CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Weili Yang,Hui Liu,Xiaowei Liu,Yuxin Cao,Xuemei Wang,Xinxin Wang,Wenwen Cao,Chunjing Guo,Daquan Chen
Acute lung injury (ALI) is a complex acute respiratory illness with a high mortality rate. Reactive oxygen species (ROS) play a pivotal role in ALI, inducing cellular damage, inflammation, and oxidative stress, thereby exacerbating the severity of the injury. In this study, inspired by the “subtractive” strategy, we developed a fucoidan-based macrophage membrane bio-nanosystem, abbreviated as MF@CB, designed as an anti-inflammatory and antioxidant agent to alleviate lipopolysaccharide (LPS)-induced inflammation in ALI. MF@CB coated with macrophage membrane for effective targeting and accumulation in ALI lesions. In addition, MF@CB activates Nrf2 transcriptional activity in macrophages, inhibiting ROS synthesis at its origin while effectively removing ROS already present in the ALI. This dual-pronged approach demonstrates robust antioxidant properties and restores the macrophage antioxidant defense barrier. In the LPS-induced ALI mouse model, MF@CB significantly mitigated lung inflammatory damage by modulating lung macrophage polarization and inhibiting the over-secretion of pro-inflammatory cytokines by activated immune cells. More importantly, unlike most surface modification strategies because it remove the molecule, this approach is easier to apply and potentially safer and may provide useful insights into the development of more effective therapeutic strategies for ALI.
研究领域:
纳米技术
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药理学
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免疫学
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呼吸医学
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DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
·
IF 5.4
Yang Gao,Shi-Qiao Liu,Jia-Long Wang,Han-Ming Cui,Qiu-Yan Zhang,Lei Wang,Yi-Xin Zhang,Jian Li,Yu Dong,Yuan-Hui Hu
Ethnopharmacological relevance Sanhuang Xiexin Decoction (SHXD), consisting of Coptis chinensis Franch., Scutellaria baicalensis Georgi and Rheum palmatum L. , is t raditionally used for relieving fever, purging fire for removing toxins, eliminating phlegm and haemostasis, eliminating the wetness-evil from the upper warmer, clearing away the heat-evil and expelling superficial evils. Each of the three herbs contained in SHXD has been indicated to have anti-inflammatory effects in vivo , but its effects on rat NK-cell phenotypes remain unexplored, and the comprehensive mechanism of this compound SHXD in curing the inflammation induced by lipopolysaccharides (LPS) remains to be revealed. Aim of the study The study aim was to assess the effect of SHXD on LPS-induced fever and inflammation in a rat model, reduce NLRP3 activation in NK cells expressing specific cell phenotype antibodies and determine the therapeutic value of this approach in vivo . Materials and methods SHXD extract was prepared and analysed by the developed ultra-performance liquid chromatography (UPLC) method for the simultaneous detection of 14 compounds. The main peaks were firstly identified on an Orbitrap via high resolution tandem mass spectrometry (MS). Then, the extract was used in the rat model of LPS-induced inflammation and fever for pharmacologically study the effects of drug treatment. Peripheral blood lymphocyte cells were isolated from the animals, including those subjected to the SHXD extract treatment, and the cell phenotype was determined prior to cell culture and after treating the cell cultures with the extract. The phenotypes of cells harvested using CD3, CD4, CD8a, CD81, CD161 and CD86 antibodies were used to verify the enhanced memory of the peripheral blood lymphocytes cells (PBMC) that were induced into nature killer (NK) cells. Results The SHXD extract was prepared, analysed and identified via quality control equipment and was observed to have pharmacological effects that reduced NLRP3 activation and fever in rats. The production of NK cells and peripheral blood lymphocytes was induced by the SHXD extract, which manifested as increased levels of CD4 + , CD8a+, CD81 + , CD161+ and CD86 + cells. The levels of CD3 + cells were significantly different between the model group and the drug-treated or control groups (p < 0.01) with dose independence, while the levels of CD4 + cells were not significantly different between the drug-treated and control groups, with a trend towards lower levels in the model group with dose independence. The levels of CD4 + cells was significantly different between the drug-treated group and the model groups with dose independence (p < 0.05). The levels of CD86 + cells were not significantly different between the drug-treated group and the model and control groups. The levels of CD8a + cells was significantly different between the model group and the drug and control groups (p < 0.05, dose 2.0 μg/ml), with higher levels in the drug-treated group. The levels of CD3 + , CD4 + , CD8a + cells in the drug treated group have dose dependence with SHXD. Conclusions This experiment revealed that SHXD reduced NLRP3 activation in the blood of LPS-treated rats, which occurred through the activation of NK cells that expressed CD3, CD8a and CD161. SHXD may possess anti-inflammatory effect via activacting the one of major pharmacology effcet of NK cells that expressed CD3, CD8a and CD161 phenotypes expression. This result demonstrates that SHXD may possess ability to enhance the memory of peripheral blood lymphocytes and natural killer cells.
研究领域:
药理学
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免疫学
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分析化学
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中医
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产品关联
DOI
PubMed
高影响因子
NUTRITION
·
2023
·
IF 4.4
Jiabao Tang,Xiaohua Li,Wei Li,Chun Cao
Objective Enteral nutrition (EN) is the key therapy in septic patients. Different formulas of EN have various effects on gastrointestinal sepsis. Therefore, we investigated the effects of EN supplemented with octanoic acid (OA) on lipopolysaccharide (LPS) induced intestinal injury and explored the potential mechanism. Methods First, to investigate the effects of EN supplemented with OA on LPS-induced intestinal injury, rats were randomly divided into four groups: the sham, LPS, LPS + EN, and LPS + EN + OA groups. Then, to explore whether EN supplemented with OA can prevent LPS-induced intestinal injury via the PPARγ/STAT-1/MyD88 pathway, rats were randomly divided into five groups: the sham, LPS, LPS + EN + OA, LPS + EN + OA +SR202, and LPS + pioglitazone groups. All rats received nutritional support for three days. We examined the serum levels of inflammatory factors, pathological changes, goblet cell density, intestinal tight junction protein expression, and the PPARγ/STAT-1/MyD88 pathway in the ileum and colon. In addition, the effect of OA on intestinal epithelium injury was also explored in vitro. Results EN supplemented with OA significantly decreased the serum levels of inflammatory factors and prevented intestinal barrier dysfunction compared with EN alone (P < 0.05). Inhibiting the PPARγ/STAT-1/MyD88 pathway exacerbated effects of EN supplemented with OA on intestinal injury (P < 0.05). Activation of the PPARγ/STAT-1/MyD88 pathway prevented intestinal injury (P < 0.05). OA also exerted a similar effect on intestinal epithelium injury in vitro. Conclusion EN supplemented with OA prevents LPS-induced intestinal injury via the PPARγ/STAT-1/MyD88 pathway.
研究领域:
营养学
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胃肠病学
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免疫学
·
分子生物学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Qiong Liu,Aizhen Zhao,Xiaopeng Wu,Xin Zhang,Xiaoru Li,Wenwen Yang,Wangrui Lei,Hui Liu,Huadong Zhao,Shuai Jiang,Yang Yang,Mingzhi Shen
Background Septic heart failure has been recognized as a puzzle since antiquity and poses a major challenge to modern medicine. Our previous work has demonstrated the potential effects of lycorine (LYC) on sepsis and septic myocardial injury. Nonetheless, further exploration is needed to elucidate the underlying cellular and molecular mechanisms. Methods In this study, we conducted transcriptome analysis and weighted gene co-expression network analysis (WGCNA) to identify the key genes and reveal the mechanism of LYC against septic heart failure. Purpose This study aims to apply bioinformatic analysis and experimental validations to explore the protective effects and underlying mechanism of LYC on the cecal ligation and puncture (CLP)-induced sepsis model mice. Results Transcriptome analysis revealed the differentially expressed genes (DEGs) following LYC treatment. WGCNA analysis identified gene modules associated with LYC-mediated protection, with BCL3 emerging as a core gene within these modules. Notably, BCL3 was an overlapping gene of DEGs and WGCNA core genes induced by LYC treatment, and is highly negatively correlated with cardiac function indicator. In vivo and in vitro study further prove that LYC exerted a protective effect against septic myocardial injury through inhibiting BCL3. BCL3 siRNA ameliorated LPS-induced cardiac injury and inflammation, while BCL3 overexpression reversed the protective effect of LYC against LPS injury. Conclusion In summary, our findings demonstrate the significant attenuation of septic myocardial disorder by LYC, with the identification of BCL3 as a pivotal target gene. This study is the first to report the role of BCL3 in sepsis and septic myocardial injury. Furthermore, the strategy for hub genes screening used in our study facilitates a comprehensive exploration of septic targets and reveals the potential targets for LYC effect. These findings may offer a new therapeutic strategy for the management of septic heart failure, highlighting the cardioprotective effect of LYC as adjunctive therapy for sepsis management.
研究领域:
心脏病学
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药理学
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分子生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2023
·
IF 4.1
Jing Cheng,Guangwen Zhang,Liu Liu,Jianming Luo,Xichun Peng
BACKGROUND Beta-glucan is widely sourced and has various physiological activities including anti-inflammation. However, the strength of the anti-inflammatory activity of β-glucans from different sources remained elusive due to the lack of rapid and effective biomarkers. Therefore, this study aimed to screen out the β-glucan with strong anti-inflammatory activity from 5 different sources and to further screen out possible biomarkers in metabolites after fermented the β-glucans by gut microorganisms. RESULTS The results showed that all five β-glucans inhibited the production of LPS-induced pro-inflammatory mediators and suppressed the mRNA expression level of TLR4/MyD88. Their anti-inflammatory mechanisms involved the inhibition of intracellular ROS production and suppression of mRNA expression of the NF-κB pathway and JNK pathway. Among them, barley β-glucan exhibited the strongest anti-inflammatory effect, followed by Ganoderma lucidum β-glucan. Enhanced anti-inflammatory activity of β-glucan after fermentation was found and may be related to the increased abundance of metabolites such as the vanillin, dihydroxyphenylacetic acid, caffeic acid, acetic acid, butyric acid, and lactic acid. They are strongly positively correlated to the abundance of beneficial bacteria such as Blautia , suggesting that the production of those metabolites may be responsible for the flourishing of the beneficial bacteria. CONCLUSION In conclusion, barley was a preferred raw material for the preparation of β-glucans with high anti-inflammatory activity. Vanillin, dihydroxyphenylacetic acid, caffeic acid, acetic acid, butyric acid, and lactic acid were the possible biomarkers that could be utilized to evaluate the anti-inflammatory effect of β-glucans. This article is protected by copyright. All rights reserved.
研究领域:
免疫学
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微生物学
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营养学
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药理学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6
Mengting Li,Lingyu Ma,Jiahao Lv,Zhe Zheng,Wenyu Lu,Xunkai Yin,Weijiang Lin,Ping Wang,Jian Cui,Lihong Hu,Jian Liu
Acute lung injury (ALI) is a severe respiratory disorder closely associated with the excessive activation of the NLRP3 inflammasome. Oridonin ( Ori ), a natural diterpenoid compound, had been confirmed as a specific covalent NLRP3 inflammasome inhibitor, which was completely different from that of MCC950 . However, the further clinical application of Ori was limited by its weak inhibitory activity against NLRP3 inflammasome (IC 50 = 1240.67 nM). Fortunately, through systematic structure-optimization of Ori , D6 demonstrated the enhancement of IL-1β inhibitory activity (IC 50 = 41.79 nM), which was better than the parent compound Ori . Then, by using SPR, molecular docking and MD simulation, D6 was verified to directly interact with NLRP3 via covalent and non-covalent interaction. The further anti-inflammatory mechanism studies were revealed that D6 could inhibit the activation of NLRP3 inflammasome without affecting the initiation phase of NLRP3 inflammasome activation, and D6 was a broad-spectrum and selective NLRP3 inflammasome inhibitor. Finally, D6 demonstrated a favorable therapeutic effect on LPS-induced ALI in mice model, and the potent pharmacodynamic effect of D6 was correlated with the specific inhibition of NLRP3 inflammasome activation in vivo . Thus, D6 is proved as a potent NLRP3 inhibitor, and has the potential to develop as a novel anti-ALI agent.
研究领域:
药理学
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炎症
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呼吸系统疾病
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药物设计
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Li Gao,Ai-ping Zhang,Lei Fu,Qian-wen Li,Xue-mei Qin,Jing Zhao
Background The incidence of neuropathic pain is progressively increasing over time. The activation of M1-type microglia plays a crucial role in the initiation and progression of neuropathic pain. Huangqin Decoction (HQD) is traditionally used to alleviate dysentery and abdominal pain. However, it remains unclear whether HQD can effectively mitigate neuropathic pain and the underlying mechanisms. Purpose The present study aims to investigate the impact of HQD on neuropathic pain induced by spared nerve injury (SNI) in mice, and to elucidate whether the analgesic effect of HQD is associated with microglia polarization. Methods The analgesic effect of HQD on SNI mice was investigated through assessments of mechanical pain threshold, thermal pain threshold, cold pain threshold, and motor ability. We elucidated the molecular mechanisms of HQD in alleviating SNI-induced neuropathic pain by focusing on microglia polarization and intestinal metabolite abnormalities. The expression levels of markers associated with microglia polarization (Iba-1, CD68, CD206, iNOS) was detected by immunofluorescence and Western blot, and the levels of inflammatory factors (IL-4, IL-10, IL-6, TNF-α) were assessed by ELISA. UPLC-QTOF-MS metabolomics was utilized to identify differential metabolites in the intestines of SNI mice. We screened the differential metabolites related to microglial polarization by correlation analysis, subsequently nicotinamide was selected for validation in LPS-induced BV-2 cells. Results Our findings demonstrated that HQD (20 g/kg) significantly enhanced the mechanical pain threshold, thermal pain threshold, and cold pain threshold, and protected the injured DRG neurons of SNI mice. Moreover, HQD (20 g/kg) obviously suppressed the expression of microglia M1 polarization markers (Iba-1, CD68, iNOS, IL-6, TNF-α), and promoted the expression of microglia M2 polarization markers (CD206, IL-10, IL-4) in the spinal cord of SNI mice. Additionally, HQD (20 g/kg) prominently ameliorated intestinal barrier damage by upregulating Claudin 1 and Occludin expression in the colon of SNI mice. Furthermore, HQD (20 g/kg) rectified 19 metabolite abnormalities in the intestine. Notably, nicotinamide (100 μM), an amide derivative with anti-inflammatory property, effectively suppresses microglia activation and polarization in LPS-induced BV-2 cells by downregulating IL-6 level and CD68 expression while upregulating IL-4 level and CD206 expression. Conclusion In summary, HQD alleviates neuropathic pain in SNI mice by regulating the activation and polarization of microglia, partially mediated through intestinal nicotinamide metabolism.
研究领域:
神经科学
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药理学
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代谢组学
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免疫学
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疼痛研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOCHEMISTRY
·
2021
·
IF 4.072
Lanlan Nie,Rui Li,Jie Huang,Lingling Wang,Mengjie Ma,Chunyue Huang,Tong Wu,Renjie Yan,Xiao Hu
Five undescribed abietane diterpenoids , dracocephalumoids A–E, together with six known analogues were isolated from the aqueous EtOH extract of aerial parts of Dracocephalum moldavica L.. The structures were elucidated through extensive analysis of spectroscopic data , and their absolute configurations were established by Mosher's method and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculation. Cell-based anti-inflammatory assays displayed that dracocephalumoid A, uncinatone, trichotomone F and caryopterisoid C showed potent suppressive effects against TNF- α , IL-1 β or NO production in LPS-induced RAW 264.7 cells, with IC 50 values ranging from 1.12 to 5.84 μM. The structure-activity relationship of these compounds was also discussed.
研究领域:
药理学
·
有机化学
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生物化学
·
药物化学
✓ 已验证
DOI
PubMed
高影响因子
CNS Neuroscience & Therapeutics
·
2023
·
IF 5.5
Xin Li,Huimei Shi,Di Zhang,Bei Jing,Zhenni Chen,Yachun Zheng,Shiquan Chang,Li Gao,Guoping Zhao
Background This study aimed to investigate the potential mechanism of paeonol in the treatment of neuropathic pain. Methods Relevant mechanisms were explored through microglial pseudotime analysis and the use of specific inhibitors in cell experiments. In animal experiments, 32 SD rats were randomly divided into the sham operation group, the chronic constrictive injury (CCI) group, the ibuprofen group, and the paeonol group. We performed behavioral testing, ELISA, PCR, Western blotting, immunohistochemistry, and immunofluorescence analysis. Results The pseudotime analysis of microglia found that RhoA, Rock1, and p38MAPK were highly expressed in activated microglia, and the expression patterns of these genes were consistent with the expression trends of the M1 markers CD32 and CD86. Paeonol decreased the levels of M1 markers (IL1β, iNOS, CD32, IL6) and increased the levels of M2 markers (IL10, CD206, ARG-1) in LPS-induced microglia. The expression of iNOS, IL1β, RhoA, and Rock1 was significantly increased in LPS-treated microglia, while paeonol decreased the expression of these proteins. Thermal hyperalgesia occurred after CCI surgery, and paeonol provided relief. In addition, paeonol decreased the levels of IL1β and IL8 and increased the levels of IL4 and TGF-β in the serum of CCI rats. Paeonol decreased expression levels of M1 markers and increased expression levels of M2 markers in the spinal cord. Paeonol decreased IBA-1, IL1β, RhoA, RhoA-GTP, COX2, Rock1, and p-p38MAPK levels in the spinal dorsal horn. Conclusion Paeonol relieves neuropathic pain by modulating microglial M1 and M2 phenotypes through the RhoA/p38 MAPK pathway.
研究领域:
药理学
·
神经科学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BRAIN BEHAVIOR AND IMMUNITY
·
2021
·
IF 7.217
Yun Wang,Ce Gao,Tianyu Gao,Lu Zhao,Shiguang Zhu,Lin Guo
A growing body of studies indicated that exosomes are one of vital players in pathological process of neuropsychiatric diseases, but their role in major depressive disorder (MDD) remains poorly understood. Here we purified plasma exosomes from depression including lipopolysaccharide (LPS)-challenged depression, chronic restraint stress (CRS)-induced depression, MDD subjects, and from control mice or volunteers. The therapeutic effect of these exogenous exosomes was assessed utilizing behavioral tests and biochemical approaches in the LPS-caused depression or microglial BV2 cells. The expression of exosomal sigma-1 receptor (Sig-1R) was evaluated by western blotting. The role of Sig-1R in the biological function of exosomes was determined using Sig-1R knockout mice and HEK 293 cells. Our results revealed that injection of exosomes from depression models or patients rather than normal controls significantly ameliorated depressive-like behaviors, deficiency of BDNF expression and neuro-inflammation in LPS-challenged mice. In addition, co-culture with exosomes from depression models or patients instead of from controls prevented LPS-induced inflammation responses in microglial BV2 cells. Moreover, Sig-1R was demonstrated for the first time to significantly be enriched in exosomes from depression models or patients compared with that from normal controls. However, Sig-1R null exosomes no longer emerged antidepressant-like action in LPS-challenged mice. Thus, we demonstrated that plasma exosomes from depression exerted antidepressant-like effects in a Sig-1R dependent manner in the LPS-induced depression. This work improves our understanding of the exosomes in depression, suggesting a novel exosomes-based approach for MDD treatment.
研究领域:
神经科学
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药理学
·
分子生物学
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精神病学
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产品关联
DOI
PubMed
高影响因子
Advanced Therapeutics
·
2022
·Vol. 6
·期 2
·2200149
·
IF 5.003
Kai Zhang,Junlong Da,Jianqun Wang,Lixue Liu,Xinpeng Liu,Haoze Yuan,Lili Jiang,Yawei Geng,Xiaoyao Liu,Zhuling Jiang,Han Jin,Ying Li,Bin Zhang
Bone damage results from the imbalance of bone homeostasis maintained by osteoblast-regulated bone formation and osteoclast-mediated bone resorption. Conventional drug therapy and gene therapy may not optimally regulate the bone remodeling process due to the unitary pharmacological mechanism of drug and the safety and targeting of gene vectors. In the present study, multifunctional fluorescent alendronate-polyethyleneimine carbon dots (Alen-PEI CDs) are innovatively synthesized, which have excellent biocompatibility, selective bone targeting, gene carrying capacity, and anti-bone absorption effect. As gene vectors, bone morphogenic protein 2 (BMP2) gene-loaded Alen-PEI CDs greatly enhance osteoblast differentiation and bone regeneration. Notably, Alen-PEI CDs are found to directly inhibit the formation and function of osteoclasts, effectively attenuating the LPS-induced skull osteolysis in mice. Furthermore, their cumulative toxicity is lower than that of Alen, indicating their potential as an anti-bone resorptive nanodrug. These results show that the bone-targeting Alen-PEI CDs significantly reverse the imbalance of bone homeostasis through a dual-directional mechanism—directly suppressing bone resorption and indirectly inducing bone formation by transfection of osteogenic therapeutic genes. Overall, the study expands the application for carbon dots in biomedicine, providing new insights for the further development of novel selectively targeted multifunctional nanodrugs for the treatment of bone-destructive diseases.
研究领域:
生物医学工程
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药学
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分子生物学
·
组织工程
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
Chinese Medicine
·
2025
·Vol. 20
·期 1
·1-18
·
IF 5.7
Wang Xu,Peng Hui-Ming,Zhang Meng-Ru,Li Jing-Jing,Zhao Chuan-Peng,Zhang Ya-Li,Wang Si-Yu,Zhu Si-Ying,Lu Jian-Kang,Yin Hai-Long,Yin Qiang,Fang Jin-Bo
Background Steroid-resistant asthma (SRA) is a form of asthma resistant to corticosteroid therapy, which is characterized by the presence of neutrophil-predominant inflammatory response and neutrophil extracellular traps (NETs) formation. Hyssopus cuspidatus Boriss., a traditional Uyghur medicine, is known for its efficacy in treating inflammatory lung conditions such as asthma. However, the therapeutic impact and underlying mechanisms of Hyssopus cuspidatus Boriss.’s volatile oil (HVO) in SRA have not been fully elucidated. Methods This study established an ovalbumin/lipopolysaccharide (OVA/LPS)-induced SRA mice model to evaluate the therapeutic effect of HVO on SRA. UPLC-QE-Orbitrap-MS was applied to analyze the serum compositions of HVO. Network pharmacology and molecular docking were employed to uncover the complex mechanisms of HVO in treating SRA and predict potential effective compounds in HVO. Furthermore, in vivo studies in SRA mice and in vitro studies using HL-60 cells and bone marrow neutrophils were conducted to validate the mechanism. Results HVO could significantly ameliorate OVA/LPS-induced SRA symptoms, including airway hyperresponsiveness, airway inflammation, mucus overproduction and airway remodeling. 41 prototype compounds, 65 Phase I metabolites and 50 Phase II metabolites were identified in serum-containing HVO. The integration of network pharmacology with experimental validation revealed that HVO can inhibit the formation of NETs by targeting neutrophil elastase, thereby exerting a therapeutic influence on SRA. Meanwhile, molecular docking results showed that 3-methoxy-4-hydroxy mandelonitrile, 1,2,3,4-tetrahydro-1,5,7-trimethyl-naphthalene, cis-calamenene and aristol-1(10)-en-9-yl isovalerate may be the therapeutic compounds of HVO in treating SRA. Conclusion These findings suggest that HVO is a promising therapeutic candidate for neutrophil-dominant SRA by targeting NETs formation.
研究领域:
药理学
·
免疫学
·
呼吸病学
·
传统医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）