Comparative Analysis of Polyphenolic Compounds in Different Amaranthus Species: Influence of Genotypes and Harvesting Year.

Amaranth is a nutritionally valuable crop, as it contains phenolic acids and flavonoids, yielding diverse plant secondary metabolites (PSMs) like phytosterol, tocopherols, and carotenoids. This study explored the variations in the contents of seventeen polyphenolic compounds within the leaves of one hundred twenty Amaranthus accessions representing nine Amaranthus species. The investigation entailed the analysis of phenolic content across nine Amaranthus species, specifically A. hypochondriacus, A. cruentus, A. caudatus, A. tricolor, A. dubius, A. blitum, A. crispus, A. hybridus, and A. viridis, utilizing ultra performance liquid chromatography with photodiode array detection (UPLC-PDA). The results revealed significant differences in polyphenolic compounds among accessions in which rutin content was predominant in all Amaranthus species in both 2018 and 2019. Among the nine Amaranthus species, the rutin content ranged from 95.72 ± 199.17 µg g-1 (A. dubius) to 1485.09 ± 679.51 µg g-1 (A. viridis) in 2018 and from 821.59 ± 709.95 µg g-1 (A. tricolor) to 3166.52 ± 1317.38 µg g-1 (A. hypochondriacus) in 2019. Correlation analysis revealed, significant positive correlations between rutin and kaempferol-3-O-ß-rutinoside (r = 0.93), benzoic acid and ferulic acid (r = 0.76), and benzoic acid and kaempferol-3-O-ß-rutinoside (r = 0.76), whereas gallic acid showed consistently negative correlations with each of the 16 phenolic compounds. Wide variations were identified among accessions and between plants grown in the two years. The nine species and one hundred twenty Amaranthus accessions were clustered into six groups based on their seventeen phenolic compounds in each year. These findings contribute to expanding our understanding of the phytochemical traits of accessions within nine Amaranthus species, which serve as valuable resources for Amaranthus component breeding and functional material development.

Gibberellic acid 3 enhanced the anticancer activity of Abeliophyllum distichum adventitious roots by activating the diterpenoid biosynthesis pathway.

The industrial value of various plants has been improved through the of plant cell culture systems with elicitation. In this study, the adventitious root of Abeliophyllum distichum (AdAR) was treated with gibberellic acid 3 (GA3) to improve its anticancer property. The hexane fraction of the GA3-treated A. distichum adventitious root exhibited a stronger cytotoxic activity against A549 cells than the hexane fraction of AdAR. Through GC/MS and principal component analysis, we identified ferruginol and sugiol as anticancer compounds, which were induced by GA3 treatment in AdAR. Gene expression analysis combined with functional characterisation suggests that the GA3 treatment increased the transcription of geranylgeranyl pyrophosphate synthases and copalyl diphosphate synthase, which led to the accumulation of diterpenoids, including ferruginol and sugiol. Overall, these findings can contribute to the advancement of metabolic engineering for enhancing the biosynthesis of active diterpenoids, and facilitate the large-scale production of bioactive compounds sourced from A. distichum.

Histone Deacetylase Inhibitor, Sodium Butyrate-Induced Metabolic Modulation in Platycodon grandiflorus Roots Enhances Anti-Melanogenic Properties.

While the status of histone acetylation is a critical regulator of chromatin's structure with a significant impact on plant physiology, our understanding of epigenetic regulation in the biosynthesis of active compounds in plants is limited. In this study, Platycodon grandiflorus was treated with sodium butyrate (NaB), a histone deacetylase inhibitor, to investigate the influence of histone acetylation on secondary metabolism. Its treatment with NaB increased the acetylation of histone H3 at lysine 9, 14, and 27 and enhanced the anti-melanogenic properties of P. grandiflorus roots. Through transcriptome and differentially expressed gene analyses, we found that NaB influenced the expression of genes that were involved in both primary and secondary metabolic pathways. In addition, NaB treatment caused the accumulation of polyphenolic compounds, including dihydroquercetin, gallic acid, and 2,4-dihydroxybenzoic acid. The NaB-induced transcriptional activation of genes in the phenylpropanoid biosynthetic pathway influenced the anti-melanogenic properties of P. grandiflorus roots. Overall, these findings suggest the potential of an epigenomic approach to enhance the medicinal qualities of medicinal plants.

Physiological and sucrose metabolic responses to waterlogging stress in balloon flower (Platycodon grandiflorus (Jacq.) A. DC).

Waterlogging stress is a major limiting factor resulting in stunted growth and loss of crop productivity, especially for root crops. However, physiological responses to waterlogging have been studied in only a few plant models. To gain insight into how balloon flower (Platycodon grandiflorus (Jacq.) A. DC) responds to waterlogging stress, we investigate changes to sucrose metabolism combined with a physiological analysis. Although waterlogging stress decreased the photosynthetic rate in balloon flower, leaves exhibited an increase in glucose (ninefold), fructose (4.7-fold), and sucrose (2.1-fold), indicating inhibition of sugar transport via the phloem. In addition, roots showed a typical response to hypoxia, such as the accumulation of proline (4.5-fold higher than in control roots) and soluble sugars (2.1-fold higher than in control roots). The activities and expression patterns of sucrose catabolizing enzymes suggest that waterlogging stress leads to a shift in the pathway of sucrose degradation from invertase to sucrose synthase (Susy), which consumes less ATP. Furthermore, we suggest that the waterlogging-stress-induced gene PlgSusy1 encodes the functional Susy enzyme, which may contribute to improving tolerance in balloon flower to waterlogging. As a first step toward understanding the waterlogging-induced regulatory mechanisms in balloon flower, we provide a solid foundation for further understanding waterlogging-induced alterations in source-sink relationships. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01310-y.

Overexpression of the Brassica rapa bZIP Transcription Factor, BrbZIP-S, Increases the Stress Tolerance in Nicotiana benthamiana.

In higher plants, S1-basic region-leucine zipper (S1-bZIP) transcription factors fulfill crucial roles in the physiological homeostasis of carbon and amino acid metabolisms and stress responses. However, very little is known about the physiological role of S1-bZIP in cruciferous vegetables. Here, we analyzed the physiological function of S1-bZIP from Brassica rapa (BrbZIP-S) in modulating proline and sugar metabolism. Overexpression of BrbZIP-S in Nicotiana benthamiana resulted in delayed chlorophyll degradation during the response to dark conditions. Under heat stress or recovery conditions, the transgenic lines exhibited a lower accumulation of H2O2, malondialdehyde, and protein carbonyls compared to the levels in transgenic control plants. These results strongly indicate that BrbZIP-S regulates plant tolerance against dark and heat stress. We propose that BrbZIP-S is a modulator of proline and sugar metabolism, which are required for energy homeostasis in response to environmental stress conditions.

PlgMYBR1, an R2R3-MYB transcription factor, plays as a negative regulator of anthocyanin biosynthesis in Platycodon grandiflorus.

Floral color plays a major role in pollinator specificity, and changes in color may result in pollinator shifts and pollinator-mediated speciation. In the purple flowers of Platycodon grandiflorus, anthocyanins are the major pigment metabolites, whereas white flowers result due to the absence of anthocyanins. The lack of anthocyanins may be due to the inhibition of the anthocyanin biosynthesis pathway. However, the molecular mechanism of anthocyanin biosynthesis in P. grandiflorus is not fully understood. Hence, we identified R2R3-MYB transcription factor, PlgMYBR1, as a negative regulator for anthocyanin biosynthesis using sequence homology and tissue-specific expression pattern analyses. A heterologous co-expression assay suggested that PlgMYBR1 inhibited the function of AtPAP1 (Arabidopsis thaliana production of anthocyanin pigment 1), indicating that PlgMYBR1 plays as a repressor of anthocyanin biosynthesis in P. grandiflorus. Our results provide a foundation for future efforts to understand the anthocyanin biosynthesis in P. grandiflorus and, thereby, to improve flower color through genetic engineering. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03490-6.

Complete Chloroplast Genome of the Inverted Repeat-Lacking Species Vicia bungei and Development of Polymorphic Simple Sequence Repeat Markers.

Background: Vicia bungei is an economically important forage crop in South Korea and China. Although detailed genetic and genomic data can improve population genetic studies, conservation efforts, and improved breeding of crops, few such data are available for Vicia species in general and none at all for V. bungei. Therefore, the main objectives of this study were to sequence, assemble, and annotate V. bungei chloroplast genome and to identify simple sequence repeats (SSRs) as polymorphic genetic markers. Results: The whole-genome sequence of V. bungei was generated using an Illumina MiSeq platform. De novo assembly of complete chloroplast genome sequences was performed for the low-coverage sequence using CLC Genome Assembler with a 200-600-bp overlap size. Vicia bungei chloroplast genome was 130,796-bp long. The genome lacked an inverted repeat unit and thus resembled those of species in the inverted repeat-lacking clade within Fabaceae. Genome annotation using Dual OrganellarGenoMe Annotator (DOGMA) identified 107 genes, comprising 75 protein-coding, 28 transfer RNA, and 4 ribosomal RNA genes. In total, 432 SSRs were detected in V. bungei chloroplast genome, including 64 mononucleotides, 14 dinucleotides, 5 trinucleotides, 4 tetranucleotides, 233 pentanucleotides, 90 hexanucleotides, and 14 complex repeated motifs. These were used to develop 232 novel chloroplast SSR markers, 39 of which were chosen at random to test amplification and genetic diversity in Vicia species (20 accessions from seven species). The unweighted pair group method with arithmetic mean cluster analysis identified seven clusters at the interspecies level and intraspecific differences within clusters. Conclusion: The complete chloroplast genome sequence of V. bungei was determined. This reference genome should facilitate chloroplast resequencing and future searches for additional genetic markers using population samples. The novel chloroplast genome resources and SSR markers will greatly contribute to the conservation of the genus Vicia and facilitate genetic and evolutionary studies of this genus and of other higher plants.

Plant Response to Cold Stress: Cold Stress Changes Antioxidant Metabolism in Heading Type Kimchi Cabbage (Brassica rapa L. ssp. Pekinensis).

Cold stress is known as the important yield-limiting factor of heading type Kimchi cabbage (HtKc, Brassica rapa L. ssp. pekinensis), which is an economically important crop worldwide. However, the biochemical and molecular responses to cold stress in HtKc are largely unknown. In this study, we conducted transcriptome analyses on HtKc grown under normal versus cold conditions to investigate the molecular mechanism underlying HtKc responses to cold stress. A total of 2131 genes (936 up-regulated and 1195 down-regulated) were identified as differentially expressed genes and were significantly annotated in the category of "response to stimulus". In addition, cold stress caused the accumulation of polyphenolic compounds, including p-coumaric, ferulic, and sinapic acids, in HtKc by inducing the phenylpropanoid pathway. The results of the chemical-based antioxidant assay indicated that the cold-induced polyphenolic compounds improved the free-radical scavenging activity and antioxidant capacity, suggesting that the phenylpropanoid pathway induced by cold stress contributes to resistance to cold-induced reactive oxygen species in HtKc. Taken together, our results will serve as an important base to improve the cold tolerance in plants via enhancing the antioxidant machinery.

Identification and Functional Characterization of FLOWERING LOCUS T in Platycodon grandiflorus.

Platycodon grandiflorus roots have been used as a foodstuff and traditional medicine for thousands of years in East Asia. In order to increase the root development of P. grandiflorus, cultivators removed the inflorescences, suggesting the possible negative effect of flowering on root development. This indicates that the genetic improvement of P. grandiflorus by late flowering is a potential approach to increase productivity. However, nothing is known about key genes integrating multiple flowering pathways in P. grandiflorus. In order to fill this gap, we identified potential homologs of the FLOWERING LOCUS T (FT) gene in P. grandiflorus. The alignment with other FT members and phylogenetic analysis revealed that the P. grandiflorus FT (PlgFT) protein contains highly conserved functional domains and belongs to the FT-like clade. The expression analysis revealed spatial variations in the transcription of PlgFT in different organs. In addition, the expression level of PlgFT was increased by high temperature but not by photoperiodic light input signals, presumably due to lacking the CONSTANS binding motif in its promoter region. Furthermore, PlgFT induced early flowering upon its overexpression in P. grandiflorus, suggesting the functional role of PlgFT in flowering. Taken together, we functionally characterized PlgFT as a master regulator of P. grandiflorus flowering under inductive high temperature, which will serve as an important target gene for improving the root productivity.

ROS-mediated plasmodesmal regulation requires a network of an Arabidopsis receptor-like kinase, calmodulin-like proteins, and callose synthases.

Plasmodesmata (PD) play a critical role in symplasmic communication, coordinating plant activities related to growth & development, and environmental stress responses. Most developmental and environmental stress signals induce reactive oxygen species (ROS)-mediated signaling in the apoplast that causes PD closure by callose deposition. Although the apoplastic ROS signals are primarily perceived at the plasma membrane (PM) by receptor-like kinases (RLKs), such components involved in PD regulation are not yet known. Here, we show that an Arabidopsis NOVEL CYS-RICH RECEPTOR KINASE (NCRK), a PD-localized protein, is required for plasmodesmal callose deposition in response to ROS stress. We identified the involvement of NCRK in callose accumulation at PD channels in either basal level or ROS-dependent manner. Loss-of-function mutant (ncrk) of NCRK induces impaired callose accumulation at the PD under the ROS stress resembling a phenotype of the PD-regulating GLUCAN SYNTHASE-LIKE 4 (gsl4) knock-out plant. The overexpression of transgenic NCRK can complement the callose and the PD permeability phenotypes of ncrk mutants but not kinase-inactive NCRK variants or Cys-mutant NCRK, in which Cys residues were mutated in Cys-rich repeat ectodomain. Interestingly, NCRK mediates plasmodesmal permeability in mechanical injury-mediated signaling pathways regulated by GSL4. Furthermore, we show that NCRK interacts with calmodulin-like protein 41 (CML41) and GSL4 in response to ROS stress. Altogether, our data indicate that NCRK functions as an upstream regulator of PD callose accumulation in response to ROS-mediated stress signaling pathways.

Antioxidant and Anti-Melanogenic Activities of Heat-Treated Licorice (Wongam, Glycyrrhiza glabra × G. uralensis) Extract.

Melanin is a brown or black pigment that protects skin from ultraviolet radiation and reactive oxygen species (ROS). However, overproduction of melanin is associated with lentigines, melasma, freckles and skin cancer. Licorice has shown antioxidant, anti-tumor, anti-platelet, anti-inflammatory and immunomodulatory activities and is used as a natural treatment for skin whitening. We aimed to confirm the potential of Wongam, a new cultivar of licorice developed by the Rural Development Administration (RDA), as a whitening agent in cosmetics. In addition, we verified the effect of heat treatment on the bioactivity of licorice by comparing antioxidant and anti-melanogenic activities of licorice extract before and after heating (130 °C). The heat-treated licorice extract (WH-130) showed higher radical-scavenging activities in the ABTS+ (2,2'-azino-bis-(3-ethylbenzothiazolin-6-sulfonic acid) diammonium salt) and DPPH (2,2-diphenyl-1-picrylhydrazyl) assays. In addition, WH-130 inhibited melanogenesis more effectively due to downregulation of tyrosinase in B16F10 melanoma cells than non-heated licorice extract. Moreover, heat treatment increased total phenolic content. In particular, isoliquiritigenin, an antioxidant and anti-melanogenic compound of licorice, was produced by heat treatment. In conclusion, WH-130, with increased levels of bioactive phenolics such as isoliquiritigenin, has potential for development into a novel skin whitening material with applications in cosmetics.

Evaluation of Genetic Diversity and Population Structure Analysis among Germplasm of Agaricus bisporus by SSR Markers.

Agaricus bisporus is a popular edible mushroom that is cultivated worldwide. Due to its secondary homothallic nature, cultivated A. bisporus strains have low genetic diversity, and breeding novel strains is challenging. The aim of this study was to investigate the genetic diversity and population structure of globally collected A. bisporus strains using simple sequence repeat (SSR) markers. Agaricus bisporus strains were divided based on genetic distance-based groups and model-based subpopulations. The major allele frequency (MAF), number of genotypes (NG), number of alleles (NA), observed heterozygosity (HO), expected heterozygosity (HE), and polymorphic information content (PIC) were calculated, and genetic distance, population structure, genetic differentiation, and Hardy-Weinberg equilibrium (HWE) were assessed. Strains were divided into two groups by distance-based analysis and into three subpopulations by model-based analysis. Strains in subpopulations POP A and POP B were included in Group I, and strains in subpopulation POP C were included in Group II. Genetic differentiation between strains was 99%. Marker AB-gSSR-1057 in Group II and subpopulation POP C was confirmed to be in HWE. These results will enhance A. bisporus breeding programs and support the protection of genetic resources.

Development of CAPS Markers for Evaluation of Genetic Diversity and Population Structure in the Germplasm of Button Mushroom (Agaricus bisporus).

Agaricus bisporus is a globally cultivated mushroom with high economic value. Despite its widespread cultivation, commercial button mushroom strains have little genetic diversity and discrimination of strains for identification and breeding purposes is challenging. Molecular markers suitable for diversity analyses of germplasms with similar genotypes and discrimination between accessions are needed to support the development of new varieties. To develop cleaved amplified polymorphic sequences (CAPs) markers, single nucleotide polymorphism (SNP) mining was performed based on the A. bisporus genome and resequencing data. A total of 70 sets of CAPs markers were developed and applied to 41 A. bisporus accessions for diversity, multivariate, and population structure analyses. Of the 70 SNPs, 62.85% (44/70) were transitions (G/A or C/T) and 37.15% (26/70) were transversions (A/C, A/T, C/G, or G/T). The number of alleles per locus was 1 or 2 (average = 1.9), and expected heterozygosity and gene diversity were 0.0-0.499 (mean = 0.265) and 0.0-0.9367 (mean = 0.3599), respectively. Multivariate and cluster analyses of accessions produced similar groups, with F-statistic values of 0.134 and 0.153 for distance-based and model-based groups, respectively. A minimum set of 10 markers optimized for accession identification were selected based on high index of genetic diversity (GD, range 0.299-0.499) and major allele frequency (MAF, range 0.524-0.817). The CAPS markers can be used to evaluate genetic diversity and population structure and will facilitate the management of emerging genetic resources.

Molecular Cloning and Functional Characterization of Heat Stress-Responsive Superoxide Dismutases in Garlic (Allium sativum L.).

Superoxide dismutases (SODs) are key antioxidant enzymes that can detoxify the superoxide radicals generated by various stresses. Although various plant SODs have been suggested to improve stress tolerance, SODs in garlic, an economically important vegetable grown worldwide, remain relatively unknown. In this study, we found that heat stress strongly induced the activities of Cu/ZnSODs, FeSODs, and MnSODs in garlic leaves. In addition, we cloned four garlic SODs (AsSODs) and suggest that heat stress-increased SOD activity was reflected at least by the induction of these AsSODs. The results of the agro-infiltration assay suggested that the cloned AsSODs encoded functional SOD enzymes belonging to the Cu/ZnSOD and MnSOD families. As a first step toward understanding the enzymatic antioxidant system in garlic plants, our results provide a solid foundation for an in-depth analysis of the physiological functions of the AsSOD family.

UPLC-ESI-Q-TOF-MS-Based Metabolite Profiling, Antioxidant and Anti-Inflammatory Properties of Different Organ Extracts of Abeliophyllum distichum.

Plant extracts have gained more attention as natural therapeutic agents against inflammation characterized by an overproduction of several inflammatory mediators such as reactive oxygen species and pro-inflammatory cytokines. Although Abeliophyllum distichum Nakai is generally known for its ornamental value, recent pharmacological research has demonstrated its potential therapeutic properties. Thus, to further evaluate the applicability of A. distichum in the food, cosmetic, and medical industries, we identified the phytochemicals in three organ extracts (fruits: AF, branches: AB, leaves: AL) of A. distichum and determined their antioxidant and anti-inflammatory activities. Using UPLC-ESI-Q-TOF-MS, a total of 19 compounds, including dendromoniliside D, forsythoside B, isoacteoside, isomucronulatol 7-O-Glucoside, plantamajoside, and wighteone were identified in the A. distichum organ extracts. AB exhibited a strong reducing power, an oxygen radical antioxidant capacity, and radical scavenging values compared with other samples, whereas AL exhibited the best anti-inflammatory properties. Gene expression, western blot, and molecular docking analyses suggested that the anti-inflammatory effect of AL was mediated by its ability to suppress lipopolysaccharide (LPS)-induced production of reactive oxygen species and/or inhibit LPS-stimulated activation of extracellular signal-regulated protein kinases (ERK1/2) in RAW264.7 cells. Collectively, these results indicate that AL is a potential source of phytochemicals that could be used to treat inflammation-associated diseases.

Establishment of a UPLC-PDA/ESI-Q-TOF/MS-Based Approach for the Simultaneous Analysis of Multiple Phenolic Compounds in Amaranth (A. cruentus and A. tricolor).

We used ultraperformance liquid chromatography coupled with a photodiode-array detector and electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-PDA/ESI-Q-TOF/MS) to rapidly and accurately quantify 17 phenolic compounds. Then, we applied this method to the seed and leaf extracts of two Amaranthus species to identify and quantify phenolic compounds other than the 17 compounds mentioned above. Compounds were eluted within 30 min on a C18 column using a mobile phase (water and acetonitrile) containing 0.1% formic acid, and the specific wavelength and ion information of the compounds obtained by PDA and ESI-Q-TOF/MS were confirmed. The proposed method showed good linearity (r2 > 0.990). Limits of detection and quantification were less than 0.1 and 0.1 µg/mL, respectively. Intra- and interday precision were less than 2.4% and 1.8%, respectively. Analysis of amaranth seed and leaf extracts using the established method showed that the seeds contained high amounts of 2,4-dihydroxybenzoic acid and kaempferol, and leaves contained diverse phenolic compounds. In addition, six tentatively new phenolic compounds were identified. Moreover, seeds potentially contained 2,3-dihydroxybenzaldehyde, a beneficial bioactive compound. Thus, our method was an efficient approach for the qualitative and quantitative analysis of phenolic compounds, and could be used to investigate phenolic compounds in plants.

Ectopic Expression of Production of Anthocyanin Pigment 1 (PAP1) Improves the Antioxidant and Anti-Melanogenic Properties of Ginseng (Panax ginseng C.A. Meyer) Hairy Roots.

The development of genetically engineered cell cultures has been suggested as a potential approach for the production of target compounds from medicinal plants. In this study, we generated PAP1 (production of anthocyanin pigment 1)-overexpressing ginseng (Panax ginseng C.A. Meyer) hairy roots to improve the production of anthocyanins, as well as the bioactivity (e.g., antioxidant and whitening activities) of ginseng. Based on differentially expressed gene analysis, we found that ectopic expression of PAP1 induced the expression of genes involved in the 'phenylpropanoid biosynthesis' (24 genes), and 'flavonoid biosynthesis' (17 genes) pathways, resulting in 191- to 341-fold increases in anthocyanin production compared to transgenic control (TC) hairy roots. Additionally, PAP1-overexpressing ginseng hairy roots exhibited an approximately seven-fold higher DPPH-free radical scavenging activity and 10-fold higher ORAC value compared to the TC. In α-melanocyte-stimulating hormone-stimulated B16F10 cells, PAP1-overexpressing ginseng hairy roots strongly inhibited the accumulation of melanin by 50 to 59% compared to mock-control. Furthermore, results obtained by quantitative real-time PCR, western blot, and tyrosinase inhibition assay suggested that the anti-melanogenic activity of PAP1-overexpressing ginseng hairy roots is mediated by tyrosinase activity inhibition. Taken together, our results suggested that the ectopic expression of PAP1 is an effective strategy for the enhancement of anthocyanin production, which improves the biological activities of ginseng root cultures.

Anti-Melanoma Activities and Phytochemical Compositions of Sorbus commixta Fruit Extracts.

Sorbus commixta Hedl. (Rosaceae family) has a long history as a medicinal plant in East Asian countries. In this study, we evaluated the effect of S. commixta fruit extracts prepared with different ethanol concentrations on anti-melanoma activity, and the extraction yield of phenolic compounds and flavonoids. Using the partitioned fractions from the EtOH extract, we found that the butanol fraction (BF) possessed strong cytotoxic activity against SK-MEL-2 cells (human melanoma cells) but not against HDFa cells (human dermal fibroblast adult cells). Additionally, BF-induced cell death was mediated by the inhibition of the mitogen-activated protein kinase/extracellular regulated kinase (MEK/ERK) signaling pathway, coupled with the upregulation of caspase-3 activity in SK-MEL-2 cells. Furthermore, HPLC analysis of polyphenolic compounds suggested that S. commixta fruits contained several active compounds including chlorogenic acid, rutin, protocatechuic acid, and hydroxybenzoic acid, all of which are known to possess anti-cancer activities. Although this study has been carried out by cell-based approach, these results suggest that S. commixta fruits contain promising anti-melanoma compounds.

Transcriptome Analysis Reveals That Abeliophyllum distichum Nakai Extract Inhibits RANKL-Mediated Osteoclastogenensis Mainly Through Suppressing Nfatc1 Expression.

Abeliophyllum distichum Nakai is known as a monotypic genus endemic to South Korea. Currently, several pharmacological studies have revealed that A. distichum extract exhibits diverse biological functions, including anti-cancer, anti-diabetic, anti-hypertensive, and anti-inflammatory activities. In this study, we present the anti-osteoporotic activity of A. distichum extract by inhibiting osteoclast formation. First, we show that the methanolic extract of the leaves of A. distichum, but not extracts of the branches or fruits, significantly inhibits receptor activator of the NF-κB ligand (RANKL)-induced osteoclast differentiation. Second, our transcriptome analysis revealed that the leaf extract (LE) blocks sets of RANKL-mediated osteoclast-related genes. Third, the LE attenuates the phosphorylation of extracellular signal-related kinase. Finally, treatment with the LE effectively prevents postmenopausal bone loss in ovariectomized mice and glucocorticoid-induced osteoporosis in zebrafish. Our findings show that the extract of A. distichum efficiently suppressed osteoclastogenesis by regulating osteoclast-related genes, thus offering a novel therapeutic strategy for osteoporosis.