ABSTRACT
Neurodegenerative diseases (NDs) are common chronic diseases arising from progressive damage to the nervous system. Here, in-house natural product database screening revealed that libertellenone C (LC) obtained from the fermentation products of Arthrinium arundinis separated from the gut of a centipede collected in our Tongji campus, showed a remarkable neuroprotective effect. Further investigation was conducted to clarify the specific mechanism. LC dose-dependently reversed glutamate-induced decreased viability, accumulated reactive oxygen species, mitochondrial membrane potential loss, and apoptosis in SH-SY5Y cells. Network pharmacology analysis predicted that the targets of LC were most likely directly related to oxidative stress and the regulation of inflammatory factor-associated signaling pathways. Further study demonstrated that LC attenuated nitrite, TNF-α, and IL-1ß production and decreased inducible nitric oxide synthase and cyclooxygenase expression in lipopolysaccharide-induced BV-2 cells. LC could directly inhibit NLRP3 inflammasome activation by decreasing the expression levels of NLRP3, ASC, cleaved Caspase-1, and NF-κB p65. Our results provide a new understanding of how LC inhibits the NLRP3 inflammasome in microglia, providing neuroprotection. These findings might guide the development of effective LC-based therapeutic strategies for NDs.
ABSTRACT
A chemical investigation on an endophytic fungus Penicillium expansum isolated from the medicinal plant Plantago depressa Willd. (Plantaginaceae) afforded one new diketopiperazine-type alkaloid, namely penicimine A (1), as well as two known congeners (2 and 3). Their structures were elucidated by widespread spectroscopic data, and the absolute configurations of 1 and 2 were further confirmed by single-crystal X-ray diffraction analyses. Compound 1 represented the first example of benzyl-containing diketopiperazine-type alkaloid bearing a methyl group attached at C-15 position. Compound 1 showed anti-inflammatory activity against LPS-induced nitric oxide (NO) production in RAW264.7 mouse macrophages with an IC50 value of 25.65 µM.
ABSTRACT
Two new nucleoside derivatives, kipukasins M (1a) and N (1b), along with one known analogue, kipukasin J (2), were obtained from the marine-derived fungus Aspergillus versicolor, which was isolated from the mud collected in the South China Sea. The structures of compounds 1a and 1b were elucidated by extensive spectroscopic analysis, mainly including 1D & 2D NMR and HRESIMS data, and the absolute configuration of 1a was further confirmed by single-crystal X-ray diffraction analysis. Interestingly, intramolecular transesterification occurs in compounds 1a and 1b, which exist as a pair of inseparable regioisomers. All isolated compounds were tested for the cytotoxic and antimicrobial activities.
Subject(s)
Aspergillus , Nucleosides , Aspergillus/chemistry , Crystallography, X-Ray , Fungi , Molecular Structure , Nucleosides/chemistryABSTRACT
Five new drimane-type sesquiterpenoids, named proversilins A-E (1-5), were isolated from the endophytic fungus Aspergillus versicolor F210 isolated from the bulbs of Lycoris radiata. Their structures and absolute configurations were characterized by extensive spectroscopic analysis, including 1D and 2D NMR and HRESIMS data, comparison of experimental and calculated electronic circular dichroism data, and X-ray crystallography. Proversilins B-E (2-5) represent the first examples of natural products featuring an N-acetyl-ß-phenylalanine moiety. Compounds 3 and 5 inhibited the growth of HL-60 cells with IC50 values of 7.3 and 9.9 µM, respectively.
