PHYTOCHEMISTRY
·
2023
·
IF 3.8
Hao-Dong Yang,Zhi-Shu Tang,Tao-Tao Xue,Huai-Li Xu,Bao-Long Hou,Ya-Ya Zhu,Zeng-Hu Su,Hong-Bo Xu
Twenty-four monoterpenoids , including three previously undescribed compounds ( 1 – 3 ), were isolated from the root bark of Acanthopanax gracilistylus W. W. Smith ( Acanthopanacis Cortex ). Their structures were unambiguously established based on spectroscopic analysis (HR-ESIMS, IR, 1D, and 2D NMR), and the absolute configurations of 1 – 3 were elucidated by comparing their experimental and calculated electronic circular dichroism spectra. In addition, the structure of 8 was confirmed by single-crystal X-ray diffraction. The inhibitory activities of 1 – 24 against neutrophil elastase , 5-lipoxygenase, and cyclooxygenase-2 (COX-2) were studied in vitro for the first time, and the results showed that compound 24 possessed a significant inhibitory effect on COX-2 with an IC 50 value of 1.53 ± 0.10 μ Μ. This research first reported the presence of monoterpenoids in Acanthopanacis Cortex , including one monoterpenoid 2 with an unusual 4/5 bicyclic lactone system, and compounds 4 and 5 have never been reported in nature.
研究领域:
药用植物学
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药理学
·
化学
·
植物科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2023
·
IF 5.6
Kun Hu,Yongjin Sun,Jie Wang,Shaojun Wu,Jie Ren,Dan Su,Lidan Tang,Jinhong Gong,Hufeng Fang,Shan Xu,Hao Yang
Hepatocyte lipid accumulation in type 2 diabetes mellitus (T2DM) promotes the development of metabolic dysfunction-associated steatosis liver disease (MASLD), whereas no specific drug treatment is available. Pinocembrin assists in the treatment of many diseases, however, little is known about its protective effect on hepatic lipid metabolism disorders induced by T2DM. In this study, the ameliorative effects of pinocembrin on T2DM-induced hepatocyte lipid accumulation were investigated by in vitro experiments combined with a comprehensive analysis strategy of network pharmacology and molecular docking. High glucose and free fatty acid co-cultured HepG2 cell line was used. The results indicated that pinocembrin reduced lipid deposition by modulating the release of Cyclooxygenase-2 (COX-2)-mediated inflammatory factors and improving insulin resistance (IR) in HepG2 cells. Overall, the findings of this study suggested that pinocembrin ameliorated lipid accumulation and IR in vitro , and thus may be a potential therapeutic agent for the treatment of T2DM-induced hepatic steatosis.
研究领域:
药理学
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细胞生物学
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代谢学
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糖尿病研究
✓ 已验证
产品关联
DOI
高影响因子
Heliyon
·
2023
·
IF 4
Ran Tu,Cheng Zhou,Wenfeng Huang,Zhengping Feng,Qiufang Zhao,Xiaofei Shi,Langjun Cui,Keke Chen
Rationale and objectives Fuzi, the dried root of Aconitum carmichaelii Debx, is one of the widely used traditional Chinese medicines. Fuzi polysaccharides are considered the most bioactive compounds with immunomodulatory functions, however, the mechanisms have not been evaluated. This study aims to systematically investigate the effects of Fuzi polysaccharides on the gut microbiota and immune function using a mouse model immunosuppressed with cyclophosphamide. Methods The short-chain fatty acid levels in cecal contents were measured by gas chromatography-mass spectrometry. The gut microbiota 16S rRNA gene were sequenced by next generation sequencing. The mRNA expression levels of NF-κB, IL-6, TNF-α, iNOS and COX-2 were measured using quantitative real-time polymerase chain reaction. The protein expression of occludin and zonula occludens-1 were analyzed by Western blot. The white blood cells were counted using automated hematology analyzer, and CD4 + FOXP3 + /CD4 + ratio was measured by flow cytometry. Results and Conclusions Fuzi polysaccharides had the function of elevating the concentration of acetic acid, propionic acid, isobutyric acid, and n-butyric acid in the cecum. Meanwhile, Fuzi polysaccharides could decrease the relative abundance of Helicobacter , Anaerotruncus , Faecalibacterium , Lachnospira , Erysipelotrichaceae _UCG-003, Mucispirillum , and Mycoplasma , and increase the relative abundance of Rhodospirillales , Ruminococcaceae _UCG-013, Mollicutes _RF39, Ruminococcus _1, Christensenellaceae _R-7_group, and Muribaculaceae in the gut. Furthermore, Fuzi polysaccharides exhibited the function of increasing spleen and thymus indices and number of white blood cells and lymphocytes. Fuzi polysaccharides could reverse the decreased mRNA expression of NF-кB, IL-6, and iNOS, differentiation of CD4 + FOXP3 + regulatory T cells as well as protein expression of occludin and zonula occludens-1 induced by cyclophosphamide. In addition, the mRNA and protein expression of cytokines were significantly correlated with the abundance of gut microbiota under Fuzi polysaccharides treatment. Collectively, the above results demonstrated that Fuzi polysaccharides could regulate inflammatory cytokines and gut microbiota composition of immunosuppressive mice to improve immunity, thereby shedding light on revealing the molecular mechanism of polysaccharides of traditional Chinese medicines in the future.
研究领域:
免疫学
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微生物学
·
药理学
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中药学
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2021
·
IF 6.4
Linming Li,Yan Chen,Qingpeng Wang,Zuojie Li,Zhifang Liu,Xuewen Hua,Jun Han,Chunxiao Chang,Zhengping Wang,Dacheng Li
Background Platinum(IV) complexes with inflammation inhibitory properties are much favored in improving antitumor activities. Nanodrug-delivery system as a preferable measure for antitumor therapy are widely explored in platinum(IV) drug delivery. Purpose The aim for this study was to develop novel bovine serum albumin (BSA) nanoparticles (NPs) based on naproxen platinum(IV) complexes to display a synergistic antitumor mechanism targeting cyclooxygenase-2 (COX-2), metalloproteinase-9 (MMP-9) and inducible nitric oxide synthase (iNOS). Methods Herein, we reported the preparation of two BSA NPs of naproxen platinum(IV) complexes, and their antitumor activities were investigated in vitro and in vivo. Results Both NPs possessed relatively uniform size and good stability for 30 days in aqueous solution. They exhibited prominent antitumor activities in vitro, and showed great potential in reversing drug resistance. Furthermore, these two NPs played superior tumor growth suppression in vivo in contrast to the free compounds, which were comparable to that of cisplatin and oxaliplatin, but induced lower toxic influences than platinum(II) drugs especially to spleen and liver. Moreover, the naproxen platinum(IV) NPs could decrease tumor inflammation targeting COX-2, MMP-9 and iNOs, and decreasing NO production, which would be in favor of enhancing the antitumor competence, and reducing toxicity. Conclusion Taken together, BSA NPs of naproxen platinum(IV) complexes demonstrated a powerful antitumor efficacy in vitro and in vivo. The platinum(IV) NPs with inflammation inhibitory competence targeting multiple enzymes reported in this work afford a new strategy for the development of antitumor therapy to overcome drawbacks of clinical platinum(II) drugs.
研究领域:
药学
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肿瘤学
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纳米技术
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药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Caihua Ye,Meng Cheng,Lin Ma,Tianzhu Zhang,Zuhao Sun,Chunshui Yu,Junping Wang,Yan Dou
Prevention of Alzheimer’s disease (AD) is a global imperative, but reliable early interventions are currently lacking. Microglia-mediated chronic neuroinflammation is thought to occur in the early stage of AD and plays a critical role in AD pathogenesis. Here, oxytocin (OT)-loaded angiopep-2-modified chitosan nanogels (AOC NGs) were designed for early treatment of AD via inhibiting innate inflammatory response. Through the effective transcytosis of angiopep-2, AOC NGs were driven intravenously to cross the blood-brain barrier, enter the brain, and enrich in brain areas affected by AD. A large amount of OT was then released and specifically bound to the pathological upregulated OT receptor, thus effectively inhibiting microglial activation and reducing inflammatory cytokine levels through blocking the ERK/p38 MAPK and COX-2/iNOS NF-κB signaling pathways. Consecutive weekly intravenous administration of AOC NGs into 12-week-old young APP/PS1 mice, representing the early stage of AD, remarkably slowed the progression of Aβ deposition and neuronal apoptosis in the APP/PS1 mice as they aged and ultimately prevented cognitive impairment and delayed hippocampal atrophy. Together, the findings suggest that AOC NGs, which show good biosafety, can serve as a promising therapeutic candidate to combat neuroinflammation for early prevention of AD.
研究领域:
神经科学
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药理学
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神经炎症
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药物递送系统
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阿尔茨海默病研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science Signaling
·
2020
·Vol. 13
·期 646
·
IF 6.467
Xiao-Wei Gu,Zi-Cong Chen,Zhen-Shan Yang,Yan Yang,Ya-Ping Yan,Yue-Fang Liu,Ji-Min Pan,Ren-Wei Su,Zeng-Ming Yang
Embryo implantation involves a sterile inflammatory reaction that is required for the invasion of the blastocyst into the decidua. Adenosine triphosphate (ATP) released from stressed or injured cells acts as an important signaling molecule to regulate many key physiological events, including sterile inflammation. We found that the amount of ATP in the uterine luminal fluid of mice increased during the peri-implantation period, and this depended on the presence of an embryo. We further showed that the release of ATP from receptive epithelial cells was likely stimulated by lactate released from the blastocyst through connexin hemichannels. The ATP receptor P2y2 was present on uterine epithelial cells during the preimplantation period and increased in the stromal cells during the time at which decidualization began. Pharmacological inhibition of P2y2 compromised decidualization and implantation. ATP-P2y2 signaling stimulated the phosphorylation of Stat3 in uterine luminal epithelial cells and the expression of early growth response 1 ( Egr1 ) and prostaglandin-endoperoxide synthase 2 ( Ptgs2, also known as Cox-2 ), all of which are required for decidualization and/or implantation, in stromal cells. Short exposure to high concentrations of ATP promoted decidualization of primary stromal cells, but longer exposures or lower ATP concentrations did not. The expression of genes encoding ATP-degrading ectonucleotidases increased in the decidua during the peri-implantation period, suggesting that they may limit the duration of the ATP signal. Together, our results indicate that the blastocyst-induced release of ATP from uterine epithelial cells during the peri-implantation period may be important for the initiation of stromal cell decidualization.
研究领域:
生殖生物学
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发育生物学
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细胞信号转导
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分子胚胎学
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免疫学（无菌性炎症）
✓ 已验证
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Meilan Xue,Xuehan Zhang,Yifan Zhou,Jiayi Yan,Haiqi Gao,Yixian Bai,Jing Shi,Yuhan Liu,Yan Xu,Nan Zhang,Lu Li,Shaobo Shi,Hui Liang
This study was aimed to reveal the neuroprotective effect of sulfated fucooligosaccharides (FOS) in an aging mouse model induced by d-galactose. The results showed that FOS treatment ameliorated inflammation, improved behavioral decline in memory and cognition, and exerted neuroprotective effects. FOS reduced microglia activation by decreasing the expression of P38 mitogen-activated protein kinase (P38 MAPK), cyclic-AMP response binding protein (CREB), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2). In addition, FOS improved intestinal mucosal barrier damage and reduced the release of lipopolysaccharide. FOS increased the diversity of the gut flora and promoted a significant enrichment of the Akkermansia genus. FOS also increased the butyric acid level and reduced the expression of histone deacetylase 3 (HDAC3), Toll-like receptor 4 (TLR4), and nuclear factor kappa-B (NF-κB). Fecal microbiota transplantation from the FOS-treated mice showed a similar effect to FOS treatment in inhibiting neuroinflammation and reduced d-galactose-induced cognitive dysfunction. The results suggested that FOS supplementation ameliorated d-galactose-induced neuron damage and exerted neuroprotective effects through the gut–brain axis.
研究领域:
神经科学
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衰老研究
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免疫学
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胃肠病学
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微生物学
·
药理学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2025
·
IF 2.5
Zebin Huang,Wanying Zhang,Qi Shu,Xiao-Chun Guo,Xi Zheng,YuJing Lu
Inflammation is an important predisposing factor for many chronic diseases. The dietary flavonoid silibinin has excellent anti-inflammatory properties in cells, but its low bioavailability in the blood compromises its therapeutic potential. This study aims to investigate the potential of dibenzoylmethane (DBM) to synergistically enhance the anti-inflammatory benefits of silibinin (SB). The synergistic effects of DBM and SB in combination were evaluated in LPS-induced RAW264.7 cells and TPA-induced mice. In addition, a network pharmacology approach and molecular docking were used to explore the key targets and signaling pathways of DBM and SB in combination. The results showed that DBM and SB synergistically inhibited the production of NO, ROS, IL-1β, and TNF-α in a 1:1 concentration ratio. These two compounds may exert their synergistic effects by modulating the NF-κB and HIF-1 signaling pathways, among others. Molecular docking revealed that both compounds exhibited high binding affinities to iNOS and COX-2. Compared with single compound use, the two compounds in combination significantly reduced ear edema and inflammatory cell infiltration, and inhibited the protein expression of iNOS and COX-2 in TPA-induced mice. This research provides a rationale for the combination of DBM and SB as an effective anti-inflammatory agent.
研究领域:
药理学
·
免疫学
·
分子生物学
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MEDICAL SCIENCE MONITOR
·
2018
·
IF 1.894
Lingling Wang,Yan Yin,Gang Hou,Jian Kang,Qiuyue Wang
Background Cigarette smoking is a well-known risk factor in multiple chronic pulmonary diseases. This study aims to investigate the role of peroxisome proliferator-activated receptor (PPAR) γ in cigarette smoking-induced inflammation. Material/Methods Cigarette smoking extract (CSE) was employed to induce inflammation in bronchial epithelial cells (BECs). After CSE administration, several autophagy-related proteins (Beclin1, autophagy-related gene (ATG)5, ATG7, p62, and LC3) and PPARγ levels were examined by western blot. Subsequently, PPARγ agonists and antagonist were used to treat CSE-induced BECs, several inflammatory factors (interleukin (IL)-6, IL-8, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2) and autophagy-related proteins were detected to measure the inflammatory and autophagy levels. Then LC3 knockdown was performed to verify the role of autophagy in CSE-induced inflammation. Finally, the AMP-activated protein kinase (AMPK) and its downstream S6 kinase (S6K) were detected in CSE-stimulated BECs. Results CSE administration caused insufficient autophagy and the decrease of PPARγ in BECs. The PPARγ agonists ameliorate the CSE-induced inflammation and promote the autophagy development, evidenced by the changes of inflammatory factors and autophagy-related proteins. Loss-of-function experiments demonstrated that the PPARg played an anti-inflammatory role in an autophagy-dependent manner. In addition, CSE administration inactivated the AMPK signaling, which was restored by PPARγ agonists. The effects of PPARγ agonists on inflammation and autophagy could be abolished by AMPK inhibitor. Conclusions We demonstrated that PPARγ played a protective role in CSE-induced inflammation and autophagy by activating AMPK signaling in BECs, which may provide investigation basis for clinical therapy of chronic pulmonary diseases.
研究领域:
肺部疾病
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分子生物学
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细胞信号传导
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炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2022
·Vol. 24
·期 3
·1-10
·
IF 2.751
Zhi-Bin Dong,Yu-Jia Wang,Wen-Jun Wan,Ji Wu,Bo-Jun Wang,Hai-Li Zhu,Min Xie,Ling Liu
Oxaliplatin (OXA) is a common chemotherapy drug and exhibits clinical activity in several cancer types. Its anticancer clinical effect is frequently accompanied by neurotoxicity. The symptoms include paresthesia and pain, which adversely affect the quality of life of patients. In the present study, five consecutive intraperitoneal injections of 4 mg/kg OXA were used to mimic chemotherapy in rats. OXA administration induced mechanical allodynia, activated spinal astrocytes and triggered the inflammatory response. To explore potential therapeutic options for OXA‑induced neuropathic pain, resveratrol (Res) was intrathecally injected into the spinal cord of OXA‑treated rats. Paw withdrawal threshold values of OXA‑treated rats were increased, indicating an antinociception effect of Res on OXA‑induced pain. Additionally, Res treatment reduced the levels of glial fibrillary acidic protein, TNF‑α, IL‑1β and NF‑κB, which were upregulated in OXA‑treated rats (compared with control). Furthermore, Auto Dock data showed that Res binds to cyclooxygenase‑2 (COX‑2) through six hydrogen bonds. Western blot analysis and reactive oxygen species (ROS) assays indicated that Res treatment decreased COX‑2 expression and suppressed ROS production. In summary, intrathecal injection of Res reduced the spinal COX‑2‑mediated ROS generation and inflammatory reaction, suppressed astrocytic activation, and alleviated OXA‑induced neuropathic pain.
研究领域:
药理学
·
神经科学
·
疼痛研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2021
·Vol. 10
·期 20
·2100862
·
IF 9.933
Xinghui Si,Guofeng Ji,Sheng Ma,Yudi Xu,Jiayu Zhao,Yu Zhang,Zichao Huang,Zhaohui Tang,Wantong Song,Xuesi Chen
Surgery remains the most preferred treatment options for colorectal cancer (CRC). Paradoxically, local recurrence and distant metastasis are usually accelerated postsurgery as a consequence of local and systemic immunosuppression caused by surgery. Therefore, modulating tumor postoperative immune microenvironment and activating systemic antitumor immunity are necessary supplementaries for CRC therapy. Here, an in-situ-sprayed immunotherapeutic gel loaded with anti-OX40 antibody (iSGels@aOX40) is reported for CRC postsurgical treatment. The iSGel is formed instantly after spraying with strong adhesion ability via crosslinking between tannic acid (TA) and poly( l -glutamic acid)- g -methoxy poly(ethylene glycol)/phenyl boronic acid (PLG- g -mPEG/PBA). TA not only serves as one component of the iSGel but also relieves the postsurgical immunosuppressive microenvironment by inhibiting the activity of cyclo-oxygenase-2 (COX-2). The aOX40 serves as an immune agonistic antibody and is released from the iSGel in a constant manner lasting for over 20 days. In a subcutaneous murine CRC model, the iSGels@aOX40 results in complete inhibition on tumor recurrence. In addition, the cured mice show resistance to tumor re-challenge, suggesting that immune memory effects are established after the iSGels@aOX40 treatment. In an orthotopic CRC peritoneal metastatic model, the iSGels@aOX40 also remarkably inhibits the growth of the abdominal metastatic tumors, suggesting great potential for clinical CRC therapy.
研究领域:
肿瘤学
·
免疫疗法
·
生物医学工程
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Kai Sun,Jiaying Yu,Jinzhong Hu,Jian Chen,Jia Song,Zhixin Chen,Zhuoer Cai,Zhuoxuan Lu,Liming Zhang,Zhifei Wang
The delivery of salicylic acid or its derivatives to tumor tissue in the form of nanomedicine is critical for the studies on their potential synergistic mechanism in tumor therapy and chemoprevention considering the dangerous bleeding in the high-dose oral administration. To deepen the understanding of their role in adjusting immunosuppressive tumor microenvironment (ITM), herein, we firstly developed a hypoxia-sensitive Fe-5,5′-azosalicylic acid nanoscale coordination polymer nanomedicines (FeNCPs) via a “old drugs new tricks” strategy for synergistic chemodynamic therapy (CDT) and remodulation of ITM to elevate antitumor immunotherapy effect. PEGylated FeNCPs could be reductively cleaved to release 5-aminosalicylic acid (5-ASA) and ferric ions by azo-reductase under hypoxic conditions, which could induce tumor cell death by Fenton reaction-catalysis enhanced CDT and 5-ASA-converted carboxylquinone to promote the production of •OH. Meanwhile, cyclooxygenase-2 (COX-2) and its enzymatic product prostaglandin E 2 (PGE 2 ), as immune negative regulatory molecules, can promote tumor progression and immune tolerance . The released 5-ASA as a COX inhibitor could suppress the expression of PGE 2 , and Fe 3+ was employed to reeducate M2-like tumor-associated macrophages (TAMs) to M1-like phenotype, which could initiate antitumor immune response to reach better antitumor immunotherapy. This work broadens the application of salicylic acid derivatives in antitumor immunotherapy, and provides a new strategy for their “old drugs new tricks”. Statement of Significance Cyclooxygenase-2 (COX-2) and its enzymatic product prostaglandin E2 (PGE 2 ), as immune negative regulatory molecules, facilitate the differentiation of immune cells into immunosuppressive cells to build the immunosuppressive tumor microenvironment, which can promote tumor progression and immune tolerance. Thus, down-regulation of COX-2/PGE 2 expression may be a key approach to tumor treatments. Meanwhile, as a class of inhibitors of COX-2/PGE 2 , the potential mechanism of aspirin or 5-aminosalicylic acid has been a mystery in tumor therapy and chemoprevention. To expand the application of aspirin family nanomedicine in biomedicine , herein, we firstly developed a hypoxia-sensitive Fe-5,5′-azosalicylic acid nanoscale coordination polymer nanomedicines via a “old drugs new tricks” strategy for synergistic chemodynamic therapy and remodulation of immunosuppressive tumor microenvironment to elevate antitumor immunotherapy effect.
研究领域:
肿瘤学
·
药学
·
免疫学
·
纳米技术
✓ 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）