New Polyketides With Anti-Inflammatory Activity From the Fungus Aspergillus rugulosa

Abstract

Two new polyketide compounds, asperulosins A and B (1–2), and one new prenylated small molecule, asperulosin C (3), along with nine known compounds (4–12), were isolated and identified from a fungus Aspergillus rugulosa. Their structures were extensively elucidated via HRESIMS, 1D, and 2D NMR analysis. The absolute configurations of the new compounds were determined by the comparison of their electronic circular dichroism (ECD), calculated ECD spectra, and the detailed discussion with those in previous reports. Structurally, compounds 1 and 2 belonged to the polyketide family and were from different origins. Compound 2 was constructed by five continuous quaternary carbon atoms, which occur rarely in natural products. All of the isolates were evaluated for anti-inflammatory activity against the production of nitric oxide (NO) in lipopolysaccharide (LPS)-induced RAW264.7 cells. Among those, compounds 1 and 5 showed a significant inhibitory effect on NO production with IC50 values of 1.49 ± 0.31 and 3.41 ± 0.85 μM, respectively. Additionally, compounds 1 and 5 markedly increased the secretion of anti-inflammatory cytokine IL10 while suppressing the secretion of pro-inflammatory cytokines IL6, TNF-α, IFN-γ, MCP-1, and IL12. Besides, 1 and 5 inhibited the transcription level of pro-inflammatory macrophage markers IL6, IL1β, and TNF-α while remarkably elevating the anti-inflammatory factor IL10 and M2 macrophage markers ARG1 and CD206. Moreover, 1 and 5 restrained the expression and nuclear translocation of NF-κB, as well as its downstream signaling proteins COX-2 and iNOS. All these results suggest that 1 and 5 have potential as anti-inflammatory agents, with better or comparable activities than those of the positive control, dexamethasone.

Discovery of a Biocontrol Strain Trichaptum laricinum: Its Metabolites and Antifungal Activity against Pathogenic Fungus Colletotrichum anthrisci

“…Six known compounds were identified as methyl anodendroate (5), 31 (R)-(Z,E)-9,11-octadecadien-13-olide (6), 32,33 a patent compound (7), 34 nigrosirpexin F (8), 35 trans-2decenedioic acid (9), 36,37 observed in the blank control (Figure 7). Among them, those treated with compound 9 exhibited the most severe damage with a flattened morphology.…”

The Plethora of Microbes with Anti-Inflammatory Activities

“…The positive control in the assays was dexamethasone, a glucocorticoid drug used for inflammatory relief. Asperulosin A and aspertetronin A were found to possess better or comparable anti-inflammatory effects in comparison to dexamethasone [ 109 ].…”

Insights into metabolic and pharmacological profiling of Aspergillus ficuum through bioinformatics and experimental techniques

“…Several secondary metabolites such as phloroglucinol and glyceollin derived from Aspergillus species have been reported for their anti-inflammatory effect [55,56]. The polyketides isolated from A. rugulosa exhibited anti-inflammatory effects better than the positive control [57]. Similarly, a review of Aspergillus genus metabolites revealed that a rich source of anti-inflammatory metabolites are synthesized by Aspergillus genus species such as, polyketides, terpenoids, butenolides, and alkaloids [58].…”