INFLAMMATION
·
2020
·Vol. 44
·期 2
·645-658
·
IF 3.212
Shao Yun-yun,Guo Yao,Feng Xiao-juan,Liu Jun-jin,Chang Zhuang-peng,Deng Gui-feng,Xu Ding,Gao Jian-ping,Hou Rui-gang
To investigate the beneficial effects of oridonin, a diterpenoid compound isolated from Rabdosia rubescens, on the inflammatory response in TNBS-induced post-inflammatory irritable bowel syndrome (PI-IBS) model and the underlying mechanism. Using the PI-IBS rat model and Caco-2 cell lines, we found that intestinal barrier function reflected by lactulose/mannitol (L/M) ratio and tight junction protein level was significantly ameliorated by oridonin. We also demonstrated that oridonin abrogated inflammation through inhibiting the phosphorylation of NF-κBp65 as well as its downstream gene (iNOS, COX-2, IL-1β, and IL-6) level. Molecular docking studies confirmed the good binding activity between oridonin and PXR. In Caco-2 cell lines, oridonin markedly inhibited LPS-induced NF-κB activation in a PXR-dependent manner. Meanwhile, PXR and its target genes CYP3A4 and P-gp were induced by oridonin, which was associated with the decreased expression of NF-κB and the recovery of intestinal barrier. This study indicated that the therapeutic effect of oridonin on experimental PI-IBS through repairing intestinal barrier function may be closely associated with the regulatory role of PXR/NF-κB signaling pathway. Oridonin may serve as a PXR ligand for the development of drugs in the therapy for PI-IBS.
研究领域:
药理学
·
胃肠病学
·
分子生物学
·
细胞生物学
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PubMed
高影响因子
Scientific Reports
·
2026
·
IF 3.9
Zhang Fangxia,Luo Kunshun,Xuan Shaoyan,Chen Teng,Chen Zhiyong,Yang Jing,Zhou Ying,Feng Tingting,Zhu Yue,Wang Zuhua
Pancreatic cancer has a dismal prognosis due to the rapid progression and inefficiency of chemotherapy. To ameliorate this inefficiency of chemotherapy drug, we developed a long-circulating PEGylated nanoliposome (ORI@PD-Lipo) with 1,2-distearoylphosphoethanolamine- polyethyleneglycol-amine (DSPE-PEG 2000 -NH 2 ) to deliver oridonin, one of the active ingredients in Rabdosia rubescens ( R. rubescens ) in this study. For improving tumor-targeting delivery of oridonin, a pancreatic cancer targeting CKAAKN peptide was used to modify the nanoliposome (ORI@CPD-Lipo). Our results showed that ORI@CPD-Lipo had good stability and biosafety with average particle size of about 100 nm, which could selectively internalize into pancreatic cancer cells BxPC-3 during the short incubation time (1–4 h) in vitro under the mediation of CKAAKN peptide, compared with HPDE6-C7 cells. Furtherly, significantly higher uptake of ORI@CPD-Lipo nanoparticles by BxPC-3 tumors (positive-CKAAKN) than normal pancreatic tissue was observed in vivo during the whole experiment process (1–48 h), with increased ratio on experiment time. Our data also indicated the treatment of BxPC-3 cells with ORI@CPD-Lipo nanoparticles showed significantly enhanced antitumor effect and therapeutic efficacy than the treatment with the free ORI, non-targeting ORI@Lipo and CKAAKN-blocking ORI@CPD-Lipo. The enhanced antitumor activity to BxPC-3 cells should be attributed to the enhanced drug cellular uptake mediated by ORI@CPD-Lipo nanoparticles, chemical toxicity of the released ORI from the nanoparticles. Our study provided a valuable reference and strategy of CKAAKN-mediated targeting cancer chemotherapy based on ORI@CPD-Lipo against the pancreatic tumor.
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International Journal of Biological Sciences
·
2026
·Vol. 22
·期 12
·6363
·
IF 11.7
Ziyang Ding,Sisi Wang,Junhui Chen,Yali Song,Zhou Zhu,Haibo Tong,Ashok Iyaswamy,Peng Chen,Xu Wei,Wei Zhang,Jigang Wang,Chuanbin Yang,Yulin Feng
Oridonin is a bioactive diterpenoid derived from the widely used traditional Chinese medicinal herb Rabdosia rubescens , exhibits broad-spectrum anti-cancer activity, with several derivatives currently in clinical trials. However, the molecular mechanism underlying its anticancer effects, especially its direct target proteins, remain to be fully elucidated. Here, we found that Oridonin promoted intracellular reactive oxygen species (ROS) accumulation, which in turn induced endoplasmic reticulum (ER) stress-mediated apoptosis. Moreover, ER stress was instrumental in inducing autophagy after Oridonin treatment, while blockade of autophagy further exacerbated Oridonin-induced cytotoxicity. Notably, using activity-based protein profiling (ABPP), we identified the anti-oxidant enzyme Peroxiredoxin 1 (PRDX1) as a key direct covalent target of Oridonin. By binding to Cysteine 173 of PRDX1, Oridonin increased intracellular ROS levels. Furthermore, PRDX1 over-expression mitigated, whereas PRDX1 knockdown potentiated, Oridonin-induced ROS accumulation, autophagy, and subsequently apoptosis. Overall, our results indicate that PRDX1 is a direct covalent binding target mediating Oridonin-induced apoptosis. These findings not only provide fresh insights into the core mechanism of Oridonin-induced cytotoxicity, but also highlight PRDX1 as a potential therapeutic target for renal cancer drug development.
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DRUG DEVELOPMENT RESEARCH
·
2020
·Vol. 81
·期 4
·526-533
·
IF 1.902
Dong Liu,Hailong Qin,Bixian Yang,Bin Du,Xuelin Yun
Liver fibrosis is characterized by the activation of hepatic stellate cells (HSCs) and accumulation of the extracellular matrix. There are limitations in the current therapies for liver fibrosis. Recently, oridonin was shown to induce apoptosis in HSCs. Thus, we aimed to determine the roles of oridonin in chronic liver injury and fibrosis. Liver fibrosis was induced by CCl 4 in mice injected intraperitoneally with oridonin for 6 weeks. The administration of oridonin significantly attenuated liver injury and reduced ALT levels. In addition, Sirius Red staining and the expression of α-smooth muscle actin (α-SMA) were significantly reduced by oridonin in murine livers with fibrosis. The expression of NLRP3, caspase-1, and IL-1β was downregulated with the oridonin treatment. Furthermore, the expression of F4/80 in liver tissues was also decreased by oridonin treatment. These results demonstrate that oridonin ameliorates chronic liver injury and fibrosis. Mechanically, oridonin may inhibit the activity of the NLRP3 inflammasome and inflammation in the liver. These results highlight the potential of oridonin as a therapeutic agent for liver fibrosis.
研究领域:
药理学
·
肝病学
·
炎症
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PubMed
高影响因子
TISSUE & CELL
·
2021
·
IF 2.466
Yujie Jia,Yu Tong,Lianqiu Min,Yanrong Li,Yan Cheng
NOD-like receptor protein 3 (NLRP3) inflammasome is tightly related to the pathogenesis of cerebral ischemia/reperfusion (I/R) injury, and oridonin (Ori) has shown the potential to alleviate ischemia/reperfusion injury with underlying mechanisms. Our study aims to figure out whether Ori protects against the cerebral ischemia/reperfusion injury by the NLRP3 inflammasome signaling. In this study, a temporary middle cerebral artery occlusion (MCAO) and reperfusion surgery was conducted on male C57BL/6 mice to mimic cerebral I/R injury in vivo. Cellular model of cerebral I/R in vitro was achieved by oxygen-glucose deprivation and reintroduction (OGD/R) in BV2 microglia cells. We found that Ori treatment significantly relieved the neurological deficits, neuronal injury and microglia activation in I/R mice according to morphological and histological analyses. Meanwhile, the inactivation of NLRP3 inflammasome was determined in Ori-treated mice with significantly down-regulated expressions of inflammasome-related genes. Western-blot analysis further demonstrated the negative effect of Ori on NF-κB signaling with diminished phosphorylation and degradation of IκBα as well as suppressed translocation of p65. Furthermore, we indicated that Ori suppressed the activation of NLRP3 inflammasome in OGD/R induced BV2 microglia cells by inhibiting NF-κB signaling. In summary, our findings make Ori a potential candidate for therapy of cerebral I/R injury in the future.
研究领域:
神经科学
·
药理学
·
炎症研究
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PubMed
高影响因子
Cancer Medicine
·
2019
·Vol. 8
·期 11
·5313-5326
·
IF 3.357
Han-Qing Zhu,Chao Zhang,Zhu-Ying Guo,Jun-Mei Yang,Jia-Hui Guo,Chen Chen,Qiang-Hua Yao,Feng Liu,Quan-Wu Zhang,Feng-Hou Gao
Oridonin could induce NB (neuroblastoma) cells growth inhibition by inducing apoptosis and cell cycle arrest, and the molecular mechanisms behind the effects deserve to be further explored. Here, oridonin was confirmed to cause the reactivation of p53 (cellular tumor antigen p53) to promote the expression of a series of apoptosis- and cell cycle arrest-related proteins for the biological effects. During the process, oridonin relied on the caspase activation to cleave p53-induced Mdm2 (E3 ubiquitin-protein ligase Mdm2) to generate Mdm2-p60. The generation of Mdm2-p60 stabilized p53, and resulted in p53 accumulation for p53 continuous activation. In our research, it was also found that the reactivation of p53 induced by oridonin was closely related with the generation of ROS (reactive oxygen species). Taken together, these findings explain that oridonin exerts its anticancer activity partially by targeting the Mdm2-p53 axis in NB cells, which lay an experimental base for future research of exploring the effects and molecular mechanisms of oridonin.
研究领域:
肿瘤学
·
细胞生物学
·
药理学
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PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2022
·
IF 3.322
Hui Feng,Yi Liu,Mengyao Zhang,Ruimin Liu,Jincheng Wang,Wenjuan Wang,Pengcheng He,Penghui Zhang,Fan Niu
Acute myeloid leukemia (AML) is the most common blood cancer in adults. Patients' 5-year overall survival is less than 30% thus having a poor prognosis. To date, the development of novel target therapies is still necessary to ameliorate patients’ survival. Antibody-drug conjugates (ADCs) represent a promising class of drugs for the treatment of AML. CD33 is highly expressed on AML cells, and the FDA-approved CD33-targeted ADC drug-gemtuzumab ozogamicin (GO) has proved the feasibility of CD33-targeted ADC drug design. In this study, we constructed a novel CD33-targeted ADC drug composed of a humanized anti-CD33 antibody and oridonin as a payload with a cleaved chemical linker. Oridonin is a natural product that has great cancer therapy potential while its poor bioavailability and targeting ability limited its clinical use. Herein, we demonstrated that antiCD33-oridonin specifically delivered oridonin in AML cells improved AML cells killing ability of oridonin. Meanwhile, it did not show any non-specific toxicity on CD33 negative cells. In summary, we developed a novel AML targeting ADC with clinical application potential, and therefore provided a new solution for the druggability improvement of oridonin.
研究领域:
肿瘤学
·
药学
·
免疫疗法
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PubMed
高影响因子
MOLECULES
·
2019
·Vol. 24
·期 18
·3369
·
IF 3.06
Gongsen Chen,Juyuan Luo,Mengru Cai,Liuying Qin,Yibo Wang,Lili Gao,Pingqing Huang,Yingchao Yu,Yangming Ding,Xiaoxv Dong,Xingbin Yin,Jian Ni
Oridonin (ORI) is a natural active ingredient with strong anticancer activity. But its clinical use is restricted due to its poor water solubility, short half-life, and low bioavailability. The aim of this study is to utilize the metal organic framework material MOF-5 to load ORI in order to improve its release characteristics and bioavailability. Herein, MOF-5 was synthesized by the solvothermal method and direct addition method, and characterized by Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD), Fourier Transform Infrared Spectrometer (FTIR), Thermogravimetric Analysis (TG), Brunauer–Emmett–Teller (BET), and Dynamic Light Scattering (DLS), respectively. MOF-5 prepared by the optimal synthesis method was selected for drug-loading and in vitro release experiments. HepG2 cells were model cells. MTT assay, 4′,6-diamidino-2-phenylindole (DAPI) staining and Annexin V/PI assay were used to detect the biological safety of blank carriers and the anticancer activity of drug-loaded materials. The results showed that nano-MOF-5 prepared by the direct addition method had complete structure, uniform size and good biocompatibility, and was suitable as an ORI carrier. The drug loading of[email protected]was 52.86% ± 0.59%. The sustained release effect was reliable, and the cumulative release rate was about 87% in 60 h.[email protected]had significant cytotoxicity (IC50:22.99 μg/mL) and apoptosis effect on HepG2 cells.[email protected]is hopeful to become a new anticancer sustained release preparation. MOF-5 has significant potential as a drug carrier material.Keywords:MOF-5;Oridonin;Antitumor;HepG2 cells;sustained release
研究领域:
药学
·
材料科学
·
癌症研究
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PubMed
高影响因子
Journal of Science-Advanced Materials and Devices
·
2025
·
IF 6.8
Kong Jiahui,Zhang Yongqiang,Yang Yuchang,Wang Ziheng,Jing Xiaohong,Lin Shuting,Chen Hongyue,Dong Xiaoxv,Qu Changhai,Cai Mengru,Ni Jian,Yin Xingbin
Malignant melanoma (MM) exhibits clinical traits of vigorous metastasis and an unfavorable prognosis. Traditional therapeutic modalities such as surgical resection, radiotherapy, and chemotherapy have restricted efficacy and notable side effects, thereby urgently demanding new drugs or treatment approaches. The iron-doped zeolite imidazole ester skeleton material (Fe-ZIF-8, FZ) exhibits outstanding biological safety and acid-responsive drug release properties, serving as an excellent nano-delivery carrier. Oridonin (Ori) is capable of inducing ferroptosis in tumor cells by targeting key genes (such as GPX4, SLC7A11, GGT1), and demonstrates a potent therapeutic effect on MM. Simultaneously, small interfering RNA (siRNA) can exert a role in gene silencing. In this study, we devised biomimetic nanoparticles (NPs) based on iron-doped zeolitic imidazolate framework-8 (FZ) for the co-delivery of Ori and siRNA targeting GPX4 (siRNA GPX4 ). FZ was employed to co-load Ori and siRNA targeting GPX4, the core regulator of ferroptosis, to play a role in drug and gene therapy for MM. The A375 tumor cell membrane was biomimetically modified to construct anti-tumor drug targeted delivery nanoparticles, thereby achieving efficient co-delivery of Ori and siRNA GPX4 . This provides a novel idea for the development of highly efficient and low-toxicity treatment of MM and the overcoming of tumor drug resistance.
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EUROPEAN POLYMER JOURNAL
·
2022
·
IF 5.546
Zhi Li,Lifen Zhang,Changning Xue,Yuman Zhang,Yao Yu,Xinhong Guo,Zhenzhong Zhang
Hydroxypropyl-β-Cyclodextrin (HP-β-CD) was used to form the HP-β-CD/Oridonin inclusion complex. Then, the novel Multi-loaded nanovesicles systems (NVs) were established to encapsulate both hydrophilic (Trehalose) and hydrophobic drugs (Oridonin inclusion complex) with peptides. NVs had an average size of 224.4 ± 10.84 nm and a zeta potential of 17.83 ± 1.05 mV. Furthermore, these NVs significantly decreased lipid over-accumulation, and reverse the formation of foam cells in RAW264.7 cells. Oridonin and Trehalose in NVs provided significant synergistic effects to inhibit lipid over-accumulation (CI < 1). In addition, NVs could modulate the release of IL-1β, IL-6 and TNF-α, promote the formation of autophagosomes. Taken together, the Multi-loaded NVs may be used as an effective drug delivery system, providing new insights into decrease the formation of foam cells and regulate the inflammation.
研究领域:
药学
·
生物技术
·
细胞生物学
·
药物递送系统
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DOI
高影响因子
Oncology Letters
·
2018
·Vol. 16
·期 2
·2289-2298
·
IF 1.664
Chunyu Li,Qi Wang,Shen Shen,Xiaolu Wei,Guoxia Li
Metastasis is the primary cause of mortality in patients with breast cancer and lacks effective therapeutic agents. Oridonin, an active diterpenoid compound isolated from Rabdosia rubescens, was identified to be the most potent anti‑tumor ingredient. However, the molecular mechanisms responsible for its anti‑metastatic effects remain unclear. In the present study, oridonin significantly suppressed the migration, invasion and adhesion of MDA‑MB‑231 and 4T1 breast cancer cells, and inhibited tube formation of human umbilical vein endothelial cells in a dose‑dependent manner. The expression levels of epithelial‑mesenchymal transition (EMT)‑associated marker and the hypoxia inducible factor 1α (HIF‑1α)/vascular endothelium growth factor (VEGF) signaling pathway mRNA and proteins were determined by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively in vitro. The results demonstrated that oridonin effectively inhibited EMT as demonstrated by the significant increases in the expression levels of E‑cadherin, and decreased expression of N‑cadherin, Vimentin and Snail. In addition, oridonin exerted its anti‑angiogenesis activity through significantly decreasing HIF‑1α, VEGF‑A and VEGF receptor‑2 protein expression. Furthermore, oridonin was demonstrated to decrease the micro‑vessel density as evidenced by the decreased expression of cluster of differentiation 31, a marker for neovasculature. In brief, oridonin inhibits tumor cell migration, invasion and adhesion, as well as tumor angiogenesis, which are mediated by suppressing EMT and the HIF‑1α/VEGF signaling pathway. The results of the present study suggest that oridonin may be a promising anti‑metastatic agent in breast cancer treatment.
研究领域:
癌症生物学
·
药理学
·
分子生物学
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DOI
PubMed
高影响因子
Discover Nano
·
2026
·Vol. 21
·期 1
·334
·
IF 6.7
Xuan Shaoyan,Yang Shenglei,Mao Yuqin,Chen Zhiyong,Zhu Yue,Zhou Ying,Huang Jie,Zhu Xiuliang,Wang Zuhua
Lung cancer remains one of the most prevalent and lethal malignancies worldwide. Oridonin (ORI) exhibits remarkable anti-lung cancer activity. Nevertheless, its clinical application in lung cancer therapy is severely hindered by poor solubility, fast metabolism, insufficient tumor penetration, and low selectivity. In this study, we developed a redox-responsive polymeric micelle (HA-cys-TOS) targeting the CD44 receptor to improve ORI bioavailability and tumor targeting. The polymer was synthesized via esterification and verified by 1 H NMR. Our data showed that ORI@HA-cys-TOS exhibited good stability, biosafety and redox-responsive sustained release. Compared to HepG2 cells, ORI@HA-cys-TOS exhibited significantly enhanced internalization ability in A549 cells, likely due to HA binding to the CD44 receptor overexpressed on A549 cells. Unexpectedly, the enhanced targeted accumulation of ORI@HA-cys-TOS micelles in vivo was also observed in both subcutaneous and in situ lung cancer tissues. In vivo and in vitro antitumor studies demonstrated that ORI@HA-cys-TOS micelles exhibited significantly greater antitumor activity compared to free ORI. Notably, no side-effects were observed during the 21 days experimental period. This study provides an experimental basis for advancing ORI toward clinical personalized lung cancer therapy by targeting CD44 and responding to the tumor redox microenvironment.
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