Psoralea Corylifolia is a herb from the plant family Leguminosae (subfamily Papilionaceae) that has some usage in Traditional Chinese Medicine under the name Bu Ghu Zhi and has some usage in Ayurveda with the name Kushtanashini; traditional records exist for Psoralea's usage in asthma, cough, nephritis, vitiligo and calvities (baldness). It is also commonly referred to as Babchi. Most parts of the plant (roots, leaves, seeds and an oil from the seeds) appear to be used, with the seeds being the most commonly used source.
The plant grows in tropical and subtropical regions of the world including Southern Africa, China, and India; It is also found throughout India in Himalayas, Dehra Dun, Oudh, Bundelkhand, Bengal, Bombay, some valley in Bihar, Deccan, and Karnataka.
Traditionally used anti-cancer and anti-inflammatory agent, with particular usage catered towards combatting menopause. Beyond that, this medicinal plant has a less enticing history relative to some other highly touted plants
The furanocoumarin and Coumestan composition of Psoralea consists of:
Psoralen and Isopsoralen, sometimes referred to as the active components at 23.6mg/g and 25.04mg/g ethyl acetate fraction and their glycosides of Psoralenoside and Isopsoralenoside, respectively
Psoralidin at 12.76mg/g ethyl acetate fraction and psoralidin-2,3-oxide diacetate
Bavacoumestan A and B as well as Sophoracoumestan
Phenyl derivative of pyranocoumarin
With various chalcone-like structures including:
Bavachalcone (as well as Neobavachalcone and Isobavachalcone), Bakuchalcone and Bavachromanol
Bavachromene and isobavachromene
Chromenoflavanone and Hydroxylonchocarpin
The bioflavonoid and isoflavone content includes:
Bavachin, Isobavachin and 7-O-methylbavachin as well as Bavachinin (9.72mg/g ethyl acetate fraction)
Corylifol A-D, with A at 3.68mg/g ethyl acetate fraction
Psoralenol and 3-hydroxypsoralenol
Psoralone and Isopsoralone
Corylifolean, Corylifolin, Corylifolinin (Seeds)
Daidzin (glycoside of Daidzein, one of the main soy isoflavones) in the fruits as well as the roots; 8-prenyldaidzein also exists at 1.6mg/g ethyl acetate fraction and Genistein as well
And various other compounds include:
Corylifonol and Isocorylifonol (Benzofuran derivatives; seeds)
Astragalin (a constituent of Astragalus Membranaceus; seeds)
Psoracorylifol F (monoterpenoid)
Angelicin (fruits; from Bituminaria bituminosa)
An essential oil (0.5% seed weight) containg volatiles such as Limonene, α- and γ-elemene, β-caryophylenoxide and linalool
Bakuchiol, an estrogenic monoterpene phenol and derivatives such as Delta-3,2-hydroxybackuchiol, at around 1g per 4kg root powder (0.25%), Bisbakuchiols A and B alongside 12'S-bisbakuchiol C, and 12,13-dihydro-12,13-dihydroxybakuchiol
Linoleic acid (67.7% of fatty acids), Palmitic acid (22.07%), Oleic acid (3.33%) and trace Myristic and Lauric 
A large variety of fairly unique compounds, but the bioactivities of Psoralea Corylifolia tend to be narrowed down to either the furanocoumarins (Psoralen and Isopsoralen in particular) or the Bakuchiol class of molecules (related to estrogenicity and neurology more than the others)
The large degree of prenylated isoflavones have potential usage and are fairly unique to this plant, but for the most part they have not been investigated beyond some studies done in vitro on bone cells where they show promise. Prenylated Isoflavones may form a third class of 'potentially useful components of this herb' alongside the furanocoumarins and Bakuchiols
When looking at the isolated compound Bakuchiol (30mg/kg orally) reached a peak concentration after approximately an hour(Tmax) which was 77.9+/-48.9ng/mL (Cmax); the oral bioavailability of isolated Bakuchiol was said to be 3.2% in rats. The authors suggested that the poor water solubility of Bakuchiol was to blame for this (and cited Resveratrol as a situation in which solubility alters pharmacokinetics orally). Relatively low serum concentrations has been noted previously with Backuchiol in rats.
For Psoralen and Isopsoralen, they have been detected in plasma following intravenous administration of 2mg/kg of either coumarin to rats; tissue deposition in the kidneys, liver, heart, and lungs were noted with minimal concentrations reaching the brain.
The clearance rate of Bakuchiol following injection into rats (15mg/kg) was found to be 59.8mL/min/kg, and the authors noted that this was higher than hepatic blood flow (indicative of hepatic metabolism) and hypothesized clearance is mainly via the liver. Psoralen and Isopsoralen, following injections, appear to be mainly excreted via the urine with half lives of 4.13 and 5.56 hours respectively.
Psoralen, Isopsoralen, and Bakuchiol have been successfully determined in plasma following oral administration; bioavailability of Psoralen-like compounds still not currently known but Bakuchiol appears to have low absorption
2.2. Enzymatic Interactions
An ethanolic extract from Psoralea Corylifolia has been noted to induce the Quinone Reductase enzyme to 1.5-fold baseline levels at a concentration of 1.2mcg/mL, which was thought to be due to Psoralen (1.5-fold induction at 0.5mcg/mL).
Three compounds from Psoralea Corylifolia have been found to inhibit DNA Polymerase (Neobavaisoflavone and Daidzein) and topoisomerase II (Bavachicin at 404μM and Daidzein).
Bakuchiol has been noted to inhibit mitochondrial lipid peroxidation and protect mitochondrial functions against oxidative stress and Psoralea Corylifolia (seed extract) elsewhere has been noted to inhibit mitochondrial complex I in neuroblastoma (SH-SY5Y) cells to approximately 50% of control at 20μg/mL (as assessed by ATP synthesis rates) and concentration-dependently reduced ATP synthesis up to 100μg/mL (20% of baseline).
Petroleum extracts of the fruits of Psoralea (Fructus Psoraleae) have been found to be able to prevent dopamine and norepinephrine reuptake in neurons when incubated at 1-10ug/mL via inhibiting transporters, with lesser efficacy being apparent with water and ethanolic extracts; serotonin and GABA uptake being unaffected up to 100ug/mL. The IC50 values of the petroleum extract were found to be 0.62ug/mL for dopamine and 0.79ug/mL for noradrenaline, with 100ug/mL being as effective as the active controls GBR12,935 (dopamine) at the same concentration and desipramine (noradrenaline) at 1ug/mL, underperforming at the same concentration. The isolated bioactive known as Delta-3,2-hydroxybakuchiol has been noted to act as a catecholamine reuptake inhibitor in vitro with IC50 values in inhibiting the dopamine and noradrenaline transporters of 0.19ug/mL (190ng/mL) and 0.31ug/mL (310ng/mL) respectively. Injections of isolated Delta-3,2-hydroxybakuchiol was able to reduce dopamine and noradrenaline uptake in a dose-dependent manner in rats, with 16.32-48.96mg/kg being as effective in inhibiting dopamine uptake as 9.75mg/kg Vanoxerine and 16.32mg/kg being as effective at inhibiting noradrenaline reputake as 6.6mg/kg Desipramine (with 48.96mg/kg outperforming Desipramine).
Aside from bakuchiol and Delta-3,2-hydroxybakuchiol, Hydroxybakuchiol and Delta-1,2-hydroxybakuchiol also have catecholamine reputake potential in vitro.
After injections of the petroleum extract of Fructus Psoraleae at 20, 200, and 500mg/kg, spontaneous locomotion was increased in a dose-dependent manner over 105 minutes (trending to decline) with no dose being more effective than 10mg/kg cocaine; all locomotion was abolished with reserpine, establishing that they were mediated by monoamines.
The Bakuchiol class of molecules appear to be catecholamine (dopamine and noradrenaline) reuptake inhibitors, with fairly high potencies (in the low micromolar and high nanomolar range). Although no oral studies exist, injections of either isolated Bakuchiols of a petroleum ether extract of the plant appear to have excitatory properties in rodents
One study screening plant sources of MAO-B inhibitors noted that Psoralea was one of four (out of 905 plants) to have potential MAO-B inhibitory potential with an IC50 below 70mcg/mL, alongside Phellodendron amurense, Licorice Root, and Cyamopsis psoralioides. This has been noted in vivo following oral ingestion of 30-50mg/kg furanocoumarins from Psoralea Corylifolia, where MAO-A and MAO-B activity was inhibited with more activity on MAO-B (47-63%) relative to MAO-A (15-47%).
Potential Monoamine oxidase (MAO) inhibiting potential, with preference for MAO-B; this may also contribute to catecholaminergic effects via reducing their rate of breakdown (causing a relative spike)
In the forced swim test model in mice, Psoralen at an oral dose of 10, 20, and 40mg/kg for 1, 7, and 14 days noted that the highest dose was associated with anti-depressive effects. Normalizations in serotonin and corticosteroid level at 20mg/kg (with 10 and 40mg/kg underperforming relative to 20mg/kg) suggest an adaptogen-like effect. Amitriptyline at 10mg/kg as an active control was as effective at reducing immobility and underperformed in regards to swimming (which was increased with Psoralen at 20-40mg/kg).
Psoralea Corylifolia furanocoumarins (30-50mg/kg) have been further tested in a model of Chronic stress, and appeared to have anti-stress effects as assessed by serum corticosterones and a sucrose-preference test.
Possible anti-stress and anti-depressive effects, although it appears to be of moderate potency (with some other adaptogen herbs showing more promise than this)
At least one study has noted that the cocaine analogue ((-)-2beta-carbomethoxy-3beta-(4-fluorophenyl) tropane) was unable to bind to the dopamine receptor in vitro when incubated with the petroleum extract of Fructus Psoreleae. This study noted that more research needed to be done, but suggests that Psoralea fruits could be useful in antagonizing cocaine's receptor affinity and thus to reduce addictive potential of cocaine.
Very preliminary evidence, but at least one study raises the possibility that Psoralea can be anti-addictive against Cocaine by competing with the dopamine receptor
4.1. Blood Flow
Neobavaisoflavone and Isobavaisoflavone (but not Bavachin) appear to have platelet inhibitory potential, with Neobavaisoflavone inhibiting aggregatio by Arachidonic Acid (IC50 0.5μM), Collagen (65.1μM) and PAF (41.6μM) and Isobavaisoflavone having similar inefficacy on Collagen with les potency on Arachidonic Acid (7.8+/-2.5μM) but more potent on PAF-induced clotting (2.5+/-0.3μM); both compounds were more effective than Aspirin on AA-induced blood clotting.
May have anti-clotting potential, with one study suggesting more potent than Aspirin
The coumarin Bakuchicin has been noted to induce vascular relaxation via a Nitric oxide-cGMP related pathway. This study was in vitro and noted a maximal relaxation in precontracted arteries of 95.94+/-0.97% at 30uM and was completely abolished by pretreatment with the nitric oxide inhibitors L-NAME and the cGMP inhibitor (ODQ) but was also attenuated by Vermapril, an L-type calcium channel blocker.
May relax the endothelium, but no living models have been used yet
5Interactions with Glucose Metabolism
Both Psoralidin and Bakuchiol have PTP1B inhibitory potential, with IC50 values of 9.4+/-0.5mM and 20.8+/-1.9mM, both comparably very weak to reference standards of Berberine and Ursolic Acid.
Currently unremarkable interactions with PTP1B, a negative regulator of the insulin receptor (normally its inhibition would increase the signalling of the insulin receptor, but this is unlikely with Psoralea as the IC50 values are very weak)
6Inflammation and Immunology
In LPS-stimulated microglia (brain cells), 4-hydroxylonchocarpin and a chromenoflavanone showed efficacy in inhibiting NO release in a concentration dependent manner with IC50 values of 11.4 and 10.2mM respectively; Bavachinin and Bavachalcone were ineffective. These two compounds also prevented iNOS induction and IκBα degradation at 10mM. A variety of other components (Psoralidin, Corylifol A, Bavachinin, Isobavachalcone, Neobavaisoflavone) have shown an ability to reduce NO production in LPS-stimulated macrophages with a potency in the range of 17-29mM (IC50 values) alongside reduced cytokine release secondary to macrophage activation. Bakuchiol as well has noted suppressive effects on LPS-stimulated NO release from macrophages, with 10uM being approximately as potent as 10uM pyrrolidine dithiocarbamate or 50uM Aminoguanidine.
At least one study has noted that STAT3 activation downstream of IL-6 was inhibited by various compounds; Bakuchiol appeared to be active (IC50 of 4.57+/-0.45uM) although the most potent appeared to be Corylifol A (0.81+/-0.15uM or 810nM).
Enzymatically, Psoralidin appears to be a dual inhibitor of both COX2 (the inducible form of COX) and 5-LOX, the latter of which appeared to be through preventing interaction between 5-LOX and its required coactivator 5-lipoxygenase activating protein (FLAP); preventing FLAP from acting upon 5-LOX abolishes 5-LOX activity in response to cellular activation.
In inflammation-stimulated macrophages, components of Psoralea may have anti-inflammatory effects. Although the anti-inflammatory effects cannot be isolated to one component (many are active) they do appear to be quite potent on an in vitro assessment
Psoralea appears to be able to stimulate Nitric Oxide induction and TNF-α production from macrophages in the presence of IFN-γ, with minimal efficacy in isolation; both of which were mediated via activation of NF-kB (abolished by specific inhibitor).
Some compounds in Psoralea appear to increase IFN-γ induced activation of NF-kB and immunostimulatory (pro-inflammatory) effects of IFN-γ, with minimal efficacy per se. Practical significance of these results unknown
A 70% methanolic fraction of Psoralea has demonstrated greater than 90% cytotoxicity in K562 and KB cell lines at 80mcg/mL concentrations (a potency similar to Doxorubicin and Vincristine sulfate at 0.12mM and 0.2mM respectively), and showed dose-dependenct between 5-80mcg/mL. The bioactives thought to be active in this fragment were Psoralen and Isopsoralen with IC50 values on cell growth of 24.4-88.1ug/mL and 49.6-69.1ug/mL respectively, although these were lower than those achieved with the whole extracted fraction (IC50 of 10-21.6ug/mL)
The extract of Psoralea itself appears to have cytotoxic effects in some cancer cells
Isolated Psoralidin (Coumarin) appears to enhance apoptosis via TRAIL (Tumor Necrosis Factor-related apoptosis-inducing ligand), which is a pathway by which the immune system can selectively destroy tumor cells by releasing TRAIL (expressed on some immune cells) into a soluble form, which then acts on death receptors on cancer cells. It appears Psoralidin upregulated expression of one of the death receptors mediating this pathway, TRAILR2/DR5, and while 100ng/mL of TRAIL itself induced 10.8+/-1% apoptosis and Psoralidin induced 2.4-11.4% (20-50uM), the combination of TRAIL with this concentration of Psoralidin induced 28.7-66.7% apoptosis mediated via mitochondrial membrane potential loss.
The aforementioned study only found TRAILR2 to be upregulated (with no influence on TRAILR1, the other death receptor) although another study in prostatic cells rather than HeLa cells noted that bother were upregulated.
Psoralidin has also been noted to reverse TRAIL resistance in vitro againt cancer cells and appears to overcome cancer cell resitance to TNF-α (both TNF-α and TRAIL belonging to the same TNF superfamily).
Some bioactives from Psoralea Corylifolia appear to synergistically augment the ability of Tumor Necrosis Factors (TNF-α and TRAIL investigated) to induce apoptosis in cancer cells. TNFs are endogenous compounds that, among other classes of molecules, mediate the interaction between the immune system and cancer (with many bioactive mushrooms such as Ganoderma Lucidum working via these means)
8Interactions with Hormones
When comparing the estrogenicity of Psoralea Corylifolia seeds (recombinant yeast assay) it was noted that the 70% of the seeds had an estrogenicity of approximately 190uM (EC50 value for signalling via the estrogen receptor alpha subset); this was outperfored by both species of Polygonum (Cuspidatum and Multiforum; the former being Japanese Knotweed), Rheum palmatum, Cassia obtusifolia, and Epimedium brevicornum while itself being more estrogenic than Pueraria lobata and Astragalus Membranaceous.
One component of Psoralea, Bakuchiol, shows greater efficacy at a concentration of 1uM was able to activate the estrogen receptor with a potency similar to Genistein (one of the soy isoflavones) and had a binding affinity to the estrogen receptors of 1.01uM and 1.6uM for alpha and beta subunits respectively, with a five-fold affinity for ERα; this affinity has been noted to merely be three-fold elsewhere, where the IC50 value was found to be 1.34mcg/mL.
Psoralen and Isopsoralen show selectivity to the alpha subunit, while four other flavonoid compounds did not show selectivity but failed to proliferate MCF-7 cells (suggesting weak estrogenicity). Most likely, Bakuchiol is the biologically relevant phytoestrogen.
A few molecules in Psoralea may be phytoestrogens, and although isolated Bakuchiol appears to be relatively potent the overall plant extract of Psoralea Corylifolia does not appear to be remarkably potent
In a rat model of testiclar toxicity (90 days supplementation of 3% psoralea corylifolia in the diet), it appears that supplementation is associated with a reduction in serum testosterone.
Secondary to possible damaging testicles, psoralea corylifolia appears to be capable of reducing testosterone concentrations
The prenylated isoflavone Neobavaisoflavone has been found to stimulate MC3T3-E1 cell differentiation at concentrations of 1-20μM, with 1μM conferring a 1.7-fold increase in ALP (biomarker of differentiation) and 10-15μM plateauing at 3.2-fold. Psoralidin and Psoralen (as well as Isopsoralen) also stimulated osteogenesis in vitro, but to a lesser degree than Neobavaisoflavone; Neobavaisoflavone also outperformed Icariin from Horny Goat Weed in this study, failed to stimulate proliferation, but increaesd bone mineralization in vitro to a maximum 3-fold at 15μM. Corylin has also been implicated in enhancing osteoblastic differentiation, suggesting numerous prenylated isoflavones from Psoralea Corylifolia are capable of this effect.
Osteoclast differentiation has been noted to be inhibited by Bavachalcone.
Both osteoblastic differentiation as well as osteoclastic inhibition have been noted with prenylated isoflavonoids from Psoralea Corylifolia, suggesting possible benefits to bone mass
One study in rabbits that induced surgical defects in bone tissues but grafted the defect with Psoralea extract (to a concentration around 100mg/mL water extract) followed for 14 days noted that, under histological examination, new bone tissue was being formed at the Psoralea-Graft interface and quantified to be 275% greater than collagen control.
In ovariectomized rats (model for menopause), isolated Psoralen was able to increase trabecular thickness over a period of three months relative to control; the mechanisms appear to be related to the Notch signalling pathway. Isolated Bakuchiol as well appears to preserve bone mass in ovariectomized rats at oral dose of 15-30mg/kg, and although Bakuchiol appears to work via estrogenic means (threefold higher affinity for ERα relative to ERβ, with a 1.34mcg/mL IC50 value on the former) it did not increase uterine weight in this study despite an increase in circulating estrogen; null effects seen elsewhere.
The whole seed extract of Psoralea Corylifolia (50mg/kg daily for 3 months) has also been implicated in increasing bone mineral density in rats although when 0.25-0.5% of the rat diet as Psoralea Corylifolia is compared to an active control of 20mcg/kg estrogen, it underperforms.
Although there is no human evidence currently, there is animal evidence to support the notion that Psoralea Corylifolia enhances bone growth in either injury models or rat models of menopause. It does not appear to be highly estrogenic
10Interactions with Organ Systems
In a torsion-induced injury of the testes (ischemia/reperfusion), oral administration of Psoralea prior to the insult could preserve cAMP-responsive element modulator-τ (CREMτ) activity and spermatogenesis thought to be via anti-oxidative means (assessed by a reduction in MDA levels when the Psoralea group was compared to injured control) although Psoralea Corylifolia itself (1g/kg bodyweight for 56 days) appears to induce mRNA of CREM as well as preserve it during testicular toxicity and as such increase possibly increase spermatogenesis. CREM is a cAMP responsive positive mediator of testicular activity and this latter study noting an induction of CREM (108.41+/-1.19% of control) noted an increase in testicular size (18.4%).
Elsewhere, it has been noted that 1.5% dietary intake of psoralea corylifolia for 90 days in rats is associated with atrophy of the seminiferous tubules and a later study using 3% of the diet as psoralea corylifolia for 12 weeks noted that the increases in testicular weight seen in a time-dependent manner associated with testicular pathology and impaired sperm production.
Appears to protect the testicles from injury and may increase spermatogenesis acutely, but prolonged intake appears to do the opposite and is somewhat of a testicular toxin in rodents
An ethanolic extract of Psoralea corylifolia at 0.375, 0.75, 1.5, or 3% of the rat diet by weight for 90 days noted decreases in weight at doses of 0.75% and above accompanied by decreased gonad weight (testes and ovaries) at doses of 1.5-3% of the diet. As a previous study on 8-methoxypsoralen was accompanied by testicular atrophy, it was thought that these doses were showing Psoralen-induced reproductive toxicity. Increased yGPT and BUN were also noted at the highest dose (3%) in both sexes, and also at 0.75-1.5% in female rats.
May exert testicular toxicology at doses which, although high, are not infeasibe for consumption
One preliminary study in rats suggested that 8g/kg bodyweight Psoralea (estimated human dose of 87g for a 150lb female) could potentially be associated with reproductive toxicity in female pregnant rats.
11.2. Case Studies
One case study exists associated with Psoralea with hepatotoxicity, and while other herbs were possible linked (Vetivexia zizaniodis, Brahmi tablets possibly containing Bacopa Monnieri) this case study suggested that the Psoralea supplement demonstrated probable causality. Another case study suggests cholestatis from a dose of Psoreala Corylifolia seeds 10-fold higher than normally recommended (exact dosage not stated).