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.

Bavachin alleviates diabetic nephropathy in db/db mice by inhibition of oxidative stress and improvement of mitochondria function.

Diabetic nephropathy (DN) is a major complication of diabetes mellitus. Psoralea corylifolia L. seed (PCS) is a traditional medicine effective against various diseases. In this study, we aimed to investigate the effect of bavachin, the major active component of PCS, on DN in db/db mice. Bavachin (10 mg/kg/day) was administered orally to 12-week-old male db/db mice for 6 wk. For in vitro experiments, SV40 MES13 cells were treated with bavachin in the presence of 25 mM glucose. Food and water intake and urine mass were significantly increased in db/db mice compared to wild-type CON mice, but bavachin administration significantly reduced these increases. Urinary microalbumin, blood urea nitrogen, and creatinine clearance which were significantly increased in db/db mice, were also decreased by bavachin administration. Glomerular area and collagen deposition in the kidney were significantly decreased in db/db mice following bavachin administration. Increased renal levels of fibrotic factors, fibronectin, COL1A1, and α-SMA, were reduced following bavachin administration. Protein expressions of antioxidant enzymes, namely SOD2, catalase, and HO-1, and mitochondrial function-related factors, namely SIRT1, PGC1α, Nrf1, and mtTFA, were reduced in the kidney tissues of db/db mice compared to wild-type CON mice, and bavachin administration upregulated these protein expressions. In vitro studies also showed that bavachin decreases mitochondria ROS production, increases the expression of PGC-1α and SIRT1, and decreases the expression of α-SMA in high glucose-treated SV40 MES13 cells. Based on these results, bavachin improved DN by inhibiting oxidative stress and enhancing mitochondrial function.

Psoralea corylifolia L.: a comprehensive review of its botany, traditional uses, phytochemistry, pharmacology, toxicology, quality control and pharmacokinetics.

Psoralea corylifolia L. (PCL), referred to as "Bu-gu-zhi" in Chinese, has great medicinal values since ancient times. PCL is the dried ripe fruit of Psoralea corylifolia L., which has been widely used in traditional Chinese medicine (TCM) for the treatment of kidney-yang deficiency, enuresis and urinary frequency, chills and pain of the waist and knees, dawn diarrhea and vitiligo. In this paper, a systematic of the botany, traditional uses, phytochemistry, pharmacology, toxicology, quality control and pharmacokinetics of PCL was presented, along with future research directions. According to the results, PCL contains approximately 163 chemical components, including coumarins, flavonoids, monoterpene phenols, benzofurans, glycosides, lipids, fatty acids, and volatile oils. PCL and its active ingredients have a variety of pharmacological activities, such as anti-inflammatory, antibacterial, antiviral, antioxidant, antitumor, antiosteoporosis, cardioprotective, neuroprotective, and immunomodulatory. Further study of quality control standards and potential mechanisms of PCL is also needed. In addition, more toxicological studies will also contribute to the progress of clinical trials.

A systematic review on the safety of Psoraleae Fructus: potential risks, toxic characteristics, underlying mechanisms and detoxification methods.

Psoraleae Fructus (PF) is an important traditional herbal medicine with a long history of clinical application. It is widely used to treat various diseases, such as osteoporosis, leucoderma and diarrhea. As a traditional nontoxic herb, it has aroused worldwide concern about the potential risks due to increasing adverse reaction events. This article reviews the botany, ancient records of medical uses, adverse reactions, toxicological research advance and detoxification methods of PF. According to clinical studies, liver injury is the most predominant in PF-related adverse reactions. The underlying mechanisms include bile acid metabolism and transport disorders, oxidative stress, mitochondrial damage, inhibition of liver cell regeneration and inflammatory reactions. Furthermore, the potential toxins of PF are summarized. Traditional methods of processing and compatibility will provide reference for reducing the toxicity of PF, which requires further research. In sum, this work systematically summarizes the reserach progress on the safety of PF, which will provide comprehensive insights into the toxicity of PF and facilitate its safe use and future development.

Odontogenic Differentiation-Induced Tooth Regeneration by Psoralea corylifolia L.

Psoralea corylifolia L. (P. corylifolia) has been used as an oriental phytomedicine to treat coldness of hands and feet in bone marrow injury. Hydroxyapatite is usually used for tooth regeneration. In this study, the role of P. corylifolia and bakuchiol, a compound originated from P. corylifolia as differentiation-inducing substances for tooth regeneration, was determined by monitoring odontogenic differentiation in human dental pulp stem cells (hDPSCs). We confirmed that P. corylifolia extracts and bakuchiol increased the odontogenic differentiation of hDPSCs. In addition, the expression of the odontogenic differentiation marker genes alkaline phosphatase (APL), Runt-related transcription factor 2 (RUNX-2), osteocalcin (OC), and dentin matrix acidic phosphoprotein-1 (DMP-1) was proved by real-time polymerase chain reaction, and protein expression of dentin matrix acidic phosphoprotein-1 (DMP-1) and dentin sialophosphoprotein (DSPP) was proved by western blotting. Further, by confirming the increase in small mothers against decapentaplegia (SMAD) 1/5/8 phosphorylation, the SMAD signaling pathway was found to increase the differentiation of odontoblasts. This study confirmed that P. corylifolia L. extracts and bakuchiol alone promote odontogenic differentiation in hDPSCs. These results suggest that bakuchiol from P. corylifolia is responsible for odontogenic differentiation, and they encourage future in vivo studies on dentin regeneration.

Psoralea corylifolia L. seed extract attenuates dexamethasone-induced muscle atrophy in mice by inhibition of oxidative stress and inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: The seeds of Psoralea corylifolia (PCS), also called "Boh-Gol-Zhee" in Korean, have been used in traditional medicine. PCS is effective for the treatment of vitiligo, cancer, inflammatory diseases, neurodegenerative diseases, kidney diseases, and musculoskeletal diseases. AIM OF THE STUDY: In this study, we validated the beneficial effects of PCS extract on dexamethasone (DEX)-induced muscle atrophy in mice. MATERIALS AND METHODS: DEX (20 mg/kg/day, 10 days) was intraperitoneally injected into C57BL/6 male mice to induce muscular atrophy. Oral administration of PCS extract (200 or 500 mg/kg/day) was started 2 days before DEX injection and continued for 12 days. RESULTS: PCS extract inhibited DEX-induced decrease in body and muscle weight, grip strength, and cross-sectional area of the tibialis anterior. PCS extract significantly increased the mRNA and protein expression levels of myosin heavy chain 1, 2A, and 2X in DEX-administered mice. DEX administration significantly increased the levels of muscle atrophy factors atrogin-1, muscle RING-finger protein-1, and myostatin, which were inhibited by the PCS extract. Additionally, PCS extract increased the expression of muscle regeneration factors, such as myoblast determination protein 1, myogenin, and embryonic myosin heavy chain, and muscle synthesis markers, such as protein kinase B and mammalian target of rapamycin signaling molecules. PCS extract also significantly decreased the DEX-induced production of 4-hydroxynonenal, an oxidative stress marker. Furthermore, PCS extract recovered superoxide dismutase 2, glutathione peroxidase, and catalase activities, which were significantly reduced by DEX administration. Moreover, DEX-induced activation of nuclear factor kappa-light-chain-enhancer of activated B cells and expression of cytokines, such as tumor necrosis factor α and monocyte chemoattractant protein-1, significantly decreased after PCS extract administration. CONCLUSIONS: Here, we demonstrated that PCS extract administration protected against DEX-induced muscle atrophy. This beneficial effect was mediated by suppressing the expression of muscle degradation factors and increasing the expression of muscle regeneration and synthesis factors. This effect was probably due to the inhibition of oxidative stress and inflammation. These results highlight the potential of PCS extract as a protective and therapeutic agent against muscle dysfunction and atrophy.

Flavonoids extract from the seeds of Psoralea corylifolia L. (PFE) alleviates atherosclerosis in high-fat diet-induced LDLR-/- mice.

BACKGROUND: The seeds of Psoralea corylifolia L., a traditional medicine popular used in China and India, have been recommended in the treatment of leucoderma, psoriasis, osteoporosis, and gynecological bleeding. Our previous studies have found that flavonoid extract from the seeds of Psoralea corylifolia L. could activate fat browning and correct the disorder of glucose and lipid metabolism in obese mice. PURPOSE: The present study aimed to investigate the anti-atherosclerosis of flavonoids extract from the seeds of Psoralea corylifolia L. METHODS: Leukocyte adhesion assay, RT-PCR, Western blot analysis, and immunofluorescent assay were carried out in ox-LDL induced endothelium injury and foam cells formation in vitro. Flavonoids from the seeds of P. corylifolia L. (PFE) was administrated 150 and 300 mg/kg/day in HFD-induced LDLR-/- mice for 12 weeks. RESULTS: Flavonoids from the seeds of P. corylifolia L. (PFE) could prevent leukocyte adhesion to the endothelium by inhibiting mRNA and protein expression of these adhesion molecules (VCAM-1, ICAM-1, and E-selectin). PFE could also prevent ox-LDL stimulated inflammation in HUVECs by inhibiting the NF-κB pathway. In addition, PFE significantly ameliorated ox-LDL induced macrophages-oriented foam cells formation through inducing cholesterol efflux via PPARγ-ABCA1/ABCG1. In HFD-induced LDLR-/- mice, PFE reversed the serum profile and circulated inflammation level. Meanwhile, PFE could remarkably alleviate atherosclerotic lesion sizes and intraplaque macrophage infiltration in aortic roots. CONCLUSION: Flavonoids from the seeds of P. corylifolia L. could alleviate atherosclerosis by preventing endothelium injury, attenuating vascular inflammation, and alleviating the formation of foam cells.

Effects of Psoralea corylifolia L. seed extract on AGEs-induced cell proliferation and fibrotic factor expression in mesangial cells.

Diabetic nephropathy is a microvascular complication of diabetes that is characterized by mesangial expansion and thickening of the glomerular basement membrane. The production of advanced glycation end products (AGEs) increases in diabetic patients. Activation of the receptor of AGE (RAGE) signaling pathway induces mesangial expansion via the reactive oxygen species (ROS)-mediated production of pro-inflammatory and extracellular matrix molecules. The Psoralea corylifolia L. seed (PCS) is a widely used herbal medicine with various biological activities. The current study investigated the effect of PCS extract on mesangial cell proliferation and the RAGE signaling pathway in SV40 MES 13 cells. SV40 MES 13 cells were harvested after treatment with various concentrations of PCS extract at 10 µg/ml AGEs for 24 h. The results revealed that the PCS extract inhibited AGEs-induced mesangial cell proliferation and cyclin protein expression in a concentration-dependent manner. In addition, the AGEs-induced expression of fibrotic factors, such as transforming growth factor ß, fibronectin and collagen, was reduced in mesangial cells after exposure to the PCS extract. The PCS extract also reduced RAGE expression and inhibited the expression of its downstream signaling pathways, such as NADPH oxidase, intracellular ROS and phospho-NF-κB. In conclusion, the data suggested that the PCS extract attenuated AGEs-induced renal mesangial cell proliferation and fibrosis via the suppression of oxidative stress and the downregulation of inflammatory and fibrotic factor expression.

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.

Psoralea corylifolia L. Ameliorates Collagen-Induced Arthritis by Reducing Proinflammatory Cytokines and Upregulating Myeloid-Derived Suppressor Cells.

Background: Rheumatoid arthritis is an autoimmune disease that may lead to severe complications. The fruit of Psoralea corylifolia L. (PCL) is widely used in traditional Chinese medicine as a well-known herbal treatment for orthopedic diseases. However, there is a lack of studies of its effects on rheumatoid arthritis. The purpose of the study was to investigate the effects and mechanisms of concentrated herbal granules of PCL on rheumatoid arthritis to provide some insights for future development of new drug for the treatment of rheumatoid arthritis. Methods: We used collagen-induced arthritis (CIA) DBA/1J mice as an experimental model to mimic human rheumatoid arthritis. The mice were immunized with collagen on days 0 and 21 and then orally administered 200 mg/kg/day PCL on days 22-49. Starch was used as a control. The mice were sacrificed on day 50. Clinical phenotypes, joint histopathology, and immunological profiles were measured. Results: Compared to the CIA or CIA + Starch group, the CIA + PCL group had significantly ameliorated clinical severity and decreased paw swelling. Histopathological analysis of the hind paws showed that PCL mitigated the erosion of cartilage and the proliferation of synovial tissues. There were significant differences in the levels of TNF-α, IL-6 and IL-17A, as measured by ELISA, and the percentages of CD4 + IL-17A+, CD4 + TNF-α+, CD4 + IFN-γ+ T cells. Furthermore, we also found that in mice treated with CIA + PCL, the percentage and number of bone marrow-derived suppressor cells (MDSCs; Gr1+ CD11b+) increased significantly. Conclusions: We provided evidence for the potential antiarthritic effects of PCL through the inhibition of inflammation and increase of MDSCs. These findings indicate that PCL may be a promising therapeutic herb for the treatment of rheumatoid arthritis.

Psoralea corylifolia L. extract ameliorates benign prostatic hyperplasia by regulating prostate cell proliferation and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoralea corylifolia L. seed (PCL), commonly known as "Poguzhi" or "BuguZhi", has been widely used to treat kidney yang deficiency in traditional Chinese medicine (TCM) where tonifying the yang deficiency is a representative understanding for treatment of hormonal deficiency disorders such as enuresis, oliguria, and prostatic diseases. Although PCL has been commonly used to treat problems of the urinary system, its efficacy against benign prostatic hyperplasia (BPH) has not yet been reported. AIM OF THE STUDY: In the present study, we aimed to assess the in vitro and in vivo efficacy of PCL against BPH, a condition which negatively impacts quality of life in men. MATERIALS AND METHODS: Normal human prostate cell lines, RWPE-1 and WPMY-1 cells, were stimulated with 10 nM dihydrotestosterone (DHT) to establish an in vitro BPH model. Subsequently, cells were treated with 100 or 200 µg/ml PCL, which inhibited cell proliferation without cytotoxicity, to evaluate the anti-BPH effect of PCL. Eight-week-old male Wistar rats were castrated, except for those in the control group (Con), and BPH was induced by subcutaneous injection of 10 mg/kg testosterone propionate (TP). Concurrent with daily TP injections, 5 mg/kg of finasteride (Fina) and 50 or 100 mg/kg PCL were orally administrated daily for four weeks, excluding the weekends. RESULTS: In DHT-stimulated RWPE-1 and WPMY-1 cells, expression of androgen receptor (AR) androgen signaling-related markers such as 5α-reductase 2 (5AR2), AR, and prostate-specific antigen (PSA) was upregulated, whereas 100 or 200 µg/ml of PCL treatment downregulated these markers. Furthermore, PCL significantly reduced the mRNA expression of anti-apoptotic genes and increased the mRNA expression of pro-apoptotic gene. In vivo, administration of PCL reduced prostate size and weight in TP-induced BPH rats. Moreover, histological alterations in epithelium thickness were significantly restored by the administration of PCL. Immunohistochemical analysis revealed increased expression of AR and proliferating cell nuclear antigen (PCNA) in TP-induced BPH prostates; these changes were suppressed by administration of 50 or 100 mg/kg PCL. CONCLUSIONS: We demonstrated the effect of PCL against BPH, mediated by the regulation of prostate cell proliferation and apoptosis, in DHT-stimulated normal human prostate cell lines and TP-induced BPH rats. These findings suggest that PCL could be a potential therapeutic agent against BPH.

Psoralea corylifolia L. extract ameliorates nonalcoholic fatty liver disease in free-fatty-acid-incubated HEPG2 cells and in high-fat diet-fed mice.

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that is closely related to metabolic syndrome. We investigated the effect of a Psoralea corylifolia L. (PC) seeds extract (PCE) on NAFLD. PC seeds were extracted using different ethanol concentrations to produce five extracts, and the 70% ethanol PCE, which had the highest phenolic content, was used in subsequent in vitro and in vivo experiments. The inhibitory effect of PCE on hepatic steatosis was estimated using HepG2 cells treated with oleic acid (OA). In addition, an in vivo NAFLD model was established using high-fat diet (HFD)-induced obese C57BL/6 mice. Obesity was induced in mice over 14 weeks. PCE (100 or 200 mg/kg/day) was administered orally to mice after 8 weeks of the 14-week treatment period for 6 weeks. PCE suppressed lipid accumulation in OA-treated HepG2 cells. PCE ameliorated the antioxidant activity suppressions induced by the HFD. In addition, both PCE100 and PCE200 groups reduced lipid accumulation and the expression levels of inflammatory proteins as compared with HFD group. PCE administration significantly attenuated hepatic steatosis in liver tissues by decreasing the expression of lipogenic protein sterol regulatory element binding protein 1-c (SREBP-1c) and its downstream protein fatty acid synthase (FAS) in HFD-fed mice and in OA-treated HepG2 cells. Furthermore, PCE administration increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase. These results suggest that PCE could be used as a functional material to prevent or ameliorate NAFLD by inhibiting lipid accumulation in liver. PRACTICAL APPLICATION: Psoralea corylifolia L. is rich in polyphenol and other phytochemicals. In this study, we identified the beneficial effects of Psoralea corylifolia L. extract on hepatic steatosis in oleic-acid-induced HepG2 cells and high-fat diet-fed mice. The result of this study will provide the evidence that a Psoralea corylifolia L. extract has potential use as a functional material for the prevention and amelioration of nonalcoholic fatty liver disease.

Quality Control of Psoralea corylifolia L. Based on High-Speed Countercurrent Chromatographic Fingerprinting.

Traditional Chinese medicine (TCM)has played an important role in promoting the health of Chinese people. The TCM Psoralea corylifolia L. has been used in the treatment of various kinds of diseases including enuresis, vitiligo, and calvities. However, therapeutic effects of P. corylifolia L. have often influenced by the quality of plants. So, it is very important to control the quality of P. corylifolia L. In this study, analytical high-speed countercurrent chromatography (HSCCC) was successfully used to fingerprint P. corylifolia L. Samples of P. corylifolia L. were extracted by ultrasonic extraction. n-hexane-ethyl acetate-methanol-water at a ratio of 5:5.5:6.5:5 (v/v) was selected as a two-phase solvent system and the condition of HSCCC were optimized in order to good separation. And the method of HSCCC was verified (reproducibility, precision, and stability). HSCCC chromatograms exhibited six common peaks, which were selected as indicator compounds for the quality control of P. corylifolia L. Within 20 types of medicinal materials, chemical components are similar, but the levels of components are quite different in HSCCC fingerprint. The present results demonstrate that the HSCCC method provides a reliable basis for the quality control of P. corylifolia L. and can also be applied to confirm the authenticity of plant materials.

Transformation of Psoralen and Isopsoralen by Human Intestinal Microbial In Vitro, and the Biological Activities of Its Metabolites.

Psoralen (P) and isopsoralen (IP) are the main active ingredients in the dried fruit of Psoralen corylifolia L. (PC), with a wide range of pharmacology activities. The intestinal bacteria biotransformation plays a central role in the metabolism of the complex ingredients in traditional Chinese medicine (TCM). Our study aimed to investigated the metabolic profile of P and IP in the intestinal condition, co-cultured with human fecal bacteria anaerobically. Four bio-transforming products were obtained, including 6,7-furano-hydrocoumaric acid (P-1) and 6,7-furano-hydro- coumaric acid methyl ester (P-2), which transformed from P, and 5,6-furano-hydrocoumaric acid (IP-1) and 5,6-furano-hydrocoumaric acid methyl ester (IP-2), which were transformed from IP. It is worth mentioning that IP-2 is a new compound that has not been published. Their structures were analyzed based on their spectroscopic data. Moreover, a highly sensitive ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was used to characterize the metabolic pathways of P, IP, and their bio-transforming products in the reaction samples. In addition, the dampening effects against the oxidative stress of P, IP, and their bio-transforming products by human intestinal flora were estimated in vitro via the human colorectal cells (HCT116) and heterogeneous human epithelial colorectal adenocarcinoma cells (Caco-2) cell lines. The results showed that the metabolites have stronger activity than P and IP, which possibly provides a basis for elucidating the treating mechanisms of PC extract against inflammatory bowel disease.

Two Novel Polysaccharides in Psoralea corylifolia L and anti-A549 Lung Cancer Cells Activity In Vitro.

Two novel water soluble heteroglycan (PCp-I and PCp-II) with anti-A549 lung cancer cells activity were isolated from Psoralea corylifolia L. Their average molecular weights were 2.721 × 104 and 2.850 × 104. PCp-I and PCp-II had the same monosaccharide composition, but their molar ratios were different. Based on methylation and NMR spectroscopy, the part structure of PCp-I was identified. The results of scanning electron microscope (SEM) showed that PCp-I had an irregular porous structure and PCp-II was flaky and irregularly curved. The results of thermogravimetry-differential scanning calorimetry (TG-DSC) showed that PCp-I and PCp-II had good thermal stability. Furthermore, PCp-I and PCp-II exhibited significant anti-A549 lung cancer cells activity (IC50 = 64.84 and 126.30 µM) in vitro.

Prenylated flavonoid-standardized extract from seeds of Psoralea corylifolia L. activated fat browning in high-fat diet-induced obese mice.

We investigated the effects of the prenylated flavonoid-standardized extract (PFE) from the seeds of Psoralea corylifolia L. on countering obesity, which increases energy expenditure and stimulates thermogenesis in subcutaneous white adipose tissue (sWAT) and brown adipose tissue (BAT). For 12 weeks, C57BL/6 mice were fed a controlled high-fat diet (HFD) or HFDs with 0.2% or 0.5% w/w PFE. In vitro, the differentiation of 3 T3-L1 cells was used to elicit thermogenesis in the presence of PFE. PFE obviously reduced body weight and fat mass in a dose-dependent manner, increased energy expenditure, improved insulin sensitivity, and prevented hepatic steatosis by increasing lipid oxidation and secretion in HFD-fed mice. Moreover, PFE induced clear browning in sWAT, significantly increased phosphorylation of AMPKα1/2 and p38, increased BAT activity and the differentiation of 3 T3-L1 by increasing the expression of uncoupling protein 1 and other thermogenic genes. Our study showed that PFE prevented obesity by increasing browning and activating thermogenic genes in sWAT and BAT, improving glucose homeostasis, and protecting hepatic steatosis.

HBX-6, Standardized Cornus officinalis and Psoralea corylifolia L. Extracts, Suppresses Benign Prostate Hyperplasia by Attenuating E2F1 Activation.

BACKGROUND: The aim of this study was to simplify and identify the contents of the herbal formula, HBX-5. This study was carried out to evaluate the therapeutic effects of HBX-6 in a mouse model of benign prostatic hyperplasia (BPH). Based on in vitro, we selected a candidate, reconstituted an experimental agent and investigated the effects on testosterone-induced BPH rats. Cell viability was determined by MTT assay in RWPE-1 and WPMY-1 cells. The expression of androgen receptor (AR) was measured in dihydrotestosterone-stimulated RWPE-1 and WPMY-1 cells. BPH was induced in mice by a subcutaneous injection of testosterone propionate for four weeks. Animals were divided into six groups: Group 1, control mice; Group 2, mice with BPH; Group 3, mice with BPH treated with finasteride; Group 4, mice with BPH treated with 200 mg/kg HBX-5; Group 5, mice with BPH treated with 100 mg/kg HBX-6; and Group 6, mice with BPH treated with 200 mg/kg HBX-6. Changes in prostate weight were measured after treatments, and the thickness of the epithelium was evaluated. The expression levels of proteins associated with prostatic cell proliferation and cell cycle-related proteins were determined. Based on previous reports and in vitro results, we selected Cornus officinalis and Psoralea corylifolia among HBX-5 components and reconstituted the experimental agent, and named it HBX-6. The result represented a new herbal formula, HBX-6 that suppressed the pathological alterations in BPH and showed a marked reduction in proliferation-related protein expression compared to mice with BPH. Our results indicate that HBX-6 has a better therapeutic effect in the BPH murine model than those of HBX-5 and finasteride, suggesting the role of HBX-6 as a new BPH remedial agent.

Highly Efficient Screening Anti-osteoporosis Activity Components of Psoralea corylifolia L. Based on Zebrafish Model Combined with HPLC Capture / 中国药学杂志

OBJECTIVE: To investigate active constituents of Psoralea corylifolia L. against osteoporosis using chromatography capture combined with zebrafish model. METHODS: High performance liquid chromatography (HPLC) was used for analysis and capture components of Psoralea corylifolia L. including coumarins, flavonoids and bakuchiol, and which anti-osteoporosis activity was evaluated by zebrafish model induced by 25 μmol•L-1 prednisolone, 25 μmol•L-1 prednisolone as model group, and 0.4% DMSO medium as vehicle group. Bone of juvenile zebrafish cultured to 8 dpf (day post fertilization) were stained with alizarin red, and inspected with optical microscope, and bone staining area was quantitative analyzed using image software. RESULTS: The RESULTS showed that coumarins and flavonoids can significantly resist bone loss of zebrafish by prednisolone, while the action of bakuchiol was relative weak with heavy toxicity, high dose of bakuchiol led to zebrafish larval death. CONCLUSION HPLC can system analysis and capture ingredients/components of Psoralea corylifolia L., and zebrafish osteoporosis model can evaluate activity of micro ingredients/components, combination of these two METHODS: can broke through double bottleneck of complex components capture and activity evaluation in vivo. It is expected to realize efficient anti-osteoporosis screening of the whole component of Chinese herbal medicine.

Psoralea corylifolia L. Seed Extract Attenuates Diabetic Nephropathy by Inhibiting Renal Fibrosis and Apoptosis in Streptozotocin-Induced Diabetic Mice.

The Psoralea corylifolia L. seed (PCS) is a widely used herbal medicine, but its possible effect against diabetic nephropathy has not been studied. To investigate the anti-nephropathic effect of PCS extracts, we performed experiments using a diabetic mouse model and high glucose-treated mesangial cells. Streptozotocin (STZ)-induced diabetic mice were orally administered PCS extract for 8 weeks (500 mg/kg/day). Increased creatinine clearance, urine volume, urine microalbumin, and mesangial expansion were observed in STZ-induced diabetic mice; these were significantly reduced by PCS extract administration. PCS extract significantly reduced fibrosis in the kidney tissue of diabetic mice as evidenced by decreased mRNA expression of collagen type IV-α2, fibronectin, PAI-1, and TGF-ß1. In addition, cleaved PARP, an apoptotic gene, was upregulated in the diabetic nephropathy mice, and this was ameliorated after PCS extract treatment. Treatment of high glucose-treated MES-13 cells with isopsoralen and psoralen, major components of PCS extract, also decreased the expression of fibrosis and apoptosis marker genes and increased cell viability. PCS extract exerts protective effects against STZ-induced diabetic nephropathy via anti-fibrotic and anti-apoptotic effects. PCS extract might be a potential pharmacological agent to protect against high glucose-induced renal damage under diabetic conditions.

The Chemical Constituents and Bioactivities of Psoralea corylifolia Linn.: A Review.

Psoralea corylifolia Linn. (P. corylifolia) is an important medicinal plant with thousands of years of clinical application. It has 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. Phytochemical studies indicated that coumarins, flavonoids, and meroterpenes are the main components of P. corylifolia, and most of these components are present in the seeds or fruits. The extracts and active components of P. corylifolia demonstrated multiple biological activities, including estrogenic, antitumor, anti-oxidant, antimicrobial, antidepressant, anti-inflammatory, osteoblastic, and hepatoprotective activities. This paper systematically summarized literatures on the chemical constituents and biological activities of P. corylifolia, which provided useful information for the further research and development toward this potent medicinal plant.