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Background Main bioactive constituents and pharmacological functions of ripened red ginseng berry (Panax ginseng Meyer) have been frequently reported. Yet, the research gap targeting the beneficial activities of transformed green ginseng berries has not reported elsewhere. Methods Ginsenosides of new green berry cultivar K-1 (GK-1) were identified by HPLC-QTOF/MS. Ginsenosides bioconversion in GK-1 by bgp1 enzyme was confirmed with HPLC and TLC. Then, mechanisms of GK-1 and β-glucosidase (bgp1) biotransformed GK-1 (BGK-1) were determined by Quantitative Reverse Transcription-Polymerase Chain Reaction and Western blot. Results GK-1 possesses highest ginsenosides especially ginsenoside-Re amongst seven ginseng cultivars including (Chunpoong, Huangsuk, Kumpoong, K-1, Honkaejong, Gopoong, and Yunpoong). Ginseng root’s biomass is not affected with the harvest of GK-1 at 3 weeks after flowering period. Then, Re is bio-converted into a promising pharmaceutical effect of Rg2 via bgp1. According to the results of cell assays, BGK-1 shows decrease of tyrosinase and melanin content in α-melanocyte-stimulating hormone challenged-murine melanoma B16 cells. BGK-1 which is comparatively more effective than GK-1 extract shows significant suppression of the nuclear factor (NF)-κB activation and inflammatory target genes, in LPS-stimulated RAW 264.7 cells. Conclusion These results reported effective whitening and anti-inflammatory of BGK-1 as compared to GK-1., Graphical abstract Image 1

더덕(Codonopsis lanceolata)은 주로 한국, 중국 등 동아시아 지역에 재배되고 있으며, 더덕의 뿌리는 기침, 기관지염, 천식, 결핵, 소화 불량의 증상을 치료하기 위한 기능성 식품 및 전통 의학으로 사용되어져 왔다. 보고된 바에 의하면 phenylpropanoids, polyacetylenes, saponins, flavonoids와 같은 다양한 식물 천연물 성분들이 항비만, 항염, 항암, 항산화, 항미생물 활성과 같은 약리학적 작용에 관여한다고 보고되어 있다. MS기반 대사체학 분석을 이용한 주산지의 마커 성분을 선정하는 것은 다른 지역에서 재배된 약용 식물의 안전성뿐만 아니라 화학적 조성과 생물학적 효능의 변화와도 관련이 있기 때문에 부작용 없이 더덕의 유익한 효과만을 보장하는데 중요하다. 본 연구에서는 국내산 더덕의 주산지 특성을 구별하기 위해 UPLC-QTOF-MS를 기반으로 하는 대사체 프로파일링과 다변량 통계분석 기법인 PCA 분석을 수행하여 판별모델을 확립하였다. 그 결과 인제(강원도), 횡성(강원도), 무주(전라북도)의 3개 그룹이 PCA와 loading plot 분석결과 tangshenoside I, lancemaside A, lancemaside G는 더덕 주산지를 구별하기 위한 잠재적 대사체 마커들로 제안하였다.

Repeated column chromatography of solvent fractions extracted from the flowers of Lilium Asiatic hybrids ensured purification of three benzyl glycosides I – III, which were reliably identified based on the analysis of various spectroscopic data. Compounds I – III (20 μg/mL) reduced nuclear factor-kappa B (NF-kB) (p-p65/p-65) by 9.64 ± 0.66%, 30.98 ± 1.08%, and 54.04 ± 1.12%, respectively. Compounds II and III markedly inhibited the expression of vascular cell adhesion molecule 1 (VCAM-1) in tumor necrosis factor (TNF)-α-stimulated human aortic smooth muscle cells (HASMCs) by 38.68 ± 2.52% and 37.9 ± 2.76%, respectively. Compound III significantly suppressed U937 monocytes attachment to the TNF-α-stimulated HASMCs.

Artemisia iwayomogi (Compositae), a perennial mugwort, is native to Korea and widely distributed in Japan, Russia, and China. A. iwayomogi and A. capillaris are similar in morphology and pharmacological activity and have been used for the same medicinal purposes in Korea. While various ingredients such as coumarins and flavonoids and their activity studies have been reported for A. capillaris, few studies have been conducted on the pharmacologically active components of A. iwayomogi. In Korea, A. capillaris is not economical because only young leaves are used as a medicinal material. Because of this, A. iwayomogi is frequently used in Korea, indicating the need to study its pharmacologically active components. Therefore, a phytochemical study was initiated to isolate active compounds from the aerial parts of A. iwayomogi. Finally, four coumarins, umbelliferone (1), esculetin (2), grevillone (3), and scoparone (4) were isolated for the first time from the aerial parts of A. iwayomogi in this study.

Many attempts have been made to obtain natural products with certain glycosidic linkages for improvement of their chemo-physical characteristics. Amylosucrase from Deinococcus geothermalis (DGAS; EC.4.2.1.4) is able to transglycosylate natural products. A model compound, isoquercitrin (IQ; quercetin-3-O-glucoside), was employed for producing new IQ glucosides (IQ-Gs). Treatment of IQ with DGAS produced monoglucoside (IQ-G1'), diglucosides (IQ-G2' and IQ-G2″), and triglucoside (IQ-G3). Structural analysis by mass and nuclear magnetic resonance spectrometry revealed that three of the four IQ-Gs were unreported new compounds possessing α-1,2-, α-1,4-, and/or α-1,6-glucosidic linkages at the 3-O-glucosyl moiety of IQ. IQ-G2' and IQ-G3 were dominantly produced at pH 5.0 and 7.2 and 1500 and 100 mM sucrose, respectively (yields of total IQ-Gs: 50-97%). Kinetic studies indicated that the production rate was dependent on buffer/pH and sucrose concentration. The diverse transglycosylations were verified with a molecular docking simulation. This study sheds light on methods for simple glycodiversification of natural products using DGAS, which can synthesize diversely branched glycosides by modulating reaction conditions.

Repeated column chromatography of Syringa dilatata flowers, a native shrub to Korea, led to the isolation of eight new oleoside-type secoiridoids, syringoleosides A–H (1–8), as well as five known s...

The production of soybean continues to increase worldwide. People are showing more interest in the beneficial health effects of soybeans than before. However, the origin and history of soybeans are still being discussed among many researchers. Chromatographic methods enable the desirable separation of a variety of isoflavones from soybeans. The structures of isolated soy isoflavones have been successfully identified in tandem with spectroscopic analytical instruments and technologies such as liquid chromatography, mass spectrometry, and nuclear magnetic resonance spectroscopy. The theoretical background behind spectroscopy may help improve the understanding for the analysis of isoflavones in soybeans and soy-derived foods. This review covers the origin of the English name of soybean and its scientific name, Glycine max (L.) Merrill, based on the evidence reported to date. Moreover, the reports of soy isoflavones discovered over a period of about 100 years have been briefly reviewed.

Brugmansia arborea L. (Solanaceae), commonly known as "angel's trumpet," is widely grown in North America, Africa, Australia, and Asia. It has been mainly used for ornamental purposes as well as analgesic, anti-rheumatic, vulnerary, decongestant, and anti-spasmodic materials. B. arborea is also reported to show anti-cholinergic activity, for which many alkaloids were reported to be principally responsible. However, to the best of our knowledge, a phytochemical study of B. arborea flowers has not yet been performed. Four flavonol glycosides (1-4) and one dihydroflavanol (5) were for the first time isolated from B. arborea flowers in this study. The flavonoids showed significant antioxidant capacities, suppressed nitric oxide production in lipopolysaccharide (LPS)-treated RAW 264.7 cells, and reduced inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) protein production increased by LPS treatment. The contents of compounds 1-4 in n-BuOH fraction were determined to be 3.8 ± 0.9%, 2.2 ± 0.5%, 20.3 ± 1.1%, and 2.3 ± 0.4%, respectively, and that of compound 5 in EtOAc fraction was determined to be 12.7 ± 0.7%, by HPLC experiment. These results suggest that flavonol glycosides (1-4) and dihydroflavanol (5) can serve as index components of B. arborea flowers in standardizing anti-inflammatory materials.

The androgen receptor (AR) plays an important role in the pathogenesis and development of prostate cancer (PCa). Mostly, PCa progresses to androgen-independent PCa, which has activated AR signaling from androgen-dependent PCa. Thus, inhibition of AR signaling may be an important therapeutic target in androgen-dependent and castration-resistant PCa. In this study, we determined the anticancer effect of a newly found natural compound, sakurasosaponin (S-saponin), using androgen-dependent and castration-resistant PCa cell lines. S-saponin induces mitochondrial-mediated cell death in both androgen-dependent (LNCaP) and castration-resistant (22Rv1 and C4-2) PCa cells, via AR expression. S-saponin treatment induces a decrease in AR expression in a time- and dose-dependent manner and a potent decrease in the expression of its target genes, including prostate-specific antigen (PSA), transmembrane protease, serin 2 (TMPRSS2), and NK3 homeobox 1 (NKX3.1). Furthermore, S-saponin treatment decreases B-cell lymphoma-extra large (Bcl-xL) and mitochondrial membrane potential, thereby increasing the release of cytochrome c into the cytosol. Moreover, Bcl-xL inhibition and subsequent mitochondria-mediated cell death caused by S-saponin were reversed by Bcl-xL or AR overexpression. Interestingly, S-saponin-mediated cell death was significantly reduced by a reactive oxygen species (ROS) scavenger, N-acetylcystein. Animal xenograft experiments showed that S-saponin treatment significantly reduced tumor growth of AR-positive 22Rv1 xenografts but not AR-negative PC-3 xenografts. Taken together, for the first time, our results revealed that S-saponin induces mitochondrial-mediated cell death in androgen-dependent and castration-resistant cells through regulation of AR mechanisms, including downregulation of Bcl-xL expression and induction of ROS stress by decreasing mitochondrial membrane potential.

고려인삼(Panax ginseng C.A. Meyer)을 70% EtOH 수용액으로 저온 추출한 뒤, 감압 농축한 추출물을SiO2, ODS column chromatograph 및 중압분취(MPLC) 장비를 반복 실시하여 4종의 인삼 사포닌 화합물을 분리 및 정제하였다. NMR 및 고분해능 질량분석 장비를 이용하여 malonyl ginsenoside Rd (1), Rc (2), Rb2 (3), 및 Rb1 (4)로 구조 동정하였다. 분리한 4종의 화합물에 대하여 UPLC-MS/MS 질량분석기를 이용하여 수삼의 5년 및 6년근 뿌리의 동체를 정량분석 하였으며, malonyl ginsenoside의 총 함량의 합은 각각 6.62 및 2.34 mg/g으로 5년근이 약 2.8배 높은 것을 확인하였다. 인삼으로부터 분리된 화합물 중 malonyl ginsenoside Rd의 경우, 알코올에 의해 저해 된 HepG2세포에 대해서 간세포를 보호하는 효과가 있음을 확인하였다.

Background Ginsenoside Rh2 is well known for many pharmacological activities, such as anticancer, antidiabetes, antiinflammatory, and antiobesity properties. Glycosyltransferases (GTs) are ubiquitous enzymes present in nature and are widely used for the synthesis of oligosaccharides, polysaccharides, glycoconjugates, and novel derivatives. We aimed to synthesize new ginsenosides from Rh2 using the recombinant GT enzyme and investigate its cytotoxicity with diverse cell lines. Methods We have used a GT gene with 1,224-bp gene sequence cloned from Lactobacillus rhamnosus (LRGT) and then expressed in Escherichia coli BL21 (DE3). The recombinant GT protein was purified and demonstrated to transform Rh2 into two novel ginsenosides, and they were characterized by nuclear magnetic resonance (NMR) techniques and evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide assay. Results Two novel ginsenosides with an additional glucopyranosyl (6→1) and two additional glucopyranosyl (6→1) linked with the C-3 position of the substrate Rh2 were synthesized, respectively. Cell viability assay in the lung cancer (A549) cell line showed that glucosyl ginsenoside Rh2 inhibited cell viability more potently than ginsenoside Rg3 and Rh2 at a concentration of 10 μM. Furthermore, glucosyl ginsenoside Rh2 did not exhibit any cytotoxic effect in murine macrophage cells (RAW264.7), mouse embryo fibroblasts cells (3T3-L1), and skin cells (B16BL6) at a concentration of 10 μM compared with ginsenoside Rh2 and Rg3. Conclusion This is the first report on the synthesis of two novel ginsenosides, namely, glucosyl ginsenoside Rh2 and diglucosyl ginsenoside Rh2 from Rh2 by using recombinant GT isolated from L. rhamnosus. Moreover, diglucosyl ginsenoside Rh2 might be a new candidate for treatment of inflammation, obesity, and skin whiting, and especially for anticancer.

The extract from Cnidium officinale rhizomes was shown in a prior experiment to markedly recover otic hair cells in zebrafish damaged by neomycin. The current study was brought about to identify the principal metabolite. Column chromatography using octadecyl SiO2 and SiO2 was performed to isolate the major metabolites from the active fraction. The chemical structures were resolved on the basis of spectroscopic data, including NMR, IR, MS, and circular dichroism (CD) data. The isolated phthalide glycosides were assessed for their recovery effect on damaged otic hair cells in neomycin-treated zebrafish. Three new phthalide glycosides were isolated, and their chemical structures, including stereochemical characteristics, were determined. Two glycosides (0.1 μM) showed a recovery effect (p < 0.01) on otic hair cells in zebrafish affected by neomycin ototoxicity. Repeated column chromatography led to the isolation of three new phthalide glycosides, named ligusticosides C (1), D (2), and E (3). Ligusticoside C and ligusticoside E recovered damaged otic hair cells in zebrafish.

Cnidium officinalis rhizomes were immersed in 80% MeOH. The extract was fractionated to water, n-butanol, and ethyl acetate fractions (Fr). Open column chromatography was repeatedly carried out on n-butanol and ethyl acetate Fr using silica gel, octadecyl silica gel, and Sephadex LH-20 as the stationary phase affording five phenyl alkanoids 1–5 including two new ones. The molecular structures including stereochemistry were decided based on spectroscopic interpretation of nuclear magnetic resonance, mass spectrometry, and infrared spectroscopy as well as chemical reaction. Three known compounds, coniferyl alcohol methyl ether (1), vanillin (2), and coniferyl aldehyde (3), were reported in the beginning for this plant by authors. Two new phenyl alkanoids were named, 7-methoxyeugenol and cnidiumoside.

(1) Background: Many flavonoids have been reported to exhibit pharmacological activity, a preparatory study confirmed that Coreopsis lanceolata flowers (CLFs) contained high flavonoid structure content, (2) Methods: CLFs were extracted in aqueous methanol (MeOH:H2O = 4:1) and fractionated into acetic ester (EtOAc), normal butanol (n-BuOH), and H2O fractions. Repeated column chromatographies for two fractions led to the isolation of two aurones and two flavonols, (3) Results: Four flavonoids were identified based on a variety of spectroscopic data analyses to be leptosidin (1), leptosin (2), isoquercetin (3), and astragalin (4), respectively. This is the first report for isolation of 2–4 from CLFs. High-performance liquid chromatography (HPLC) analysis determined the content levels of compounds 1–4 in the MeOH extract to be 2.8 ± 0.3 mg/g (1), 17.9 ± 0.9 mg/g (2), 3.0 ± 0.2 mg/g (3), and 10.9 ± 0.9 mg/g (4), respectively. All isolated compounds showed radical scavenging activities and recovery activities in Caco-2, RAW264.7, PC-12, and HepG2 cells against reactive oxygen species. MeOH extract, EtOAc fraction, and 1–3 suppressed NO formation in LPS-stimulated RAW 264.7 cells and decreased iNOS and COX-2 expression. Furthermore, all compounds recovered the pancreatic islets damaged by alloxan treatment in zebrafish, (4) Conclusions: The outcome proposes 1–4 to serve as components of CLFs in standardizing anti-oxidant, pro-inflammatory inhibition, and potential anti-diabetic agents.

Acanthopanax sessiliflorus (Araliaceae) have been reported to exhibit many pharmacological activities. Our preliminary study suggested that A. sessiliflorus fruits include many bioactive 3,4-seco-triterpenoids. A. sessiliflorus fruits were extracted in aqueous EtOH and fractionated into EtOAc, n-BuOH, and H2O fractions. Repeated column chromatographies for the organic fractions led to the isolation of 3,4-seco-triterpenoid glycosides, including new compounds. Ultra-high-performance liquid chromatography (UPLC) mass spectrometry (MS) systems were used for quantitation and quantification. BV2 and RAW264.7 cells were induced by LPS, and the levels of pro-inflammatory cytokines and mediators and their underlying mechanisms were measured by ELISA and Western blotting. NMR, IR, and HR-MS analyses revealed the chemical structures of the nine noble 3,4-seco-triterpenoid glycosides, acanthosessilioside G–O, and two known ones. The amounts of the compounds were 0.01–2.806 mg/g, respectively. Acanthosessilioside K, L, and M were the most effective in inhibiting NO, PGE2, TNF-α, IL-1β, and IL-6 production and reducing iNOS and COX-2 expression. In addition, it had inhibitory effects on the LPS-induced p38 and ERK MAPK phosphorylation in both BV2 and RAW264.7 cells. Nine noble 3,4-seco-triterpenoid glycosides were isolated from A. sessiliflorus fruits, and acanthosessilioside K, L, and M showed high anti-inflammatory and anti-neuroinflammatory effects.

Repeated column chromatography using Sephadex LH-20, silica gel (SiO2), and octadecyl SiO2 (ODS) as well as preparative HPLC column chromatography led to isolation of a new dibenzocyclooctadiene lignan along with four known ones, gomisin L2 (1), L1 (2), M1 (3), and M2 (4). Their chemical structures were fixed based on MS, IR, and NMR data analyses. In addition, the stereochemistry of atropisomers, the absolute configuration of the axial chirality in a biphenyl structure, was confirmed by a CD experiment. The new lignan was named gomisin M3 (5).

A new neolignan glucoside has been isolated from Chrysanthemum morifolium ‘Baekma’ cultivar through repeated silica gel and octadecyl silica gel (ODS) column chromatographies. On the basis of spectroscopic data including NMR, MS, and IR, the chemical structure of the new neolignan glucoside was determined to be (7S,8S)-7-O-[1′-(4′,5′-dihydroxy-3′-methoxyphenyl)propanol]guaiacylglycerol 4-O-β-D-glucopyranoside (1), named baekmaoside A.

β-Glucosylglycerol (β-GG) and their derivatives have potential applications in food, cosmetics and the healthcare industry, including antitumor medications. In this study, β-GG and its unnatural glycosides were synthesized through the transglycosylation of two enzymes, Sulfolobus shibatae β-glycosidase (SSG) and Deinococcus geothermalis amylosucrase (DGAS). SSG catalyzed a transglycosylation reaction with glycerol as an acceptor and cellobiose as a donor to produce 56% of β-GGs [β-D-glucopyranosyl-(1→1/3)-D-glycerol and β-D-glucopyranosyl- (1→2)-D-glycerol]. In the second transglycosylation reaction, β-D-glucopyranosyl-(1 → 1/3)-Dglycerol was used as acceptor molecules of the DGAS reaction. As a result, 61% of α-Dglucopyranosyl-( 1→4)-β-D-glucopyranosyl-(1→1/3)-D-glycerol and 28% of α-D-maltopyranosyl- (1→4)-β-D-glucopyranosyl-(1→1/3)-D-glycerol were synthesized as unnatural glucosylglycerols. In conclusion, the combined enzymatic synthesis of the unnatural glycosides of β-GG was established. The synthesis of these unnatural glycosides may provide an opportunity to discover new applications in the biotechnological industry.

꼬리겨우살이(Loranthus tanakae) 전초를 80% MeOH 수용액으로 4회 반복 추출한 뒤, 감압 농축한 추출물을 ethyl acetate(EtOAc), n-butyl alcohol (n-BuOH)과 H2O층으로 계통 분획을 실시하였다. n-BuOH 분획에 대하여 silica gel (SiO2), octadecyl silica gel (ODS), Sephadex LH-20 column chromatographies를 반복실시하여 1종의 cyclofarnesane sesquiterpene glucoside 화합물을 분리 및 정제하였다. 스펙트럼 데이터를 분석하여 입체 구조를 포함한 화합물의 구조를 (1''R,3''S,5''R, 8''S,2E,4E)-dihydrophaseic acid 3''-O-β-D-glucopyranoside로 구조동정 하였다. 이 화합물은 이번 실험을 통하여 꼬리겨우살이로부터는 최초로 분리되었다. 분리한 단일 물질은 AGS (Caucasian gastric adenocarcinoma cells)와 Hepatocyte carcinoma cells에 대하여 50 μg/mL 이상에서 농도 의존적으로 유의한 정도의 세포독성을 보이는 것이 확인되었다.

Begonia semperflorens Link et Otto has been broadly raised up for ornamental purpose as well comestible blossom. As the reproductive structures of phanerogams, flowers contain various secondary metabolites and have many biological activities. Accordingly, we began the contrivance for isolation and analysis of flavonoids contained in B. semperflorens flowers. MeOH extraction of B. semperflorens followed solvent fractionation was prosecuted. Column chromatography of non-polar fraction gave four flavonoids using several resins. Identification of the flavonols were established as quercetin (1), kaempferol (2), astragalin (3), and isoquercetin (4) by interpreting a variety of spectral information. Quercetin (1) and kaempferol (2) inhibited NO production and protected against t-BHP-induced oxidative stress. Kaempferol (2) also protected cell death of glutamate-treated HT22. Quantitative analysis of flavonoid content in B. semperflorens flowers was also performed using HPLC experiment.

Repeated column separation yielded four enterolactone type lignans from Forsythia koreana flowers (FKF), whose chemical structures were identified using several spectral technics. FKF MeOH extract (FKFM) and four lignans significantly recovered aloxan induced pancreatic islet in zebrafish. Especially, aglycones, 1 and 3, exhibited relatively higher activity than the lignan glycosides, 2 and 4. Therefore, FKFM was fermented using a Microbacterium esteraromaticum, BGP1, to yield the fermented FKFM (FKFM-BGP1). FKFM and FKFM-BGP1 were extracted using n-butanol to give n-BuOH fraction of each, FKFM-nB and FKFM-BGP1-nB, respectively. FKFM-BGP1-nB showed higher activity than FKFM-nB, as well the content of the aglycones, 1 and 3, in FKFM-BGP1-nB, 2.42 ± 0.01% and 1.15 ± 0.01%, was revealed to be much higher than that in FKFM-nB, 0.01 ± 0.01% and 0.01 ± 0.01%, respectively. In conclusion, the lignan aglycones 1 and 3 as well FKFM-BGP1-nB from F. koreana flowers were proved to be potential anti-diabetic agents. Furthermore, we suggest that antidiabetic efficacy of FKFM-BGP1-nB might be related to lignan aglycones 1 and 3.

Abeliophyllum distichum (Oleaceae), which is the only species in the monotypic genus and is grown only on the Korean peninsula, has a high scarcity value. Its five variants (white, pink, round, blue, and ivory) have different morphological characteristics in terms of the color of petals and sepals or shape of the fruits. Despite its high value, there has been no study on variant classification except in terms of their morphological characteristics. Thus, we performed a volatile component analysis of A. distichum flowers and multivariate data analyses to reveal the relationship between fragments emitted from five variants of A. distichum flowers with their morphological characteristics. As a result, 66 volatile components of this plant were identified by headspace solid-phase microextraction gas chromatography&ndash, mass spectrometry (HS-SPME-GC-MS), showing unique patterns for each set of morphological characteristics, especially the color of the petals. These results suggest that morphological characteristics of each variant are related to the volatile composition.

An amendment to this paper has been published and can be accessed via the original article.

Soil has been used for treatment of wound and skin diseases and for cosmetic purposes. Fusidium coccineum (FC) SA-1FC (Ascomycota) is a fungus found in nature, and its by-products are present in humid soils with plant humus. This study investigates the medium of fermented FC as a covering for all skin problems, including dryness, inflammation, and wounds. A preliminary study revealed that an alcohol extract of FC had a skin-enhancing effect, and thin-layer chromatography revealed a major component in a non-polar fraction. Here we identify a major compound isolated from a non-polar fraction as β-glucogallin. The mRNA levels of filaggrin and HAS3 are upregulated by FC and β-glucogallin treatment in keratinocytes and immortalized human keratinocytes cells. In addition, FC and β-glucogallin exert anti-inflammatory effects by suppressing expression of interleukin-4/poly(I:C)-induced chemokines and inflammatory cytokines. In fibroblasts, Hs68 cells, FC and β-glucogallin stimulate cell migration. These results suggest that FC and β-glucogallin can enhance skin barrier function.

Various cucurbitacins have been isolated, and their structures have been elucidated. Owing to their economic potential and importance as active pharmacological compounds, their cytotoxicity in various cancer cells has been assessed. Here, we mined several candidate genes with potential involvement in cucurbitacin biosynthesis in watermelon (Citrullus lanatus) and performed in vitro enzymatic assays and instrumental analyses using various substrates to identify cucurbitacin functions and products. Enzymatic activities of two acetyltransferases (ACTs) and one UDP-glucosyltransferase (UGT) against cucurbitacins were confirmed, resulting in the synthesis of novel cucurbitacins in vivo and/or in vitro to our knowledge. As ACTs and UGT are involved in the dynamic conversion of cucurbitacins by catalyzing acetylation and glucosylation at moieties in the cucurbitacins skeleton, these findings improve our knowledge on how these genes contribute to the diversity of cucurbitacins., Kim et al. use RNAseq of two watermelons to select candidate genes coding for enzymes that catalyze modifications of cucurbitacins. They characterise four of the 16 candidate enzymes (3 different acetyltransferases and one UDP-glucosyltransferase) by HPLC, LC-MS, NMR, and in vitro enzymatic assay. They further show with in vivo assay in Drosophila, that acetylation of cucurbitacin increases neuronal activity in insects.

Repeated chromatographic separations of the EtOAc fraction of Schisandra chinensis fruits on silica gel, octadecyl silica gel, and Sephadex LH-20 led to the isolation and identification of seven dibenzocyclooctadiene lignans (1–7). The NMR data reported in the literature for angeloyl gomisin H (5) were shown to be incorrect. We unambiguously identified the compounds based on detailed analysis of the 1D and 2D NMR data, especially from HMBC and NOESY experiments. In addition, MTT assays and cell viability experiments verified the cytotoxicity of the isolated dibenzocyclooctadiene lignans against the human cancer cell lines AGS, HeLa, and HT-29.

(1) Background: Many flavonoids derived from natural sources have been reported to exhibit antioxidant and anti-inflammatory effects. Our preliminary study suggested that Coreopsis lanceolata flowers (CLFs) include high flavonoid content, (2) Methods: CLFs were extracted in 80% (v/v) aqueous methanol and fractionated into ethyl acetate, n-butanol, and water fractions. Repeated column chromatographies for the organic fractions led to the isolation of seven flavanones. Quantitative analysis of the flavanones was carried out using reversed-phase high-performance liquid chromatography. All flavanones were evaluated for their antioxidant and pro-inflammatory inhibition effects, (3) Results: Spectroscopic analyses revealed the chemical structure of five new flavanones, coreolanceolins A&minus, E, and two known ones. The content of the seven flavanones in extracts were determined from 0.8 &plusmn, 0.1 to 38.8 &plusmn, 0.3 mg/g. All flavanones showed radical scavenging activities (respectively 104.3 &plusmn, 1.9 to 20.5 &plusmn, 0.3 mg vitamin C equivalents (VCE)/100 mg and 1278.6 &plusmn, 26.8 to 325.6 &plusmn, 0.2 mg VCE/100 mg) in the DPPH and 2,2&prime, Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays and recovery activities in Caco-2 (59.7 to 41.1%), RAW264.7 (87.8 to 56.0%), and PC-12 (100.5 to 69.9%) cells against reactive oxygen species. Furthermore, all flavanones suppressed nitric oxide production (99.5% to 37.3%) and reduced iNOS and COX-2 expression in lipopolysaccharide-treated RAW 264.7 cells, (4) Conclusions: Five new and two known flavanones were isolated from CLF, and most of them showed high antioxidant and pro-inflammatory inhibition effects.

Panax ginseng is processed to diversify efficacy. Four processed ginsengs containing white ginseng (WG), tae-geuk ginseng (TG), red ginseng (RG), and black ginseng (BG) were analyzed using nuclear magnetic resonance (NMR) spectroscopy for screening overall primary metabolites. There were significant differences in the sugar content among these four processed ginseng products. WG had a high sucrose content, TG had a high maltose content, and BG had high fructose and glucose content. In the multivariate analyses of NMR spectra, the PCA score plot showed significant discrimination between the four processed ginsengs. For effective clustering, orthogonal partial least squares discriminant analyses (OPLS-DA) with a 1:1 comparison were conducted and all OPLS models were validated using the permutation test, the root mean square error of estimation (RMSEE), and the root mean square error of prediction (RMSEP). All OPLS-DA score plots showed clear separations of processed ginseng products, and sugars such as sucrose and fructose mainly contributed to these separations.

Ginger (Zingiber officinale Roscoe) and its active compounds (gingerols, shogaols and paradols) have been reported as having beneficial functions for several diseases, including diabetes. In this study, we revealed that the steaming process could enhance the anti-diabetic potential of ginger. To confirm the anti-diabetic effect of steamed ginger extract (GG03), we assessed pancreatic islets impaired by alloxan in zebrafish and demonstrated anti-hyperglycemic efficacy in a mouse model. The EC50 values of ginger extract (GE) and GG03 showed that the efficacy of GG03 was greater than that of GE. In addition, LC50 values demonstrated that GG03 had lower toxicity than GE, and the comparison of the Therapeutic Index (TI) proved that GG03 is a safer functional food. Furthermore, our data showed that GG03 significantly lowered hyperglycemia in a diabetic mouse model. HPLC was performed to confirm the change in the composition of steamed ginger. Interestingly, GG03 showed a 375% increase in 1-dehydro-6-gingerdione (GD) compared with GE. GD has not yet been studied much pharmacologically. Thus, we identified the protective effects of GD in the damaged pancreatic islets of diabetic zebrafish. We further assessed whether the anti-diabetic mechanism of action of GG03 and GD involves insulin secretion. Our results suggest that GG03 and GD might stimulate insulin secretion by the closure of KATP channels in pancreatic &beta, cells.

Brain cell damage that results from oxidative toxicity contributes to neuronal degeneration. The transcription factor nuclear factor‑E2‑related factor 2 (Nrf2) regulates the expression of heme oxygenase (HO)‑1 and glutathione (GSH), and serves a key role in the pathogenesis of neurological diseases. Brassica rapa is a turnip that is unique to Ganghwa County, and is used mainly for making kimchi, a traditional Korean food. In the current study, brassicaphenanthrene A (BrPA) from B. rapa was demonstrated to exhibit protective effects against neurotoxicity induced by glutamate via Nrf2‑mediated HO‑1 expression. Similarly, BrPA increased the expression of cellular glutathione and glutamine‑cysteine ligase genes. Furthermore, BrPA caused the nuclear translocation of Nrf2 and increased antioxidant response element (ARE) promoter activity. Nrf2 also mediated HO‑1 induction by BrPA through the PI3K/Akt and JNK regulatory pathways. The results of the present study indicated the neuroprotective effect of BrPA, a natural food component from B. rapa.

국화(C. morifolium)품종인 ‘백마’ 줄기를 80% MeOH 수용액으로 3회 반복 추출한 뒤, 감압농축한 추출물을 EtOAc, n-butyl alcohol과 H2O층으로 계통분획을 실시하였다. EtOAc분획에 대하여 SiO2 및 ODS column chromatography를 반복실시하여 2종의 지방산 화합물을 분리 및 정제하였다. Nuclear magnetic resonance, infrared spectrometry, FAB-MS, GC-MS data를 해석하여, 화합물 1과 2를 각각 (2S)-1-O-β-D-galactopyranosyl-2,3-dilinoleoylglycerol과 (2S)-1-O-β-D-galactopyranosyl-2,3-dipalmitoylglycerol로 구조동정 하였다.

A repeated column chromatography for Forsythia koreana Nakai. flowers afforded a phenylethane glycoside, which was identified as 8′-(3,4-dihydroxyphenyl)ethyl-O-α-l-rhamnopyranosyl-(1 → 4)-2-O-(E)-caffeoyl-α-l-arabinopyranoside based on spectroscopic analyses of 1D NMR (1H-NMR, 13C-NMR, DEPT), 2D NMR (gCOSY, gHSQC, gHMBC), FAB/MS, specific rotation, and IR spectrometry. This compound was isolated from F. koreana flower for the first time in this study. The compound showed scavenge activities in ORAC and DPPH radicals with the values of 0.83 ± 0.01 and 84.66 ± 0.75% (at the concentration of 500 ppm), respectively. It also inhibited production of NO for RAW 264.7 stimulated by LPS and protected oxidative stress induced by glutamate in HT22-immortalized hippocampal. The IC50 on inhibition of NO production and EC50 value on protective efficacy of oxidative stress were 78.72 ± 1.43 μM and 176.25 ± 7.23 μM, respectively. These results demonstrate that the phenylethanoid glycoside might be useful as a neuroprotective agent because of their antioxidant, anti-inflammatory, and neuroprotective effects.

A preliminary study revealed that a 10 µg/mL n-BuOH fraction of Malva verticillata aerial parts significantly enhanced splenocyte proliferation and induced significant enhancement of natural-killer (NK) cell activity against tumor cells (YAC-1). This study was initiated to identify the principal components that exhibited these activities, and four glycerides were isolated through repeated SiO2 and ODS column chromatography. Structures of compounds 1–4 were determined to be (2S)-1-O-palmitoyl glyceride, (2S)-1-O-stearoyl glyceride, (2S)-1-O-linolenoyl glyceride, and (2S)-1,2-di-O-linoleoyl glyceride, respectively. Compounds 1–3 showed potential immune-enhancing activity in murine splenocyte and natural-killer (NK) cells at 10 µM. In contrast, compound 4 showed weak activity, indicating the monoacyl glycerides (1–3) are more effective than diacyl glyceride (4). Also, the longer the carbon number of the fatty acid in monoacyl glyceride, the better the activity, and the monoacyl glyceride including an unsaturated fatty acid (3) is more effective than the glycerides including the saturated fatty acids (1–2).

The prebiotic effects of GOS (galactooligosaccharides) are known to depend on the glycosidic linkages, degree of polymerization (DP), and the monosaccharide composition. In this study, a novel form of α-GOS with a potentially improved prebiotic effect was synthesized using bifidobacterial α-galactosidase (α-Gal) purified from recombinant Escherichia coli. The carbohydrate produced was identified as α-d-galactopyranosyl-(1→6)-O-α-d-glucopyranosyl-(1→2)-[α-d-galactopyranosyl-(1→6)-O-β-d-fructofuranoside] and was termed stachyobifiose. Among 17 nonprobiotics, 16 nonprobiotics showed lower growth on stachyobifiose than β-GOS. In contrast, among the 16 probiotics, 6 probiotics showed higher growth on stachyobifiose than β-GOS. When compared with raffinose, stachyobifiose was used less by nonprobiotics than raffinose. Moreover, compared with stachyose, stachyobifiose was used less by Escherichia coli, Enterobacter cloacae, and Clostridium butyricum. The average amounts of total short-chain fatty acids (SCFA) produced were in the order of stachyobifiosestachyoseraffinoseβ-GOS. Taken together, stachyobifiose is expected to contribute to beneficial changes of gut microbiota.

Background Ginsenoside F1 has been described to possess skin-whitening effects on humans. We aimed to synthesize a new ginsenoside derivative from F1 and investigate its cytotoxicity and melanogenesis inhibitory activity in B16BL6 cells using recombinant glycosyltransferase enzyme. Glycosylation has the advantage of synthesizing rare chemical compounds from common compounds with great ease. Methods UDP-glycosyltransferase (BSGT1) gene from Bacillus subtilis was selected for cloning. The recombinant glycosyltransferase enzyme was purified, characterized, and utilized to enzymatically transform F1 into its derivative. The new product was characterized by NMR techniques and evaluated by MTT, melanin count, and tyrosinase inhibition assay. Results The new derivative was identified as (20 S )-3 β ,6 α ,12 β ,20-tetrahydroxydammar-24-ene-20- O - β -D-glucopyranosyl-3- O - β -D-glucopyranoside (ginsenoside Ia), which possesses an additional glucose linked into the C-3 position of substrate F1. Ia had been previously reported; however, no in vitro biological activity was further examined. This study focused on the mass production of arduous ginsenoside Ia from accessible F1 and its inhibitory effect of melanogenesis in B16BL6 cells. Ia showed greater inhibition of melanin and tyrosinase at 100 μmol/L than F1 and arbutin. These results suggested that Ia decreased cellular melanin synthesis in B16BL6 cells through downregulation of tyrosinase activity. Conclusion To our knowledge, this is the first study to report on the mass production of rare ginsenoside Ia from F1 using recombinant UDP-glycosyltransferase isolated from B. subtillis and its superior melanogenesis inhibitory activity in B16BL6 cells as compared to its precursor. In brief, ginsenoside Ia can be applied for further study in cosmetics.

A new lignan (1) was isolated from the flowers of Forsythia koreana along with one known lignan, 4,4′-di-O-β-D-glucosylpinoresinol (2). The molecular structures were determined using spectral methods. These compounds were isolated from F. koreana flowers for the first time.

A simple method to prepare a high-content rutin fraction from Forsythia koreana flowers (HRFK) is described. Rutin, isolated for the first time from the flowers, was identified from spectroscopic data including nuclear magnetic resonance, mass spectrometry, and infrared. As a result of HPLC quantitative analysis, the content of rutin was found to be 80.0 ± 0.02% in HRFK. Our previous study reported that F koreana MeOH extract (FK) significantly recovered alloxan-induced pancreatic islets in zebrafish. However, HRFK as well as rutin exhibited an enhanced anti-diabetic effect compared to FK in our latest experiments. In conclusion, HRFK, as well as rutin and FK, have potential as anti-diabetic agents.

3107 Background: Poly ADP-ribose polymerase (PARP) is an enzyme that is central to the repair of DNA replication errors known as single-strand breaks (SSBs). PARP inhibitors are currently approved for ovary, breast, pancreatic and prostate cancers which harbor germline or somatic BRCA1/2 mutations (g/sBRCAmt) and/or homologous recombinant repair mutation (g/sHRRmt). In this phase 1 dose finding study of venadaparib, we determined the maximum tolerated dose for venadaparib monotherapy and explored the safety, tolerability, pharmacokinetics, pharmacodynamics and anticancer efficacy of venadaparib in patients with advanced solid tumor which progressed after an attempt of standard-of-care therapy and for which effective therapy does not exist. Methods: Subjects who satisfied all of the inclusion/exclusion criteria and provided written informed consent were enrolled in this study. The investigational product was administered orally once daily continuously in a 3 weekly cycle. Enrolled subjects were assessed for safety and evaluated on tumor response using RECIST 1.1. The study was carried out in a conventional 3+3 design, starting from 2 mg up to 240 mg. Dose limiting toxicities (DLTs) and pharmacokinetics were assessed during the first cycle. Results: As of 08 Feb 2021, enrollment is completed with 32 patients enrolled. Most common tumor types enrolled are breast cancer (16 patients) and ovarian cancer (11 patients). Other tumor types include cancers of endometrium, fallopian tube, uterus and prostate. No DLTs were observed up to the maximum tested dose of 240 mg. Frequently observed adverse drug reactions were as follows – Anemia (56%), nausea (38%) and neutropenia (25%). Overall objective response rate (ORR) was 16% and clinical benefit rate (CBR) was 47%. Partial response was observed starting from 40 mg and clinical benefit was observed from the lowest dose of 2 mg. From optional tumor tissue samples, venadaparib exhibited ≥ 90% PAR inhibitory effect in pharmacodynamic analysis from 10 mg. For patients with known germline or somatic BRCA status either from local lab results or examined at a central lab retrospectively, ORR and CBR was 22% and 44% respectively for BRCAm(+) (9) patients. Interestingly, clinical efficacy was observed in BRCAm(-) (18) patients also, with ORR and CBR of 17% and 50% respectively. Conclusions: Safety and tolerability of the venadaparib monotherapy was confirmed with preliminary efficacy signals observed, even in BRCAm(-) patients. Clinical benefit was observed from the lowest tested dose, suggesting the potential to combine with other chemotherapeutic agents. Further studies to explore efficacy and safety of venadaparib in other tumor types and combinations, as well as to explore adequate biomarkers are warranted. Clinical trial information: NCT03317743.