Adenosine Deaminase Inhibitory Activity of Medicinal Plants: Boost the Production of Cordycepin in Cordyceps militaris.

Cordycepin, also known as 3'-deoxyadenosine, is a major active ingredient of Cordyceps militaris with diverse pharmacological effects. Due to its limited supply, many attempts have been conducted to enhance the cordycepin content. As part of this study, eight medicinal plants were supplemented with cultivation substrates of Cordyceps to increase the cordycepin content. Cordyceps cultivated on brown rice supplemented with Mori Folium, Curcumae Rhizoma, Saururi Herba, and Angelicae Gigantis Radix exhibited increased cordycepin content compared to a brown rice control. Among them, the addition of 25% Mori Folium increased the cordycepin content up to 4 times. Adenosine deaminase (ADA) modulates the deamination of adenosine and deoxyadenosine, and the inhibitors have therapeutic potential with anti-proliferative and anti-inflammatory properties. As ADA is also known to be involved in converting cordycepin to 3'-deoxyinosine, the inhibitory activity of medicinal plants on ADA was measured by spectrophotometric analysis using cordycepin as a substrate. As expected, Mori Folium, Curcumae Rhizoma, Saururi Herba, and Angelicae Gigas Radix strongly inhibited ADA activity. Molecular docking analysis also showed the correlation between ADA and the major components of these medicinal plants. Conclusively, our research suggests a new strategy of using medicinal plants to enhance cordycepin production in C. militaris.

A New Ceanothane-Type Triterpenoid Saponin Isolated from Gouania leptostachya DC. var. tonkinensis Pit. and Its Underlying Anti-Inflammatory Effects.

Metabolites from medicinal plants continue to hold significant value in the exploration and advancement of novel pharmaceuticals. In the search for plants containing compounds with anti-inflammatory effects, we observed that the ethanol (EtOH) extract obtained from the aerial components of Gouania leptostachya DC. var. tonkinensis Pit. exhibited substantial suppression of nitric oxide (NO) in vitro. In a phytochemical study on an EtOH extract of G. leptostachya, 11 compounds were purified, including one unreported compound namely gouanioside A (1). Their chemical structures were unambiguously determined through the use of various spectroscopic techniques, such as 1 and 2D NMR, IR, and HR-ESI-MS, and by producing derivatives via chemical reactions. The EtOH extract, fractions, and a new compound exerted inflammatory effects by altering NO synthesis in murine RAW264.7 macrophage cells stimulated with lipopolysaccharide. The underlying inflammatory mechanism of the new compound 1 was also explored through various in vitro experiments. The results of this study indicate the potential usefulness of new compound 1 from G. leptostachya as a treatment for inflammatory diseases.

Cell extraction method coupled with LC-QTOF MS/MS analysis for predicting neuroprotective compounds from Polygonum tinctorium.

The cell extraction method coupled with LC-QTOF-MS/MS is a biological screening technique in which cells are incubated with extracts of natural products, which results in potential bioactive compounds selectively combining with various extracellular and intracellular targets. Although the neuroprotective effects of the plant Polygonum tinctorium are unknown, the ethyl acetate (EtOAc) fraction exhibits significant neuroprotective effects against ʟ-glutamate-induced cytotoxicity in HT22 cells. In this study, we attempted to identify the neuroprotective compounds in the EtOAc fraction of P. tinctorium using the cell extraction method coupled with LC-QTOF MS/MS. Potential neuroprotective components derived from P. tinctorium were combined selectively with HT22 cells, and cell-derived metabolites were identified. A new flavonoid compound, 3,5,3',4'-tetrahydroxy-6,7-methylendioxyflavone-3-O-ß-ᴅ-glucopyranoside (1), and 14 known compounds (2-15), with compounds 2, 3, 8, 13, and 15 detected by the cell extraction method, were isolated from the EtOAc fraction of P. tinctorium. Compounds 2, 8, 12, and 14 showed strong neuroprotective effects, with compounds 2 and 14 identified in this plant for the first time in this study. Our results indicate that the cell extraction method coupled with LC-QTOF MS/MS is a useful tool for screening and identifying neuroprotective compounds in natural products.

Steroid glycosides isolated from Paris polyphylla var. chinensis aerial parts and paris saponin II induces G1/S-phase MCF-7 cell cycle arrest.

In our previous research on Vietnamese medicinal plants, we found that the ethanolic extract of the aerial parts of Paris polyphylla var. chinensis exhibited cytotoxic effects in vitro in the MCF-7 human cancer cell line. Here, we used combined chromatographic separations to isolate six compounds including a new steroid glycoside, paripoloside A (3), and five known compounds, from the butanol extract of the aerial parts of P. polyphylla. We unambiguously elucidated their structures based on spectroscopic data (proton and carbon-13 nuclear magnetic resonance, heteronuclear single quantum coherence, heteronuclear multiple bond correlation, correlation spectroscopy, and high-resolution electrospray ionization mass spectroscopy data), and chemical reactions. Among the isolated compounds, paris saponin II (PSII) had the strongest cytotoxic effects against MCF-7 breast cancer cells. Interestingly, PSII significantly increased the expression of p53, p21, p27, and Bax protein levels and significantly suppressed the expression of cyclin D1 and retinoblastoma protein. These data suggest that PSII may induce G1/S phase cell cycle arrest and apoptosis pathway development in MCF-7 cells. Furthermore, the MCF-7 breast cancer cells mechanism of PSII was also investigated using molecular docking. Together, our results demonstrate that isolated compounds from P. polyphylla are promising candidates as breast cancer inhibitors.

Antibacterial Activities of Prenylated Isoflavones from Maclura tricuspidata against Fish Pathogenic Streptococcus: Their Structure-Activity Relationships and Extraction Optimization.

Streptococcus zoonotic bacteria cause serious problems in aquaculture with clinical effects on humans. A structure-antibacterial activity relationships analysis of 22 isoflavones isolated from M. tricuspidata (leaves, ripe fruits, and unripe fruits) against S. iniae revealed that prenylation of the isoflavone skeleton was an important key for their antibacterial activities (minimum inhibitory concentrations: 1.95-500 µg/mL). Through principal component analysis, characteristic prenylated isoflavones such as 6,8-diprenlygenistein (4) were identified as pivotal compounds that largely determine each part's antibacterial activities. M. tiricuspidata ripe fruits (MTF), which showed the highest antibacterial activity among the parts tested, were optimized for high antibacterial activity and low cytotoxicity on fathead minnow cells using Box-Behnken design. Optimized extraction conditions were deduced to be 50%/80 °C/7.5 h for ethanol concentration/extraction temperature/time, and OE-MTF showed contents of 6,8-diprenlygenistein (4), 2.09% with a MIC of 40 µg/mL. These results suggest that OE-MTF and its active isoflavones have promising potential as eco-friendly antibacterial agents against streptococcosis in aquaculture.

Characterization of α-glucosidase inhibitory constituents of the fruiting body of lion's mane mushroom (Hericium erinaceus).

ETHNOPHARMACOLOGICAL RELEVANCE: Hericium erinaceus, commonly called lion's mane mushroom, is an edible and medicinal mushroom that has been traditionally used for the treatment of metabolic disorders, gastrointestinal diseases and memory impairment. In this study, potential anti-hyperglycemic constituents were identified to support the traditional usage of H. erinaceus. MATERIALS AND METHODS: The components of H. erinaceus were purified using various column chromatography techniques. The structure of the separated compounds was determined based on spectroscopic data analysis, i.e., 1D and 2D NMR analysis. The anti-hyperglycemic activity of the isolated compounds was evaluated by measuring the inhibitory effects on α-glucosidase activity. Molecular docking analysis was also conducted for elucidation of α-glucosidase inhibitory activity of isolated compounds. RESULTS: Ten compounds including four new compounds, erinacenols A-D (1-4), were isolated from the fruiting bodies of H. erinaceus. Investigation of the anti-hyperglycemic effect of isolated compounds demonstrated that erinacenol D (4), 4-[3',7'-dimethyl-2',6'-octadienyl]-2-formyl-3-hydroxy-5-methyoxybenzylalcohol (6), hericene A (7), hericene D (8) and hericenone D (9) strongly inhibited α-glucosidase activity with IC50 values of <20 µM. The structure activity relationship suggested the importance of long side chain for α-glucosidase inhibitory activity. Further analysis by molecular docking demonstrated the interaction of α-glucosidase and isolated compounds, which supported the inhibitory activity of α-glucosidase. CONCLUSION: Our present study demonstrated the beneficial effect of H. erinaceus by characterization of α-glucosidase inhibitory compounds, including four new compounds. This approach can be valuable support for the traditional use of H. erinaceus for the treatment of diabetes and metabolic diseases, which needs to be clarified by further in-vivo study.

Characterization of Anti-Inflammatory and Antioxidant Constituents from Scutellaria baicalensis Using LC-MS Coupled with a Bioassay Method.

An effective and previously demonstrated screening method for active constituents in natural products using LC-MS coupled with a bioassay was reported in our earlier studies. With this, the current investigation attempted to identify bioactive constituents of Scutellaria baicalensis through LC-MS coupled with a bioassay. Peaks at broadly 17-20 and 24-25 min on the MS chromatogram displayed an inhibitory effect on NO production in lipopolysaccharide-induced BV2 microglia cells. Similarly, peaks at roughly 17-19 and 22 min showed antioxidant activity with an 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS)/2,2-diphenyl-1- picrylhydrazyl (DPPH) assay. For confirmation of LC-MS coupled with a bioassay, nine compounds (1-9) were isolated from an MeOH extract of S. baicalensis. As we predicted, compounds 1, 8, and 9 significantly reduced lipopolysaccharide (LPS)-induced NO production in BV2 cells. Likewise, compounds 5, 6, and 8 exhibited free radical-scavenging activities with the ABTS/DPPH assay. In addition, the structural similarity of the main components was confirmed by analyzing the total extract and EtOAc fractions through molecular networking. Overall, the results suggest that the method comprised of LC-MS coupled with a bioassay can effectively predict active compounds without an isolation process, and the results of molecular networking predicted that other components around the active compound node may also be active.

Phenylpropanoid-Conjugated Triterpenoids from the Leaves of Actinidia arguta and Their Inhibitory Activity on α-Glucosidase.

Actinidia arguta, commonly called hardy kiwifruit or kiwiberry, has cold-resistant properties and can be cultivated in Asia, including Korea. Seven new triterpenoids (2-4 and 8-11) along with eight known triterpenoids were isolated from the leaves of A. arguta through various chromatographic techniques. The new triterpenoids were defined as actiniargupenes A-C (2-4), actinidic acid derivatives with phenylpropanoid constituent units, dehydroisoactinidic acid (8), and actiniargupenes D-F (9-11), asiatic acid derivatives with phenylpropanoid substituents, on the basis of 1D and 2D NMR and MS data. Among the triterpenoids, those with a phenylpropanoid constituent unit showed inhibitory activity on α-glucosidase, which suggested the importance of the phenylpropanoid moiety. Molecular docking analysis demonstrated the interaction between the 4'-OH group of the phenylpropanoid moiety and α-glucosidase.

Rapid and Efficient Separation of Decursin and Decursinol Angelate from Angelica gigas Nakai using Ionic Liquid, (BMIm)BF4, Combined with Crystallization.

Ionic liquids (ILs) have gained much attention as alternative solvents to volatile organic solvents due to their attractive properties. This study aimed to develop an efficient method for the selective separation of decursin (D) and decursinol angelate (DA) from Angelica gigas Nakai (A. gigas) using ILs and crystallization. The IL 1-butyl-3-methylimidazolium tetrafluoroborate ((BMIm)BF4) was the most efficient at extracting D and DA. Parameters including solid-to-liquid ratio, time, and temperature were optimized by response surface methodology (RSM). Under optimal extraction conditions (1 g/6.5 mL solid-to-liquid ratio, 60 °C temperature, and 120 min time), the extraction yields of D and DA were 43.32 mg/g (97.06%) and 17.87 mg/g (97.12%), respectively. Moreover, drowning out crystallization using deionized water (DW) as an anti-solvent offered an excellent ability to recover D and DA from the A. gigas-(BMIm)BF4 extraction solution. The rates of recovery and the total purity of D and DA were found to be greater than 97%. Therefore, a rapid and efficient method of combining ILs with crystallization was effectively achieved for the selective separation of D and DA. This approach is assumed to be beneficial in the pharmaceutical industry for the effective obtention of D- and DA-enriched products.

Anti-acne properties of hydrophobic fraction of red ginseng (Panax ginseng C.A. Meyer) and its active components.

Acne is a chronic inflammatory disease of the skin that occurs when bacteria abnormally grow in hair follicles. The most common treatment is antibiotics, but they are limited due to antibiotic resistance. The purpose of this study was to identify the active ingredients of the antimicrobial effects of red ginseng (Panax ginseng C.A. Meyer), compare it to existing antibacterial substances, and determine its potential efficacy as a natural drug product. The hydrophobic fraction in red ginseng ethanol extract (RGEF) showed the same or better antimicrobial activity against Propionibacterium acnes than benzoyl peroxide or azelaic acid. In addition, the antimicrobial component derived from red ginseng selectively showed a high antimicrobial effect on P. acnes. Nuclear magnetic resonance spectroscopic analysis showed that the active antimicrobial substance in this fraction was panaxynol and panaxydol. Twenty subjects who had acne symptoms were treated with cream containing 3 mg/g of RGEF for 4 weeks. It was found that oxidized sebum contents and redness of the skin were reduced, and symptoms of the early to middle stage of acne were effectively improved. This study showed that red ginseng extract containing panaxynol and panaxydol can effectively control the symptoms of acne.

Icariin abrogates osteoclast formation through the regulation of the RANKL-mediated TRAF6/NF-κB/ERK signaling pathway in Raw264.7 cells.

BACKGROUND: Icariin is pharmacologically active prenylated flavonoid glycoside that has various biologic effects such as antioxidant, anticancer, and anti-inflammatory activities. In addition, icariin has been used in Chinese medicine for thousands of years to treat osteoporosis and it is still being used today. However, direct mechanism of icariin in the treatment of bone disease is not understood. PURPOSE: The purpose of this study is to investigate whether icariin influences RANKL-induced osteoclast formation in murine macrophages. METHODS: Osteoclastogenesis was determined by TRAP staining and activity assay. Inhibition of signaling pathways and marker protein expression were evaluated by western blot analysis. The NF-κB (p65) nuclear localization was detected by immunofluorescence assay, and NF-κB/DNA-binding activity was detected by electrophoretic mobility shift assay (EMSA). RESULTS: In our study, icariin inhibited the differentiation of pre-osteoclast cells into osteoclasts and suppressed expression of various genes involved in osteoclast formation and bone resorption. Also, icariin blocked the osteoclastogenesis induced by MCF7 and MDA-MB-231 breast cancer cells through inhibition of NF-κB activation. We found that icariin inhibited RANKL-stimulated TRAF-6 expression, and subsequently suppressed the phosphorylation of ERK, but icariin did not show an effect on p38, JNK, and Akt activation. CONCLUSION: These results indicate that icariin is likely to be a candidate for bone-related disease treatment and that icariin provides insights into the molecular mechanisms that influence RANKL-induced osteoclast differentiation.

Comparison of antibacterial activity and phenolic constituents of bark, lignum, leaves and fruit of Rhus verniciflua.

Rhus verniciflua is commonly known as a lacquer tree in Korea. The bark of R. verniciflua has been used as an immunostimulator in traditional medicine, but also causes allergic dermatitis due to urushiol derivatives. For the development of active natural resources with less toxicity, the antibacterial activity of various parts of R. verniciflua such as bark, lignum, leaves and fruit, together with chemical composition, were investigated. Among the various parts of R. verniciflua, lignum showed the most potent antibacterial activity against fish pathogenic bacteria such as Edwardsiella tarda, Vibrio anguillarum and Streptococcus iniae. Measurement of total phenolic content and flavonoid content clearly showed a high content of phenolic and flavonoids in lignum among the various parts of R. verniciflua. Further analysis showed a close correlation between antibacterial activity and phenolic content. In addition, methyl gallate and fustin, the major constituents of bark and lignum, showed antibacterial activity, which suggested phenolic constituents as active constituents. The content of urushiols, however, was highest in bark, but there was a trace amount in lignum. LC-MS-MS and PCA analysis showed good discrimination with the difference of phenolic composition in various parts of R. verniciflua. Taken together, phenolic compounds are responsible for the antibacterial activity of R. verniciflua. The lignum of R. verniciflua contains high content of phenolic compounds with less urushiols, which suggests efficient antibacterial activity with less toxicity. Therefore, the lignum of R. verniciflua is suggested as a good source for antibacterial material to use against fish bacterial diseases.

Characterization of inhibitory constituents of NO production from Catalpa ovata using LC-MS coupled with a cell-based assay.

An effective screening method for inhibitors of NO production in natural products using LC-QTOF MS/MS coupled with a cell-based assay was proposed. The ethyl acetate fraction of Catalpa ovata exhibited a strong inhibitory effect on NO production in lipopolysaccharide-induced BV2 microglia cells. We attempted to identify the active constituents of C. ovata by using LC-QTOF MS/MS coupled with a cell-based assay. Peaks at approximately 14-15 min on the MS chromatogram were estimated to be the bioactive constituents. A new iridoid compound, 6-O-trans-feruloyl-3ß-hydroxy-7-deoxyrehamaglutin A (4), and nine known compounds (1-3, 5-10) were isolated from the ethyl acetate fraction of C. ovata by repeated column chromatography. Compounds 3, 4, 5, 7, and 8 significantly attenuated lipopolysaccharide-stimulated NO production in BV2 cells. Our results indicate that LC-QTOF MS/MS coupled with a cell-based NO production inhibitory assay successfully predicted active compounds without a time-consuming isolation process.

Identification of Polygonum orientale constituents using high-performance liquid chromatography high-resolution tandem mass spectrometry.

Our primary focus in this research was to identify and characterize its bioactive compounds for potential therapeutic use. Twenty-seven metabolites of Polygonum orientale were identified using LC-QTOF tandem mass spectrometry. Interestingly, P. orientale extracts included several highly oxygenated flavonoids were isolated from P. orientale by column chromatography. 13C NMR data of highly oxygenated flavonoids (1-7) are reported here for the first time. In addition, nitric oxide, 1,1-diphenyl-2-picrylhydrazyl, and water-soluble tetrazolium salt assays were carried out on the isolated compounds to investigate their anti-inflammatory, anti-oxidant, and neuroprotective activities, respectively. Compounds 1, 2, 3, 5, 7, and 8 significantly attenuated lipopolysaccharide-stimulated NO production in BV2 cells without affecting cell viability. Compounds 9-12 exhibited significant antioxidant activity, while compounds 8, 9, and 12 exhibited protective effects against glutamate-induced neurotoxicity in HT22 cells. Our results indicate that P. orientale is a promising source of natural agents for the potential treatment of inflammation and neurodegenerative diseases.

Characterization of tyrosinase inhibitory constituents from the aerial parts of Humulus japonicus using LC-MS/MS coupled online assay.

In the screening of natural products for the development as cosmetic ingredients, the EtOAc-soluble fraction of Humulus japonicus showed tyrosinase inhibitory activity. HPLC-MS/MS coupled online tyrosinase assay of EtOAc-soluble fraction of H. japonicus characterized the twenty-eight constituents including two unknown ones and their tyrosinase inhibitory activity. Fractionation of H. japonicus using various chromatographic techniques yielded thirty-eight compounds. The chemical structures of isolated compounds were identified by spectroscopic analysis. As characterized by HPLC-MS/MS analysis, we isolated twenty-four predicted compounds and further identified two unknown ones, named humulusides A (1) and B (2). Additional ten compounds were also identified by purification. Tyrosinase inhibitory activity of isolated compounds were evaluated, which was closely correlated with the results from HPLC-MS/MS coupled online tyrosinase assay. Consistent with predicted data, two major compounds, trans-N-coumaroyltyramine (14) and cis-N-coumaroyltyramine (15) showed tyrosinase inhibition with IC50 values of 40.6 and 36.4 µM. Taken together, H. japonicus is suggested as whitening ingredient in cosmetic products. In addition, HPLC-MS/MS coupled tyrosinase assay is powerful tool for predicting active compounds with short time and limited amounts, although identification of new compounds and verification of predicted data are also needs to be demonstrated by further experiment.

Screening and identification of neuroprotective compounds from Scrophularia buergeriana using cell extraction coupled with LC-MS.

In the cell extraction_LC-MS method, when cells are incubated with natural product extracts, bioactive compounds selectively bind to extracellular or intracellular targets. The extracts and major compounds (phenylpropanoids and iridoid glycosides) of Scrophularia buergeriana Miquel have been reported to show neuroprotective effects both in vitro and in vivo. In this study, the cell extraction_LC-MS strategy was applied to screen and identify potential neuroprotective compounds from S. buergeriana by using immortalized mouse hippocampal HT22 cells. The results showed that two known compounds from S. buergeriana selectively bound HT22 cells. Additionally, metabolomics analyses were performed using the Mass Profiler Professional and Limma differential expression package of R to identify significant differences between HT22 cells treated with S. buergeriana and untreated cells. The cell extraction approach more accurately reflects in vivo conditions compared with other methods and can be readily used for screening bioactive components from natural products.

Root bark of Ulmus davidiana var. japonica restrains acute alcohol-induced hepatic steatosis onset in mice by inhibiting ROS accumulation.

Alcohol-induced hepatic steatosis and inflammation are key drivers of alcohol-induced liver injury, mainly caused by oxidative stress. The roots bark of Ulmus davidiana var. japonica is well known for its substantial antioxidative and antitumorigenic potency. In this study, we examined whether this plant can ameliorate alcohol-induced liver injuries characterized by hepatic steatosis and inflammation through its antioxidative activity. C57BL/6J mice were treated with the root bark extract of Ulmus davidiana var. japonica (RUE; 100 mg of extract/kg bodyweight; oral gavage) and alcohol (1 g/kg of bodyweight; oral gavage) for 5 days. Markers of acute alcohol-induced hepatic steatosis were determined and putative molecular mechanisms responsible for the protection of RUE were investigated. RUE noticeably protected against alcohol-induced hepatic steatosis and inflammation. Reactive oxygen species (ROS), over-produced by alcohol, negatively orchestrated various signaling pathways involved in the lipid metabolism and inflammation. These pathways were restored through the ROS scavenging activity of RUE in the liver. In particular, the expression of lipogenic genes (e.g., SREBP-1, ACC, and FAS) and inflammatory cytokines (e.g., IL-1ß, and NF-κB p65) significantly decreased with RUE treatment. Conversely, the expression of fatty acid oxidation-related genes (e.g., SIRT1, AMPKα, and PGC1α) were increased in mice treated with RUE. Thus, the results indicate that RUE counteracts and thus attenuates alcoholic hepatic steatosis onset in mice, possibly by suppressing ROS-mediated steatosis and inflammation.

Optimization of pancreatic lipase inhibitory and antioxidant activities of Ilex paraguariensis by using response surface methodology.

Response surface methodology (RSM) using a Box-Behnken design was used to optimize the extraction conditions for obtaining pancreatic lipase inhibitory and antioxidant principles from Ilex paraguariensis leaves. Three influencing factors: extraction time (min), the liquid-solid ratio, and ethanol concentration (%, v/v) were investigated in the ultrasonic extraction process. Optimization of the extraction conditions to obtain a product with minimum PL activity, maximum antioxidant activity, and maximum yield was performed using RSM by focusing on the three target influencing factors. The optimum conditions were established as the ethanol concentration (54.8 %), liquid-solid ratio (35.4), and extraction time (70.0 min). Under these conditions, the 2,2-diphenyl-1-picrylhydrazyl scavenging activity, PL activity, extraction yield were 59.3 ± 3.5, 35.3 ± 3.0, and 34.4 ± 0.4 %, respectively, similar to the theoretical predicted values of 59.7, 35.2, and 34.3 %, respectively.

Anti-inflammatory effects of Viola yedoensis and the application of cell extraction methods for investigating bioactive constituents in macrophages.

BACKGROUND: Viola yedoensis (VY, Violaceae) is a popular medicinal herb used in traditional eastern medicine for treating lots of diseases, including inflammation and its related symptoms. However, the anti-inflammatory properties of VY have not been demonstrated. In the present study, we investigated the anti-inflammatory effects of VY ethanol extract (VYE) on macrophages and attempted to identify the bioactive components of VYE. METHODS: We assessed the effects of VYE on secretion of nitric oxide (NO) and inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß. In addition, we explored the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and changes in heme oxygenase (HO)-1, nuclear factor (NF)-kB, and mitogen-activated protein kinase (MAPK) signaling pathways in RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). In addition, a rapid and useful approach to identify potential bioactive components in VYE with anti-inflammatory effects was developed using murine macrophage cell extraction coupled with high-performance liquid chromatography tandem mass spectrometry (LC-MS). RESULTS: We found that VYE exerted anti-inflammatory activity by inhibiting the production of key inflammation mediators and related products, as well as suppression of HO-1, NF-kB, and MAPK signaling pathway activation in RAW 264.7 cells. In addition, we identified two compounds in VYE via the cell extraction method. CONCLUSIONS: Our results revealed that VYE exerts anti-inflammatory activities and its detailed inhibitory mechanism in macrophages. Furthermore, we identified bioactive components of VYE.

New Alkyl Phloroglucinol Derivatives from Rhus trichocarpa Roots and Their Cytotoxic Effects on Human Gastric Adenocarcinoma AGS Cells.

The phytochemical investigation of the roots of Rhus trichocarpa led to this isolation of five new alkyl phloroglucinol derivatives, characterized as (Z)-15-hydroxy-1-(2,4,6-trihydroxyphenyl)-9-octadecen-1-one (named trichocarpol A, 1), (Z)-15-hydroxy-1-(2,6-dihydroxy-4-methoxyphenyl)-9-octadecen-1-one (named trichocarpol B, 2), (Z)-17-hydroxy-1-(2,4,6-trihydroxyphenyl)-9-octadecen-1-one (named trichocarpol C, 3), (Z)-18-hydroxy-1-(2,4,6-trihydroxyphenyl)-9-octadecen-1-one (named trichocarpol D, 4), and (9Z,12Z)-18-hydroxy-1-(2,4,6-trihydroxyphenyl)-9,12-octadecadien-1-one (named trichocarpol E, 5), together with a known compound, 4-(2,6-dihydroxy-4-methoxyphenyl)-4-oxobutanoic acid (6). In vitro cytotoxic activity of compounds 1-6 was evaluated in the human gastric adenocarcinoma AGS cell line and compounds 1-5 showed significant cytotoxicity. Our results indicate that R. trichocarpa, especially the alkyl phloroglucinol derivatives in it, is a good source of promising natural agents for the treatment of gastric cancer.