Lignans and triterpenoids from Vitex negundo var. heterophylla and their biological evaluation

Abstract

Three new phenylnaphthalene-type lignans, vitexnegheteroins E-G (1–3), and a new polyoxygenated ursane-type triterpene, vitexnegheteroin H (9), were isolated from the seeds of Vitex negundo var. heterophylla, together with ten known compounds. Their structures were established on the basis of extensive 1D and 2D NMR experiments, as well as their mass spectroscopic data. The absolute configurations of compounds 1 and 2 were determined by comparing their experimental ECD spectra with that calculated by the time-dependent density functional theory (TDDFT) method. The isolates were evaluated for their cytotoxicities against three human cancer cell lines, inhibitory activities on lipopolysaccharide-induced NO production in murine microglial BV-2 cells, and antioxidant activities for ABTS radical scavenging.

Introduction

The genus Vitex (Verbenaceae) consists of small trees and shrubs, with about 270 species distributed mainly in tropical and subtropical regions. About 14 species, seven varieties, and three forms are found in China [1]. Phytochemical and related biological investigations for the plants of Vitex genus have been reported in the past decades [2], [3]. Phytochemical investigations indicated the presence of flavonoids, phenylpropanoids, diterpenoids, triterpenoids, iridoid glycosides, phytoecdysteroids, phenolic glycosides, and essential oils in Vitex plants, which exhibit a wide range of bioactivities including antibacterial, antimalarial, antiviral, antifeedant, antiproliferative, hepatoprotective, antioxidant, antiaging, anti-inflammatory, antipyretic, analgesic, and potential effects on menopausal symptoms [2], [3], [4], [5]. Vitex negundo L. var. heterophylla (Franch.) Rehd., an aromatic shrub, is widely distributed in the hilly areas of the north, northeast, northwest, and central regions of China. All parts of this plant have been commonly used as folk medicine. Its leaves have been used to treat cold, fever, stroke, and urinary bleeding. Its roots and branches are used for the therapy of bronchitis, malaria, and hepatitis. The essential oils from the seeds and leaves are utilized for the treatment of chronic bronchitis [6], [7].

Previous investigations on V. negundo var. heterophylla focused on the components of the essential oil analyzed by gas chromatography–mass spectrometry [8], [9], [10], and the herbicidal and anti-inflammatory activities of the ethanol extracts [11], [12]. To the best of our knowledge, though increasing interests have been given to the genus Vitex, especially V. negundo, phytochemical and pharmacological studies of V. negundo var. heterophylla were limited. In this study, the phytochemical investigation on the seeds of V. negundo var. heterophylla led to the isolation of four new, vitexnegheteroins E-H (1–3, and 9) and ten known compounds. Their structures were elucidated on the basis of spectroscopic analyses (IR, UV, HRESIMS, and 1D and 2D NMR) and the TDDFT ECD calculations. The cytotoxicity, inhibitory effects on LPS-induced NO production in murine microglial BV-2 cells, and antioxidant activities of these isolates were also assessed. Herein, this contribution describes the isolation, structure elucidation, and biological assessment of the isolates.