Marine Drugs
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2020
·Vol. 18
·期 11
·575
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IF 4.073
Wenjuan Ding,Chokkalingam Uvarani,Fangfang Wang,Yaxin Xue,Ning Wu,Liming He,Danmei Tian,Mei Chen,Youwei Zhang,Kui Hong,Jinshan Tang
Deep-sea fungi have become a new arsenal for the discovery of leading compounds. Here five new ophiobolins1–5, together with six known analogues6–11, obtained from a deep-sea derived fungus WHU0154. Their structures were determined by analyses of IR, HR-ESI-MS, and NMR spectra, along with experimental and calculated electronic circular dichroism (ECD) analysis. Pharmacological studies showed that compounds4and6exhibited obvious inhibitory effects on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine macrophage RAW264.7 cells. Mechanical study revealed that compound6could inhibit the inducible nitric oxide synthase (iNOS) level in LPS-stimulated RAW264.7 cells. In addition, compounds6,9, and10could significantly inhibit the expression of cyclooxygenase 2 (COX 2) in LPS-induced RAW264.7 cells. Preliminary structure-activity relationship (SAR) analyses revealed that the aldehyde group at C-21 and the α, β-unsaturated ketone functionality at A ring in ophiobolins were vital for their anti-inflammatory effects. Together, the results demonstrated that ophiobolins, especially for compound6, exhibited strong anti-inflammatory effects and shed light on the discovery of ophiobolins as new anti-inflammatory agents.Keywords:deep-sea derived fungus;secondary metabolites;ophiobolin;anti-inflammatory effect
研究领域:
海洋生物学
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药理学
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有机化学
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产品关联
DOI
PubMed
高影响因子
PeerJ
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2020
·
IF 2.379
Yuanyuan Shi,Shengxiang Zhang,Daiyin Peng,Chunmiao Shan,Liqiang Zhao,Bin Wang,Jiawen Wu
Cnidium monnieri (L.) Cuss ( C. monnieri ) is one of the most widely used traditional herbal medicines, exhibiting a wide range of pharmacological functions for treating asynodia, trichomonas vaginitis, and osphyalgia. Its important medicinal value comes from its abundance of coumarins. To identify genes involved in coumarin biosynthesis and accumulation, we analyzed transcriptome data from flower, leaf, root and stem tissues of C. monnieri . A total of 173,938 unigenes with a mean length of 1,272 bp, GC content of 38.79%, and N50 length of 2,121 bp were assembled using the Trinity program. Of these, 119,177 unigenes were annotated in public databases. We identified differentially expressed genes (DEGs) based on expression profile analysis. These DEGs exhibited higher expression levels in flower tissue than in leaf, stem or root tissues. We identified and analyzed numerous genes encoding enzymes involved in coumarin biosynthesis, and verified genes encoding key enzymes using quantitative real-time PCR. Our transcriptome data will make great contributions to research on C. monnieri and provide clues for identifying candidate genes involved in coumarin metabolic pathways.
研究领域:
植物学
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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
BIOMEDICINE & PHARMACOTHERAPY
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2025
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IF 7.5
Yinlan Xu,Hejun Liu,Haonan Guo,Jinmei Zheng,Ling Tao,Weidong Wu
Non-small cell lung cancer (NSCLC) is the major type of malignant tumor in the lungs. Emerging epidemiological evidence implicates environmental copper exposure as a potential risk modulator for NSCLC progression. This study investigated the effects of low-dose Copper (Cu) exposure on A549 cells and evaluated the therapeutic potential of two natural compounds, osthole and matrine. The results demonstrated that Cu exposure (5 μg/mL, 12 h) significantly promoted the migration, invasion and colony formation of A549 cells ( P < 0.05), accompanied by a reduction in cell apoptosis, a decrease in ROS levels and an increase in mitochondrial membrane potential. Meanwhile, osthole and matrine treatment could reverse these phenotypes and arrest the cell cycle of A549 in the G1 phase. Transmission electron microscopy results revealed that Cu exposure induced slightly swollen mitochondria and as well as the increase in the number of mitochondria, while osthole and matrine treatments resulted in severe degenerative changes in mitochondria. Both qPCR and Western blot examinations indicated that Cu exposure promoted the expression of PGC-1α but inhibited the expressions of STAT1, TNF-α and IL-2. Osthole treatment could down-regulate the expression of PGC-1α and up-regulate the expressions of STAT1, TNF-α and IL-2, while matrine treatments could up-regulate the expressions of STAT1 and TNF-α and down-regulate the expressions of PGC-1α and IL-2. Taken together, these findings indicate that low-dose Cu exposure can promote the proliferation, migration, invasion and mitochondrial damage of A549 cells, while osthole and matrine treatments inhibit Cu effects by regulating the STAT1, BGC-1 α, TNF-α and IL-2.
研究领域:
肿瘤学
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环境毒理学
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药理学
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细胞生物学
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分子生物学
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天然产物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
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2023
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IF 4.1
Yujie Guo,Puyang Gong,Yin Qian,Haichun Liu,Boyang Yu,Jin Qi
In the present study, a comprehensive strategy integrating affinity ultrafiltration high-performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UF-HPLC-Q-TOF-MS), in silico molecular docking and bioassays was established to rapidly screen natural SOD activators from traditional Chinese medicines. As illustrative case studies, Schisandra chinensis, Fructus cnidii and Radix ophiopogonis were chosen to develop and verify the strategy. The HPLC-Q-TOF-MS was used to identify the compounds in comparison with reference standards and literature data. A total of eight compounds, including four biphenyl-cyclooctene ligands from Schisandra chinensis and four coumarins from Fructus cnidii, were found to potentially increase SOD activities. No ligands were found in the extract of Radix ophiopogonis. Then, in silico molecular docking was performed to investigate the binding site and binding affinity of the candidates on SOD. Compared to the nonspecific ligands screened from the extract, the specific ligands presented stronger binding affinities. In addition, the activity and kinetic parameters of the SOD-ligand were investigated through an improved pyrogallol autoxidation method. Gomisin J and xanthotoxin showed a stronger ability to increase SOD activities. The present study indicated that combining UF-HPLC-Q-TOF-MS and in silico molecular docking offers a powerful and meaningful tool to rapidly screen SOD activators from traditional Chinese medicines.
研究领域:
药理学
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分析化学
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生物信息学
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中医药
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产品关联
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
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2024
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IF 2.3
Shu-Hang Li,Meng-Ying Li,Tao-Tao Yuan,Guo-Wei Wang,Jian-Bin Zeng,Zhimian Shi,Jian-Hang Liu,Jun-Cheng Su
Osthole (also known as Osthol) is the main anti-inflammatory coumarin found in Cnidium monnieri and severs as the exclusive quality-controlled component according the Chinese Pharmacopoeia. However, its underlying anti-inflammatory mechanism remains unknown. In this study, we demonstrated that Osthole treatment significantly inhibited the generation of TNF-α, but not IL-6 in the classical LPS-stimulated RAW264.7 macrophage model. In addition, LPS induced the activation of both MAPK and NF-κB signalling pathways, of which the former was dose-dependently restrained by Osthole via suppressing the phosphorylation of JNK and P38 proteins, while the phosphorylation of IκB and P65 proteins remained unaffected. Interestingly, Osthole dose-dependently up-regulated the expression of the key cholinergic anti-inflammatory pathway regulator α7nAChR, and the TNF-α inhibition effect of Osthole was also significantly alleviated by the treatment of α7nAChR antagonist methylbetaine. These results demonstrate that Osthole may regulate TNF-α by promoting the expression of α7nAChR, thereby activate the vagus nerve-dependent cholinergic anti-inflammatory pathway.
研究领域:
药理学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Chunlei Wei,Lingjiao Wu,Yuyi Wu,Chunyi Xu,Huiling Hu,Zhanguo Wang
Ethnopharmacological relevance As a representative local medicinal herb produced in China, Vladimiriae Radix (VR) has been proven to exert hepatoprotective and choleretic effects, with particular therapeutic efficacy in cholestatic liver injury (CLI), as demonstrated by the VR extract (VRE). However, the quality markers (Q-markers) of VRE for the treatment of CLI remain unclear. Aim of the study A new strategy based on the core element of “efficacy" was proposed, using a combination of spectrum-effect relationship, pharmacokinetics, and molecular docking methods to select and confirm Q-markers of VRE. Material and methods First, the HPLC fingerprinting of 10 batches of VRE was studied, and the in vivo pharmacological index of anti-CLI in rats was determined. The spectrum-effect relationship was utilized as a screening method to identify the Q-markers of VRE. Secondly, Q-markers were used as VRE pharmacokinetic markers to measure their concentrations in normal and CLI rat plasma, and to analyze their disposition. Finally, molecular docking was utilized to predict the potential interaction between the identified Q-markers and crucial targets of CLI. Results The fingerprints of 10 batches of VRE was established. The in vivo pharmacological evaluation of rats showed that VRE had a significant therapeutic effect on CLI. The spectrum-effect correlation analysis showed that costunolide (COS) and dehydrocostus lactone (DEH) were the Q-markers of VRE anti-CLI. The pharmacokinetic results showed that AUC (0-t) , C max , CL Z/F , and V Z/F of COS and DEH in CLI rats had significant differences ( P < 0.01). They were effectively absorbed into the blood plasma of CLI rats, ensuring ideal bioavailability, and confirming their role as Q-markers. Molecular docking results showed that COS, DEH had good affinity with key targets (FXR, CAR, PXR, MAPK, TGR5, NRF2) for CLI treatment (Binding energy < −4.52 kcal mol −1 ), further verifying the correctness of Q-marker selection. Conclusions In this study, through the combination of experimental and theoretical approaches from the aspects of pharmacodynamic expression, in vivo process rules, and interaction force prediction, the therapeutic effect of VRE and Q-markers (COS、DEH) were elucidated. Furthermore, a new idea based on the principle of “efficacy" was successfully proposed for screening and evaluating Q-markers.
研究领域:
民族药理学
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药理学
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分析化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2024
·
IF 10.5
Jianwei Wang,Xiaojia Lv,Ying Li,Haiqiang Wu,Meiwan Chen,Hua Yu,Jianwei Wu,Chenyang Li,Wei Xiong
Intestinal mucosal barrier loss is responsible for the chronic and recurrent ulcerative colitis. Myosin light chain kinase (MLCK) is a potential therapeutic target of the intestinal mucosal barrier dysfunction. Here, we developed a reactive oxygen species (ROS)-sensitive hydrogel (ATG-CS-Gel) derived from a diselenide-bridged arctigenin (ATG) and chitosan (CS) conjugate, with the aims of targeting to inflamed mucosa and modulating MLCK. Our results demonstrated that ATG-CS-Gel achieved ROS-responsive release and significantly inhibited ROS production and mitochondrial depolarization in the Caco-2 and HT-29/MTX-E12 cells under H 2 O 2 -induced stress conditions. Compared with normal tissues, orally-administrated ATG-CS-Gel preferentially adhered to the inflamed mucosa for 24 h, which was attributed to the adhesion between CS and mucin. Therapeutically, ATG-CS-Gel reduced inflammatory symptoms, accelerated intestinal mucosal healing, scavenged excessive ROS, reshaped intestinal flora, and eventually achieved much better therapeutic efficacy in DSS-induced colitis mice when compared to 5-aminosalicylic acid. Moreover, ATG-CS-Gel was demonstrated to reverse intestinal mucosal barrier loss by blocking MLCK activation and maintaining tight junction expression. In summary, this study highlights the potential of MLCK modulation in the restoration of intestinal mucosal barrier using ATG-CS-Gel. The development of ATG-CS-Gel represents a novel and promising strategy for the treatment of ulcerative colitis.
研究领域:
药理学
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胃肠病学
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生物材料科学
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炎症性肠病
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产品关联
DOI
PubMed
高影响因子
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