Norditerpenoids with Selective Anti-Cholinesterase Activity from the Roots of Perovskia atriplicifolia Benth.

Abstract

Inhibition of cholinesterases remains one of a few available treatment strategies for neurodegenerative dementias such as Alzheimer’s disease and related conditions. The current study was inspired by previous data on anticholinesterase properties of diterpenoids from Perovskia atriplicifolia and other Lamiaceae species. The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition by the three new natural compounds—(1R,15R)-1-acetoxycryptotanshinone (1), (1R)-1-acetoxytanshinone IIA (2), and (15R)-1-oxoaegyptinone A (3)—as well as, new for this genus, isograndifoliol (4) were assessed. Three of these compounds exhibited profound inhibition of butyrylcholinesterase (BChE) and much weaker inhibition of acetylcholinesterase (AChE). All compounds (1–4) selectively inhibited BChE (IC50 = 2.4, 7.9, 50.8, and 0.9 µM, respectively), whereas only compounds 3 and 4 moderately inhibited AChE (IC50 329.8 µM and 342.9 µM). Molecular docking and in silico toxicology prediction studies were also performed on the active compounds. Natural oxygenated norditerpenoids from the traditional Central Asian medicinal plant P. atriplicifolia are selective BChE inhibitors. Their high potential makes them useful candidate molecules for further investigation as lead compounds in the development of a natural drug against dementia caused by neurodegenerative diseases.

Metabolomics and DNA-Based Authentication of Two Traditional Asian Medicinal and Aromatic Species of Salvia subg. Perovskia

“…Two dehydrogenation products, didehydrotanshinone and didehydromiltirone, which were previously detected in n-hexane root extract of S. yangii , were not present in our methanolic root extract, neither in S. yangii nor in S. abrotanoides . Interestingly, isograndifoliol, reported recently in n-hexane root extract of S. yangii [ 66 ] was also detected in the methanolic root extract of S. yangii and was proved to contribute most to chemical differentiation between S. yangii and S. abrotanoides .…”

“…In contrast, the roots of both species are phytochemically distinct at first sight, and chemometric analysis has verified this fact. Isograndifoliol ( Figure 2 , peak 27), a hydroxylated norditerpenoid present only in S. yangii, is a rarely detected compound that has a high pharmacological potential [ 66 ], and its presence in a relatively high amount points out S. yangii as an especially valuable medicinal plant. Sugiol, even if a minor compound only, also has significant pharmacological potential, reviewed recently by Bajpai et al 2020 [ 83 ], that can, for example, attenuate STAT3-dependent proliferation and unlocks apoptosis pathways in cancer cells and can block virus entry to cells.…”

Non-Alkaloid Cholinesterase Inhibitory Compounds from Natural Sources

“…Several terpenoids from natural sources have been reported as cholinesterase inhibi-tors [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. The compounds 1 – 11 , as shown in Supplementary Material ( Table S1 ), are of the Abietane-type diterpene skeletons isolated from Salvia austriaca , Salvia glutinosa , Caryopteris mongolica, and Perovskia atriplicifolia [ 14 , 15 , 16 ].…”

Inhibition of Butyrylcholinesterase and Human Monoamine Oxidase-B by the Coumarin Glycyrol and Liquiritigenin Isolated from Glycyrrhiza uralensis

“…As regards other natural compounds, inhibition of BChE by GC was greater than that by boldine (IC 50 = 321 µM) [ 45 ], hyperforin and hyuganin C (IC 50 = 141.60 and 38.86 μM, respectively) [ 46 ], cremaphenanthrene F (14.62) [ 47 ], scopoletin (IC 50 = 9.11 µM) [ 48 ], and broussonin A and sagachromanol I (IC 50 = 7. 50 and 10.79 µM, respectively) [ 49 ], but less than those of norditerpenoids isograndifoliol and (1 R ,15 R )-1-acetoxycryptotanshinone (IC 50 = 0.9 and 2.4 µM, respectively) [ 50 ]. Notably, these IC 50 values were much greater than those for AChE inhibition by tannic acid (IC 50 = 0.087 µM) [ 51 ], or hesperidin (IC 50 = 0.00345 µM) [ 52 ].…”