PMID: 

Mediators Inflamm. 2015 ;2015:409596. Epub 2015 Dec 14. PMID: 26788020

Abstract Title: 

Lactoferrin: A Modulator for Immunity against Tuberculosis Related Granulomatous Pathology.

Abstract: 

There is great need for a therapeutic that would limit tuberculosis related pathology and thus curtail spread of disease between individuals by establishing a"firebreak"to slow transmission. A promising avenue to increase current therapeutic efficacy may be through incorporation of adjunct components that slow or stop development of aggressive destructive pulmonary pathology. Lactoferrin, an iron-binding glycoprotein found in mucosal secretions and granules of neutrophils, is just such a potential adjunct therapeutic agent. The focus of this review is to explore the utility of lactoferrin to serve as a therapeutic tool to investigate"disruption"of the mycobacterial granuloma. Proposed concepts for mechanisms underlying lactoferrin efficacy to control immunopathology are supported by data generated based on in vivo models using nonpathogenic trehalose 6,6'-dimycolate (TDM, cord factor).

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PMID: 

Molecules. 2018 Mar 8 ;23(3). Epub 2018 Mar 8. PMID: 29518051

Abstract Title: 

Multi-Target Anti-Alzheimer Activities of Four Prenylated Compounds from Psoralea Fructus.

Abstract: 

Alzheimer's disease (AD) is an age-related neurodegenerative disease that is mediated by multiple signaling pathways. In recent years, the components of(PF) have demonstrated some anti-Alzheimer effects both in vitro and in vivo. To further reveal the active compounds of PF and their mechanisms regulating key targets of AD, in this study, we identified four prenylated compounds from the 70% ethanolic aqueous extract of PF, namely bavachin, bavachinin, bavachalcone, and isobavachalcone. Multi-target bioactivity analysis showed that these compounds could differentially inhibit neuroinflammation, oxidative damage, and key AD-related protein targets, such as amyloidβ-peptide 42, β-secretase, glycogen synthase kinase 3β, and acetylcholinesterase. These compounds may generate beneficial effects in AD prevention and treatment.

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PMID: 

J Neuroinflammation. 2020 Feb 17 ;17(1):61. Epub 2020 Feb 17. PMID: 32066466

Abstract Title: 

Zerumbone ameliorates behavioral impairments and neuropathology in transgenic APP/PS1 mice by suppressing MAPK signaling.

Abstract: 

BACKGROUND: Alzheimer's disease (AD) is a major clinical problem, but there is a distinct lack of effective therapeutic drugs for this disease. We investigated the potential therapeutic effects of zerumbone, a subtropical ginger sesquiterpene, in transgenic APP/PS1 mice, rodent models of AD which exhibit cerebral amyloidosis and neuroinflammation.METHODS: The N9 microglial cell line and primary microglial cells were cultured to investigate the effects of zerumbone on microglia. APP/PS1 mice were treated with zerumbone, and non-cognitive and cognitive behavioral impairments were assessed and compared between the treatment and control groups. The animals were then sacrificed, and tissues were collected for further analysis. The potential therapeutic mechanism of zerumbone and the signaling pathways involved were also investigated by RT-PCR, western blot, nitric oxide detection, enzyme-linked immunosorbent assay, immunohistochemistry, immunofluorescence, and flow cytometry analysis.RESULTS: Zerumbone suppressed the expression of pro-inflammatory cytokines and induced a switch in microglial phenotype from the classic inflammatory phenotype to the alternative anti-inflammatory phenotype by inhibiting the mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B signaling pathway in vitro. After a treatment period of 20 days, zerumbone significantly ameliorated deficits in both non-cognitive and cognitive behaviors in transgenic APP/PS1 mice. Zerumbone significantly reduced β-amyloid deposition and attenuated pro-inflammatory microglial activation in the cortex and hippocampus. Interestingly, zerumbone significantly increased the proportion of anti-inflammatory microglia among all activated microglia, potentially contributing to reduced β-amyloid deposition by enhancing phagocytosis. Meanwhile, zerumbone also reduced the expression of key molecules of the MAPK pathway, such as p38 and extracellular signal-regulated kinase.CONCLUSIONS: Overall, zerumbone effectively ameliorated behavioral impairments, attenuated neuroinflammation, and reducedβ-amyloid deposition in transgenic APP/PS1 mice. Zerumbone exhibited substantial anti-inflammatory activity in microglial cells and induced a phenotypic switch in microglia from the pro-inflammatory phenotype to the anti-inflammatory phenotype by inhibiting the MAPK signaling pathway, which may play an important role in its neuroprotective effects. Our results suggest that zerumbone is a potential therapeutic agent for human neuroinflammatory and neurodegenerative diseases, in particular AD.

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PMID: 

Oncotarget. 2016 Mar 22 ;7(12):14616-27. PMID: 26910280

Abstract Title: 

Bakuchiol suppresses proliferation of skin cancer cells by directly targeting Hck, Blk, and p38 MAP kinase.

Abstract: 

Bakuchiol is a meroterpene present in the medicinal plant Psoralea corylifolia, which has been traditionally used in China, India, Japan and Korea for the treatment of premature ejaculation, knee pain, alopecia spermatorrhea, enuresis, backache, pollakiuria, vitiligo, callus, and psoriasis. Here, we report the chemopreventive properties of bakuchiol, which acts by inhibiting epidermal growth factor (EGF)-induced neoplastic cell transformation. Bakuchiol also decreased viability and inhibited anchorage-independent growth of A431 human epithelial carcinoma cells. Bakuchiol reduced A431 xenograft tumor growth in an in vivo mouse model. Using kinase profiling, we identified Hck, Blk and p38 mitogen activated protein kinase (MAPK) as targets of bakuchiol, which directly bound to each kinase in an ATP-competitive manner. Bakuchiol also inhibited EGF-induced signaling pathways downstream of Hck, Blk and p38 MAPK, including the MEK/ERKs, p38 MAPK/MSK1 and AKT/p70S6K pathways. This report is the first mechanistic study identifying molecular targets for the anticancer activity of bakuchiol and our findings indicate that bakuchiol exhibits potent anticancer activity by targeting Hck, Blk and p38 MAPK.

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PMID: 

J Biol Chem. 2015 Nov 13 ;290(46):28001-17. Epub 2015 Oct 7. PMID: 26446794

Abstract Title: 

Bakuchiol Is a Phenolic Isoprenoid with Novel Enantiomer-selective Anti-influenza A Virus Activity Involving Nrf2 Activation.

Abstract: 

Influenza represents a substantial threat to human health and requires novel therapeutic approaches. Bakuchiol is a phenolic isoprenoid compound present in Babchi (Psoralea corylifolia L.) seeds. We examined the anti-influenza viral activity of synthetic bakuchiol using Madin-Darby canine kidney cells. We found that the naturally occurring form, (+)-(S)-bakuchiol, and its enantiomer, (-)-(R)-bakuchiol, inhibited influenza A viral infection and growth and reduced the expression of viral mRNAs and proteins in these cells. Furthermore, these compounds markedly reduced the mRNA expression of the host cell influenza A virus-induced immune response genes, interferon-β and myxovirus-resistant protein 1. Interestingly, (+)-(S)-bakuchiol had greater efficacy than (-)-(R)-bakuchiol, indicating that chirality influenced anti-influenza virus activity. In vitro studies indicated that bakuchiol did not strongly inhibit the activities of influenza surface proteins or the M2 ion channel, expressed in Chinese hamster ovary cells. Analysis of luciferase reporter assay data unexpectedly indicated that bakuchiol may induce some host cell factor(s) that inhibited firefly and Renilla luciferases. Next generation sequencing and KeyMolnet analysis of influenza A virus-infected and non-infected cells exposed to bakuchiol revealed activation of transcriptional regulation by nuclear factor erythroid 2-related factor (Nrf), and an Nrf2 reporter assay showed that (+)-(S)-bakuchiol activated Nrf2. Additionally, (+)-(S)-bakuchiol up-regulated the mRNA levels of two Nrf2-induced genes, NAD(P)H quinone oxidoreductase 1 and glutathione S-transferase A3. These findings demonstrated that bakuchiol had enantiomer-selective anti-influenza viral activity involving a novel effect on the host cell oxidative stress response.

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PMID: 

Mol Med Rep. 2017 Dec ;16(6):8977-8982. Epub 2017 Oct 3. PMID: 28990045

Abstract Title: 

Anti‑tumor effects of bakuchiol on human gastric carcinoma cell lines are mediated through PI3K/AKT and MAPK signaling pathways.

Abstract: 

Bakuchiol is extracted from Psoralea corylifolia, a member of the Leguminosae family, has been used in Indian Ayurvedic and Chinese traditional medicine, and it possesses an anticancer effect. The primary aim of the present study was to identify the molecular mechanisms underlying the anticancer effect of bakuchiol monoterpenes. Bakuchiol treatment significantly inhibited NUGC3 human gastric cancer cell viability in a concentration dependent manner. In addition, bakuchiol significantly increased the apoptotic cell population in the sub‑G1 phase, and Annexin‑V‑fluorescein isothiocyanate/propidium iodide double staining confirmed the increase in apoptosis. Nuclear fragmentation and the formation of apoptotic organelles were promoted in bakuchiol‑treated NUGC3 cells. Western blotting results indicated that bakuchiol treatment significantly decreased procaspase‑3,6,8,9 and poly (ADP‑ribose) polymerase (PARP) expression levels, increased cleaved caspase‑3 and cleaved PARP expression levels, and increased the B cell lymphoma‑2 associated X, apoptosis regulator:B cell lymphoma‑extra large ratio. Bakuchiol‑treated NUGC3 cells demonstrated significantly reduced phosphorylated (p‑) protein kinase B (AKT)protein expression levels and elevated p‑extracellular signal related kinase 1/2 (ERK1/2), p‑c‑Jun N‑terminal kinase (JNK) and p‑p38. Bakuchiol‑induced cell death was mitochondrial dependent, through modulation of phosphoinositide 3‑kinase/AKT and mitogen‑activated protein kinase signaling pathways. These findings demonstrated that bakuchiol possesses potential for treating human gastric cancer.

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PMID: 

Cell Biol Int. 2019 Jul 22. Epub 2019 Jul 22. PMID: 31329322

Abstract Title: 

Psoralen attenuates bleomycin-induced pulmonary fibrosis in mice through inhibiting myofibroblast activation and collagen deposition.

Abstract: 

Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by excessive deposition of extracellular matrix (ECM) and chronic inflammation with limited therapeutic options. Psoralen, a major active component extracted from Psoralea corylifolia L. seed, has several biological effects. However, the role of psoralen in IPF is still unclear. Here, we hypothesized that psoralen played an essential role in IPF in the inhibition of fibroblast proliferation and inflammatory response. A murine model of IPF was established by injecting bleomycin (BLM) intratracheally, and psoralen was administered for 14 days from the 7to 21day after BLM injection. Our results demonstrated that psoralen treatment reduced body weight loss and improved the survival rate of mice with IPF. Histological and immunofluorescent examination showed that psoralen alleviated BLM-induced lung parenchymal inflammatory and fibrotic alteration. Furthermore, psoralen inhibited proliferation and collagen synthesis of mouse fibroblasts and partially reversed BLM-induced expression of α-smooth muscle actin at both the tissue and cell level. Moreover, psoralen decreased the expression of transforming growth factor-β1, interleukin-1β, and tumor necrosis factor-α in the lungs of BLM-stimulated mice. Our results reveale for the first time that psoralen exerts therapeutic effects against IPF in a BLM-induced murine model.

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PMID: 

Biomed Pharmacother. 2018 Apr ;100:486-494. Epub 2018 Feb 23. PMID: 29477912

Abstract Title: 

Bavachin induces the apoptosis of multiple myeloma cell lines by inhibiting the activation of nuclear factor kappa B and signal transducer and activator of transcription 3.

Abstract: 

Bavachin is a phytoestrogen purified from natural herbal plants such as Psoralea corylifolia. In this study, we examined the effect of bavachin in multiple myeloma (MM) cell lines. We found that bavachin decreased the viability of MM cell lines, but was not cytotoxic towards normal cells. It inhibited the activation of nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3). Furthermore, bavachin increased the expression of p53 and NOXA, and decreased the expression of X-linked inhibitor of apoptosis protein (XIAP), survivin, B cell lymphoma-extra large (Bcl-xL), and Bcl-2. Additionally, bavachin induced apoptosis by the activation of caspase-3 and caspase-9, implicating the involvement of the mitochondrial pathway. Our results suggest that bavachin induces apoptosis through the inhibition of NF-κB and STAT3 activation in MM cell lines. Most importantly, few NF-κB and STAT3 inhibitors with highefficiency, specificity, and safety are currently available for clinical cancer therapy. Hence, bavachin, which targets NF-κB and STAT3, is a potential anticancer agent for the treatment of MM.

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PMID: 

J Nat Prod. 1998 Mar ;61(3):362-6. PMID: 9544566

Abstract Title: 

DNA polymerase and topoisomerase II inhibitors from Psoralea corylifolia.

Abstract: 

An ethanol extract of Psoralea corylifolia caused strong DNA polymerase inhibition in a whole cell bioassay specific for inhibitors of DNA replication enzymes. Bioassay-directed purification of the active compounds led to the isolation of the new compound corylifolin (1) and the known compound bakuchiol (2) as DNA polymerase inhibitors. On the basis of the structures of 1 and 2, resveratrol (3) was tested and found to be active as a DNA polymerase inhibitor in this bioassay. Neobavaisoflavone (4) was isolated as a DNA polymerase inhibitor, daidzein (5) as a DNA polymerase and topoisomerase II inhibitor, and bakuchicin (6) as a topoisomerase II inhibitor.

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PMID: 

Evid Based Complement Alternat Med. 2013 ;2013:678028. Epub 2013 Aug 29. PMID: 24069053

Abstract Title: 

Protective Role of Psoralea corylifolia L. Seed Extract against Hepatic Mitochondrial Dysfunction Induced by Oxidative Stress or Aging.

Abstract: 

The accumulation of oxidative damage and mitochondrial dysfunction is an important factor that contributes to aging. The Psoralea corylifolia seeds (PCS), commonly known as"Boh-Gol-Zhee"in Korea, have been used traditionally as a medicinal remedy. We investigated whether an extract of PCS has protective effects on oxidative stress and mitochondrial function in hepatocytes. The PCS extract showed an antisenescence effect on human diploid fibroblasts as evidenced by a decreased expression of p16(INK4a) mRNA and senescence-associatedβ -galactosidase staining. PCS extract treatment reduced H2O2-induced reactive oxygen species (ROS) production in HepG2 cells, inhibited ROS production in hepatocytes of aged mice, and increased superoxide dismutase activity. In H2O2-treated HepG2 cells, PCS extract treatment recovered ATP production. PCS extract treatment recovered the oxygen consumption rate and inhibited reduction of mitochondrial membrane potential induced by oxidative stress, suggesting improvement of mitochondrial function. In addition, PCS extract treatment recovered peroxisome proliferator-activated receptor γ coactivator 1 α and carnitine palmitoyltransferase 1 mRNA and protein expression, and inhibited mitochondrial genome damage. Treatment with the major component of PCS extract, bakuchiol, also recovered mitochondrial dysfunction. On the basis of these results, we conclude that PCS extract inhibits ROS production and mitochondrial dysfunction induced by oxidative stress in hepatocytes.

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