Sesquiterpenoids from the Fruits of Alpinia oxyphylla and Their Anti‐Acetylcholinesterase Activity

Abstract

Fourteen sesquiterpenoids were isolated from the fruits of Alpinia oxyphylla Miq. Their structures were elucidated based on NMR analyses (1H, 13C, DEPT, 1H,1H‐COSY, HMQC, HMBC, and NOESY) and identified as 12‐nornootkaton‐6‐en‐11‐one (3), (+)‐(3S,4aS,5R)‐2,3,4,4a,5,6‐hexahydro‐3‐isopropenyl‐4a,5‐dimethyl‐1,7‐naphthoquinone (5), nootkatene (6), 9β‐hydroxynootkatone (7), 2β‐hydroxy‐δ‐cadinol (8), 4‐isopropyl‐6‐methyl‐1‐tetralone (11), oxyphyllone E (12), oxyphyllone D (13), oxyphyllanene B (15), oxyphyllone A (16), oxyphyllol E (17), (9E)‐humulene‐2,3;6,7‐diepoxide (18), mustakone (20), and pubescone (21). Among them, 3 was a new norsesquiterpenoid, 8 was a new natural product, and 5, 6, 11, 20, 21 were isolated from A. oxyphylla for the first time. Twenty sesquiterpenoids, 1–5 and 7–21, were investigated for their in vitro acetylcholinesterase (AChE) inhibitory activities, including previously isolated seven sesquiterpenoids from A. oxyphylla, (11S)‐12‐chloronootkaton‐11‐ol (1), (11R)‐12‐chloronootkaton‐11‐ol (2), nootkatone (4), oxyphyllenodiol A (9), oxyphyllenodiol B (10), 7‐epiteucrenone B (14), and alpinenone (19). TLC‐Bioautographic assay indicated that 1–4, 7, 14, 16, 18, 19, and 21 displayed anti‐AChE activities at 10 nmol. Microplate assay confirmed that 19, 18, 16, and 21 displayed moderate‐to‐weak anti‐AChE activities at the concentration of 100 μM, and 19 was the most potent inhibitor with an IC50 value of 81.6±3.5 μM. The presence of anti‐AChE sesquiterpenoids in A. oxyphylla may partially support the traditional use of this fruit for the treatment of dementia.

New Sesquiterpene Oxidations with CYP260A1 and CYP264B1 from Sorangium cellulosum So ce56

“…The oxidized sesquiterpenes obtained in this study have been shown to exhibit antiproliferative( compound 3) [47] and NO-synthesis-inhibiting (compounds 3 and 11)a bilities. [45][46] The products 7-10 are structurally close to the acetylcholinesterase-inhibiting agent 24 [28] and, therefore, likely to show similar properties. The oxidized sesquiterpenes can serve as precursors for compound libraries for the improvemento ft hese pharmaceutically interesting properties.…”

“…[47] The oxidized zerumbone (6)p roducts 7-10 are structurally close to (9E)-humulene-2,3;6,7-diepoxide( < Scheme 3, 24), ap romisinga nti-acetylcholinesterase agent for the treatment of Alzheimer's disease. [28] Compounds 7-10 could thusbetested for similarfunctions. Generally,the introduction of functional groupsbyP 450s paves the way for further derivatizations.…”

Hyperhubeins A–I, Bioactive Sesquiterpenes with Diverse Skeletons from Hypericum hubeiense

“…Compared with LPS-treated cells, preincubation with 12 suppressed LPS-induced expression of TLR-4, iNOS, and cyclooxygenase-2 (COX-2) and reduced the p-NF-κB/NF-κB ratio (Figure ). Compound 12 was previously reported in phytochemical studies on grapefruit juice and the fruits of Alpinia oxyphylla . ,, This compound inhibited LPS-induced NO production and protected against oxidative stress-induced adipose-derived mesenchymal stem cells. , A possible mechanism of action has not been proposed. In the present study, Western blotting and molecular docking indicated that compound 12 exerted anti-neuroinflammatory activity probably via regulation of TLR-4/NF-κB signaling, and so it has the potential to be developed as a possible therapeutic agent to treat NDDs.…”

Microbial Transformation of Yakuchinone A and Cytotoxicity Evaluation of Its Metabolites

“…It has been used as traditional medicine for the treatment of nephrotic syndrome, ulceration, dementia, and intestinal disorders for more than a thousand years [ 1 ]. Pharmacological and phytochemical investigations of A. oxyphylla have led to the identification of a variety of biologically active components including fruit oil, flavonoids, sesquiterpenes, diarylheptanoids, and phenolic compounds [ 2 , 3 ]. Among them, diarylheptanoids have been identified as a major class of characteristic constituents in A .…”