Acylphloroglucinols with acetylcholinesterase inhibitory effects from the fruits of Eucalyptus robusta.

Eleven new acylphloroglucinols, including six new formylated phloroglucinol-monoterpene meroterpenoids, eucalyprobusals A-F (1-6), one monomeric acylphloroglucinol, eucalyprobusone B (7), and four dimeric acylphloroglucinols, eucalyprobusones C-F (8-11) were purified from the fruits of Eucalyptus robusta. The establishment of the structures of 1-11 was achieved by a combination of NMR and HRESIMS data analyses, electron circular dichroism (ECD), and single-crystal X-ray diffraction. Compounds 6, 8, and an inseparable mixture of 10 and 11 were found to be potent AChE inhibitors with IC50 values of 3.22 ± 0.36, 3.82 ± 0.22, and 2.55 ± 0.28 µΜ, respectively. Possible interaction sites of 6, 8, 10, and 11 with AChE were investigated by means of molecular docking studies, and the results revealed that AChE residues Asn87, Ser125, Thr83, Tyr133, Tyr124, Tyr337, and Tyr341 played crucial roles in the observed activity of the aforementioned compounds.

Improving the acetylcholinesterase inhibitory effect of Illigera aromatica by fermentation with Clonostachys rogersoniana.

Illigera aromatica was fermented by Clonostachys rogersoniana. The acetylcholinesterase (AChE) inhibitory effects of unfermented and fermented I. aromatica revealed that C. rogersoniana-fermented I. aromatica (CFIA) induced significantly more AChE inhibitory activity (IC50: 35.4 ± 2.1 µg/mL). The biotransformation of actinodaphnine (1) into (4R,6aS)-4-hydroxyactinodaphnine (2) was found during the fermentation, which played an important role in the improvement of the AChE inhibitory activity of I. aromatica. Subsequently, the fermentation conditions-including the solid-liquid ratio, fermentation temperature, and fermentation time-were optimized. I. aromatica immersed in 100-200% water and fermented with C. rogersoniana at ambient temperature for 30 days was conducive to the biotransformation of actinodaphnine (1) and improved the AChE inhibitory activity of I. aromatica. The present study provides a novel approach for improving the pharmacological effect of I. aromatica and suggests that CFIA may be used as an alternative AChE inhibitor.

Acetylcholinesterase Inhibitors from Angelica polymorpha Stem

Fourteen compounds were isolated from the stem of Angelica polymorpha. On the basis of spectral data, these compounds were identified as isoimperatorin (1), phellopterin (2), bergapten (3), xanthyletin (4), cnidilin (5), geijerine (6), (−)-3'-acetyl hamaudol (7), 7-demethylsuberosine (8), dehydrogeijerin (9), (−)-hamaudol (10), (+)-visamminol (11), divaricatol (12), scopoletin (13), and decursidate (14), respectively. Among them, compounds 4 - 6, 8, 9, 13, and 14 were isolated for the first time from A. polymorpha. Dehydrogeijerin (6) and geijerin (9) were isolated for the first time from genus Angelica. All isolates tested for inhibitory activity against acetylcholinesterae. Compounds 1 to 13 showed acetylcholinesterase inhibitory activity with IC₅₀ values ranging from 1.4 to 37.5 µM.