Phytochemical and Pharmacological Studies on the Genus Psoralea: A Mini Review

The genus Psoralea, which belongs to the family Fabaceae, comprises ca. 130 species distributed all over the world, and some of the plants are used as folk medicine to treat various diseases. Psoralea corylifolia is a typical example, whose seeds have been widely used in many traditional Chinese medicine formulas for the treatment of various diseases such as leucoderma and other skin diseases, cardiovascular diseases, nephritis, osteoporosis, and cancer. So, the chemical and pharmacological studies on this genus were performed in the past decades. Here, we give a mini review on this genus about its phytochemical and pharmacological studies from 1910 to 2015.


Introduction
The genus Psoralea, which belongs to the family Fabaceae, comprises ca. 130 species mainly distributed in South Africa, North and South America, and Australia, a few of which are native to Asia and temperate Europe [1]. Among them, several species have been widely used as herbal medicine in China, India, and other countries. Modern pharmacological researches show that the plants in Psoralea genus have antimicrobial, antipregnancy, estrogenic, antitumor, antioxidant, and many other pharmacological activities [1,2]. For example, P. corylifolia is the sole species of the genus distributing in China, and its seeds are used as a famous traditional Chinese medicine (TCM), having the effects of kidney impotence and warming spleen and stopping diarrhea and included by Pharmacopoeia of People's Republic of China [3]. Here, we review the progress achieved in phytochemical studies on the genus Psoralea, list the compounds isolated from this genus over the past decades, and introduce the biological activities of these ingredients.

Phytochemistry
To the best of our knowledge, the first phytochemical investigation on the genus Psoralea can be traced back to 1910 [4]. In 1933, Jois and his coworkers obtained the first pure compound called psoralen (51) from P. corylifolia [4]. Up to 2015, the total number of identified secondary metabolites from the genus Psoralea amounts to 129, including flavonoids, coumarins, phenols, benzofurans, benzopyrans, quinines, sesquiterpenoids, triterpenoids, steroids, and some other components. The structures of these compounds are shown in Figure 1. Their names and the corresponding plant sources are compiled in Table 1.

Flavonoids. Previous chemical investigations have indi-
cated that flavonoids were the most frequently occurring constituents of the genus Psoralea. Fifty flavonoids, 1∼50, have been isolated and elucidated from the genus Psoralea, most of which were isolated from P. corylifolia, while isovitexin (2) was got from P. plicata [5]. Various

Antipregnancy and Estrogenic
Activity. Some articles have reported that angelicin (55) and bakuchiol (76) have significant anti-implantation activity on mice [1,18]. And psoralidin (58), a coumestan analogue, has been considered to have a novel biological activity as an agonist for both estrogen receptor alpha (ER ) and ER and activate the classical ERsignaling pathway in both ER-positive human breast and endometrial cell lines as well as non-human cultured cells transiently expressing ER or ER [45].  [85,86]. Another study showed that isobavachalcone/eorylifolin (34) could induce apoptotic cell death in neuroblastoma via the mitochondrial pathway and has no cytotoxicity against normal cells, which indicated isobavachalcone/eorylifolin (34) may be applicable as an efficacious and safe drug [87]. O-Methyl-bakuchiols (120) and O-ethyl-bakuchiols (121) were proved to inhibit HIF-1 (IC 50 values: 8.7 and 26.3 M, resp.) and NF-B (IC 50 values: 5.7 and 12.2 M, resp.) activation without significantly decreasing the viability of the human gastric cancer cell and human cervical adenocarcinoma cell, respectively [54]. The ethanolic extract of P. corylifolia was found to be cytotoxic against L929-cells in cell culture. Bakuchiol (76) was responsible for the activity [88][89][90].

Antioxidant Activity.
There is considerable interest in more potent antioxidant compounds to treat diseases involving oxidative stress [18]. When examined for the antioxidant activity using the 2,2V-azinobis[3-ethylbenzothiazoline-6sulfonate] (ABTS) assay, P. corylifolia seed's solvent extract showed higher antioxidant activity [91]. In Jiangning et al. 's research, the powder and extracts of P. corylifolia were investigated in lard at 100 ∘ C by using Oxidative Stability Instrument (OSI) and were proved to have strong antioxidant activity. When the compounds isolated from P. corylifolia are tested individually and compared with butylated hydroxytoluene (BHT) and -tocopherol by the OSI at 100 ∘ C, corylin (24), psoralidin (58), and bakuchiol (76) showed strong antioxidant activity, and especially psoralidin (58) (stronger antioxidant property than BHT). The specific antioxidant effect of the compounds decreases in the following order: psoralidin (58) > BHT > -tocopherol > bakuchiol (76) > corylifolin (71) > corylin (24) > isopsoralen/angelicin (55) ∼ psoralen (51) [11]. Isobavachin (10) and isobavachalcone/eorylifolin (34) were proved to have broad antioxidative activities in rat liver microsomes and mitochondria [91]. In addition, the relationship between isoflavones and their antioxidant Evidence-Based Complementary and Alternative Medicine 13 activities in P. corylifolia was studied and the research determined the antioxidant activity of extracts using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and phosphomolybdenum assays; as a result, the antioxidant activities were correlated with the content of total phenolics in the extracts [8]. In another study, some antioxidant components were isolated from P. corylifolia by a combinative method using high-speed countercurrent chromatography (HSCCC) and thin layer chromatography (TLC) as an antioxidant autographic assay [92].
3.5. Immunomodulatory Activity. Polysaccharide was reported to enhance the immunity of mice [8]. Wang et al. 's experiments have shown that P. corylifolia could effectively increase the proliferation rate of diploid fibroblasts and increase the ability of nonspecific immunity [93]. The flavonoids isolated from P. corylifolia have also been shown to have immunological function [94]. In another study, the seeds extracts of P. corylifolia obtained in alcohol have been found to stimulate the immune system in mice by increasing cell mediated and humoral immune responses [77].
3.6. Anti-Inflammatory Activity. The petroleum ether extract, dichloromethane extract, and methanol extract of the aerial part of P. glandulosa had significant anti-inflammatory activity [95]. Another study has reported that bakuchiol (76) from Psoralea corylifolia could inhibit the expression of inducible nitric oxide synthase (iNOS) gene via the inactivation of nuclear transcription factor-B in RAW 264.7 macrophages [96].

Antiviral
Activity. The volatiles isolated from P. drupacea's leaves and stem barks have antiviral activity [1].

Photosensitization.
Ethanol extract of P. corylifolia has an effect on tyrosinase and increases the volume and speed of melanin by improving the activity of tyrosinase [102,103]. Isopsoralen/angelicin (55) has been known as photosensitivity [4]. Psoralen (51) is a photosensitive compound, and its photosensitivity is much better than isopsoralen (55). It plays a key role in treating vitiligo. In addition, psoralen (51) has good effect on treating psoriasis and alopecia areata [4,104].
3.11. Antiasthma Activity. Experiments have shown that coumarins isolated from P. corylifolia had antiasthma activity [105,106]. In another study, a Chinese herbal decoction, which contains 6 herbs, along with 15 g seeds of P. corylifolia, could prompt treatment for asthma in the convalescent stage to prevent emphysema [107].
3.12. Antifilarial Activity. Qamaruddin et al. reported that the aqueous and alcohol extracts of the leaves and seeds of P. corylifolia possessed significant antifilarial activity against Setaria cervi [108]. The extracts caused the inhibition of spontaneous movements of the whole worm and the nerve muscle preparation of S. cervi [108].
3.13. Antiplatelet Activity. The methanolic extract of seeds of P. corylifolia was identified to inhibit the aggregation of rabbit platelets induced by arachidonic acid, collagen, and platelet activating factor [109].
3.16. Antipyretic Activity. The petroleum ether extract, dichloromethane extract, and methanol extract of the aerial part of P. glandulosa have antipyretic activity [95].

Conclusion
Although the genus Psoralea contains more than 130 species in the world, only several plants were chemically and pharmacologically reported in the past literatures. Up to 2015, 129 compounds have been isolated from this genus. Among them, flavonoids (50 compounds) are the characteristic constituents, and coumarins, phenols, benzofurans and benzofurans glycosides, quinines, meroterpene phenols, sesquiterpenoids, and triterpenes are also found in the genus.
14 Evidence-Based Complementary and Alternative Medicine The pharmacological activities, for example, antimicrobial, antitumor, antioxidant, immunomodulatory, anti-inflammatory, hepatoprotective, photosensitization, and antiasthma activities, have been often reported in the past few decades. In this review, we compiled the pharmacological activities of the extracts and the compounds from the plants of genus Psoralea. We believe there will be more researches on this genus in the future, and the bioactive constituents from this genus await further investigation.