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.