Isoflavones and anti-inflammatory constituents from the fruits of Psoralea corylifolia

Highlights

• Three previously undescribed isoflavones were isolated from the fruits of Psoralea corylifolia.

• Their chemical structures were determined on the basis of extensive spectroscopic analysis.

• The isolated compounds were evaluated for anti-inflammatory activity.

Abstract

The fruits of Psoralea corylifolia, known as Psoraleae Fructus (Buguzhi in Chinese), are traditionally used for the treatment of spermatorrhea, nephritis, asthma, pollakiuria, and various inflammatory diseases. Three previously undescribed isoflavone derivatives, 7-O-methylcorylifol A, 7-O-isoprenylcorylifol A, and 7-O-isoprenylneobavaisoflavone, have been isolated from the fruits of P. corylifolia, together with 9 known compounds. The structures of these compounds were determined through spectroscopic and MS analyses. Among the isolated compounds, 7-O-methylcorylifol A and psoralen exhibited potent inhibition (IC₅₀ values ≤ 10.89 μM) of superoxide anion generation by human neutrophils in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB). 7-O-Isoprenylcorylifol A, 7-O-isoprenylneobavaisoflavone, and 12,13-dihydro-12,13-epoxybakuchiol inhibited fMLP/CB-induced elastase release with IC₅₀ values ≤ 14.30 μM. In addition, 7-O-isoprenylcorylifol A, bakuchiol, 12,13-dihydro-12,13-epoxybakuchiol, and psoralidin showed potent inhibition with IC₅₀ values ≤ 36.65 μM, against lipopolysaccharide (LPS)-induced nitric oxide (NO) generation.

Introduction

Psoralea corylifolia L. (Leguminosae) is an annual herb distributed in India, Malay peninsula, Indonesia, China, and Taiwan (Huang and Ohashi, 1993). Dry fruit of P. corylifolia Linn is one of the most popular Traditional Chinese Medicine (TCM) and officially listed in Chinese Pharmacopoeia (Pharmacopoeia of the People's Republic of China, 2005). This crude drug has been used for the treatment of spermatorrhea, nephritis, asthma, pollakiuria, and various inflammatory diseases (Chopra et al., 2013). Various flavonoids (Anand et al., 1978, Lee et al., 2005, Tsai et al., 1996, Xin et al., 2010, Yin et al., 2004), coumarins (Xin et al., 2010), chalcones (Lee et al., 2005, Yin et al., 2004), isoflavones (Yin et al., 2004), meroterpenes (Xin et al., 2010, Yin et al., 2006), coumestans (Gupta et al., 1990), and their derivatives were isolated from this plant in previous studies. Many of these compounds exhibit anti-inflammatory (Anand et al., 1978), phytoestrogen (Xin et al., 2010), anti-nitric oxide synthase (iNOS) (Lee et al., 2005), anti-platelet aggregation (Tsai et al., 1996), antibacterial (Yin et al., 2004), and anti-Helicobacter pylori (Yin et al., 2006) activities.

Human neutrophils are known to play crucial roles in host defense against microorganisms and in pathogenesis of various diseases such as asthma, chronic obstructive pulmonary disease (COPD), ischemia-reperfusion injury, and rheumatoid arthritis (Witko-Sarsat et al., 2000). In response to different stimuli, activated neutrophils secrete a series of cytotoxins, such as the superoxide anion radical (O₂^•–), a precursor to other reactive oxygen species (ROS), granule proteases, bioactive lipids, and neutrophil elastase, a major contributor to destruction of tissue in chronic inflammatory disease (Borregaard, 1998, Witko-Sarsat et al., 2000, Faurschou and Borregaard, 2003, Roos et al., 2003). Nitric oxide (NO) is a mediator in the inflammatory response involved in host defense (Vane et al., 1994). Suppression of the extensive or inappropriate activation of neutrophils and/or macrophages by drugs has been proposed as a way to ameliorate inflammatory diseases. The effects on pro-inflammatory responses of isolates were evaluated by suppressing fMLP-induced O₂^•− and elastase generation by human neutrophils and by inhibiting LPS-induced NO release by murine macrophages. In a screening program searching for anti-inflammatory compounds from medicinal plants, P. corylifolia has been found to be an active species. The MeOH extract of the fruits of P. corylifolia showed potent inhibitory effects on superoxide anion and elastase generation by human neutrophils in response to fMLP and on NO generation by murine macrophages in response to LPS. Fig. 1 illustrates the structures of three new isoflavone derivatives, 7-O-methylcorylifol A (1), 7-O-isoprenylcorylifol A (2), and 7-O-isoprenylneobavaisoflavone (3). Nine known compounds (4–12), have been isolated and identified from the fruits of P. corylifolia and their structures are depicted in Fig. 2.