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. 2023 Dec 7;21(12):631.
doi: 10.3390/md21120631.

Cytosporones with Anti-Inflammatory Activities from the Mangrove Endophytic Fungus Phomopsis sp. QYM-13

Guisheng Wang  1   2 , Yilin Yuan  3 , Zhaokun Li  1 , Junhao Zhu  1 , Zhigang She  2 , Yan Chen  1
Affiliations

Cytosporones with Anti-Inflammatory Activities from the Mangrove Endophytic Fungus Phomopsis sp. QYM-13

Guisheng Wang et al. Mar Drugs. .

Abstract

Six previously undescribed cytosporone derivatives (phomotones A-E (1-5) and phomotone F (13)), two new spiro-alkanol phombistenes A-B (14-15), and seven known analogs (6-12) were isolated from the mangrove endophytic fungus Phomopsis sp. QYM-13. The structures of these compounds were elucidated using spectroscopic data analysis, electronic circular dichroism (ECD), and 13C NMR calculations. Compound 14 features an unprecedented 1,6-dioxaspiro[4.5]decane ring system. All isolates were evaluated for their inhibitory effect on nitric oxide (NO) in LPS-induced RAW264.7 cells. The results showed that compounds 1, 6, 8, and 11 exhibited potent bioactivities by comparing with positive control. Then, compound 1 displayed the anti-inflammatory effect by inhibiting the MAPK/NF-κB signaling pathways. Molecular docking further revealed the possible mechanism of compound 1 interaction with ERK protein.

Keywords: Phomopsis sp.; anti-inflammatory; cytosporone; mangrove endophytic fungus.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The structures of 1–15.
Figure 2
Figure 2
The key 1H-1H COSY and HMBC correlations of compounds 1–5 and 13–15.
Figure 3
Figure 3
NOESY correlations of 14–15.
Figure 4
Figure 4
Comparisons of calculated and experimental 13C NMR data of 14.
Figure 5
Figure 5
Experimental and calculated ECD spectra of 14 and 15.
Figure 6
Figure 6
Influences of compound 1 on iNOS, COX-2, and β-actin protein expression were detected using western blotting (A); the ratio of the content of iNOS/β-actin and COX-2/β-actin (B). Data rendered are the mean ± SD, n = 3. In comparison to the control, *** p < 0.001. In comparison to the LPS group, ### p < 0.001, ## p < 0.01.
Figure 7
Figure 7
Influences of compound 1 on the MAPK and NF-κB pathway detected with western blotting. (A) The expression levels of p-JNK, p-ERK, p-P38, and GAPDH detected with Western blotting. (B) The proportion of p-JNK, p-ERK, and p-P38 to GAPDH content. (C) The expression levels of p-P65 and β-actin detected with western blotting. (D) The proportion of p-P65 to β-actin content. Data rendered are the mean ± SD, n = 3. In comparison to the control, *** p < 0.001. In comparison to the LPS, # p < 0.05, ## p < 0.01, ### p < 0.001.
Figure 8
Figure 8
Molecular docking models for ERK (PDB:5v60) inhibition of compound 1 (A). Hydrogen bonding active pocket of compound 1 (B). 2D interaction diagrams of compound 1 (C).
See this image and copyright information in PMC

References

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