Seong-Man Kim, Hyung Won Ryu, Ok-Kyoung Kwon, Jae-Hong Min, Jin-Mi Park, Doo-Young Kim, Sei-Ryang Oh, Seung Jin Lee, Kyung-Seop Ahn, and Jae-Won Lee. Microbiol. Biotechnol. Lett. 2022;50:310-8. https://doi.org/10.48022/mbl.2112.12007

Dendropanax morbifera extracts were obtained from three different tissues: the heartwood, stem bark, and leaves. The 95% ethanol extract from leaf showed the strongest inhibitory activity (88% inhibition at 50 mu g/mL with HepG2 cells) against triglyceride (TG) biosynthesis. Bioactivity-guided fractionation and metabolite investigation of the leaf extracts resulted in the separation and identification of three polyacetylene derivatives that inhibited newly synthesized TG in HepG2 cells. A method for the profile and contents analyses of the leaf extracts were measured using QTOF-MS with a charged aerosol detector (CAD), including (9Z,16S)-16-hydroxy-9,17-octadecadiene-12,14-diynoic acid (1), which was decomposed during the temperature and storage studies. All metabolites decomposed at different temperatures, especially the polyacetylene, which was rapidly oxidized when the isolated form was exposed to air. However, it was fairly stable in the extract at low temperature <-20 degrees C. The aim of this study was to provide a way to protect the active ingredients in the process of developing and distributing functional foods containing D. morbifera. The application of this quality control/quality assurance step may improve the chemistry, manufacturing, and control for raw materials.

Background: Lowering blood glucose levels by increasing glucose uptake in insulin target tissues, such as skeletal muscle and adipose tissue, is one strategy to discover and develop antidiabetic drugs from natural products used as traditional medicines. Purpose: Our goal was to reveal the mechanism and activity of acacetin (5,7-dihydroxy-4'-methoxyflavone), one of the major compounds in Agastache rugose, in stimulating glucose uptake in muscle cells. Methods: To determine whether acacetin promotes GLUT4-dependent glucose uptake in cultured L6 skeletal muscle cells, we performed a [C-14] 2-deoxy-D-glucose (2-DG) uptake assay after treating differentiated L6-GLUT4myc cells with acacetin. Results: Acacetin dose-dependently increased 2-DG uptake by enhancing GLUT4 translocation to the plasma membrane. Our results revealed that acacetin activated the CaMKII-AMPK pathway by increasing intracellular calcium concentrations. We also found that aPKC lambda/zeta phosphorylation and intracellular reactive oxygen species (ROS) production were involved in acacetin-induced GLUT4 translocation. Moreover, acacetin-activated AMPK inhibited intracellular lipid accumulation and increased 2-DG uptake in HepG2 cells. Conclusion: Taken together, these results suggest that acacetin might be useful as an antidiabetic functional ingredient. Subsequent experiments using disease model animals are needed to verify our results.

Rational and efficient approaches to research and development are becoming more popular for increasing value enhancement in bioactive materials. In this study, metabolite profiles of 17 different Lagerstroemia species from different countries were performed using UPLC-QTof-MS combined with chemometric tools to identify potential metabolite predictors of antidiabetic activity. PLS-DA of the Lagerstroemia samples indicated two large, distinct clusters in the score plot. On the loading scatter plot, significant changes in metabolites of antidiabetic candidates were found between species, and two flavonol glycosides and corosolic acid were evaluated as key markers among the 25 analyzed metabolites. Based on the screening results, samples high in two triterpenic acids (corosolic acid and asiatic acid) showed a tendency to inhibit glucose uptake, which could have contributed to the correlation of active and inactive extracts. Therefore, these comprehensive results support our biochemometric models and contribute to the rational and efficient studies of pharmacologically active metabolites.

Methyl linderone (ML), a cyclo-pentenedione, was isolated from the fruit of Lindera erythrocarpa Makino (family Lauraceae). This plant has well-known anti-inflammatory effects; however, the anti-cancer effects of ML have not yet been reported. Thus, in the present study we investigated the effects of ML on the metastasis of human breast cancer cells. We used 12- O-tetradecanoyl phorbol-13-acetate (TPA)-stimulated MCF-7 cells as the cell model to study the effects of ML on invasion and migration. ML was found to reduce the invasion and migration rate of TPA-stimulated MCF-7 cells. Moreover, it inhibited two metastasis-related factors, matrix metalloproteinase-9 (MMP-9) and interleukin-8 (IL-8), at the mRNA and protein expression levels, in TPA-treated MCF-7 cells. The mechanism by which ML exerted these effects was through the inhibition of translocation of activator protein-1 (AP-1) and signal transducer and activator of transcription-3 (STAT3), mediated via phosphorylation of extracellular signal-regulated kinase (ERK). Taken together, our findings indicated that ML attenuated the TPA-stimulated invasion and migration of MCF-7 cells by suppressing the phosphorylation of ERK and its downstream factors, AP-1 and STAT3. Therefore, ML is a potential agent for the treatment of breast cancer metastasis.

A number of species of the genus Trichilia (Meliaceae) exhibit anti-inflammatory effects. However, the effect of Trichilia martiana C. DC. (TM) on lipopolysaccharide (LPS)-induced inflammation has not, to the best of our knowledge, yet been determined. Therefore, in the present study, the antiinflammatory effect of TM on LPS-stimulated RAW264.7 macrophages was evaluated. The ethanol extract of TM (TMEE) significantly inhibited LPS-induced nitric oxide (NO), prostaglandin 2 (PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). TMEE also reduced the levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β and IL- 6. The upregulation of mitogen-activated protein kinases (MAPKs) and NF-κB activation was revealed to be downregulated following TMEE pretreatment. Furthermore, TMEE was indicated to lead to the nucleus translocation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and the expression of heme oxygenase-1 (HO-1). In H292 airway epithelial cells, the pretreatment of TMEE significantly downregulated the production of LPS-stimulated IL-1β, and TMEE was indicated to increase the expression of HO-1. In animal models exhibiting LPS-induced acute lung injury (ALI), treatment with TMEE reduced the levels of macrophages influx and TNF-α production in the bronchoalveolar lavage fluid (BALF) of ALI mice. Additionally, TMEE significantly downregulated the activation of ERK, JNK and IκB, and upregulated the expression of HO-1 in the lungs of ALI mice. In conclusion, the results of the current study demonstrated that TMEE could exert a regulatory role in the prevention or treatment of the endotoxin-mediated inflammatory response.

Longifolioside A is an iridoid glucoside compound isolated from Pseudolysimachion rotundum var. subintegrum, which has been used in traditional herbal medicines to treat respiratory inflammatory diseases. Logifolioside A is a potent antioxidant; however, its underlying pharmacological mechanisms of action in inflammatory diseases are unknown. Here, we investigated the inhibitory effects of longifolioside A in lipopolysaccharide (LPS)-stimulated toll-like receptor 4 (TLR4) signal transduction systems using human THP-1 macrophages and HEK293 cells stably expressing human TLR4 protein (293/HA-hTLR4). Longifolioside A significantly reduced the release of inflammatory cytokines such as interleukin (IL)-6, -8, and tumor necrosis factor (TNF)-α in LPS-stimulated THP-1 macrophages. Furthermore, longifolioside A inhibited the expression of inflammatory mediator genes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 that produce nitric oxide (NO) and prostaglandin E2 (PGE2), respectively. Longifolioside A suppressed the phosphorylation of PKCδ, IRAK4, IKKα/β, IκBα, and mitogen-activated protein (MAP) kinases (ERK 1/2 and JNK, but not p38), thereby inactivating the nuclear localization of NF-κB and AP-1, and thus decreasing the expression of inflammatory response genes. Notably, longifolioside A disrupted the interaction between human TLR4 and the TIR domain-containing adaptor protein (TIRAP), an early step during TLR4 activation, thereby reducing IL-8 secretion in 293/HA-hTLR4 cells. This inhibitory effect was comparable to that of TAK-242 (a TLR4 inhibitor, or resatorvid). Our results indicate that longifolioside A prevents inflammatory response by suppressing TLR4 activation required for NF-κB and AP-1 activation.

Pistacia weinmannifolia (PW) has been used in traditional Chinese medicine to treat headaches, dysentery, enteritis and influenza. However, PW has not been known for treating respiratory inflammatory diseases, including chronic obstructive pulmonary disease (COPD). The present in vitro analysis confirmed that PW root extract (PWRE) exerts anti‑inflammatory effects in phorbol myristate acetate‑ or tumor necrosis factor α (TNF‑α)‑stimulated human lung epithelial NCI‑H292 cells by attenuating the expression of interleukin (IL)‑8, IL‑6 and Mucin A5 (MUC5AC), which are closely associated with the pulmonary inflammatory response in the pathogenesis of COPD. Thus, the aim of the present study was to evaluate the protective effect of PWRE on pulmonary inflammation induced by cigarette smoke (CS) and lipopolysaccharide (LPS). Treatment with PWRE significantly reduced the quantity of neutrophils and the levels of inflammatory molecules and toxic molecules, including tumor TNF‑α, IL‑6, IL‑8, monocyte chemoattractant protein‑1, neutrophil elastase and reactive oxygen species, in the bronchoalveolar lavage fluid of mice with CS‑ and LPS‑induced pulmonary inflammation. PWRE also attenuated the influx of inflammatory cells in the lung tissues. Furthermore, PWRE downregulated the activation of nuclear factor‑κB and the expression of phosphodiesterase 4 in the lung tissues. Therefore, these findings suggest that PWRE may be a valuable adjuvant treatment for COPD.

Scutellaria baicalensis Georgi (Scutellariae Radix) has been widely used as a dietary ingredient and traditional herbal medicine such as diuretic, hyperlipidemia, antibacterial, antiallergy, anti-inflammatory and anticancer properties. In this study, the isolation of biomarkers or bioactive compounds from complex S. baicalensis extracts represents an essential step for de novo identification and bioactivity assessment. The bioactive fraction consisted of eight compounds which was chromatographed on an analytical high performance liquid chromatography column using two different gradient runs. A simulative replacement of the analytical column with a medium pressure liquid chromatography and open column allowed the determination of gradient profile to allow sufficient separation in the preparative scale. From the optimized method, eight standard compounds have been identified in the fractions. In addition, MS, UV, HRMS detection was provided by ultraperformance liquid chromatographyequadrupole time-of-flight mass spectrometry (UPLC-QTof-MS) of all fractions. Therefore, this scale up procedure was successfully applied to a S. baicalensis extract.

Luteolin is known to have anticancer activity in various cancers. Recent studies have shown that luteolin glycosides, such as luteolin-8-C-β-fucopyranoside, 7-methoxy-luteolin-8-C-β-(6- deoxyxylopyranos-3-uloside) and luteolin-8-C-β-d-glucopyranoside, flavonoids that are present in Arthraxon hispidus, exert antimigratory and anti-invasive effects, but no cytotoxic effect in estrogen receptor-positive MCF7 breast cancer cells. In the present study, we further investigated and compared differential effects of luteolin and its glycosides in MDA-MB-231 triple-negative breast cancer cells. Luteolin suppressed the expression of matrix metalloproteinase-9 and inhibited migration and invasion in MDA-MB-231 cells treated with the tumor promotor 12-O-tetradecanoylphorbol-13-acetate at non-cytotoxic concentrations (0, 5, and 10 μM). Furthermore, at cytotoxic concentrations (20 and 40 μM), luteolin induced apoptosis via extrinsic and intrinsic pathways in MDA-MB-231 cells. However, luteolin glycosides did not exert any cytotoxic, antimigratory, or anti-invasive effect in MDA-MB-231 cells. In brief, luteolin had both antimetastatic and cytotoxic effects on MDA-MB-231 cells, whereas luteolin glycosides had no effect on this cell line. Taking together the present results and our previous findings on the differential effects of luteolin and its glycosides on MDA-MB-231 and MCF-7 breast cancer cells, luteolin and its glycosides can be suggested as a potential candidate for breast cancer therapy.

Context Methyl lucidone (ML) from the dried fruit of Lindera erythrocarpa Makino (Lauraceae) exhibits cytotoxic effects in various cancer cell lines. However, its effects on ovarian cancer cells remain unknown. Objective This study evaluates the mechanism of ML-induced apoptosis, cell cycle distribution in ovarian cells. Materials and methods The cytotoxic effect of ML (2.5–80 µM) on OVCAR-8 and SKOV-3 cells was evaluated by MTS assay for 24 and 48 h. Apoptosis and cell cycle arrest were analysed by flow cytometry. PCR, western blot analyses were performed to examine the related signalling pathways. Results ML induced significant cellular morphological changes and apoptosis in ovarian cancer cells, leading to an antiproliferative effect (IC50 = 33.3–54.7 µM for OVCAR-8 and 48.8-60.7 µM for SKOV-3 cells). Treatment with ML induced cleavage of caspase-3/9 and PARP and release of cytochrome c from the mitochondria. Moreover, ML downregulated the expression of Bcl-2 and Bcl-xL and induced cell cycle arrest in the G2/M phase. Additionally, ML suppressed the expression of cyclin-A/B and promoted that of the cyclin-dependent kinase inhibitors p21 and p27. The expression of death receptors was not altered. Interestingly, ML also inhibited the activity of PI3K/Akt and NF-κB. Discussion and conclusions ML caused G2/M phase arrest and apoptosis in ovarian cancer cells by activating intrinsic apoptotic pathways and suppressing the PI3K/Akt survival pathway. ML may be a potential anticancer agent to suppress ovarian cancer proliferation; thus, to improve the survival rate of cancer patients.

Artemisia species are widely used as food ingredients and raw material in traditional medicine.However, to date, the secondary metabolites of Artemisia gmelinii Weber ex Stechm.have not been sufficiently investigated.The secondary metabolites of A. gmelinii, which was collected from representative regions in Chungbuk, Gangwon, and Gyeongbuk, were analyzed using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTof MS) combined with an unsupervised principal component analysis (PCA) multivariate analysis.In the loading scatter plot of PCA, significant changes in metabolites were observed between the regions, ten metabolites (3: 5-Ocaffeoylquinic acid, 4: 4-O-caffeoylquinic acid, 8: transmelilotoside, 12: quercetin 3-O-hexoside, 15: 3,4-O-dicaffeoylquinic acid, 17: 3,5-O-dicaffeoylquinic acid, 18: 4,5-O-dicaffeoylquinic acid, 19: syringaldehyde, 20: caffeoylquinic acid derivative, and 23: icariside II) were evaluated as key markers among twenty-five identified metabolites.Interestingly, the contents of the identified marker significantly differed between the three groups.This is the first study to report the presence of marker metabolites and their correlating geographical cultivation in A. gmelinii.

Indoleamine 2,3-dioxygenase 1 (IDO1), a tryptophan catabolising enzyme, is known as a tumour cell survival factor that causes immune escape in several types of cancer. Flavonoids of Sophora flavescens have a variety of biological benefits for humans; however, cancer immunotherapy effect has not been fully investigated. The flavonoids (1-6) isolated from S. flavescens showed IDO1 inhibitory activities (IC50 4.3-31.4 mu M). The representative flavonoids (4-6) of S. flavescens were determined to be non-competitive inhibitors of IDO1 by kinetic analyses. Their binding affinity to IDO1 was confirmed using thermal stability and surface plasmon resonance (SPR) assays. The molecular docking analysis and mutagenesis assay revealed the structural details of the interactions between the flavonoids (1-6) and IDO1. These results suggest that the flavonoids (1-6) of S. flavescens, especially kushenol E (6), as IDO1 inhibitors might be useful in the development of immunotherapeutic agents against cancers.

Xanthium strumarium (XS) has been traditionally used as a medicinal herb for treating inflammatory diseases, such as appendicitis, chronic bronchitis, rheumatism, and rhinitis. In this study, we yielded ethanol extracts from XS and investigated whether they could inhibit the progression of hepatocellular carcinoma (HCC) and its underlying mechanism. The XS-5 and XS-6 extracts dose-dependently inhibited the growth and proliferation in HCC cell lines. The apoptotic effects of them were observed via increased levels of cleaved caspase-3 and cleaved PARP, as well as elevated numbers of terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling- (TUNEL-) positive apoptotic cells. They also decreased XIAP and Mcl-1 expression via loss of mitochondrial membrane potential. Additionally, they inhibited the invasion and migration of HCC cells. In an ex vivo model, the extracts significantly inhibited tumor cell growth and induced apoptosis by increasing the expression of the cleaved caspase-3. A mechanistic study revealed that they effectively suppressed PI3K/AKT/mTOR signaling pathways in HCC cells. Taken together, our findings demonstrate that they could efficiently not only induce apoptosis but also inhibit cell growth, migration, and invasion of human HCC cells by blocking the PI3K/AKT/mTOR pathway. We suggest XS-5 and XS-6 as novel natural anti-HCC agents.

Osthenol (6), a prenylated coumarin isolated from the dried roots of Angelica pubescens, potently and selectively inhibited recombinant human monoamine oxidase-A (hMAO-A) with an IC50 value of 0.74 mu M and showed a high selectivity index (SI > 81.1) for hMAO-A versus hMAO-B. Compound 6 was a reversible competitive hMAO-A inhibitor (K-i = 0.26 mu M) with a potency greater than toloxatone (IC50 = 0.93 mu M), a marketed drug. Isopsoralen (3) and bakuchicin (1), furanocoumarin derivatives isolated from Psoralea corylifolia L., showed slightly higher IC50 values (0.88 and 1.78 mu M, respectively) for hMAO-A than 6, but had low SI values (3.1 for both). Other coumarins tested did not effectively inhibit hMAO-A or hMAO-B. A structural comparison suggested that the 8-(3,3-dimethylallyl) group of 6 increased its inhibitory activity against hMAO-A compared with the 6-methoxy group of scopoletin (4). Molecular docking simulations revealed that the binding affinity of 6 for hMAO-A (-8.5 kcal/mol) was greater than that for hMAO-B (-5.6 kcal/mol) and that of 4 for hMAO-A (-7.3 kcal/mol). Docking simulations also implied that 6 interacted with hMAO-A at Phe208 and with hMAO-B at Ile199 by carbon hydrogen bondings. Our findings suggest that osthenol, derived from natural products, is a selective and potent reversible inhibitor of MAO-A, and can be regarded a potential lead compound for the design of novel reversible MAO-A inhibitors.

Cedrela odorata L. is a native plant of the Amazon region. The bark is used in folk remedies for the treatment of diarrhea, vomiting, fever and inflammation. Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease accompanied by itching. It is a complex disease involving environmental factors and genetic factors. In the present study, the anti-inflammatory and anti-allergic effects of C. odorata L. methanol extract (COEE) on tumor necrosis factor (TNF)-α and interferon (IFN)-γ-stimulated HaCaT keratinocyte cells were investigated. ELISA and RT-PCR analysis revealed that the extract had anti-inflammatory effects, and reduced the interleukin (IL)-6 and IL-8 levels of the HaCaT cells. In addition, COEE exhibited anti-allergic effects, comprising a reduction in the thymus and activation-regulated chemokine and macrophage-derived chemokine levels. In addition, pathway analysis and comparison with Bay11-7082 indicated that these effects are due to the inhibition of nuclear factor (NF)-κB in TNF-α/IFN-γ-induced HaCaT cells. Therefore, the results of the present study suggest that COEE has anti-inflammatory and anti-allergic properties in TNF-α and IFN-γ-stimulated HaCaT cells, which are associated with the inhibition of pro-inflammatory cytokines and chemokines via the NF-κB pathway.

Physalis peruviana L. (PP) is well known for its various properties, including its antioxidant property. In our previous study, the protective effects of PP against cigarette smoke‑induced airway inflammation were confirmed. The purpose of the present study was to evaluate the anti‑inflammatory effect of PP against ovalbumin (OVA)‑induced airway inflammation. Treatment with PP inhibited the numbers of eosinophils and the levels of inflammatory cytokines, including interleukin (IL)‑4, IL‑5 and IL‑13, in the bronchoalveolar lavage fluid (BALF) of animal models with OVA‑induced allergic asthma. PP also significantly decreased the production of total immunoglobulin E in the serum. Lung sections stained with hematoxylin and eosin revealed that the influx of inflammatory cells was decreased in the lungs of mice treated with PP compared with cells in the OVA group. The increased expression levels of monocyte chemoattractant protein‑1 (MCP‑1) and T cell marker KEN‑5 were also reduced following PP treatment in the lung tissues compared with those in the OVA group. The PAS staining results showed that PP attenuated the overproduction of mucus in the lung. Additionally, western blot analysis revealed that PP significantly downregulated the activation of nuclear factor‑κB/p38 mitogen‑activated protein kinase/c‑Jun N‑terminal kinase, and upregulated the expression of heme oxgenase‑1 in the lungs. In an in vitro experiment, PP effectively reduced the levels of LPS‑stimulated MCP‑1 in a concentration‑dependent manner. Taken together, these results indicate that PP has considerable potential in the treatment of allergic asthma.

A novel compound named 'kanakugiol' was recently isolated from Lindera erythrocarpa and showed free radical-scavenging and antifungal activities. However, the details of the anticancer effect of kanakugiol on breast cancer cells remain unclear. We investigated the effect of kanakugiol on the growth of MCF-7 human breast cancer cells. Kanakugiol affected cell cycle progression, and decreased cell viability in MCF-7 cells in a dose-dependent manner. It also enhanced PARP cleavage (50 kDa), whereas DNA laddering was not induced. FACS analysis with annexin V-FITC/PI staining showed necrosis induction in kanakugiol-treated cells. Caspase-9 cleavage was also induced. Expression of death receptors was not altered. However, Bcl-2 expression was suppressed, and mitochondrial membrane potential collapsed, indicating limited apoptosis induction by kanakugiol. Immunofluorescence analysis using α-tubulin staining revealed mitotic exit without cytokinesis (4N cells with two nuclei) due to kanakugiol treatment, suggesting that mitotic catastrophe may have been induced via microtubule destabilization. Furthermore, cell cycle analysis results also indicated mitotic catastrophe after cell cycle arrest in MCF-7 cells due to kanakugiol treatment. These findings suggest that kanakugiol inhibits cell proliferation and promotes cell death by inducing mitotic catastrophe after cell cycle arrest. Thus, kanakugiol shows potential for use as a drug in the treatment of human breast cancer.

BACKGROUND:Spinal muscular atrophy (SMA) is a rare neuromuscular disease and a leading genetic cause of infant mortality. SMA is caused primarily by the deletion of the survival motor neuron 1 (SMN1) gene, which leaves the duplicate gene SMN2 as the sole source of SMN protein. The splicing defect (exon 7 skipping) of SMN2 leads to an insufficient amount of SMN protein. Therefore, correcting this SMN2 splicing defect is considered to be a promising approach for the treatment of SMA.PURPOSE:This study aimed to identify active compounds and extracts from plant resources to rescue SMA phenotypes through the correction of SMN2 splicing.STUDY DESIGN:Of available plant resources, candidates with SMA-related traditional medicine information were selected for screening using a robust luciferase-based SMN2 splicing reporter. Primary hits were further evaluated for their ability to correct the splicing defect and resultant increase of SMN activity in SMA patient-derived fibroblasts. Confirmed hits were finally tested to determine the beneficial effects on the severe Δ7 SMA mouse.METHODS:SMN2 splicing was analyzed using a luciferase-based SMN2 splicing reporter and subsequent RT-PCR of SMN2 mRNAs. SMA phenotypes were evaluated by the survival, body weights, and righting reflex of Δ7 SMA mice.RESULTS:In a screen of 492 selected plant extracts, we found that Brucea javanica extract and its major constituent Bruceine D have SMN2 splicing-correcting activity. Their ability to correct the splicing defect and the resulting increased SMN activity were further confirmed in SMA fibroblasts. Importantly, both B. javanica and Bruceine D noticeably improved the phenotypic defects, especially muscle function, in SMA mice. Reduced expression of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) contributed to the correction of splicing by B. javanica.CONCLUSION:Our work revealed that B. javanica and Bruceine D correct the SMN2 splicing defect and improve the symptoms of SMA in mice. These resources will provide another possibility for development of a plant-derived SMA drug candidate.

Hispidol, an aurone, isolated from Glycine max Merrill, was found to potently and selectively inhibit an isoform of recombinant human monoamine oxidase-A (MAO-A), with an IC50 value of 0.26 mu M, and to inhibit MAO-B, but with lower potency (IC50 = 2.45 mu M). Hispidol reversibly and competitively inhibited MAO-A with a K-i value of 0.10 mu M with a potency much greater than toloxatone (IC50 = 1.10 mu M), a marketed drug. It also reversibly and competitively inhibited MAO-B (K-i = 0.51 mu M). Sulfuretin, an analog of hispidol, effectively inhibited MAO-A (IC50 = 4.16 mu M) but not MAO-B (IC50 > 80 mu M). A comparison of their chemical structures showed that the 3'-hydroxyl group of sulfuretin might reduce its inhibitory activities against MAO-A and MAO-B. Flexible docking simulation revealed that the binding affinity of hispidol for MAO-A (-9.1 kcal/mol) was greater than its affinity for MAO-B (-8.7 kcal/mol). The docking simulation showed hispidol binds to the major pocket of MAO-A or MAO-B. The findings suggest hispidol is a potent, selective, reversible inhibitor of MAO-A, and that it be considered a novel lead compound for development of novel reversible inhibitors of MAO-A. (C) 2018 Elsevier Ltd. All rights reserved.