Function-oriented mechanism discovery of coumarins from Psoralea corylifolia L. in the treatment of ovariectomy-induced osteoporosis based on multi-omics analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoraleae Fructus (Bu Gu Zhi) is the fruit of Psoralea corylifolia L. (PCL) and has been used for centuries in traditional Chinese medicine formulas to treat osteoporosis (OP). A new drug called "BX" has been developed from PCL, but its mechanism for treating OP is not yet fully understood. AIM OF THE STUDY: To explore the mechanism of action of BX in the treatment of ovariectomy-induced OP based function-oriented multi-omics analysis of gut microbiota (GM) and metabolites. MATERIALS AND METHODS: C57BL/6 mice were bilaterally ovariectomized to replicate the OP model. The therapeutic efficacy of BX was evaluated by bone parameters (BMD, BV/TV, Tb.N, Tb.Sp), hematoxylin and eosin (H&E) staining results, and determination of bone formation markers procollagen type Ⅰ amino-terminal peptide (PⅠNP) and bone-specific alkaline phosphatase (BALP). Serum and fecal metabolomics and high-throughput 16S rDNA sequencing were performed to evaluate effects on endogenous metabolites and GM. In addition, an enzyme-based functional correlation algorithm (EBFC) algorithm was used to investigate functional correlations between GM and metabolites. RESULTS: BX improved OP in OVX mice by increasing BMD, BV/TV, serum PⅠNP, BALP, and improving Tb.N and Tb.Sp. A total of 59 differential metabolites were identified, and 9 metabolic pathways, including arachidonic acid metabolism, glycerophospholipid metabolism, purine metabolism, and tryptophan metabolism, were found to be involved in the progression of OP. EBFC analysis results revealed that the enzymes related to purine and tryptophan metabolism, which are from Lachnospiraceae_NK4A136_group, Blautia, Rs-E47_termite_group, UCG-009, and Clostridia_UCG-014, were identified as the intrinsic link between GM and metabolites. CONCLUSIONS: The regulation of GM and restoration of metabolic disorders may be the mechanisms of action of BX in alleviating OP. This research provides insights into the function-oriented mechanism discovery of traditional Chinese medicine in the treatment of OP.

Psoralea corylifolia L. and its active component isobavachalcone demonstrate antibacterial activity against Mycobacterium abscessus.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoralea corylifolia L. (Fabaceae) is a traditional medicinal herb used to treat various diseases, including kidney disease, asthma, psoriasis and vitiligo. AIM OF THE STUDY: To explore the antibacterial activity of Psoralea corylifolia L. and its bioactive components against Mycobacterium abscessus (M. abscessus). MATERIALS AND METHODS: Ultra high performance liquid chromatography was utilized to analyze the bioactive fractions and compounds present in 30%, 60%, and 90% ethanol extracts of Psoralea corylifolia L.. The antibacterial effects of Psoralea corylifolia L. and potential active ingredients were determined by minimum inhibitory concentration (MIC). The bactericidal activity of the active ingredient isobavachalcone was evaluated and then scanning electron microscopy was used to explore the bactericidal mechanism of isobavachalcone. RESULTS: The 90% ethanol extracts of Psoralea corylifolia L. showed significant antibacterial activity against M. abscessus, with an MIC of 156 µg/mL. Isobavachalcone was identified as the bioactive ingredient, and testing of 118 clinical isolates of M. abscessus indicated their MICs ranged from 2 to 16 µg/mL, with an average MIC of 8 µg/mL. Furthermore, the minimum bactericidal concentration/MIC ratio and the time-kill test indicated rapid bactericidal activity of isobavachalcone against M. abscessus. Finally, we found that the bactericidal mechanism of isobavachalcone involved damage to the bacterial cell membrane, causing wrinkled and sunken cell surface and a noticeable reduction in bacterial length. CONCLUSION: Psoralea corylifolia L. ethanol extracts as well as its active component isobavachalcone show promising antimicrobial activity against M. abscessus.

Antiparasitic efficacy of flavonoids identified from Psoralea corylifolia against Tetrahymena piriformis in guppy (Poecilia reticulate).

Tetrahymena piriformis belongs to the ciliated protists (ciliates), causing severe economic losses in aquaculture. Chemical drugs currently used usually have toxic side effects, and there is no specific drug against Tetrahymena. Therefore, it is an urgent need to identify new antiparasitic lead compounds. In the present study, the in vitro parasiticidal activity of ethyl acetate (EtOAc) extracts and water extracts from 22 selected traditional Chinese medicines (TCMs) were evaluated against T. piriformis. The EtOAc extract of P. corylifolia turned out to be the most active with the minimum parasiticidal concentration of 100 mg/L within 3 h. Thus, it was separated into 12 fractions by the first-dimensional (D1) normal phase liquid chromatography (NPLC), meanwhile combining with in vitro antiparasitic tests for activity tracking. Subsequently, 8 flavonoids were identified in the active fractions by the second-dimensional (D2) reverse phase liquid chromatography (RPLC) tandem high-resolution mass spectrometry. According to the results, 5 flavonoids were selected for in vitro antiparasitic test, of which isobavachalcone showed the minimum parasiticidal concentration of 3.125 mg/L in 2 h. Bathing treatment of infected guppies with isobavachalcone could significantly reduce the burden of T. piriformis, obtaining a 24-h median effective concentration (24-h EC50) value of 1.916 mg/L. And the concentration of isobavachalcone causing guppies to die within 24 h is 39 times than that of 24-h EC50. The results demonstrated that isobavachalcone has the potential to be developed into a novel commercial fish drug against T. piriformis.

Exploring the mechanism and phytochemicals in Psoraleae Fructus-induced hepatotoxicity based on RNA-seq, in vitro screening and molecular docking.

Psoraleae Fructus (PF) is a widely-used herb with diverse pharmacological activities, while its related hepatic injuries have aroused public concerns. In this work, a systematic approach based on RNA sequencing (RNA-seq), high-content screening (HCS) and molecular docking was developed to investigate the potential mechanism and identify major phytochemicals contributed to PF-induced hepatotoxicity. Animal experiments proved oral administration of PF water extracts disturbed lipid metabolism and promoted hepatic injuries by suppressing fatty acid and cholesterol catabolism. RNA-seq combined with KEGG enrichment analysis identified mitochondrial oxidative phosphorylation (OXPHOS) as the potential key pathway. Further experiments validated PF caused mitochondrial structure damage, mtDNA depletion and inhibited expressions of genes engaged in OXPHOS. By detecting mitochondrial membrane potential and mitochondrial superoxide, HCS identified bavachin, isobavachalcone, bakuchiol and psoralidin as most potent mitotoxic compounds in PF. Moreover, molecular docking confirmed the potential binding patterns and strong binding affinity of the critical compounds with mitochondrial respiratory complex. This study unveiled the underlying mechanism and phytochemicals in PF-induced liver injuries from the view of mitochondrial dysfunction.

Bakuchiol, a natural constituent and its pharmacological benefits.

Background and aims: Natural compounds extracted from medicinal plants have recently gained attention in therapeutics as they are considered to have lower Toxicity and higher tolerability relative to chemically synthesized compounds. Bakuchiol from Psoralea corylifolia L. is one such compound; it is a type of meroterpene derived from the leaves and seeds of Psoralea corylifolia plants. Natural sources of bakuchiol have been used in traditional Chinese and Indian medicine for centuries due to its preventive benefits against tumors and inflammation. It plays a strong potential role as an antioxidant with impressive abilities to remove Reactive Oxygen Species (ROS). This review has focused on bakuchiol's extraction, therapeutic applications, and pharmacological benefits. Methods: A search strategy has been followed to retrieve the relevant newly published literature on the pharmacological benefits of bakuchiol. After an extensive study of the retrieved articles and maintaining the inclusion and exclusion criteria, 110 articles were finally selected for this review. Results: Strong support of primary research on the protective effects via antitumorigenic, anti-inflammatory, antioxidative, antimicrobial, and antiviral activities are delineated. Conclusions: From ancient to modern life, medicinal plants have always been drawing the attention of human beings to alleviate ailments for a healthy and balanced lifestyle. This review is a comprehensive approach to highlighting bona fide essential pharmacological benefits and mechanisms underlying their therapeutic applications.

Psoraleae Fructus Ethanol Extract Induced Hepatotoxicity via Impaired Lipid Metabolism Caused by Disruption of Fatty Acid ß-Oxidation.

Herb-induced liver injury (HILI) is gradually increasing, and Psoraleae Fructus (PF) has been reported to induce hepatotoxicity. However, its underlying toxicity mechanism has been only poorly revealed. In this paper, we attempted to explore the liver injury and mechanism caused by Psoraleae Fructus ethanol extract (PFE). First, we administered PFE to mice for 4 weeks and evaluated their serum liver function indices. H&E staining was performed to observe the pathological changes of the livers. Oil red O staining was used to visualize hepatic lipids. Serum-untargeted metabolomics and liver proteomics were used to explore the mechanism of PF hepatotoxicity, and transmission electron microscopy was determined to assess mitochondria and western blot to determine potential target proteins expression. The results showed that PFE caused abnormal liver biochemical indicators and liver tissue injury in mice, and there was substantial fat accumulation in liver tissue in this group. Furthermore, metabolomic analysis showed that PFE changed bile acid synthesis, lipid metabolism, etc., and eight metabolites, including linoleic acid, which could be used as potential biomarkers of PFE hepatotoxicity. Proteomic analysis revealed that differential proteins were clustered in the mitochondrial transmembrane transport, the long-chain fatty acid metabolic process and purine ribonucleotide metabolic process. Multiomics analysis showed that eight pathways were enriched in both metabolomics and proteomics, such as bile secretion, unsaturated fatty acid biosynthesis, and linoleic acid metabolism. The downregulation of SLC27A5, CPT1A, NDUFB5, and COX6A1 and upregulation of cytochrome C and ABCC3 expressions also confirmed the impaired fatty acid oxidative catabolism. Altogether, this study revealed that PFE induced hepatotoxicity by damaging mitochondria, reducing fatty acid ß-oxidation levels, and inhibiting fatty acids ingested by bile acids.

Flavonoids dimers from the fruits of Psoralea corylifolia and their cytotoxicity against MCF-7 cells.

Nine new flavonoids dimers, psocorylins R-Z (1-9), were isolated from the fruits of Psoralea corylifolia L. (Psoraleae Fructus), a traditional Chinese medicine. The structures of these compounds were elucidated via multiple spectroscopic techniques and X-ray diffraction. Psocorylins R (1) and S (2) were rare cyclobutane-containing chalcone dimers, and psocorylins T-Z (3-9) were established by CC or COC bond of two flavonoid monomers. The structural-types, flavonoids dimers, were isolated from the plant for the first time, enriching the chemical diversity. The cytotoxicity assay suggested that compounds 1, 2, 4, 5, 6 and 8 exhibited cytotoxic activities against MCF-7 cells. Furthermore, compounds 1 and 8 significantly increased intracellular ROS levels, decreased MMP and induced apoptosis of MCF-7 cells. They markedly upregulated the expression of Bax and cleaved caspase-3, and suppressed Bcl-2 and caspase-3 levels, indicating their mechanism of Bcl-2/Bax/Cleaved caspase-3 pathway. Hence, our findings not only promoted the chemical investigation of Psoraleae Fructus, but also provided potential bioactive natural products for anti-cancer.

Biological Importance, Therapeutic Benefits, and Analytical Aspects of Active Flavonoidal Compounds 'Corylin' from Psoralea corylifolia in the Field of Medicine.

BACKGROUND: Flavonoidal class phytochemicals are the best examples of secondary metabolite found in different natural sources, including 'fruits, grains, vegetables, broccoli, tea, berries, wine, strawberries, apples, grapes, lettuce, and citrus fruit. Natural products are a rich source of flavonoidal compounds present in our diet source. OBJECTIVE: Flavonoidal class chemicals can be subcategorized into chalcones, isoflavone, flavonols, catechin, flavones, flavanones, and anthocyanidin with respect to their basic chemical structures. Psoralea corylifolia L. belongs to the family Fabaceae and is an herbal medicine used in traditional Chinese Medicine for the treatment of inflammatory disorders, bacterial infections, and cancerous disorders. METHODS: In the present work, scientific data have been collected from different databases and analyzed in order to find the therapeutic potential of corylin in medicine. Different scientific databases such as Google, Scopus, PubMed, Science Direct, etc., have been searched to collect the needed scientific information on corylin. Scientific information on corylin has been collected in the present work in order to know the pharmacological activities and medicinal uses of corylin in the scientific fields. However, analytical techniques data of corylin have also been collected and analyzed for standardization of Psoralea corylifolia and other medicinal plants. RESULTS: Scientific data analysis of research works revealed the medicinal importance of Psoralea corylifolia and its important phytoconstituents corylin in medicine. Scientific data analysis revealed that corylin is a flavonoidal class phytochemical found in the nuts of Psoralea corylifolia L. Biological importance of corylin in bone differentiation, bone growth, and osteoporosis has been proven in this scientific research work. The anti-inflammatory, anti-oxidant, and antitumor activity of corylin has been also described in this medical literature. The biological importance of corylin in hyperlipidemia, insulin resistance, atherosclerosis, hepatocellular carcinoma, and neurodisorders have also been presented in this work. CONCLUSION: Scientific data analysis revealed the biological importance and therapeutic potential of corylin in the field of medicine.

Anti-hyperlipidemia on rats in vivo and new compounds from the seeds of Psoralea corylifolia.

In this study, it was confirmed at first time that the crude extracts of Psoralea corylifolia seeds (PCE34) can reduce serum lipids (AST, ALT, TG, TC, LDL, ALP, ACP and LDH), body weight and serum sugar, increase HDL and serum insulin in hyperlipidemic wistar rat induced by high-fat diet in vivo. Furthermore, eight new chalcones 1-8, one new flavanone 12, one new coumarin 14, three new meroterpenes 15-17 and one new bakuchiol 20 together with seven known compounds (9-11, 13, 18-19 and 21) were isolated from the PCE34. Their structures were elucidated based on analyses of their spectroscopic (UV, CD, NMR and HREIMS) data. All the isolates were evaluated for in vitro inhibitory activity against DGAT1/2, PTP1B and α-Glucosidase. Among them, compounds 1-3, 8-11, 14-17, 19 and 20 were found to exhibit selective inhibitory activity on DGAT1 with IC50 values ranging from 66.7 ± 1.2 to 87.2 ± 1.3 µM; 1, 8-12, 14 and 20 has the best inhibit active on PTP1B with IC50 values ranging from 13.8 ± 1.1 to 19.1 ± 1.6 µM; 1-12 and 14 displayed the significant inhibitory activities on α-Glucosidase with IC50 values ranging from 29.1 ± 1.2 to 79.4 ± 1.2 µM.

Exploration of Antimicrobial Ingredients in Psoralea corylifolia L. Seed and Related Mechanism against Methicillin-Resistant Staphylococcus aureus.

With the abuse of antibiotics, bacterial antibiotic resistance is becoming a major public healthcare issue. Natural plants, especially traditional Chinese herbal medicines, which have antibacterial activity, are important sources for discovering potential bacteriostatic agents. This study aimed to develop a fast and reliable method for screening out antimicrobial compounds targeting the MRSA membrane from Psoralea corylifolia Linn. seed. A UPLC-MS/MS method was applied to identify the prenylated flavonoids in major fractions from the extracts of Psoralea corylifolia Linn. seed. The broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of different fractions and compounds. The morphological and ultrastructural changes of MRSA were determined by scanning electron microscopy (SEM). The membrane-targeting mechanism of the active ingredients was explored by membrane integrity assays, membrane fluidity assays, membrane potential assays, ATP, and ROS determination. We identified eight prenylated flavonoids in Psoralea corylifolia Linn. seed. The antibacterial activity and mechanism studies showed that this type of compound has a unique destructive effect on MRSA cell membranes and does not result in drug resistance. The results revealed that prenylated flavonoids in Psoralea corylifolia Linn. seeds are promising candidates for the development of novel antibiotic agents to combat MRSA-associated infections.

Antiobesity Potential of Bioactive Constituents from Dichloromethane Extract of Psoralea corylifolia L. Seeds.

Purpose: Effectively controlling the accumulation of adipose tissue can be a therapeutic strategy for treating obesity, which is a global problem. The present study was designed for comparative assessment of in vitro antiobesity activities of the Psoralea corylifolia-dichloromethane seed extract (DCME) and the isolated phytochemicals, bakuchiol, isopsoralen, and psoralen, through antiadipogenesis and pancreatic lipase (PL) inhibition assays. Material and Methods. In vitro pancreatic lipase activity was determined spectrophotometrically by measuring the hydrolysis of p-nitrophenyl butyrate (p-NPB) to p-nitrophenol at 405 nm, and adipogenesis was assayed in 3 T3-L1 adipocytes (by using Oil Red O staining) using P. corylifolia-dichloromethane seed extract (DCME) and individual compounds, isolated from the extract. Result: Antilipase as well as antiadipogenesis activity was displayed by both the DCME and the compounds. Maximum antilipase property was recorded in DCME (26.02 ± .041%) at 100 µg/ml, while, among the isolated compounds, bakuchiol exhibited a higher activity (24.2 ± 0.037%) at 100 µg/ml concentration, compared to other isolates. DCME was found to exhibit antiadipogenesis property, 75 ± 0.003% lipid accumulation, compared to the control at 100 µg/ml dose. Bakuchiol, isopsoralen, and psoralen inhibited the lipid accumulation in 3T3-L1 preadipocytes, 78.06 ± 0.002%, 80.91 ± 0.004%, and 80.91 ± 0.001%, respectively, lipid accumulation in comparison to control at 25 µM dose. Conclusion: The present study highlights the antiobesity potential of P. corylifolia and its active constituents. Thus, it can be concluded that P. corylifolia has the potential to treat obesity and related diseases; however, further research on dose standardization and clinical trials are required.

[Hypoglycemic mechanism of Psoraleae Fructus and its main chemical constituents].

With the rise of incidence, fatality rate, and number of young cases, diabetes mellitus has been one of the seven major diseases threatening human health. Although many antidiabetic drugs(oral or for injection) are available, the majority have serious side effects during the long-term use. Thus, it is of particularly vital to develop new drugs with low risk and definite effect. Psoraleae Fructus, a traditional medicinal widely used in the folk, has hypoglycemic, anti-osteoporosis, antitumor, estrogen-like, and anti-inflammatory effects. Thus, it has great clinical application potential. Chinese medicine and the active ingredients, characterized by multiple targets, multiple pathways, and multiple effects in the treatment of diabetes mellitus, have distinct advantages in clinical application. However, the safety of Chinese medicine remains to be a challenge, and one of keys is to clarifying the mechanism of a single Chinese medicinal and its active ingredients. With the method of literature research, this study summarized and analyzed the hypoglycemic mechanisms of Psoraleae Fructus and its main active ingredients over the last decade: regulating glucose metabolism, improving insulin resistance, and directly acting on pancreatic ß-cells. The result is expected to serve as a reference for further research on the effects of Psoraleae Fructus and its main chemical constituents in lowering blood glucose and preventing diabetes mellitus and the clinical application.

Constituents promoting osteogenesis from the fruits of Psoralea corylifolia and their structure-activity relationship study.

The mature fruit of Psoralea corylifolia L. is a common traditional Chinese medicine used to tonify the kidney and yang, and as well as to treat osteoporosis. Systematic phytochemical investigations have established the most comprehensive constituent library to date, covering over 180 compounds. In this study, 109 chemical constituents containing 37 undescribed compounds were reported and incorrect structures of four known coumarins were corrected. The structures of these undescribed compounds were elucidated using spectroscopic methods, single-crystal X-ray diffraction, Rh2(OCOCF3)4 and Mo2(OAc)4-induced circular dichroism spectra. To identify potentially active compounds and investigate their structure-activity relationship (SAR), 89 constituents in the library were evaluated for their osteogenic differentiation and mineralisation activities in MC3T3-E1 cells. We found that coumarins, isoflavones, flavonones, and meroterpenoids were the material basis for Psoralea corylifolia-based treatment of osteoporosis, with some compounds exhibiting excellent activities. These compounds function via the estrogen receptor (ER) pathway and were natural phytoestrogen. Further SAR analysis showed that compounds with an intact isopentenyl replacement possessed superior activities, which was explained by their improved affinity with the ER.

Combination of molecular docking and liver transcription sequencing analysis for the evaluation of salt-processed psoraleae fructus-induced hepatotoxicity in ovariectomized mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Salt-processed Psoraleae fructus (SPF) is widely used as a phytoestrogen-like agent in the treatment of osteoporosis. However, SPF-associated hepatotoxicity is a known health hazard. Cholestasis is often associated with SPF-induced hepatotoxicity. Notably, clinical liver injury is a common side effect of SPF in the treatment of osteoporosis; however, the exact mechanism underlying this phenomenon is unclear. AIM OF THE STUDY: To evaluate SPF-induced hepatotoxicity in an ovariectomized murine model of estrogen deficiency and examine the mechanisms underlying this process. MATERIALS AND METHODS: To explore the molecular mechanism of SPF-induced cholestatic liver injury, different concentrations of SPF (5 and 10 g/kg) were intragastrically administered to ovariectomized and non-ovariectomized female ICR mice for 30 days. RESULTS: SPF-treated mice showed noticeably swollen hepatocytes, dilated bile ducts, and elevated levels of serum biochemical markers. Compared to ovariectomized mice, these changes were more prominent in non-ovariectomized mice. According to the sequence data, a total of 6689 mRNAs were identified. Compared with the control group, 1814 differentially expressed mRNAs were identified in the group treated with high SPF doses (SPHD), including 939 upregulated and 875 downregulated mRNAs. Molecular docking and Western blot experiments showed that liver injury was closely related to the estrogen levels. Compared with the negative control group, the expression levels of FXR, Mrp2, CYP7a1, BSEP, SULT1E1, HNF4a, and Nrf2 decreased in the estradiol-treated (E2), low-dose SPF-treated (SPLD), and SPHD groups. Interestingly, the expression levels of FXR, CYP7a1, SULT1E1, and HNF4α were significantly higher in the ovariectomized groups than in the non-ovariectomized groups (#P < 0.05; ###P < 0.001). CONCLUSIONS: Overall, this study demonstrates that SPF downregulates key enzymes involved in cholesterol and bile acid biosyntheses, posing a risk for cholestatic liver injury. SPF also regulates the FXR-SULT1E signaling pathway via HNF4α, which is an important causative factor of cholestasis. Moreover, the severity of liver damage was significantly lower in the ovariectomized groups than in the non-ovariectomized group. These results suggest that the estrogen level is the most critical factor determining liver injury.

Hypoglycemic mechanism of Psoraleae Fructus and its main chemical constituents / 中国中药杂志

With the rise of incidence, fatality rate, and number of young cases, diabetes mellitus has been one of the seven major diseases threatening human health. Although many antidiabetic drugs(oral or for injection) are available, the majority have serious side effects during the long-term use. Thus, it is of particularly vital to develop new drugs with low risk and definite effect. Psoraleae Fructus, a traditional medicinal widely used in the folk, has hypoglycemic, anti-osteoporosis, antitumor, estrogen-like, and anti-inflammatory effects. Thus, it has great clinical application potential. Chinese medicine and the active ingredients, characterized by multiple targets, multiple pathways, and multiple effects in the treatment of diabetes mellitus, have distinct advantages in clinical application. However, the safety of Chinese medicine remains to be a challenge, and one of keys is to clarifying the mechanism of a single Chinese medicinal and its active ingredients. With the method of literature research, this study summarized and analyzed the hypoglycemic mechanisms of Psoraleae Fructus and its main active ingredients over the last decade: regulating glucose metabolism, improving insulin resistance, and directly acting on pancreatic β-cells. The result is expected to serve as a reference for further research on the effects of Psoraleae Fructus and its main chemical constituents in lowering blood glucose and preventing diabetes mellitus and the clinical application.

Identification and pharmacokinetics of bioavailable anti-resorptive phytochemicals after oral administration of Psoralea corylifolia L.

Osteoporosis and resulting bone fractures are the major health issues associated with morbidity in the aging population; however, there is no effective treatment that does not cause severe side effects. In East Asia, dried seeds of Psoralea corylifolia L. (PC) have traditionally been used as an herbal medicine to manage urinary tract, cutaneous, and gastrointestinal disorders, as well as bone health. However, the mechanism of action and active biocomponents of PC are unclear. Here, we adopted a pharmacokinetic (PK) study aiming to identify the bioavailable phytochemicals in aqueous and ethanolic extracts of PC (APC) and (EPC), respectively. In addition, we aimed to determine anti-resorptive constituents of PC, which accounted for its beneficial effects on bone health. To this end, we used ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). A rapid, sensitive, and reliable UPLC-MS/MS method was developed and determined the 17 PC ingredients. In the PK study, nine components (two chalcones, two coumarins, one coumestan, two flavonoids, and two isoflavonoids) were observed between 36 and 48 h after oral administration of APC or EPC. Among the bioavailable ingredients, four PC constituents (psoralidin, isobavachin, corylifol A, and neobavaisoflavone) inhibited M-CSF-and RANKL-induced osteoclast differentiation in bone marrow-derived macrophages. In addition, two chalcones and two isoflavonoids markedly inhibited cathepsin K activity, and their binding modes to cathepsin K were determined by molecular docking. In summary, our data suggest that bioavailable multicomponents of PC could contribute to the management of bone health.

The benzofuran glycosides from the fruits of Psoralea corylifolia L.

Six new glucosides of benzofuran (1-6), together with three known glucosides of benzofuran (8, 9, 14), nine flavonoids (12, 13, 15, 18, 19, 20, 21, 22 and 24), three coumarins (16, 17, 23) and four other-typic compounds (7, 10, 11 and 25) were isolated from the fruits of Psoralia corylifolia L. Their structures were elucidated by extensive spectroscopic methods. The biosynthesis pathway of benzofuran system was discussed. Besides, all isolated compounds and additional ring-opening derivatives of psoralen/isopsoralen (P-1, P-2, IP-1 and IP-2) were assayed for inhibition of nitric oxide (NO) production on lipopolysaccharides-induced RAW 264.7 macrophage cells. The results of the assay showed that the glycosides showed weaker or no effects, while most isolated non-glycoside compounds showed moderate or high activities. And the structure-activity relationships of non-glycoside compounds were discussed.

Neobavaisoflavone May Modulate the Activity of Topoisomerase Inhibitors towards U-87 MG Cells: An In Vitro Study.

Despite many advances in therapy, glioblastoma (GB) is still characterized by its poor prognosis. The main reason for this is unsuccessful treatment, which slightly extends the duration of remission; thus, new regimens are needed. One of many types of chemotherapeutics that are being investigated in this field is topoisomerase inhibitors, mainly in combination therapy with other drugs. On the other hand, the search for new anti-cancer substances continues. Neobavaisoflavone (NBIF) is a natural compound isolated from Psoralea corylifolia L., which possesses anti-oxidant, anti-inflammatory, and anti-cancer properties. The aim of this study was to evaluate the effect of NBIF in human U-87 MG glioblastoma cells in comparison to normal human NHA astrocytes, and to examine if it influences the activity of irinotecan, etoposide, and doxorubicin in this in vitro model. We demonstrated that NBIF decreases U-87 MG cells viability in a dose-dependent manner. Furthermore, we found that it inhibits cell growth and causes glutathione (GSH) depletion more intensely in U-87 MG cells than in astrocytes. This study also provides, for the first time, evidence of the potentialization of the doxorubicin effect by NBIF, which was shown by the reduction in the viability in U-87 MG cells.

Isobavachalcone as an Active Membrane Perturbing Agent and Inhibitor of ABCB1 Multidrug Transporter.

Isobavachalcone (IBC) is an active substance from the medicinal plant Psoralea corylifolia. This prenylated chalcone was reported to possess antioxidative, anti-inflammatory, antibacterial, and anticancer activities. Multidrug resistance (MDR) associated with the over-expression of the transporters of vast substrate specificity such as ABCB1 (P-glycoprotein) belongs to the main causes of cancer chemotherapy failure. The cytotoxic, MDR reversing, and ABCB1-inhibiting potency of isobavachalcone was studied in two cellular models: human colorectal adenocarcinoma HT29 cell line and its resistant counterpart HT29/Dx in which doxorubicin resistance was induced by prolonged drug treatment, and the variant of MDCK cells transfected with the human gene encoding ABCB1. Because MDR modulators are frequently membrane-active substances, the interaction of isobavachalcone with model phosphatidylcholine bilayers was studied by means of differential scanning calorimetry. Molecular modeling was employed to characterize the process of membrane permeation by isobavachalcone. IBC interacted with ABCB1 transporter, being a substrate and/or competitive inhibitor of ABCB1. Moreover, IBC intercalated into model membranes, significantly affecting the parameters of their main phospholipid phase transition. It was concluded that isobavachalcone interfered both with the lipid phase of cellular membrane and with ABCB1 transporter, and for this reason, its activity in MDR cancer cells was presumptively beneficial.

Isobavachalcone ameliorates cognitive deficits, and Aß and tau pathologies in triple-transgenic mice with Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects 50 million people worldwide. The current medicines have modest benefits in preventing or curing AD. Thus, it is urgent to discover drugs with the potential to change the progression of the disease. The primary clinical symptoms are memory loss and anxiety, while the critical pathological characteristics are Aß plaques and hyperphosphorylated tau tangles. In this study, isobavachalcone (ISO), isolated from Psoralea corylifolia, was administered to 3×Tg-AD mice. It has been shown that this compound could significantly improve anxiety, memory and recognition deficits in the AD mice, attenuate the accumulation of Aß oligomers, reduce the hyperphosphorylation of tau, and prevent the production of tau filaments. The metabolomic analysis implicates that the most probable pathways affected by ISO were bile secretion, tyrosine metabolism, and purine metabolism. In summary, ISO possesses the potential for further development as a drug candidate for AD.