1.Influences of ginsenoside Rg1 on blood-brain barrier damage and neuroinflam-mation in rats with experimental cerebral hemorrhage by regulating miR-144-3p/FPR2/p38 signaling pathway
Yalin BAI ; Zhanhai FANG ; Chenzhe DING ; Yanping LAN ; Dailin LIU ; Gaoyang QI ; Lei CHEN ; Juncheng WANG
Chinese Journal of Immunology 2023;39(12):2534-2539
Objective:To investigate influences of ginsenoside Rg1 regulating miR-144-3p on neuroinflammation and blood-brain barrier damage in rats with experimental cerebral hemorrhage,and its regulation on formyl peptide receptor 2(FPR2)/p38 path-way.Methods:Ninety SD rats were randomly divided into control group,cerebral hemorrhage group,ginsenoside Rg1 low-dose group(10 mg/kg),ginsenoside Rg1 high-dose group(40 mg/kg),ginsenoside Rg1 high-dose+ago-miR-144-3p group(40 mg/kg ginseno-side Rg1+ago-miR-144-3p),with 18 mice in each group.Except for control group,experimental intracerebral hemorrhage rat model was constructed by injecting collagenase Ⅱ into right caudate nucleus,and then each group was given intraperitoneal administration and intracerebral injection as required.Neurological damage in rats was scored;rat brain water content was determined by dry-wet spe-cific gravity method;levels of TNF-α,IL-6 and IL-1β in rat brain tissues homogenate were determined by ELISA;ultrastructure around cerebral edema was observed by electron microscope;permeability of blood-brain barrier in rats was determined by Evans blue(EB)method;expressions of miR-144-3p/FPR2/p38 pathway were determined by qRT-PCR and Western blot.Results:Compared with control group,blood-brain barrier damage was aggravated in cerebral hemorrhage group,neurological function damage score,brain water content,miR-144-3p,TNF-α,IL-6,IL-1β,p38 mRNA,p-p38/p38 expressions in brain homogenate were increased(P<0.05),FPR2 mRNA and protein expressions were decreased(P<0.05);compared with cerebral hemorrhage group,blood-brain barrier damage was reduced in ginsenoside Rg1 low-dose group and ginsenoside Rg1 high-dose group,neurological function damage score,brain water content,miR-144-3p,TNF-α,IL-6,IL-1β,p38 mRNA,p-p38/p38 expressions in brain homogenate were decreased(P<0.05),FPR2 mRNA and protein expressions were increased(P<0.05);ago-miR-144-3p was able to reverse protective effects of gin-senoside Rg1 on blood-brain barrier and neuroinflammation in rats(P<0.05).Conclusion:Ginsenoside Rg1 may inhibit blood-brain barrier damage and neuroinflammation in rats by regulating miR-144-3p/FPR2/p38 axis.
2.Steroids and dihydroisocoumarin glycosides from Xylaria sp. by the one strain many compounds strategy and their bioactivities.
Dong GAN ; Chenzhe LI ; Yan SHU ; Jiapeng WANG ; Chengyao WANG ; Li ZHU ; Yujun YANG ; Jiaqi LIU ; Bijian HE ; Le CAI ; Zhongtao DING
Chinese Journal of Natural Medicines (English Ed.) 2023;21(2):154-160
The fungus Xylaria sp. KYJ-15 was isolated from Illigera celebica. Based on the one strain many compounds (OSMAC) strategy, the strain was fermented on potato and rice solid media, respectively. As a result, two novel steroids, xylarsteroids A (1) and B (2), which are the first examples of C28-steroid with an unusual β- and γ-lactone ring, respectively, along with two new dihydroisocoumarin glycosides, xylarglycosides A (3) and B (4), were identified. Their structures were elucidated by spectroscopic methods, X-ray diffraction and electronic circular dichroism (ECD) experiments. All isolated compounds were evaluated for cytotoxicity, DPPH radical scavenging activity, acetylcholinesterase inhibitory and antimicrobial effect. Compound 1 exhibited potent AChE inhibitory activity with an IC50 value of 2.61 ± 0.05 μmol·L-1. The β-lactone ring unit of 1 is critical for its AChE inhibitory activity. The finding was further confirmed through exploring the interaction of 1 with AChE by molecular docking. In addition, both compounds 1 and 2 exhibited obvious antibacterial activity against Bacillus subtilis with a minimum inhibitory concentration (MIC) of 2 μg·mL-1. Compounds 3 and 4 exhibited antibacterial activities against Staphylococcus aureus with MICs of 4 and 2 μg·mL-1, respectively, which also exhibited DPPH radical scavenging activity comparable to the positive control with IC50 values of 9.2 ± 0.03 and 13.3 ± 0.01 μmol·L-1, respectively.
Humans
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Acetylcholinesterase
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Molecular Docking Simulation
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Anti-Bacterial Agents
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Glycosides
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Lactones
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Pain