Flavonoid glycosides from the leaves of Michelia champaca.

Michelia champaca L. (Magnoliaceae) was cultivated in large scale for flowers as cosmetic raw materials, whereas the value of its leaves remains to be discovered. Our chemical study on the leaves yielded four new flavonol diglycosides, champaflavosides A-D (1-4), together with twenty-three known flavonoid glycosides (5-27). Their structures were determined by spectroscopic and chemical methods. Compounds 5-21 and 23-27 were not previously reported from the genus Michelia, and kaempferol 3-O-rutinoside (22) was obtained from this species for the first time. All the compounds were evaluated for antioxidant activity by four in vitro assays. Compounds 3-12 and 20 showed more potent 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity than l-ascorbic acid (l-AA). Compounds 2-23, 25, and 27 exhibited 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical cation scavenging activity superior to l-AA. The ferric reducing antioxidant powers (FRAP) of compounds 2-13, 17, and 19 were higher than l-AA. Further, eighteen compounds demonstrated cellular reactive oxygen species (ROS) scavenging activity, of which champaflavoside D (4), rhamnetin 3-O-neohesperidoside (8), quercetin 3-O-(6-O-E-p-coumaroyl)-neohesperidoside (9), and liquiritin (27) were more potent than curcumin. The results revealed that the renewable leaves of M. champaca are a rich source of flavonoids and antioxidants.

Multi-omics analysis reveals promiscuous O-glycosyltransferases involved in the diversity of flavonoid glycosides in Periploca forrestii (Apocynaceae).

Flavonoid glycosides are widespread in plants, and are of great interest owing to their diverse biological activities and effectiveness in preventing chronic diseases. Periploca forrestii, a renowned medicinal plant of the Apocynaceae family, contains diverse flavonoid glycosides and is clinically used to treat rheumatoid arthritis and traumatic injuries. However, the mechanisms underlying the biosynthesis of these flavonoid glycosides have not yet been elucidated. In this study, we used widely targeted metabolomics and full-length transcriptome sequencing to identify flavonoid diversity and biosynthetic genes in P. forrestii. A total of 120 flavonoid glycosides, including 21 C-, 96 O-, and 3 C/O-glycosides, were identified and annotated. Based on 24,123 full-length coding sequences, 99 uridine diphosphate sugar-utilizing glycosyltransferases (UGTs) were identified and classified into 14 groups. Biochemical assays revealed that four UGTs exhibited O-glycosyltransferase activity toward apigenin and luteolin. Among them, PfUGT74B4 and PfUGT92A8 were highly promiscuous and exhibited multisite O-glycosylation or consecutive glycosylation activities toward various flavonoid aglycones. These four glycosyltransferases may significantly contribute to the diversity of flavonoid glycosides in P. forrestii. Our findings provide a valuable genetic resource for further studies on P. forrestii and insights into the metabolic engineering of bioactive flavonoid glycosides.

Acylated flavonoid glycosides from Barringtonia pendula and their inhibition on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells.

Six new acylated flavonoid glycosides namely barringosides J - O (1-6) along with tephrokaempferoside and barringoside D were isolated from the branches and leaves of Barringtonia pendula. The structural elucidation was confirmed by extensive analysis of their spectroscopic data including HRQTOFMS, 1D and 2D NMR experiments. Moderate inhibitory effects on LPS-induced NO production in RAW264.7 cells were observed for barringosides M (4) and N (5) with IC50 values of 48.40 ± 3.01 and 56.61 ± 3.87 µM, whereas weak inhibition was found for compounds 1-3, 6, and 7 with IC50 values ranging from 64.91 ± 3.68 to 79.80 ± 3.90 µM.

Cytotoxic constituents from the leaves and stems of Panax quinquefolius.

Four new isolates including one new butanediamide glycoside (1), one new flavonoid glycoside (2) and two new flavonone glycosides (3, 4) were identified from the leaves and stems of Panax quinquefolius, among which 1 possessed the firstly reported N,N'-(5-hydroxy-1,3-phenylene) butanediamide skeleton with an unique 6/9 ranged dual-ring structure. The structures were elucidated by the NMR data, ECD analysis and chemical acid hydrolysis. All the compounds (1-4) were tested for their cytotoxicity against two human cancer cell lines of HepG2, A549 and HCT116 by the MTT method. Outstandingly, compound 1 exhibited targeted inhibitory proliferation of HCT116 cell with IC50 value of 12.1 µM, whereas compounds 3 and 4 exhibited targeted inhibitory proliferation of HepG2 cell with IC50 values of 15.3 and 17.3 µM, as well as no obvious cytotoxicity of compounds 1-4 against A549.

Chemical Profiles of Korean Bee Pollens and Their Catechol-O-methyltransferase Inhibitory Activities.

Bee pollen is an apicultural product collected by honeybees from flower stamens and is consumed to help maintain a healthy diet. In this study, the chemical profiles of 11 Korean bee pollens were investigated using molecular networking analysis. This analysis elucidated the presence of two major clusters, hydroxycinnamoyl acid amides (HCAAs, molecular network 1 (MN1)) and flavonoid glycosides (MN2), in the bee pollen samples. The inhibitory properties of the bee pollens and the isolated HCAAs toward human catechol-O-methyltransferase (COMT), a key neurotransmitter involved in Parkinson's disease and depression, were determined. N1,N5,N10-(E)-tricaffeoylspermidine ((E,E,E)-1) exhibited the highest activity of the four compounds isolated, with an IC50 value 16 µM, and inhibited COMT competitively. Quantitative analysis of HCAAs showed that the amounts of N1,N10-dicaffeoyl-N5-p-coumaroylspermidine (2) and N10-caffeoyl-N1,N5-di-p-coumaroylspermidine (3) contributed to the observed differences in the COMT inhibitory activities of Korean bee pollens. This study may lead to the prevention and treatment of Parkinson's disease and depression using bee pollens.

A new flavonoid glycoside from Tapinanthus sp. (Loranthaceae) and evaluation of anticancer activity of extract and some isolated compounds.

The present work describes the isolation and anticancer activity of Tapinanthus sp. which is a hemi parasitic plant harvested on Combretum glutinosum, the host plant. Phytochemical study afforded a new flavonoid glycoside, tapinantoside (1) isolated for the first time from natural source, alongside six known compounds (2-7). Structure of compounds were elucidated by extensive spectroscopic analyses including 1 D and 2 D NMR, mass spectrometry and by comparison with literature data. The anticancer activity of extract and some isolated compounds were evaluated on glioblastoma (U87MG, C6) and prostate (PC-3) cancer cells. The methanol leaves extract showed good anticancer activity against U87 (IC50 = 21.40 µg/mL) and PC-3 cells (IC50 = 10.26 µg/mL). Compound 3 powerfully inhibits the proliferation of C6 (IC50 = 38.84 µM) and PC-3 cells (IC50 = 21.33 µM), while its effect was moderated on U87MG cells. Compound 1 and 7 were not active on all tested cancer cell lines.

Chemical constituents of Impatiens chapaensis Tard. and their α-glucosidase inhibition activities.

Sixteen compounds (1-16) were isolated from Impatiens chapaensis. Chemical structures were determined by spectroscopic analyses and comparisons with previously published data. This report is the first to identify compounds 1, 5-7, 10, 12-14, and 16 from the genus Impatiens. Seven chosen isolates (5, 7, 10, 11, 12, 15, and 16) were submitted for α-glucosidase inhibition assays with acarbose as the positive control (IC50 = 227.14 ± 13.71 µM). Flavonoid 5 exhibited a significant inhibitory effect (IC50 = 101.00 ± 9.01 µM).

Flavonoid Glycosides from Ziziphus jujuba var. inermis (Bunge) Rehder Seeds Inhibit α-Melanocyte-Stimulating Hormone-Mediated Melanogenesis.

Ziziphus jujuba extracts possess a broad spectrum of biological activities, such as antioxidant and anticancer activities in melanoma cancers. Nevertheless, the compounds contain high antioxidant capacities and anticancer activities in melanoma cells, shown to be effective in hyperpigmentation disorders, but whether flavonoid glycosides from Z. jujuba regulate anti-melanogenesis remains unclear. In this study, we evaluated the anti-melanogenic activity of five flavonoid glycosides from Z. jujuba var. inermis (Bunge) Rehder seeds, including jujuboside A (JUA), jujuboside B (JUB), epiceanothic acid (EPA), betulin (BTL), and 6'''-feruloylspinosin (FRS), in B16F10 melanoma cells and zebrafish larvae. According to our results, JUB, EPA, and FRS potently inhibited α-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis and prevented hyperpigmentation in zebrafish larvae. In particular, under α-MSH-stimulated conditions, FRS most significantly inhibited α-MSH-induced intracellular and extracellular melanin content in B16F10 melanoma cells. Additionally, JUB, EPS, and FRS remarkably downregulated melanogenesis in α-MSH-treated zebrafish larvae, with no significant change in heart rate. Neither JUA nor BTA were effective in downregulating melanogenesis in B16F10 melanoma cells and zebrafish larvae. Furthermore, JUB, EPA, and FRS directly inhibited in vitro mushroom tyrosinase enzyme activity. JUB, EPA, and FRS also downregulated cyclic adenosine monophosphate (cAMP) levels and the phosphorylation of cAMP-response element-binding protein (CREB), and subsequent microphthalmia transcription factor (MITF) and tyrosinase expression. In conclusion, this study demonstrated that JUB, EPA, and FRS isolated from Z. jujuba var. inermis (Bunge) Rehder seeds exhibit potent anti-melanogenic properties by inhibition of the cAMP-CERB-MITF axis and consequent tyrosinase activity.

Phytochemicals in Chinese Chive (Allium tuberosum) Induce the Skeletal Muscle Cell Proliferation via PI3K/Akt/mTOR and Smad Pathways in C2C12 Cells.

Chinese chive (Allium tuberosum) is a medicinal food that is cultivated and consumed mainly in Asian countries. Its various phytochemicals and physiological effects have been reported, but only a few phytochemicals are available for skeletal muscle cell proliferation. Herein, we isolated a new compound, kaempferol-3-O-(6″-feruloyl)-sophoroside (1), along with one known flavonoid glycoside (2) and six amino acid (3-8) compounds from the water-soluble fraction of the shoot of the Chinese chive. The isolated compounds were identified using extensive spectroscopic methods, including 1D and 2D NMR, and evaluated for their proliferation activity on skeletal muscle cells. Among the tested compounds, newly isolated flavonoid (1) and 5-aminouridine (7) up-regulated PI3K/Akt/mTOR pathways, which implies a positive effect on skeletal muscle growth and differentiation. In particular, compound 1 down-regulated the Smad pathways, which are negative regulators of skeletal muscle growth. Collectively, we suggest that major constituents of Chinese chive, flavonoids and amino acids, might be used in dietary supplements that aid skeletal muscle growth.

Implications for glycosylated compounds and their anti-cancer effects.

Glycosylated compounds are major secondary metabolites of plants, which have various therapeutic effects on human diseases, by acting as anti-cancer, antioxidant, and anti-inflammatory agents. Glycosylation increases stability, bioactivity, and solubility of compounds and improves their pharmacological properties. Two well-known examples of glycosylated compounds include cardiac and flavonoid, the anti-tumor activities of which have been emphasized by several studies. However, little is known about their role in the treatment or prevention of cancer. In this review, recent studies on anti-tumor properties of cardiac and flavonoid glycosides, and their mechanisms of action, have been investigated. More specifically, this review is aimed at focusing on the multifactorial properties of cardiac and flavonoid compounds as well as their correlation with signaling pathways in the treatment of cancer.

Acylated flavonoid glycosides from Barringtonia racemosa.

Using various chromatographic separations, three new acylated flavonoid glycosides, namely barringosides G-I (1-3), were isolated from the water-soluble extract of Barringtonia racemosa branches and leaves. The structure elucidation was performed by extensive analysis of the 1D and 2D NMR and HR-QTOF-MS data. Of the isolated compounds, barringoside I (3) showed moderate inhibitory effects on LPS-induced NO production in RAW264.7 cells with an IC50 of 52.48 ± 1.04 µM.

Iridoid, phenylethanoid and flavonoid glycosides from Forsythia suspensa.

As part of our continuing efforts to explore bioactive compounds from natural resources, a new iridoid glycoside, adoxosidic acid-6'-oleuroperic ester (1), together with one known phenylethanoid glycoside (2) and two known flavonoid glycosides (3-4) were isolated from the fruit of Forsythia suspensa. The structure of the new compound (1) was elucidated through 1D and 2D NMR spectroscopic data and HR-ESIMS. Interestingly, compound 1 was a monoterpene ester of one iridoid glycoside. Compounds 2-4 were identified as calceolarioside A (2), kaempferol-3-O-rutinoside (3), kampferol-3-O-robinobioside (4) on the basis of NMR spectroscopic data analyses and comparison with the data reported in the literature. The antiviral activity aganisist influenza A (H5N1) virus of compound 1 was studied as well.

A new epicatechin glucopyranoside derivative from Styrax suberifolius.

A new derivative of epicatechin glucopyranoside, (2R,3R)-3,7,4'-trihydroxy-5,3'-dimethoxyflavan 7-O-ß-d-glucopyranoside (1), together with three mononuclear phenolic acid esters, methyl orsellinate (2), ethyl orsellinate (3) and methyl ß-orcinolcarboxylate (4) were isolated from the bark of Styrax suberifolius. The structures of 1-4 were determined on the basis of extensive analysis of NMR and MS spectra combined with chemical hydrolysis. The antifungal activities of the isolated compounds against three plant pathogenic fungi, Alternaria solani, Fusarium oxysporum and Phomopsis cytospore were evaluated using radial growth inhibition assay. Compounds 2, 3 and 4 exerted selective inhibitory activities against the tested fungi. Among of them, methyl ß-orcinolcarboxylate (4) exhibited obvious inhibitory effect against P. cytospore, with an inhibition rate of 86.72% at 100 µg/ml.

Constituents of the leaves and twigs of Elaeagnus umbellata and their proliferative effects on human keratinocyte HaCaT cells.

Bioassay-guided fractionation of an extract of leaves and twigs of Elaeagnus umbellata led to the isolation of a serotonin derivative, N-[2-(5-hydroxyl-1H-indol-3-yl)ethyl]-butanamide (1), along with six flavonoid glycosides, kaempferol-3-O-ß-d-xylopyranosyl(1 → 2)-ß-d-galactopyranoside-7-O-α-l-rhamnopyranoside (2), kaempferol-3-O-ß-d-galactopyranoside-7-O-α-l-rhamnopyranoside (3), kaempferol-3-O-α-l-rhamnopyranosyl(1 → 6)-ß-d-galactopyranoside-7-O-α-l-rhamnopyranoside (4), kaempferol-3-O-ß-d-xylopyranosyl(1 → 2)-ß-d-galactopyranoside (5), kaempferol-3-O-rutinoside (6), and kaempferol-3-O-ß-d-glucopyranosyl(1 → 2)-ß-d-galactopyranoside-7-O-α-l-rhamnopyranoside (7). Their structures were elucidated using 1D/2D nuclear magnetic resonance spectroscopy and mass spectrometry. Compounds 1-6 were evaluated for their proliferative effects on HaCaT keratinocytes; 1-5 promoted keratinocyte proliferation dose dependently. Compounds 3 and 4 showed potent activities. These results suggest that the leaves and twigs of E. umbellata have wound healing and skin cell regeneration potentials.

Four New Compounds Isolated from the Aerial Part of Belamcanda chinensis (L.) and Their Effect on Vascular Smooth Muscle Cell (VSMC) Proliferation.

Bio-guided fractionation of the 70% ethanol extract of Belamcanda chinensis (L.) DC. revealed four new compounds, including 6″-O-acetylembinin (5), 3″-O-acetylembinin (6), irigenin 3'-O-ß-glucopyranoside (8), and 2'-acetyl-1,3-O-diferuloylsucrose (9), along with five known compounds (1-4, 7). Their chemical structures were determined using extensive NMR data, mass spectroscopy, and comparison with published literature. Among the isolates, compounds 1 and 4-7 achieved good regulation of the growth and proliferation of vascular smooth muscle cells.

Cycloartane-type triterpenoid derivatives and a flavonoid glycoside from the burs of Castanea crenata.

Five undescribed cycloartane-type triterpenoids, which were isolated for the first time from the genus, and a flavonoid glycoside together with 11 known compounds were isolated from the burs of Castanea crenata. The structures were elucidated based on the spectroscopic analysis of 1D and 2D NMR and MS data. All isolated compounds were evaluated for antiviral activities against HRV1B-, CVB3-, and PR8-infected cells. Most kaempferol derivatives showed statistically significant antiviral activities against HRV1B-infected cells. Among the tested compounds, kaempferol-3-O-[2″,6″-di-O-Z-p-coumaroyl]-ß-d-glucopyranoside exhibited the most consistent and effective antiviral activities against all infections.

A novel icariin type flavonoid from Epimedium pseudowushanense.

A novel icariin type flavonoid glycoside with a malonaldehydic acid intramolecular ester and two known flavonoid glycosides were isolated from Epimedium pseudowushanense. Their structures were elucidated on the basis of spectroscopic analysis and comparison of their data to the values reported in the literatures. The anti-inflammatory activities of these compounds icariin 3'''-O-malonaldehydic acid intramolecular 1'''', 2''' ester (1), icariin (2) and epimedin C (3) were tested. The results indicated that compounds 1, 2 and 3 showed maximal inhibitory ratio of 27.91, 44.80 and 46.61%, respectively in in vitro anti-inflammatory activity on LPS-induced TNF-α secretion in RAW264.7 cells. Compounds icariin (2) and epimedin C (3) were found to inhibit the secretion of TNF-α to a comparable degree as quercetin.

Recent Trends in Potential Therapeutic Applications of the Dietary Flavonoid Didymin.

Didymin (isosakuranetin 7-O-rutinoside) is an orally bioactive dietary flavonoid glycoside first found in citrus fruits. Traditionally, this flavonoid has long been used in Asian countries as a dietary antioxidant. Recent studies have provided newer insights into this pleiotropic compound, which could regulate multiple biological activities of many important signaling molecules in health and disease. Emerging data also presented the potential therapeutic application of dietary flavonoid glycoside didymin against cancer, neurological diseases, liver diseases, cardiovascular diseases, and other diseases. In this review, we briefly introduce the source and extraction methods of didymin, and summarize its potential therapeutic application in the treatment of various diseases, with an emphasis on molecular targets and mechanism that contributes to the observed therapeutic effects. The dietary flavonoid didymin can be used to affect health and disease with multiple therapeutic targets, and it is anticipated that this review will stimulate the future development of this potential dietary medicine.

[Determination of flavonoids constituents in epimedium total flavone capsule and research on its anti-osteoporosis activity].

To develop a rapid resolution liquid chromatography (RRLC) method for the simultaneous determination of epimedoside A, epimedin A1, epimedin A, epimedin B, epimedin C, icariin, baohuosideⅡ, icarisideⅠ, sagittatoside B, 2"-O-rhamnosyl icarisideⅡ, and baohuosideⅠin epimedium total flavone capsule. At the same time, the effects of the above 11 compounds on osteogenic differentiation of MC3T3-E1 cells were investigated by detecting the content of alkaline phosphatase (AKP). The results showed that baohuoside Ⅱ had the highest activities, and both the activities of baohuoside Ⅱ and icariside Ⅰ were stronger than those of icariin.In this study, the content determination method of flavonoid glycosides was established, and the anti-osteoporosis effect of monomers was compared, providing technical support for the study of the pharmacodynamic and mechanism of Epimedium total flavone capsule.

Lignan Glycosides and Flavonoid Glycosides from the Aerial Portion of Lespedeza cuneata and Their Biological Evaluations.

Lespedeza cuneata (Fabaceae), known as Chinese bushclover, has been used in traditional medicines for the treatment of diseases including diabetes, hematuria, and insomnia. As part of a continuing search for bioactive constituents from Korean medicinal plant sources, phytochemical analysis of the aerial portion of L. cuneata led to the isolation of two new lignan glycosides (1,2) along with three known lignan glycosides (3⁻7) and nine known flavonoid glycosides (8⁻14). Numerous analysis techniques, including 1D and 2D NMR spectroscopy, CD spectroscopy, HR-MS, and chemical reactions, were utilized for structural elucidation of the new compounds (1,2). The isolated compounds were evaluated for their applicability in medicinal use using cell-based assays. Compounds 1 and 4⁻6 exhibited weak cytotoxicity against four human breast cancer cell lines (Bt549, MCF7, MDA-MB-231, and HCC70) (IC50 < 30.0 µM). However, none of the isolated compounds showed significant antiviral activity against PR8, HRV1B, or CVB3. In addition, compound 10 produced fewer lipid droplets in Oil Red O staining of mouse mesenchymal stem cells compared to the untreated negative control without altering the amount of alkaline phosphatase staining.