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. 2020 Oct 22;11:571459. doi: 10.3389/fphar.2020.571459

TABLE 1.

The most relevant information, including the preclinical pharmacological activities and mechanism of action of PSO.

Biologic effect PSO tested Model Methods Results/mechanisms Reference
Anticancer PSO/seeds HeLa human cervical cancer cells/in vitro Cytotoxicity: MTT assayCellular apoptosis: fluorescence microscopyDeath receptor expression TRAIL-R1, TRAIL-R2: flowcytometry ↑apoptosis, ↑TRAIL-R2 death, ↑mitochondrial damage synergistic effects: TRAIL 100 ng/ml + PSO 20/50 μMIC50 20–50 μM Bronikowska et al. (2012)
PSO/(commercial sample) SW480 human colon cancer cells/in vitro Viability: MTT assayCellular apoptosis: DAPI staining assay, caspase-3 colourimetric assay, flow cytometric analysisNF-κB activity: ELISA, Western blot ↓NF-κB, p65, ↓Bcl-2, ↑Bax protein expression, ↑caspase-3↓cell viability, ↑apoptosisIC50 20 μM Jin et al. (2016a)
PSO/(commercial sample) A549, MCF-7 breast cancer cells/in vitro Cancer cell proliferation: MTT assayDNA damage: comet assay autophagic vacuoles: MDCROS: a fluorescent probeNOX4: immunofluorescence staining ↑cell deaths, ↑autophagy↑DNA damage, ↓ROS generationIC50 2.5–10 µM Ren et al. (2016)
PSO/(commercial sample) Eca9706 esophageal carcinomaCells/in vitro Cell proliferation, viability: MTTCellular apoptosis: flow cytometryApoptosis: DAPI staining assayCaspase-3 activity: colourimetric assayNF-κB: ELISA, Western blot ↓proliferation, ↑apoptosis↓PI3K, ↓AktIC50 10–20 μM Jin et al. (2016b)
PSO/(commercial sample) PC-3DU-145 prostate cancer cells/in vitro Cell viability, apoptosis: MTT, luciferase assaysNF-κB: transcription factor assayIκB-α activation: ELISA, Western blot, kinase assays ↑phosphorylation of Akt in PC-3 (IC50 60 μmol/L) and DU-145 (IC50 45 μmol/L)↑PI3K in a dose and time-dependent manner. Selectively targets cancer cellsNo toxicity on normal prostate epithelial cells Kumar et al. (2009)
PSO/leaves PC-3DU-145LNCaP4-2B prostate cancer cells/in vitro Cell viability, apoptosis: MTT, kinase assay, Western blot analysis, ERK and JNK kinase assays, transient transfection and promoter assays immunohistochemical analysis using pEGFR (Tyr 1173) and pc-Jun antibodies ↓EGF-induced pEGFR expression in PC-3 and DU-145 cells↑EGF-mediated inhibition in PC-3 and DU-145↓JNK kinase activity, ↓prostate cancer growth. No toxicity↑EGFR activation, ↑apoptosis, ↓MAPK signaling, ↓cell proliferationIC50 45–60 μM Kumar et al. (2010)
PSO/(commercial sample) WPE-1 prostate epithelial cells/in vitro Apoptosis: MTTProteins: Western blotNF-κB: RT-PCR ↓NF-kB signaling in cadmium-transformed prostate epithelial cellsIC50 4 μM Pal et al. (2017b)
PSO/(commercial sample) PC-3, DU-145 androgen-independent prostate cancer cell lines PzHPV-7 normal prostate epithelial cells/in vitro Cell viability, apoptosis assays: MTTNF-kB, p65: ELISA, RT–PCR, Western blotCaspase-3 activation: fluorometryImmunohistochemistry: JC-1 staining ↓TNF-α↓NF-κB, ↑proapoptotic proteins↑caspase cascade→↑apoptosis↑death receptor-mediated apoptosisIC50 45 μM Srinivasan et al. (2010)
PSO/(commercial samples) NCA prostate cancer cells/in vitro Cytotoxicity: MTT, LDH assaysApoptosis: fluorescence microscopy ↑apoptosis, ↓COX-2, ↓NF-kBIC50 100 μM Yang et al. (2011)
PSO/seeds methanol extract Mouse Hepa 1c1c7 cells/in vitro Cytotoxicity: measuring cell survival using the crystal violet staining Chemopreventive effectIC50 0.5 μg/ml Lee et al. (2009)
PSO/seeds extract MCF-7 human breast cancer cell linesIshikawa endometrial cancer cell line/in vitro Estrogenic activity: molecular docking ↑endogenous estrogen-responsive gene ↑pS2↑ER-signalling pathwayClinical importance: novel estrogenic modulator. IC50 10 μM Liu et al. (2014)
PSO (commercial samples) ALDH, ALDHþ breast cancer stem cells/in vitro Cell viability, apoptosis, colony formation, invasion, migration, small interfering RNA transfectionAldefluor assay for separation of the ALDH population: flow cytometry ↓growth of cancer cells↑apoptosis, ↓NOTCH1 signaling↓β-catenin and vimentin↑E-cadherin →↓migration, ↓invasionIC50 0.5 μM Sun et al. (2016)
PSO/seed methanol extract HT-29 colon MCF-7 breast human cancer cellsA541 (lung) hepG2 (liver hepatoma) cancer cells/in vitro Cytotoxicity: MTT assay ↑cytotoxicity against HT-29 (colon) and MCF-7 (breast)PSO was not active against the A541 (lung) and HepG2 (liver hepatoma) cellsIC50 0.3–0.4 μg/ml Mar et al. (2001)
PSO/(commercial sample) Human liver microsomes, human intestine microsomesExpressed UGT enzymes/in vitro Kinetic evaluation: Michaelis–Menten modelQuantification of glucuronides: UPLC analyses, immunoblotting protein levels: Western blot Strong correlation PSO-3-O-glucuronidation and UGT1A9PSO-3-O-glucuronidation: in vitro marker for UGT1A9IC50 5 μM Sun et al. (2015)
PSO/seeds HeLa cells/in vitro Cytotoxicity: MTT, LDH assays Apoptosis, ↑expression of TRAIL-R2, death receptor, mitochondrial membrane potential, ↑cytotoxicity, ↑apoptosisIC50 20–50 μM Bronikowska et al. (2012)
PSO/seeds hepG2 human liver cancer cells/in vitro Viability: MTTApoptosis: flow cytometryProteins: Western blot ↓viability, ↑activities of caspase-3, -8, and -9, ↑p53↓pro-survival genes Bcl-2, Bcl-xL↓caspase-3 proteinIC50 64 μM Yu et al. (2019)
Anti-osteoporosis PSO/whole plantPSO/(commercial sample)PSO/seeds Bone marrow mesenchymal stem cells (bmscs)Preosteoblast MC3T3-E1 cells preadipocyte 3T3-L1 cells/in vitroNewborn Sprague-Dawley rats/in vivo rat calvarial osteoblasts/in vitroOvariectomized rats/in vivo Cytotoxicity: MTT, LDH assaysProteins: Western blotAlkaline phosphatase: colourimetric assayOsteogenesis-related genes: qPCROsteogenic proteins: Western blot, ELISATRAP activity: Colourimetric assayDEXA, biomechanical analysis, tomographyProteins: Western blot MC3T3-E1 cells: ↑osteogenesis, ↓adipogenesis, ↑calcium nodule formation, ↑alkaline phosphatase, ↑osteocalcin3T3-L1 cells: ↓adipocyte formation, ↓mRNA, ↓protein synthesis, ↑osteogenesis via mediating classical ER pathwayIC50 1–10 μM↑osteoblasts proliferation, ↑differentiation↑ROB cell proliferation, ↑ALP activities, ↑calcified nodules, ↓COX-2, ↓ROS, ↑bone formation, ↑osteoblasts, ↓bone resorption of osteoclastsIC50 10–6 mol/L↑bone formation↓bone resorption Cao et al. (2019) Zhai et al. (2017) Zhai et al. (2018)
PSO/(commercial sample) BBMMs bone marrow macrophages/in vitro Viability, apoptosis: MTT, LDH and DAPI stainingBone proteins: Western blot ↓TRAP-positive osteoclasts↓p-ERK, ↓p-38, ↓p-JNK↓NF-κb, ↓c-Fos/NFATC1, ↓TRAP, ↓cathepsin K, ↑RANKL, ↑OPGIC50 0.1–30 μM Kong et al. (2017)
Anti-inflammatory PSO/fruits Murine macrophages/in vitro Neutrophil proinflammatory response: monitoring the inhibition of superoxide anion generation and elastase release superoxide anion generation: SOD-inhibition reductionNitrite concentration: ELISAViability: MTT ↓NO generation by murine macrophages in response to LPSIC50 27, 46 μM Chen et al. (2017)
PSO/seeds LPS-activated RAW264.7 cells/in vitro NO synthesis: RT-PCR, Western blot ↓PI3K/Akt, ↓LPS induced iNOS expressionIC50 1–30 μM Chiou et al. (2011)
PSO/(commercial sample) Human normal lung fibroblasts/in vitro Viability: MTT, Western blot, luciferase reporter gene assay, cell migration assay ↓IR-induced COX-2, ↓PGE2 ↓PI3K/Akt, ↓NF-κB↓proinflammatory cytokines (TNF-α, TGF-β, IL-6, IL-1 a/b)IC50 50–100 μM Yang et al. (2011)
Antibacterial PSO/seeds S. aureus, S. epidermidis, P. aeruginosa, K. pneumoniae, P. mirabilis, P. vulgaris, E. coli/in vitro Diffusion method ↓bacterial grow at 1× 106 cfu/mL stronger activity against Gram (−)Maximum inhibition against K. pneumonie Borate et al. (2014)
Antiviral against SARS-CoV PSO/dried seeds ethanol extract SARS-CoV/in silico Kinetics of enzymes: Lineweaver–Burk plots Reversible mixed type I mechanisms Kim et al. (2014)
Neuro-protective PSO/seeds ethanol extract BV-2 microglial cellsHT22 mouse hippocampal cells/in vitro NO assay Anti-neuroinflammatory↓LPS-induced NO production in BV-2 cells Kim et al. (2016)
Anti-vitiligo PSO/ethanol extract Tyrosinase/in silico HPLC tyrosinase activity: oxidation rate of levodopa assay ↑tyrosinase, a rate-limiting enzyme of melanogenesis Shi et al. (2018)
Antiprotozoal PSO/methanol extract Ichthyophthirius multifiliis/in vitro Bioassay-guide isolation and identification of active compounds efficacy assay of fractions against I. multifiliis Detrimental effect on I. Multifiliis trophont in situ Song et al. (2015)
Vasodilatory action PSO/seeds ethanol extract Male Sprague-Dawley rats/in vivo Isometric tension recordings of rat aortic ringsIonic currents through TRPC3PSO concentration extract: 10–600 μg/ml ↑vasodilatation↑NO/cGMP↑prostaglandins Gebremeskel et al. (2017)
Anti-apoptotic PSO/seeds Sprague-Dawley rats/in vivo Annexin V/propidium iodide double-labelling fluorescence-activated cell sorting analysis Protected rat chondrocytes from IL-1β-induced apoptosis, ↑Bcl-2↓Bax, ↓caspase-3, ↓caspase-9, ↓MMP-1, ↓MMP-13, ↑ ROS, ↑NO, ↑NF-κb Rao et al. (2018)
Antidepressant-like effects PSO/seeds Male mice/in vivo Open-field test in miceACTH, corticosterone: enzyme immunoassay ↓immobility time↑swimming behavior↑5-HT, ↑5-HIAA, ↑DA↓CRF, ↓ACTH, ↓corticosterone Xu et al. (2008)

↓, Decrease; ↑, increase; 5-HIAA, 5-hydroxyindoleacetic acid; 5-HT, 5-hydroxytryptamine; ACTH, adrenocorticotropic hormone; Bcl-xL, B-cell lymphoma-extralarge; BMMs, bone marrow macrophages; BMSCs, bone marrow mesenchymal stem cells; COX-2, cyclooxygenase 2; CRF, corticotropin-releasing factor; CYP450, cytochrome P450; DA, dopamine; DAPI, 4′,6-diamidino-2-phenylindole; EGFR, epidermal growth factor receptor; ERK, extracellular-signal-regulated kinase; IκB-α, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha; IL, interleukin; JNK, jun N-terminal kinase; MAPK, mitogen-activated protein kinase; MDC, autofluorescent compound monodansylcadaverine; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NF-κB, nuclear factor kappa B; NFATC1, nuclear factor of activated T cell cytoplasmic 1; NO, nitric oxide; NOTCH1, notch homolog 1 translocation-associated; NOX4, NADPH oxidase 4; LC-MS/MS, liquid chromatography–mass spectrometry; LDH, lactate dehydrogenase; LPS, lipopolysaccharide; OPG, osteoprotegerin; PI3K/Akt, phosphatidylinositol 3 kinase; PSO, psoralidin; RANKL, receptor activator for NF-κB; ROB, rat calvarial osteoblasts; ROS, reactive oxygen species; RT-PCR reverse transcription polymerase chain reaction; SAPK, stress-activated protein kinases; SARS-CoV, severe acute respiratory syndrome coronavirus; SOD, superoxide dismutase; TGF-β, transforming growth factor-beta; TNF, tumor necrosis factor; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand; TRAP, tartrate-resistant acid phosphatase; TRPC3, transient receptor potential cation channel subfamily c member 3; UGT, UDP-glucuronosyltransferase; UPLC, ultra-performance liquid chromatography.