In Vitro and in Silico Analysis of Phytochemicals From Fallopia dentatoalata as Dual Functional Cholinesterase Inhibitors for the Treatment of Alzheimer’s Disease

Abstract

Current studies have found that butyrylcholinesterase (BuChE) replaces the biological function of acetylcholinesterase (AChE) in the late stage of Alzheimer’s disease. Species in the genus of Fallopia, rich in polyphenols with diverse chemical structures and significant biological activities, are considered as an important resource for screening natural products to against AD. In this study, thirty-four compounds (1–34) were isolated from Fallopia dentatoalata (Fr. Schm.) Holub, and their inhibitory effects against AChE and BuChE were assessed. Compounds of the phenylpropanoid sucrose ester class emerged as the most promising members of the group, with 31–33 displaying moderate AChE inhibition (IC50 values ranging from 30.6 ± 4.7 to 56.0 ± 2.4 µM) and 30–34 showing potential inhibitory effects against BuChE (IC50 values ranging from 2.7 ± 1.7 to 17.1 ± 3.4 µM). Tacrine was used as a positive control (IC50: 126.7 ± 1.1 in AChE and 5.5 ± 1.7 nM in BuChE). Kinetic analysis highlighted compounds 31 and 32 as non-competitive inhibitors of AChE with Ki values of ∼30.0 and ∼34.4 µM, whilst 30–34 were revealed to competitively inhibit BuChE with Ki values ranging from ∼1.8 to ∼17.5 µM. Molecular binding studies demonstrated that 30–34 bound to the catalytic sites of BuChE with negative binding energies. The strong agreement between both in vitro and in silico studies highlights the phenylpropanoid sucrose esters 30–34 as promising candidates for use in future anti-cholinesterase therapeutics against Alzheimer’s disease.

New Pyranone Derivatives and Sesquiterpenoid Isolated from the Endophytic Fungus Xylaria sp. Z184

“…Thus, the planar structure of 4 was established as shown (Figure 1) and named fallopiaxylarol A. Initially, the ROESY correlation between H 3 -13 and H 2 -9 and the lack of correlation of H 3 -13/H-10 assigned the E-geometry of ∆ 10,11 , which was also supported by the J value of H-10 (7.5) (Figure 5). In addition, the ROESY correlations of H-1/3-OH/H 3 -15/H-5α/H-6α suggested the cis orientation of the H-1, 3-OH, and H 3 -15.…”

“…As part of our group's ongoing effort to identify bioactive natural products from medicinal plants and endophytic fungi [9][10][11], the fungus Xylaria sp. Z184, isolated from the leaves of Fallopia convolvulus (L.) Á. Löve for the first time, has attracted our attention for Molecules 2024, 29, 1728 2 of 13 its impressive compound abundance in TLC and HPLC analyses (Figure S106).…”

“…Molecules 2024, 29, x FOR PEER REVIEW 2 of 13 leaves of Fallopia convolvulus (L.) Á. Löve for the first time, has attracted our attention for its impressive compound abundance in TLC and HPLC analyses (Figure S106). Our current investigation on this strain led to the isolation of three new pyranone derivatives, called fallopiaxylaresters A-C (1-3), a new bisabolane-type sesquiterpenoid fallopiaxylarol A (4) (Figure 1), and the first complete set of the spectroscopic data for the previously disclosed pestalotiopyrone M (5), as well as a suite of known compounds consisting of six pyranone derivatives (6)(7)(8)(9)(10)(11), three sesquiterpenoids (12)(13)(14), three isocoumarin derivatives (15)(16)(17), and one aromatic allenic ether (18). Herein, the details of the isolation, structure elucidation of all new compounds and their anti-inflammatory, antimicrobial, and α-glucosidase-inhibitory activities were described.…”

Anti‐Neuroinflammatory Activity of New Naturally Occurring Benzylated Hydroxyacetophenone Analogs from the Endophytic Fungus Alternaria sp. J030

“…In the continuation of our longstanding research into the discovery of bioactive natural products from medicinal plants and their endophytes, [2,13,14] we herein disclose the results of a study on the chemical constituents of the culture broth of Alternaria sp. J030, an endophytic fungus isolated from the leaves of Bauhinia variegata Linn.…”

A Preliminary Assessment of the Nutraceutical Potential of Acai Berry (Euterpe sp.) as a Potential Natural Treatment for Alzheimer’s Disease

“…The following supporting information can be downloaded at: , Table S1: Chemical compounds detected in acai berry extracts with possible cholinesterase inhibitor activity and recognized antioxidant activity [ 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 ,…”