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| Main Authors: | , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Marine drugs
2025
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| Online Access: | https://pubmed.ncbi.nlm.nih.gov/40422771/ |
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| _version_ | 1868266198754394113 |
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| author | Ban, Fangfang Zhou, Longjian Yang, Zhiyou Liu, Yayue Zhang, Yi |
| author_facet | Ban, Fangfang Zhou, Longjian Yang, Zhiyou Liu, Yayue Zhang, Yi Ban, Fangfang Zhou, Longjian Yang, Zhiyou Liu, Yayue Zhang, Yi |
| collection | PubMed - marine biology |
| contents | Aspergillusidone G Exerts Anti-Neuroinflammatory Effects via Inhibiting MMP9 Through Integrated Bioinformatics and Experimental Analysis: Implications for Parkinson's Disease Intervention. Ban, Fangfang Zhou, Longjian Yang, Zhiyou Liu, Yayue Zhang, Yi Matrix Metalloproteinase 9 Animals Aspergillus Mice Parkinson Disease Computational Biology Nitric Oxide Anti-Inflammatory Agents Neuroprotective Agents Depsides Matrix Metalloproteinase Inhibitors Cell Line Lipopolysaccharides Humans Natural products have extensive attractiveness as therapeutic agents due to their low toxicity and high efficiency. Our previous study has identified a depside-type Aspergillusidone G (Asp G) derived from DLEP2008001, which shows excellent neuroprotective activity for 1-methyl-4-phenylpyridinium (MPP)-induced primary cortical neurons and anti-neuroinflammatory property, promising to be a potential therapeutic agent for Parkinson's disease (PD). To further explore the anti-PD potential and mechanisms of Asp G, we employed network pharmacology, cellular experiments, and various biological techniques for analysis and validation. The analysis of network pharmacology suggested that Asp G's anti-PD potential might be attributed to its modulation of inflammation. The data from nitric oxide (NO) detection, qRT-PCR, and Western blot confirmed that Asp G dose-dependently inhibited lipopolysaccharide (LPS)-stimulated NO production, with 40 μM Asp G suppressing 90.54% of the NO burst compared to the LPS group, and suppressed the overproduction of inflammatory-related factors in LPS-induced BV2 cells. Further protein-protein interaction analysis indicated that matrix metalloproteinase 9 (MMP9), a promising target for PD intervention, was the most likely anti-PD target of Asp G, and the results of gelatin zymography, qRT-PCR, and Western blot validated that Asp G could inhibit the active and inactive forms of MMP9 directly and indirectly, respectively. Notably, the inhibition of 67 kDa-MMP9 by Asp G is expected to compensate for the inability of TIMP-1 to inhibit this form. Furthermore, a selective inhibitor of MMP9 (20 μM SB-3CT) further potentiated the anti-inflammatory effects of Asp G (20 μM), with inhibition rate on NO increasing from 27.57% to 63.50% compared to LPS group. In summary, our study revealed that Asp G exerts anti-neuroinflammatory effects by inhibiting MMP9, which provides a valuable lead compound for the development of anti-neuroinflammatory drugs and offers insights into the intervention of PD-associated neuroinflammation. Future studies will further investigate the upstream regulatory mechanisms of Asp G-mediated MMP9 inhibition and its effects in in vivo PD models. |
| format | Artículo científico |
| id | pubmed_40422771 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Marine drugs |
| record_format | pubmed |
| spellingShingle | Aspergillusidone G Exerts Anti-Neuroinflammatory Effects via Inhibiting MMP9 Through Integrated Bioinformatics and Experimental Analysis: Implications for Parkinson's Disease Intervention. Ban, Fangfang Zhou, Longjian Yang, Zhiyou Liu, Yayue Zhang, Yi Matrix Metalloproteinase 9 Animals Aspergillus Mice Parkinson Disease Computational Biology Nitric Oxide Anti-Inflammatory Agents Neuroprotective Agents Depsides Matrix Metalloproteinase Inhibitors Cell Line Lipopolysaccharides Humans Aspergillusidone G Exerts Anti-Neuroinflammatory Effects via Inhibiting MMP9 Through Integrated Bioinformatics and Experimental Analysis: Implications for Parkinson's Disease Intervention. Ban, Fangfang Zhou, Longjian Yang, Zhiyou Liu, Yayue Zhang, Yi Matrix Metalloproteinase 9 Animals Aspergillus Mice Parkinson Disease Computational Biology Nitric Oxide Anti-Inflammatory Agents Neuroprotective Agents Depsides Matrix Metalloproteinase Inhibitors Cell Line Lipopolysaccharides Humans Natural products have extensive attractiveness as therapeutic agents due to their low toxicity and high efficiency. Our previous study has identified a depside-type Aspergillusidone G (Asp G) derived from DLEP2008001, which shows excellent neuroprotective activity for 1-methyl-4-phenylpyridinium (MPP)-induced primary cortical neurons and anti-neuroinflammatory property, promising to be a potential therapeutic agent for Parkinson's disease (PD). To further explore the anti-PD potential and mechanisms of Asp G, we employed network pharmacology, cellular experiments, and various biological techniques for analysis and validation. The analysis of network pharmacology suggested that Asp G's anti-PD potential might be attributed to its modulation of inflammation. The data from nitric oxide (NO) detection, qRT-PCR, and Western blot confirmed that Asp G dose-dependently inhibited lipopolysaccharide (LPS)-stimulated NO production, with 40 μM Asp G suppressing 90.54% of the NO burst compared to the LPS group, and suppressed the overproduction of inflammatory-related factors in LPS-induced BV2 cells. Further protein-protein interaction analysis indicated that matrix metalloproteinase 9 (MMP9), a promising target for PD intervention, was the most likely anti-PD target of Asp G, and the results of gelatin zymography, qRT-PCR, and Western blot validated that Asp G could inhibit the active and inactive forms of MMP9 directly and indirectly, respectively. Notably, the inhibition of 67 kDa-MMP9 by Asp G is expected to compensate for the inability of TIMP-1 to inhibit this form. Furthermore, a selective inhibitor of MMP9 (20 μM SB-3CT) further potentiated the anti-inflammatory effects of Asp G (20 μM), with inhibition rate on NO increasing from 27.57% to 63.50% compared to LPS group. In summary, our study revealed that Asp G exerts anti-neuroinflammatory effects by inhibiting MMP9, which provides a valuable lead compound for the development of anti-neuroinflammatory drugs and offers insights into the intervention of PD-associated neuroinflammation. Future studies will further investigate the upstream regulatory mechanisms of Asp G-mediated MMP9 inhibition and its effects in in vivo PD models. |
| title | Aspergillusidone G Exerts Anti-Neuroinflammatory Effects via Inhibiting MMP9 Through Integrated Bioinformatics and Experimental Analysis: Implications for Parkinson's Disease Intervention. |
| topic | Matrix Metalloproteinase 9 Animals Aspergillus Mice Parkinson Disease Computational Biology Nitric Oxide Anti-Inflammatory Agents Neuroprotective Agents Depsides Matrix Metalloproteinase Inhibitors Cell Line Lipopolysaccharides Humans |
| url | https://pubmed.ncbi.nlm.nih.gov/40422771/ |