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Culén is the popular term used in Chile for the only endemic species of the Fabaceae family, Psoralea glandulosaLinn. It is one of the most widely used medicinal plants in Chile and in some regions of South America, not only as a home remedy, but also recommended by medicine and widely used in the gastronomic industry. Many properties are known, supported by biological tests both in vitroand in vivo. Because it is so highly appreciated, it is included in the book "Medicamentos HerbariosTradicionales" (Traditional Herbal Medicines) of the Chilean Ministry of Health. Given the great interest in this plant since time immemorial, this review contains information on its history, popular uses and scientific studies, for a better knowledge, management and sustainable care of this Chilean natural resource.
Culén es el término popular utilizado en Chile para la única especie endémica de la familia Fabaceae, Psoralea glandulosaLinn. Se trata de una de las plantas medicinales más utilizadas en Chile y en algunas regiones de Sudamérica, no solamente como remedio curativo casero, sino también recomendada por la medicina y con amplia utilización en la industria gastronómica. De ella se conocen un gran número propiedades avaladas por ensayos biológicos tanto in vitrocomo in vivo. Por ser tan apreciada, se encuentra incluida en el libro "Medicamentos Herbarios Tradicionales" del Ministerio de Salud de Chile. Dado el gran interés que despierta esta planta desde tiempos inmemoriales, se recoge en este capítulo la información sobre su historia, usos populares y estudios científicos, para un mejor conocimiento, manejo y cuidado de manera sustentable de este recurso natural chileno.
Subject(s)
Plants, Medicinal , Psoralea , ChileABSTRACT
ObjectiveTo explore the differences in response to bakuchiol-induced hepatotoxicity between Institute of Cancer Research （ICR） mice and Kunming （KM） mice. MethodThe objective manifestations of bakuchiol-induced hepatotoxicity in mice were confirmed by acute and subacute toxicity animal experiments， and enrichment pathways of differential genes between normal ICR mice and KM mice were compared by transcriptomics. The real-time quantitative polymerase chain reaction （real-time qPCR） assay was used to verify the mRNA expression of key genes in the related pathways to confirm the species differences of bakuchiol-induced liver injury. ResultIn the subacute toxicity experiment， compared with the normal mice， the ICR mice showed increased serum content of alkaline phosphatase （ALP）， and 5′-nucleotidase （5′-NT）， without significant difference， and no manifest change was observed in KM mice. Pathological results showed that hepatocyte hypertrophy was the main pathological feature in ICR mice and hepatocyte steatosis in KM mice. In the acute toxicity experiment， KM mice showed erect hair， mental malaise， and near-death 3 days after administration. The levels of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in KM mice （400 mg·kg-1） significantly increased（P<0.01）， and the activity of total reactive oxygen species （SOD） in liver significantly decreased（P<0.01）compared with those in normal mice， while the serum content of 5′-NT and cholinesterase （CHE） in ICR mice （400 mg·kg-1） were significantly elevated （P<0.01）. The liver/brain ratio in ICR mice increased by 20.34% and that in KM mice increased by 29.14% （P<0.01）. The main pathological manifestation of the liver in ICR mice was hepatocyte hypertrophy， while those in KM mice were focal inflammation， hepatocyte hypertrophy， and hepatocyte steatosis. Kyoto Encyclopedia of Genes and Genomes（KEGG）and Reactome pathway enrichment analyses showed that the differential gene expression between ICR mice and KM mice was mainly involved in oxidative phosphorylation， bile secretion， bile acid and bile salts synthesis， and metabolism pathway. CYP7A1 was up-regulated in all groups with drug intervention （P<0.01） and MRP2 was reduced in all groups with drug intervention of KM mice （P<0.01） and elevated in all groups with drug intervention of ICR mice （P<0.01） compared with those in the normal group. The expression of BSEP was lowered in ICR mice with acute liver injury （400 mg·kg-1） （P<0.05）. SHP1 was highly expressed in KM mice with acute liver injury （400 mg·kg-1）. The expression of FXR was diminished in ICR mice with subacute liver injury （200 mg·kg-1） （P<0.01）. SOD1， CAT， and NFR2 significantly decreased in KM mice with acute liver injury （400 mg·kg-1）， and CAT dwindled in KM mice with subacute liver injury （200 mg·kg-1） （P<0.01）. GSTA1 and GPX1 significantly increased in KM mice with acute liver injury （400 mg·kg-1） （P<0.01） and SOD1， CAT， NRF2， and GSTA1 significantly increased in ICR mice with subacute liver injury （200 mg·kg-1） （P<0.01）. CAT and NRF2 significantly increased in ICR mice with acute liver injury （400 mg·kg-1） （P<0.01）. ConclusionWith the increase in the dosage of bakuchiol， the liver injury induced by oxidative stress in KM mice was gradually aggravated， and ICR mice showed stronger antioxidant capacity. The comparison of responses to bakuchiol-induced hepatotoxicity between ICR mice and KM mice reveals that ICR mice are more suitable for the investigation of the mechanisms related to bile secretion and bile acid metabolism in the research on bakuchiol-induced hepatotoxicity in mice. KM mice are more prone to liver injury caused by oxidative stress.
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Objective: To study bakuchiol and its derivatives of cyclohexane soluble part in 70% ethanol aqueous extract of Psoraleae Fructus and their inhibition on nitric oxide (NO) production in lipopolysaccharides (LPS)-activated murine macrophage RAW 264.7 cell lines. Methods: The compounds were separated and purified by silica gel column and high performance liquid chromatographies, and their structures were determined by spectroscopic data analyses. Using LPS-activated RAW 264.7 cell line models in vitro, all of the isolated compounds were evaluated for the inhibition against NO production. Results: Twelve compounds were obtained and identified as bakuchiol (1), 12,13-dihydro-12,13-epoxybakuchiol (2), Δ3,2-hydroxylbakuchiol (3), 12-oxobakuchiol (4), psoracorylifol B (5), psoracorylifol C (6), (12’S)-bisbakuchiol C (7), Δ1,3-bakuchiol (8), 13-methoxyisobakuchiol (9), bisbakuchiol B (10), bisbakuchiol A (11), and 12,13-dihydro-12,13-dihydroxybakuchiol (12), respectively. For the inhibition of NO production in the LPS-activated RAW 264.7 cell line model, a positive inhibitor, L-N6-(1-iminoethyl)-lysine (L-NIL), was used and showed the half maximal inhibitory concentration (IC50) value of (10.29 ± 1.10) μmol/L. The IC50 values of the assayed compounds 1, 3, 5, 10 and 11 were all more than 50 μmol/L, compounds 8, 9 and 12 were comparable to that of L-NIL, whereas the IC50 values of compounds 2, 4 and 7 were less than that of the positive inhibitor with statistically significance. Conclusion: Compound 4 is a new natural product. The results of the bioactivity assays indicated that compounds 2, 4, 7, 8, 9 and 12 are potential anti-inflammatory agents.
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Objective: To investigate the cell growth inhibitory effect and molecular mechanism of bakuchiol against human breast cancer MCF-7 cells. Methods: The growth inhibitory effect of bakuchiol on MCF-7 cells was tested by MTT assay. Flow cytometry was used to investigate the distribution of cell cycle and ROS generation. Fluorescence microscope was used to observe the change of cell nucleus. Western blotting was used to detect the expression of the protein related to cell cycle and MAPK family. The ROS scavenger and inhibitors of MAPK family were introduced to investigate the effect on the growth inhibitory rate and the levels of cell cycle related protein by bakuchiol. Results: Bakuchiol inhibited the cell growth on the MCF-7 cells in dose- and time-dependent manner, which showed stronger effect than that of 5-fluorouracil. Furthermore, bakuchiol induced S-phase arrest in MCF-7 cells via ROS generation. The production of ROS up-regulated p-p53 and p21 expression, and then decreased CDK2 and CyclinA2. The changes of bakuchiol on these proteins could be reversed by the ROS scavenger Trion, indicating that ROS was associated with bakuchiol-induced S-phase arrest. In addition, pretreatment with p38MAPK inhibitor SB203580 decreased bakuchiol-caused ROS generation, suggesting that the production of ROS was dependent on p38MAPK pathway. Conclusion: The proliferation inhibitory effect of bakuchiol on MCF-7 cells is related with S-phase cell cycle arrest, and ROS plays a role in the bakuchiol-induced S-phase arrest.
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OBJECTIVE： To investigate the vasodilatory effect mechanism of psoralen and bakuchiol. METHODS： The rat thoracic aorta was isolated to prepare vascular rings and de-endothelium vascular rings. Using contraction rate as index， the intact endothelium or de-endothelium vascular rings were pre-incubated with N-nitro-L-arginine methyl ester （L-NAME， 100 μmol/L）； vasodilatory effect of low-dose， medium-dose and high-dose of psoralen or bakuchiol（0.1，1，10 μmol/L）on aortic vessels pre- contracted with norepinephrine （NE， 1 μmol/L） or potassium chloride （KCl， 60 mmol/L） were investigated. The de-endothelium vascular rings were pre-incubated with calcium dependent potassium channel inhibitors tetraethylammonium chloride （TEA， 0.1 mmol/L） and inward rectifying potassium channel inhibitor barium chloride （BaCl2，0.1 mmol/L）； vasodilatory effect of low-dose， medium-dose and high-dose of bakuchiol （0.1， 1， 10 μmol/L） on de-endothelium vascular vessels pre-contracted with NE （1 μmol/L） were investigated. The microvascular endothelial cells were isolated by collagenase-neutral protease digestion； the effects of low-dose， medium-dose and high-dose of psoralen or bakuchiol （0.1， 1， 10 μmol/L） on the expression of eNOS protein were studied by ELISA. RESULTS： Psoralen and bakuchiol could significantly reduce the contraction rate of endothelium-intact aortic rings pre-contracted with NE（P＜0.01）； medium-dose and high-dose of psoralen and bakuchiol could significantly reduce the contraction rate of endothelium-intact aortic rings pre-contracted with KCl（P＜0.05 or P＜0.01）； while the contraction rate could be increased by de-endothelium and NOS inhibition significantly （P＜0.05 or P＜0.01）. The medium-dose and high-dose of bakuchiol could significantly reduce the contraction rate of de-endothelium vascular vessels pre-contracted with NE （P＜0.05 or P＜0.01）. The contraction rate could be increased by inhibiting inward rectifier potassium channels in vascular smooth muscle （P＜0.01）. Different dosages of psoralen and bakuchiol could significantly increase the expression levels of eNOS protein in rat cardiac microvascular endothelial cells（P＜0.01）. CONCLUSIONS： Psoralen and bakuchiol may play a role in vasodilation via endothelium-dependent NO pathway and by promoting eNOS protein expression in endothelial cells； bakuchiol may play a role in vasodilation via non-endothelium dependent pathway as opening inward rectifying potassium channel.
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OBJECTIVE: To investigate the metabolic characteristics of bakuchiol mediated by cytochrome P450 enzyme (CYP) and UDP-glucuronosyltransferase (UGT) in rat liver microsomes (RLMs) or human liver microsomes (HLMs), and to compare the metabolic gender differences. METHODS: Bakuchiol was incubated at 37? with male and female RLMs or HLMs in the presence of nicotinamide adenine dinucleotide phosphate (NADPH) or uridine 5′-diphosphoglucuronic acid (UDPGA). The residual concentrations of bakuchiol were measured in each incubation system using high performance liquid chromatography (HPLC). The metabolic stability and metabolic gender differences of bakuchiol were evaluated by the remaining percentage of bakuchiol after incubation.RESULTS: When bakuchiol was metabolized by CYP in RLMs, the intrinsic clearance (Clint) value in male RLMs ?(326.6±15.4) mL·min-1·kg-1?was significantly higher than that of female RLMs ?(77.2±4.8) mL·min-1·kg-1? (P<0.01). When bakuchiol was metabolized by UGT in RLMs, female RLMs had a significantly higher Clint value ?(419.1±24.1) mL·min-1·kg-1? than male RLMs ?(164.5±8.4) mL·min-1·kg-1? (P<0.01). When bakuchiol was metabolized by both CYP and UGT in RLMs, male RLMs had a significantly higher Clint value ?(1063.1±27.2) mL·min-1·kg-1? than female RLMs ?(781.2±16.5) mL·min-1·kg-1?(P<0.01). When bakuchiol was metabolized by CYP in HLMs, male HLMs had a significantly higher Clint value ?(24.8±2.1) mL·min-1·kg-1? than female HLMs ?(17.6±1.0) mL·min-1·kg-1? (P<0.01). There were no significant gender differences in the metabolism of bakuchiol when it was metabolized by UGT in HLMs. The Clint values were 176.4±26.5 and (165.9±8.6) mL·min-1·kg-1, respectively. The metabolic parameters of bakuchiol mediated by CYP and UGT in HLMs had no significant gender differences. The Clint values were 262.5±20.9 and (236.2±10.5) mL·min-1·kg-1, respectively. CONCLUSION Bakuchiol can be metabolized by CYP and UGT in RLMs or HLMs, and the metabolic parameters exhibit species differences and gender differences.
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Objective: To establish UPLC method for the simultaneous determination of 10 components, such as psoralen, isopsoralen, psoralidin, bavachinin, isobavaenin, corylifolin, isobavachalcone, corylin, neobavaisoflavone, and bakuchiol in Psoralea Fructus, and to study the effect of processing time on 10 components in stir-frying Psoralea Fructus with salt solution. Methods: The chromatographic separation was achieved on a C18 column (50 mm×4.6 mm, 1.8 μm) with acetonitrile (A)-water (B) as mobile phase at the flow rate of 1.0 mL/min for gradient elution; The column temperature was 30℃. The determination wavelength was 250 nm. Results: The 10 components were well separated within 15 min. The RSD values of reproducibility were less than 3%. The stability was good in 24 h. The linear relationship between the concentration and peak areas of the 10 components was good (r≥0.9970). The average recoveries were 96%-105% and the RSD values were all less than 3%. Conclusion: The method is simple, reliable and accurate, could be used for the quality control of Psoralea Fructus. With processing time prolonged, the content of coumarins showed first decreased, then increased and last decreased. Flavonoids, bakuchiol and the total content of 10 components above were decreased.
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OBJECTIVE:To establish a method for content determination of bavachin and bakuchiol in Psoralea corylifolia.METHODS:HPLC method was adopted.The determination was performed on Shim-Pack VP-ODS column with mobile phase consisted of acetonitrile-water (gradient elution) at the flow rate of 1.0 mL/min.The detection wavelength was set at 246 nm,the column temperature was 30 ℃,and the sample size was 10 μL.RESULTS:The linear ranges of bavachin and bakuchiol were 48.9-489 ng(r=0.999 8),784-7 840 ng(r=0.999 9).RSDs of precision,stability and reproducibility tests were all lower than 2.0％.Average recoveries ranged 95.30％-99.63％ (RSD=1.45％,n=9),96.89％-100.82％ (RSD=1.36％,n=9).CONCLUSIONS:The method is simple,accurate,stable and reproducible,and can be used for the simultaneous determination of bavachin and bakuchiol in P corylifolia.
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Objective: To optimize the processing technology for Psoraleae Fructus by D-optimal response surface methodology with UHPLC. Methods: Based on the content variations of nine main constituents (psoralen, isopsoralen, neobavaisoflavone, bavachin, psoralidin, corylifolinin, corylin, bavachalcone, and bakuchiol) determined by UHPLC, the D-optimal response surface methodology combined with single factor experiment was used to optimize the moistened time, stir-fried temperature, salted dosage, and stir-fried time in the processing technology for Psoraleae Fructus. Results: The optimal processing technology for Psoraleae Fructus was as follows: 100 g Psoraleae Fructus was mixed with 2.10 g salt, moistened for 12 h, and stir-fried for 30 min at 80℃. Conclusion: The processing technology for Psoraleae Fructus optimized by D-optimal response surface methodology with UHPLC could be used to optimize the process parameters, to promote the stability and repeatability of the processing technology, which provides the technique support for improving the quality uniformity of Psoraleae Fructus and safety in clinic application.
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OBJECTIVE To study the nephrotoxicity induced by bakuchiol alone and bakuchiol combined with psoralen and to explore its mechanism. METHODS The cytotoxicities of bakuchiol and bakuchiol combined with psoralen were investigated using human renal tubular epithelial cell lines (HK-2), in presence or absence of hepatic S9 mixture. The HK-2 cells were exposed to culture medium alone (blank control), 0.5% DMSO (vehicle control), aristolochic acid Ⅰ (AAⅠ;positive control), psoralen 5 μmol·L~(-1) group, bakuchiol 5,10,20,30 and 40 μmol·L~(-1) groups, and bakuchiol+psoralen (20+5), (30+5) and (40+5)μmol·L~(-1) groups, respectively. The cell viabilities were examined by MTT assay; cell membrane injuries were examined by detecting lactate dehydrogenase (LDH) release rate; and the morphological changes in HK-2 cells were observed with contrast microscope. The rate of cell apoptosis was detected by AnnexinⅤ/PI staining, and cell cycle was detected by PI staining with flow cytometry. RESULTS No cytotoxicity was found in psoralen 5 μmol·L~(-1) group. The HK-2 cell viabilities were significantly reduced after 4, 24, 48 and 72 h of exposure to either bakuchiol 20, 30 and 40 μmol·L~(-1)groups or bakuchiol+psoralen (20+5), (30+5) and (40+5)μmol·L~(-1) groups in a time- and concentration-dependent manner. The IC_(50) values of bakuchiol were (26.4±4.8), (21.8±0.6) and (24.1±0.8)μmol·L~(-1) for 24, 48 and 72 h exposure, respectively. The cytotoxicity of bakuchiol was significantly decreased in presence of hepatic S9 mixture. The LDH release rate of HK-2 cell increased significantly after 24 h of exposure to bakuchiol 20,30 and 40 μmol·L~(-1) or bakuchiol+psoralen groups. With the concentration and time increasing, the HK-2 cells became more and more contracted and rounded. In bakuchiol 40 μmol·L~(-1) or bakuchiol+psoralen (20+5), (30+5) and (40+5)μmol·L~(-1) groups, HK-2 cells showed apoptotic characters. In bakuchiol or bakuchiol+psoralen groups, apoptotic cells significantly increased and cells in G2 phase markedly decreased. CONCLUSION Bakuchiol has a significant cytotoxicity in HK-2 cells, and combined with psoralen can not decrease its toxicity. The cytotoxicity of bakuchiol is significantly reduced in the presence of hepatic S9 mixture. The possible mechanisms of the renal cytorotoxicity of bakuchiol are as follows: ① direct damage to the cell membrane; ② inducing cell apoptosis; ③ inhibiting intracellular DNA synthesis and block cell mitosis and proliferation.