results In vivo , Geniposide reversed high-fat diet-induced hyperlipidemia, plaque progression, and inflammation. In vitro , Geniposide inhibited VSMC-derived foam cell formation by suppressing lipid stack, apoptosis, and the expressions of foam cell markers. Network pharmacological analysis and in vitro validation suggested that Geniposide treated AS by enhancing lipophagy via suppressing the PI3K/AKT signaling pathway. The benefits of Geniposide in alleviating AS were offset by Chloroquine in vivo and in vitro . Inhibiting PARP1 using Olaparib promoted lipophagy and alleviated AS progression, while PARP1 overexpression exacerbated foam cell formation and lipophagy blockage. The above effects of PARP1 were weakened by PI3K inhibitor LY294002. PARP1 also inhibited the combination of the ABCG1 and PLIN1. Conclusion Geniposide alleviated AS by restoring PARP1/PI3K/AKT signaling pathway-suppressed lipophagy. This study is the first to present the lipophagy-inducing effect of Geniposide and the binding of ABCG1 and PLIN1 inhibited by PARP1.
研究领域:
心血管疾病
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药理学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2022
·
IF 5.895
Jiaxin Li,Hengju Ge,Yang Xu,Jiahong Xie,Fujie Yan,Wei Chen
Geniposide (GEN), a main compound extracted from Gardenia jasminoides fruit, has various biological activities including anti-inflammation, cellular damage alleviation, neuroprotection, and others. However, the effect of GEN on oxidative stress in hepatic cells is yet to be investigated. Our study uncovered that GEN eliminated excess intracellular free radicals by activating the Nrf2/ARE signaling pathway in H2O2-treated hepatocytes, while the protective effect was blocked by ML385 (an inhibitor of Nrf2). Moreover, H2O2 led to upregulation of miR-27b-3p in L02 cells, which was restrained by GEN. Overexpression of miR-27b-3p greatly weakened the antioxidant capacity of GEN in hepatocytes via directly targeting the Nrf2 gene. Our findings indicated that GEN treatment recovered H2O2-induced oxidative stress via targeting miR-27b-3p and thereby enhanced the antioxidant capacity by stimulating nuclear translocation and accumulation of Nrf2. These findings suggest that inhibition of miR-27b-3p to activate the Nrf2/ARE pathway by GEN is a potential alternative for hepatic oxidative damage alleviation.
研究领域:
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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DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2021
·Vol. 35
·期 7
·3799-3811
·
IF 5.882
Min Wen,Yubei Liu,Ruiying Chen,Ping He,Feihua Wu,Rui Li,Yining Lin
Sclerosing cholangitis, characterized by biliary inflammation, fibrosis, and stricturing, remains one of the most challenging conditions of clinical hepatology. Geniposide (GE) has anti-inflammatory, hepatoprotective, and cholagogic effects. Whether GE provides inhibition on the development of sclerosing cholangitis is unknown. Here, we investigated the role of GE in a mouse model in which mice were fed with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for 4 weeks to induce sclerosing cholangitis. The results demonstrated that the increased hepatic gene expressions of pro-inflammatory (IL-6, VCAM-1, MCP-1, and F4/80) and profibrogenic markers (Col1α1, Col1α2, TGF-β, and α-SMA) in DDC feeding mice were reversed after treatment with GE. GE also suppressed expressions of CK19 and Ki67 in DDC-fed mice, suggesting that GE could ameliorate DDC-induced hepatocytes and cholangiocytes proliferation. In addition, GE significantly increased bile acids (BAs) secretion in bile, which correlated with induced expressions of hepatic FXR, BAs secretion transporters (BSEP, MRP2, MDR1, and MDR2), and reduced CYP7A1 mRNA expression. Furthermore, higher expressions of ileal FXR-FGF15 signaling and reduced ASBT were also observed after GE treatment. Taken together, these data showed that GE could modulate inflammation, fibrosis, and BAs homeostasis in DDC-fed mice, which lead to efficiently delay the progression of sclerosing cholangitis.
研究领域:
肝病学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2023
·
IF 4.3
Xinyue Peng,Luyi Tan,Jia Song,Yuefei Lai,Susu Yu,Feifei Xu,Qinzhi Wei,Zhini He,Wenli Cheng,Wenjuan Zhang,Xingfen Yang
Geniposide (GP) is the homology of medicine and food with bioactive effects of antioxidation and resistance to apoptosis in the liver. It's of great significance to explore the biosafety exposure limits and action mechanisms of GP. This study detected the global DNA methylation microenvironment and the regulation of specific genes in GP against cellular apoptosis induced by hydrogen peroxide (H 2 O 2 ) of human hepatocyte L-02 cells. The half inhibitory concentration (IC 50 ) of GP on normal L-02 cells was 57.7 mg/mL. GP exerted new epigenetic activity, increased DNMT1 , decreased TET1 and TET2 expression, and reversed the demethylation effect to some extent, thereby increasing the overall genomic DNA methylation level at the concentration of 900 μg/mL. GP pretreatment could also adjust the level of P53, Bcl-2 and AKT altered by H 2 O 2 , reducing their specific DNA methylation levels in the promoter regions of AKT and Bcl-2 to inhibit apoptosis. Taken together, GP regulates the global DNA methylation level and controls the expression changes of P53, Bcl-2 and AKT, jointly inhibiting the occurrence of apoptosis in human hepatocytes and providing the newly theoretical references for its safety evaluation.
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PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Xiaoju Zhuge,Xiaosheng Jin,Tingting Ji,Rongzhou Li,Liwei Xue,Weilai Yu,Zijiao Quan,Haibin Tong,Fang Xu
Ethnopharmacological relevance The dried fruit of Gardenia jasminoides Ellis (Zhizi in Chinese) is a traditional medicine used for thousands of years in China, Japan and Korea. Zhizi was recorded in Shennong Herbal , as a folk medicine, it reduces fever and treats gastrointestinal disturbance with antiphlogistic effects. Geniposide , an iridoid glycoside , is an important bioactive compound derived from Zhizi and possesses remarkable antioxidant and anti-inflammatory capacities. The pharmacological efficacy of Zhizi is highly related to the antioxidant and anti-inflammatory effects of geniposide. Aim of the study Ulcerative colitis (UC) is a common chronic gastrointestinal disease as a global public health threat. Redox imbalance is an essential factor in the progression and recurrence of UC. This study aimed to explore the therapeutic effect of geniposide on colitis and uncover the underlying mechanisms of geniposide-mediated antioxidant and anti-inflammatory activities. Experimental design The study design involved investigating the novel mechanism by which geniposide ameliorates dextran sulfate sodium (DSS)-induced colitis in vivo and lipopolysaccharide (LPS)-challenged colonic epithelial cells in vitro . Materials and methods The protective effect of geniposide against colitis was evaluated by histopathologic observation and biochemical analysis of colonic tissues in DSS-induced colitis mice. The antioxidant and anti-inflammatory effects of geniposide were evaluated in both DSS-induced colitis mice and LPS-challenged colonic epithelial cells. Immunoprecipitation , drug affinity responsive target stability (DARTS), and molecular docking were performed to identify the potential therapeutic target of geniposide and the potential binding sites and patterns. Results Geniposide ameliorated the symptoms of DSS-induced colitis and colonic barrier injury, inhibited pro-inflammatory cytokine expression, and suppressed activation of the NF-κB signaling in colonic tissues of DSS-challenged mice. Geniposide also ameliorated lipid peroxidation and restored redox homeostasis in DSS-treated colonic tissues. In addition, in vitro experiments also showed that geniposide exhibited significant anti-inflammatory and antioxidant activity , as evidenced by suppressed IκB-α and p65 phosphorylation and IκB-α degradation, and enhanced the phosphorylation and transcriptional activity of Nrf2 in LPS-treated Caco2 cells. ML385, a specific Nrf2 inhibitor, abolished the protective effect of geniposide against LPS-induced inflammation. Mechanistically, geniposide could bind to KEAP1 , thereby disrupting the interaction between KEAP1 and Nrf2, preventing Nrf2 from degradation and activating the Nrf2/ARE signaling pathway, ultimately suppressing the onset of inflammation caused by redox imbalance. Conclusions Geniposide ameliorates colitis by activation of Nrf2/ARE signaling, while preventing colonic redox imbalance and inflammatory damage, indicating that geniposide can be considered as a promising lead compound for the treatment of colitis.
研究领域:
药理学
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胃肠病学
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分子生物学
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民族药理学
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产品关联
DOI
PubMed
高影响因子
CURRENT MEDICINAL CHEMISTRY
·
2026
·Vol. 33
·期 18
·3729-3749
·
IF 3.2
Yang Wei,Qian Zhou,Dan Li,Honghong He,Yao Su,Guanglei Chang,Youqin Jiang
Background Cardiac remodeling Post-Myocardial Infarction (MI) drives heart failure. Geniposide (GP), a traditional Chinese medicine-derived compound, exhibits cardioprotective potential, yet its mechanisms remain unclear. This study explored the GP’s role in post-MI remodeling via Parkin-dependent mitophagy. Methods Murine MI and cardiomyocyte Chronic Hypoxia (CH) models were established. MI mice received GP; cardiac function, histopathology, apoptosis, fibrosis/autophagy markers, and mitochondrial clearance were assessed. in vitro, Parkin-silenced hypoxic cardiomyocytes were used to evaluate GP’s effects on viability, oxidative stress, mitochondrial function, autophagy proteins, and autophagosome formation. Results In vivo, GP improved cardiac function, reduced fibrosis/apoptosis, and suppressed fibrosis-related genes (Col1a1, Col3a1, Tgfb1, Mmp9). GP enhanced clearance of damaged mitochondria via autophagy, mitigating oxidative stress. in vitro, GP’s protection against hypoxia required Parkin: it preserved mitochondrial homeostasis, inhibited ROS-mediated apoptosis, and reduced autophagosome accumulation. Mechanistically, GP attenuated excessive mitophagy by modulating Parkin, thereby maintaining mitochondrial quality and reducing oxidative injury. Discussion The mechanism by which GP regulates Parkin-dependent mitophagy identified in this study addresses the limitations of existing standard therapies that lack targeted regulation of mitochondrial quality. However, the upstream and downstream molecular regulatory mechanisms of the GP-Parkin pathway, as well as GP’s long-term safety and pharmacokinetic interactions with standard drugs, remain to be further elucidated. Future studies may explore the synergistic efficacy and optimal dose ratio of GP combined with first-line drugs via in vitro liver microsome experiments and in vivo animal models, and conduct chronic toxicity studies to support its clinical translation. Conclusion GP alleviates post-MI remodeling by suppressing Parkin-dependent hyperactivated mitophagy, reducing cardiomyocyte loss and fibrosis. Parkin is central to GP’s therapeutic effects, highlighting its potential as a target for MI-related heart failure. This study elucidates GP’s cardioprotective mechanism and proposes Parkin pathway modulation as a novel strategy to counteract pathological cardiac remodeling.
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DOI
高影响因子
CELL BIOCHEMISTRY AND BIOPHYSICS
·
2025
·
IF 2.5
Ma Qi,Ma Yu,Sun Shizhuo,Yang Lei,Shi Tian,Zhang Boxi,Shang Bo,Zhou Ruiyuan,Liu Jingyuan,He Jiao,Hu Jing,Cao Yanjun
Geniposide (GE), an iridoid glycoside from Gardenia jasminoides J.Ellis , exhibits anti-inflammatory, antioxidant, antidepressant, and neuroprotective properties. The excessive presence of corticosterone (CORT) can lead to neurotoxicity and inflict harm upon nerve cells. This study aimed to examine GE’s neuroprotective effects on CORT-induced damage in PC12 cells. Cells were pre-treated with GE for 3 h, then exposed to CORT for 24 h. Cell viability and lactate dehydrogenase (LDH) leakage were measured, apoptosis was assessed via flow cytometry, and immunofluorescence was used to detect MAP2 and PSD95 expression. The detection of glutamate (Glu) receptor, BDNF pathway, synaptic plasticity-related protein, and apoptosis pathway were performed using Western blot. The findings indicated that GE effectively prevented the reduction in cell viability, apoptosis, and LDH release caused by CORT. In PC12 cells, the expression of MAP2 and PSD95 were significantly enhanced by GE. Furthermore, GE reduced NR1, NR2A, NR2B, and Bax levels, increased EAAT2/3, Bcl-2, and proteins linked to BDNF and synaptic plasticity, and inhibited Caspase-3 and Caspase-9. GE shows neuroprotective and anti-apoptotic properties against CORT-induced cellular damage through BDNF pathway activation and Bax/Bcl-2 pathway suppression.
研究领域:
神经药理学
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细胞生物学
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植物化学
·
分子生物学
·
神经科学
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PubMed
高影响因子
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