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. 2022 Nov 2;12(1):18481.
doi: 10.1038/s41598-022-22799-5.

Neuroprotective metabolites via fungal biotransformation of a novel sapogenin, cyclocephagenol

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Neuroprotective metabolites via fungal biotransformation of a novel sapogenin, cyclocephagenol

Melis Küçüksolak et al. Sci Rep. .

Abstract

Cyclocephagenol (1), a novel cycloartane-type sapogenin with tetrahydropyran unit, is only encountered in Astragalus species. This rare sapogenin has never been a topic of biological activity or modification studies. The objectives of this study were; (i) to perform microbial transformation studies on cyclocephagenol (1) using Astragalus endophyte, Alternaria eureka 1E1BL1, followed by isolation and structural characterization of the metabolites; (ii) to investigate neuroprotective activities of the metabolites; (iii) to understand structure-activity relationships towards neuroprotection. The microbial transformation of cyclocephagenol (1) using Alternaria eureka resulted in the production of twenty-one (2-22) previously undescribed metabolites. Oxidation, monooxygenation, dehydration, methyl migration, epoxidation, and ring expansion reactions were observed on the triterpenoid skeleton. Structures of the compounds were established by 1D-, 2D-NMR, and HR-MS analyses. The neuroprotective activities of metabolites and parent compound (1) were evaluated against H2O2-induced cell injury. The structure-activity relationship (SAR) was established, and the results revealed that 1 and several other metabolites had potent neuroprotective activity. Further studies revealed that selected compounds reduced the amount of ROS and preserved the integrity of the mitochondrial membrane. This is the first report of microbial transformation of cyclocephagenol (1).

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Neuroprotective activity of cycloastragenol and 1 against H2O2 toxicity. Error bars are the standard deviations (n = 3). p-Values were calculated with respect to H2O2-treated cells (*p < 0.05, **p < 0.01, ***p < 0.001).
Figure 2
Figure 2
Biotransformation products of cyclocephagenol (1) by Alternaria eureka 1E1BL1.
Figure 3
Figure 3
Selected metabolites abbreviated H2O2-induced oxidative stress in SH-SY5Y cells. Data are presented as means ± S.D. (n = 3).
Figure 4
Figure 4
Selected metabolites protect SH-SY5Y cells from H2O2-induced mitochondrial damage. (a) Representative microscopy images of cells stained with MitoTracker Red. (b) Quantification of MitoTracker Red fluorescence intensities per cell volume (n = 30 cells). Data are presented as means ± S.E. (n = 30).

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