Diterpenoids and Diacetylenes from the Roots of Aralia cordata with Inhibitory Effects on Nitric Oxide Production

Abstract

Bioactivity-guided isolation of a MeOH extract of Aralia cordata led to the isolation of four new ent-pimarane diterpenoids (1−4) and a diacetylene (5) together with 21 known compounds (6−26). Their structures were established based on the interpretation of one-and twodimensional NMR and HRESIMS data. The absolute configurations of the new isolates were determined by electronic circular dichroism data analysis, single crystal X-ray diffraction, and Mosher's esterification method. All compounds exhibited inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages with IC 50 values ranging from 1.1 to 69.4 μM.Aralia cordata Thunb. is a perennial herb belonging to the Araliaceae family and is mainly distributed in East Asia, mostly in Korea, Japan, and mainland China. It has been used as traditional folk medicine in Korea for the treatment of rheumatism, lumbago, and lameness. 1 Previous phytochemical studies revealed the presence of essential oils, polyacetylenes, triterpenoids, and diterpenoids, 2 of which ent-pimarane and ent-kaurane type diterpenoids are considered to be its major components. 3,4 Some of these compounds exhibit a broad range of pharmacological effects including anti-inflammatory, antiasthmatic, cholinesterase, and BACE1 inhibitory activities. 3−6 As part of an ongoing study toward the discovery of plant-derived anti-inflammatory agents, the MeOH extract of the roots of A. cordata, and the subsequent n-hexane and CH 2 Cl 2 -soluble fractions, were found to exhibit inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 cells (IC 50 = 24.6, 13.6, and 23.1 μg/mL, respectively). Chromatographic purification of the nhexane and CH 2 Cl 2 -soluble fractions afforded four new entpimarane diterpenoids (1−4) and a diacetylene (5) together with 21 known compounds. Herein, we describe the isolation and structure determination of compounds 1−5 and the inhibitory effects of all isolated compounds on NO production in LPS-stimulated RAW 264.7 cells.

Isosteroidal Alkaloids from Fritillaria verticillata Willd. and Their NMR Spectroscopic Characteristics

“…The ( R )‐MTPA ester of 10 was prepared in the same manner to afford 10b . [ 42‐43 ] HR‐ESI‐MS spectra of 10a and 10b both showd m / z 862.4094 [M + H] + (calcd. for C 47 H 57 F 3 NO 7 , 862.4112).…”

Computational methods and points for attention in absolute configuration determination

“…Electronic circular dichroism (ECD) spectra have been used for AC determination since the 1960s. ECD was originally known more simply as CD, and, more recently, many reports use the term ECD for AC assignment (Guo et al, 2020;Zhang et al, 2021b;Kim et al, 2021;Nhoek et al, 2021;Quan et al, 2021). As mentioned above, a detailed conformational search should first be performed (Mazzeo et al, 2014).…”

Utilization of Inedible Parts of Aralia cordata with High-Content Chlorogenic Acid Cultivated in Tokyo

“…In this study, the utilization of A. cordata roots cultivated in Tokyo might lead to sustainability of producing crude drugs and income for farmers. Some recent studies have reported various components of A. cordata, such as diterpenoids and diacetylenes, as active compounds of inhibitors against nitric oxide production and triacylglycerol biosynthesis [6,7]. Our Comprehensive Medicinal Plant Database (http://mpdb.nibiohn.go.jp, accessed on 22 December 2023) of crude drugs reveals that one of the major components of "dokukatsu" is chlorogenic acid (CA).…”