Inhibition Of NO Production Research Articles

New chromones from the roots of Saposhnikovia divaricata (Turcz.) Schischk with anti-inflammatory activity

Fifteen new chromones, sadivamones A-E (1–5), cimifugin monoacetate (6), sadivamones F-N (7–15), together with fifteen known chromones (16–30), were isolated from the ethyl acetate portions of 70% ethanol extract of Saposhnikovia divaricata (Turcz.) Schischk roots. The structures of the isolates were determined using 1D/2D NMR data and electron circular dichroism (ECD) calculations. Meanwhile, LPS induced RAW264.7 inflammatory cell model was used to determine the potential anti-inflammatory activity of all the isolated compounds in vitro. The results showed that compounds 2, 8, 12–13, 18, 20–22, 24, and 27 significantly inhibited the production of lipopolysaccharide (LPS)-induced NO in macrophages. To determine the signaling pathways involved in the suppression of NO production by compounds 8, 12 and 13, we investigated ERK and c-Jun N-terminal protein kinase (JNK) expression by western blot analysis. Further mechanistic studies demonstrated that compounds 12 and 13 inhibited the phosphorylation of ERK and the activation of ERK and JNK signaling in RAW264.7 cells via MAPK signaling pathways. Taken together, compounds 12 and 13 may be valuable candidates for the treatment of inflammatory diseases.

(+)/(-)-Yanhusamides A-C, three pairs of unprecedented benzylisoquinoline-pyrrole hetero-dimeric alkaloid enantiomers from Corydalis yanhusuo.

A chemical investigation on the aqueous extract of Corydalis yanhusuo tubers led to the isolation and structural elucidation of three pairs of trace enantiomeric hetero-dimeric alkaloids, (+)/(-)-yanhusamides A-C (1-3), featuring an unprecedented 3,8-diazatricylco[5.2.2.02,6]undecane-8,10-diene bridged system. Their structures were exhaustively characterized by X-ray diffraction, comprehensive spectroscopic data analysis, and computational methods. Guided by the hypothetical biosynthetic pathway for 1-3, a gram-scale biomimetic synthesis of (±)-1 was achieved in 3 steps using photoenolization/Diels-Alder (PEDA) [4+2] cycloaddition. Compounds 1‒3 exhibited potent inhibition of NO production induced by LPS in RAW264.7 macrophages. The invivo assay showed that oral administration of 30mg/kg of (±)-1 attenuated the severity of rat adjuvant-induced arthritis (AIA). Additionally, (±)-1 induced a dose-dependent antinociceptive effect in the acetic acid-induced mice writhing assay.

Three Neolignan Glycosides from the Root of Nothopanax davidii

Three neolignan glycosides, including a new compound (7S,8R)-dihydro-3'-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1'-benzofuranpropanol-9-O-β-D-xylopyranoside (1), were isolated from the root of Nothopanax davidii. Their structures were determined by extensive spectroscopic analyses, particularly NMR, HR-ESI-MS, and ECD experiments, and the absolute configuration of 2 was first definitively determined. The anti-tumor activity was assessed on four tumor cells by MTT assay, the anti-inflammatory activity was determined by inhibition of NO production in LPS reduced RAW264.7 cells, and the interaction with iNOS was predicted by molecular docking. At the dose of 100 μM, the three neolignan glycosides showed no cytotoxic activity against HepG2, HCT116, HeLa and A549 human tumor cells, but significantly inhibited LPS induced NO generation in RAW264.7 cells with inhibition rates of 31.53 %, 23.95 %, and 20.79 %, respectively, showing weak anti-inflammatory activity, possibly due to their binding to key residues of iNOs involved in inhibitor binding.

Achyranbidens A–C: three new compounds from Achyranthes bidentata Blume

Phytochemical study on the roots of Achyranthes bidentata Blume led to the isolation of sixteen compounds including three new ones (1–3). Their chemical structures were determined as oleanolic acid 28-O-β-D-glucopyranoside-3-O-[β-D-glucopyranosyl-(1→3)-β-D-galactopyranoside) (1), methyl (8Z,11Z)-5,6,7-trihydroxytetradeca-8,11-dienoate (2), methyl (6E,11Z)-5,8,9-trihydroxytetradeca-6,11-dienoate (3), fulgidic acid (4), (9E,11E)-13-oxooctadeca-9,11-dienoic acid (5), (9Z,11E,15Z)-13-hydroxyoctadeca-9,11,15-trienoic acid (6), oleanolic acid 28-O-β-D-glucopyranoside-3-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucuronopyranoside (7), oleanolic acid 28-O-β-D-glucopyranoside-3-O-β-D-glucopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→3)]-β-D-glucuronopyranoside (8), oleanolic acid 3-O-β-D-glucopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→3)]-β-D-glucuronopyranoside (9), oleanolic acid 3-O-α-L-rhamnopyranosyl-(1→3)-β-D-glucuronopyranoside (10), blumenol C glucoside (11), citroside A (12), 6S,9S-roseoside (13), ginsenoside Rg1 (14), 20-hydroxyecdysone (15), and benzyl α-L-rhamnopyranosyl-(1→6)]-β-D-glucopyranoside (16) by spectroscopic analysis. Compounds 1, 7 and 11–16 inhibited NO production in LPS-activated RAW264.7 cells with IC50 values in the range from 28.03 to 54.23 µM (positive control, L-NMMA: IC50 = 35.52 µM). Compounds 14 and 15 showed anti α-glucosidase activity with IC50 values of 176.24 and 156.92 µM, respectively, compared with the positive control, acarbose, IC50 = 160.99 μM.

Amber Extract Suppressed Mast Cell-Mediated Allergic Inflammation via the Regulation of Allergic Mediators—An In Vitro Study

The various clinical approaches for treating allergy-related diseases have shown modest progress in low side effects and improved clinical outcomes. Therefore, finding alternative anti-allergic agents is crucial. The present study explored the anti-allergic effects of amber extract (fossilized tree resin) in RBL-2H3 mast cells stimulated with different allergens. In order to support the information on the inflammatory effect of the amber extract, NO production analysis on RAW 264.7 cells was conducted. β-Hexosaminidase release, an indicator of the efficacy of the amber extract in preventing mast cell activation and degranulation, reactive oxygen species (ROS) generation, and the effect of the amber extract on key cytokines production on RBL-2H3 cells, was evaluated. The results demonstrated that amber extract at concentrations up to 50 μg/mL had no cytotoxic effect on RAW 264.7 and RBL-2H3 cells. Amber extract inhibited NO production in RAW 264.7 cells. Treatment with amber extract significantly suppressed the release of β-hexosaminidase, especially at 50 μg/mL. Furthermore, amber extract suppressed the significantly increased ROS levels induced by allergen stimulation and allergy-associated cytokines. The results also suggested that amber extract exerts anti-allergic inflammatory effects by inhibiting the MAPK and NF-κB signaling pathways, resulting in decreased cytokines production. Thus, the amber extract is a promising anti-allergic agent.

Piperlongosides A–C, Three New Phenolic Constituents From Piper longum L.

Phytochemical study on the methanolic extract of the aerial parts of this plant led to the isolation of 7 phenolic compounds (1-7), including 3 new ones (1-3). Their chemical structures were determined to be (7,8- threo)-1 -O-β-D-[6′ -O-syringoylglucopyranosyl]-2-methoxy-7,8,9-trihydroxyphenylpropane (1), (7,8- threo)-8 -O-(2′′-methoxyacetophenone-1′′-yl)-1 -O-β-D-glucopyranosyl-2-methoxy-7,9-dihydroxyphenylpropane (2), 1 -O-β-D-glucopyranosyl-2 -O-(2′′-methoxy-4′′-acetylphenyl)-3-hydroxypropane (3), (−)-isolariciresinol 4 -O-β-D-glucopyranoside (4), (−)-isolarisiresinol 9′ -O-β-D-glucopyranoside (5), (+ )-lyoniresinol 9′ -O-β-D-glucopyranoside (6), (+ )-isolarisiresinol 9′ -O-β-D-glucopyranoside (7) by the spectroscopic data and in comparison with those reported in the literature. Compounds 3 to 7 significantly inhibited NO production in LPS-activated RAW264.7 cells with IC50 values ranging from 32.09 ± 3.34 to 38.16 ± 1.35 µM, similar to those of the positive control, NG-monomethyl-L-arginine acetate (IC50 32.51 ± 3.70 µM).

Physiologic and epigenetic effects of nutrients on disease pathways.

Epigenetic regulation by nutrients can influence the development of specific diseases. This study sought to examine the effect of individual nutrients and nutrient families in the context of preventing chronic metabolic diseases via epigenetic regulation. The inhibition of lipid accumulation and inflammation by nutrients including proteins, lipids, vitamins, and minerals were observed, and histone acetylation by histone acetyltransferase (HAT) was measured. Correlative analyses were also performed. Nutrients were selected according to information from the Korean Ministry of Food and Drug Safety. Selected nutrient functionalities, including the attenuation of fatty acid-induced lipid accumulation and lipopolysaccharide-mediated acute inflammation were evaluated in mouse macrophage Raw264.7 and mouse hepatocyte AML-12 cells. Effects of the selected nutrients on in vitro HAT inhibition were also evaluated. Nitric oxide (NO) production correlated with HAT activity, which was regulated by the amino acids group, suggesting that amino acids potentially contribute to the attenuation of NO production via the inhibition of HAT activity. Unsaturated fatty acids tended to attenuate inflammation by inhibiting NO production, which may be attributable to the inhibition of in vitro HAT activity. In contrast to water-soluble vitamins, the lipid-soluble vitamins significantly decreased NO production. Water- and lipid-soluble vitamins both exhibited significant inhibitory activities against HAT. In addition, calcium and manganese significantly inhibited lipid accumulation, NO production, and HAT activity. Several candidate nutrients and their family members may have roles in the prevention of diseases, including hepatic steatosis and inflammation-related diseases (i.e., nonalcoholic steatohepatitis) via epigenetic regulation. Further studies are warranted to determine which specific amino acids, unsaturated fatty acids and lipid-soluble vitamins or specific minerals influence the development of steatosis and inflammatory-related diseases.

가공방법에 따른 꾸지뽕잎차의 항산화 활성 연구

This study examines the general ingredients and antioxidant activities of control, hot air-dried leaves tea (HDT), pan-fried tea (PFT), and Ddeok-cha (DDC) made from Kkujippong (Cudrania tricuspidata) leaves. The general ingredient contents obtained for all processing methods were similar. However, the crude protein contents were relatively higher in HDT, whereas the highest contents of crude ash were obtained in PFT. The pH of the extracts was in the range 5.61-6.09. The total polyphenol and flavonoid contents were the highest in the PFT extract (247.79 mg/100 g and 173.27 mg/100 g, respectively). The PFT extract also had the highest DPPH and ABTs radical scavenging activity, and α-glucosidase inhibition activity. The Kkujippong leaf processed as tea imparted no cytotoxicity in the cell viability assay and exerted no concentration-dependent NO-production inhibition activity. The lowest NO-production inhibition activity at 500 μg/mL concentration was obtained for PFT. In conclusion, we recommend that the pan-fired tea using Kkujippong leaves can be used as alternative tea due to the better functionality and higher stability.

Antioxidant, Whitening, Antiwrinkle, and Anti-Inflammatory Effect of Ajuga spectabilis Nakai Extract.

Since ancient times, plants have been a good source of natural antioxidants. Plants remove active oxygen through antioxidants and contain various active ingredients. These active ingredients of plants are used to alleviate skin aging and chronic diseases. Ajuga spectabilis Nakai (AS) is a perennial plant, is endemic to Korea, and has the characteristics of alpine plants. The aim of this study was to assure the possibility of using AS as a functional natural and cosmetic material. For this, we carried out biologically activated material characteristic evaluations about antioxidant, wrinkle reduction, and anti-inflammatory effects using AS extract. To carry out this experiment, we extracted AS extract from AS water extract (AS-W) and AS 70% ethanol extract (AS-E). AS-E showed the highest DPPH activity and tyrosinase inhibitory activity. After, the measurement of metalloprotease (MMP)-1 inhibition effect showed the AS-W and AS-E activation at the concentration of 100 µg/mL. In addition, at the same concentration, from the result of the measurement of the biosynthesis quantity of pro-collagen type-1 we knew that its excellent effect appeared in AS-E (CCD-986sk). The inhibition of NO production in AS-W and AS-E was confirmed in LPS-induced mouse macrophage RAW264.7 cells. On cell viability, it was judged that AS-E had no toxicity because it showed a high cell viability at a high concentration, and it was used for the anti-inflammatory activity. Inhibition of NO production worked only in AS-E; inflammatory cytokine TNF-α and IL-6 were suppressed in a concentration-dependent manner in AS-E. AS is believed to be used as a natural cosmetic material because it has been proven to have antioxidant, whitening, wrinkle-improving, and anti-inflammatory effects. Therefore, the results indicate that AS extract can play an important role as a functional natural material and a cosmetic material for whitening, wrinkle reduction, and anti-inflammatory effect.

Sesquiterpenoids from the Florets of Carthamus tinctorius (Safflower) and Their Anti-Atherosclerotic Activity.

(1) Background: The florets of Carthamus tinctorius L. are traditionally used as a blood-activating drug and can be used for the treatment of atherosclerosis, but no compounds with anti-atherosclerotic activity have been reported. (2) Methods: This study investigated the chemical compounds from the florets of C. tinctorius. Comprehensive spectroscopic techniques revealed their structures, and ECD calculations established their absolute configurations. Nile Red staining, Oil Red O staining, and cholesterol assessment were performed on these compounds and their aglycones for the inhibitory activity against the formation of foam cells induced by oxidized low-density lipoprotein (ox-LDL) in RAW264.7 macrophages. In addition, RAW264.7 macrophages were tested for their anti-inflammatory activity by measuring the inhibition of NO production caused by LPS. (3) Results: Five new sesquiterpenoids (1-5) isolated from the florets of C. tinctorius were identified as (-)-(1R,4S,9S,11R)-caryophyll-8(13)-en-14-ol-5-one (1), (+)-(1R,4R,9S,11R)-caryophyll-8(13)-en-14-ol-5-one (2), (-)-(3Z,1R,5S,8S,9S,11R)-5,8-epoxycaryophyll-3-en-14-O-β-D-glucopyranoside (3), (+)-(1S,7R,10S)-guai-4-en-3-one-11-O-β-D-fucopyranoside (4), and (-)-(2R,5R,10R)-vetispir-6-en-8-one-11-O-β-D-fucopyranoside (5). All compounds except for compound 3 reduced the lipid content in ox-LDL-treated RAW264.7 cells. Compounds 3 and 4 and their aglycones were found to reduce the level of total cholesterol (TC) and free cholesterol (FC) in ox-LDL-treated RAW264.7 cells. However, no compounds showed anti-inflammatory activity. (4) Conclusion: Sesquiterpenoids from C. tinctorius help to decrease the content of lipids, TC and FC in RAW264.7 cells, but they cannot inhibit NO production, which implies that their anti-atherogenic effects do not involve the inhibition of inflammation.

The chemical constituents from Valeriana jatamansi and their anti-influenza virus and anti-inflammatory effects

Twenty-seven compounds, including six new iridoids, valeransins A−F ( 1 − 6 ), were isolated from the n -BuOH soluble fraction of Valeriana jatamansi . Structurally, compounds 1 and 2 are rare 8, 11-epoxy iridoids, and their absolute configuration was determined based on their experimental and calculated electronic circular dichroism (ECD) spectra. In addition, compounds 5 and 24 exhibited significant anti-influenza virus activities, with IC 50 values of 7.23 and 19.83 μM, respectively. Additionally, compound 24 showed inhibition of NO production stimulated by lipopolysaccharide in RAW 264.7 cells, with an IC 50 value of 27.22 μM. • Six new iridoids, valeransins A−F, were isolated from Valeriana jatamansi . • Valeransins A and B are two rare 8, 11-epoxy iridoids. • Valeransin E and ferulaldehyde showed significant anti-influenza virus activities. • Ferulaldehyde exhibited inhibitory effect on NO production.

Withania somnifera deploys immunomodulation and exerts anticancer effects on lung adenocarcinoma cells

Immunomodulation using phytochemicals is the alternate therapeutic modality to treat cancer. Withania somnifera (L.) Dunal is known to possess several pharmacological activities such as anti-inflammatory, anti-arthritic, neuroprotective and antitumor activity . In this study, we have evaluated the immunomodulatory and anticancer effects of W. somnifera (L.) Dunal ethanolic extract on lung adenocarcinoma cells. Anti- inflammatory effect was assessed using albumin denaturation method. Cell viability of murine macrophage cells was evaluated using MTT assay and nitric oxide scavenging capacity was assessed using Griess method. Compatibility of the extract on RAW 267.4 and THP 1 cells was assessed using morphological assessment, AO-EB and Hoechst staining methods. Further, RAW 267.4 (macrophage) and THP 1 (monocyte) cells were treated with the extract to assess the arginase, phagocytic and pinocytic activity. W. somnifera (L.) Dunal extract was administered to lung adenocarcinoma cells and evaluated for the induction of ROS to indicate the apoptotic effects. Further, immunofluorescence and immunoblotting was performed using the cell lysates to study the effect of extract on the expression of CTLA 4, HIF-1 α , TNF- α , and PECAM-1. In this study we found that, W. somnifera (L.) Dunal extract showed a dose dependent inhibition of protein denaturation and the extract did not show any cytotoxicity on RAW 267.4 cells. Griess assay performed with the culture supernatants revealed that the extract exhibited a dose dependent inhibition of NO production. RAW 267.4 and THP 1 cells showed a significant inhibition of arginase activity with ⁎⁎⁎ p <0.0005. At higher concentration of treatment, both the immune cells displayed a significant increase in the phagocytic and pinocytic effect. W. somnifera (L.) Dunal treatment increased the ROS production in lung adenocarcinoma cells and downregulated the expressions of CTLA-4, HIF-1 α , TNF- α , and PECAM-1. This study confirmed that W. somnifera (L.) Dunal ethanol extract possesses immunomodulatory effect, to enhance the cell death in lung cancer cells via ROS generation. • Ashwagandha has the ability to enhance nitric oxide scavenging activity, along with decreased activity of arginase, which is responsible for the cancer cell invasion and metastasis. • Ashwagandha regulates the phagocytic and pinocytic property in macrophages and monocytes, indicating the cellular defense against abnormal cells. • ROS generation is responsible for the apoptosis of the cells, upon treatment of ashwagandha A549 lung adenocarcinoma cells showed apoptosis by increasing the expression of ROS. • Decreased expression of HIF-1 α & TNF- α promotes cancer cell death.

Chemical constituents from the arial of Crinum asiaticum L

Crinum asiaticum L. (locally known Nang hoa trang), belonging to the Crinum genus of the Amaryllidaceae family, has been widely used in oriental and traditional medicine around the world for the treatment of various diseases and exerts diverse promising pharmacological effects. To find out new inhibitors for the treatment of inflammatory and Alzheimer’s diseases, a methanol extract of the aerial part of C. asiaticum was investigated to afford six compounds, chrysophanol (1), emodin (2), physcion (3), thymine (4), thymidine (5), and 5-(hydroxymethyl)-2-furfural (6) by using various chromatographic separations. Their structures were identified by the extensive analysis of 1H- and 13C-NMR data as well as a comparison with those of previously reported data. This is the first report of these compounds (1-6) from C. asiaticum. In addition, all compounds evaluated the inhibitory activities of NO production and acetylcholinesterase (AChE). Among them, emodin (2) significantly inhibited NO production with an IC50 of 5.13±0.42 μM. This result indicated that emodin (2) may be beneficial in the treatment of anti-inflammatory diseases. Besides, all compounds (1-6) also showed weak inhibitory effects on the AChE enzyme with a range of IC50 values from 82.98±9.19 to 237.63±13.8 µM.

Epoxymicheliolide prevents dextran sulfate sodium-induced colitis in mice by inhibiting TAK1-NF-κB pathway and activating Keap1-NRF2 signaling in macrophages.

Ulcerative colitis (UC) is an unspecific colorectal inflammation associated with macrophages overactivation. Therefore, macrophage-targeted treatment has been considered a promising strategy for UC therapy. Epoxymicheliolide (EMCL) is a compound from Aucklandia lappa Decne, a TCM for treating gastrointestinal inflammatory diseases. The purpose of this study is to investigate the therapeutic effect of EMCL on DSS-induced mice colitis through the anti-inflammatory activity on macrophages and its underlying mechanisms. We found that EMCL inhibited the release of NO and PGE2 by down-regulating the expression of iNOS and COX2, while suppressed the expression of IL-1β, IL-6, and TNF-α in LPS-stimulated RAW264.7 macrophages. EMCL also inhibited NO production in LPS-activated peritoneal macrophages and TNFα-stimulated RAW264.7 cells. Moreover, EMCL blocked the phosphorylation of TAK1, IKKα/β, and IκBα, as well as IκBα degradation, thereby inhibiting the NF-κB pro-inflammatory signaling. Furthermore, EMCL decreased the intracellular ROS, by activating the NRF2 antioxidant pathway. CETSA and molecular docking showed that EMCL might form a covalent bond with Cys174 of TAK1 or Cya151 of Keap1, which may contribute to EMCL-mediated actions. Additionally, a thiol donor β-mercaptoethanol obviously abolished EMCL-mediated actions in vitro, suggesting the crucial role of the α, γ-unsaturated lactone of EMCL on its anti-inflammatory effects. Furthermore, EMCL not only ameliorated symptoms of colitis and colon barrier injury, but also decreased the levels of pro-inflammatory cytokines, MPO, NO, and MDA in DSS-challenged mice. Thus, our study demonstrated that EMCL ameliorated UC by targeting NF-κB and Nrf2 pathways, indicating it may server as a promising drug candidate for UC therapy.

Chemical constituents from the arial of Crinum asiaticum L.

Crinum asiaticum L. (locally known Nang hoa trang), belonging to the Crinum genus of the Amaryllidaceae family, has been widely used in oriental and traditional medicine around the world for the treatment of various diseases and exerts diverse promising pharmacological effects. To find out new inhibitors for the treatment of inflammatory and Alzheimer’s diseases, a methanol extract of the aerial part of C. asiaticum was investigated to afford six compounds, chrysophanol (1), emodin (2), physcion (3), thymine (4), thymidine (5), and 5-(hydroxymethyl)-2-furfural (6) by using various chromatographic separations. Their structures were identified by the extensive analysis of 1H- and 13C-NMR data as well as a comparison with those of previously reported data. This is the first report of these compounds (1-6) from C. asiaticum. In addition, all compounds evaluated the inhibitory activities of NO production and acetylcholinesterase (AChE). Among them, emodin (2) significantly inhibited NO production with an IC50 of 5.13±0.42 μM. This result indicated that emodin (2) may be beneficial in the treatment of anti-inflammatory diseases. Besides, all compounds (1-6) also showed weak inhibitory effects on the AChE enzyme with a range of IC50 values from 82.98±9.19 to 237.63±13.80 µM.

Three Pairs of Novel Enantiomeric 8-O-4' Type Neolignans from Saussurea medusa and Their Anti-inflammatory Effects In Vitro.

Three pairs of novel enantiomeric 8-O-4' type neolignans (1a/1b-3a/3b), together with seven known analogues (4-10), were isolated from the whole plants of Saussurea&amp;nbsp;medusa. Their structures were elucidated by extensive spectroscopic data analysis and electric circular dichroism (ECD) calculations after chiral separations. All compounds were obtained from S. medusa for the first time, and compounds 1-3 and 5-10 had never been obtained from the genus Saussurea previously. The anti-inflammatory activities of the compounds were evaluated by determining their inhibitory activities on the production of NO and inducible nitric oxide synthase (iNOS) expression in LPS-stimulated RAW 264.7 cells. Compounds (+)-1a, (-)-1b and 5-7 inhibited NO production and had IC50 values ranging from 14.3 ± 1.6 to 41.4 ± 3.1 μM. Compound 7 induced a dose-dependent reduction in the expression of iNOS in LPS-treated RAW 264.7 cells. Molecular docking experiments showed that all active compounds exhibited excellent docking scores (&lt;-7.0 kcal/mol) with iNOS. Therefore, compounds (+)-1a, (-)-1b and 5-7 isolated from the whole plants of S. medusa may have therapeutic potential in inflammatory diseases.

Phytochemical constituents from Elsholtzia ciliata (Thunb.) Hyl. and their nitric oxide production inhibitory activities

A new megastigmane glycoside, (3S,4R,7E)-megastigma-5,7-diene-9-one-3,4-diol 3-O-β-D-apiofuranosyl-(1→2)-β-D-glucopyranoside (1) and a new cyanogenic glycosyl derivative, (S)-2-(6′-O-R-rosmarinoyl-β-D-glucopyranosyloxy)-phenylacetonitrile (2) were isolated from the methanol extract of the Elsholtzia ciliata together with twelve known compounds, 1-O-β-D-glucopyranosyl-2-hydroxy-4-allylbenzene (3), citrusin C (4), 1,2-di-O-β-D-glucopyranosyl-4-allylbenzene (5), manglieside B (6), 4-allyl-2-hydroxyphenyl 1-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside (7), (-)-isolariciresinol 3α-β-D-glucopyranoside (8), 7R,8R-threo-4,7,9-trihydroxy-3,3′-dimethoxy-8-O-4′-neolignan-9′-O-β-D-glucopyranoside (9), 7R,8R-threo-4,7,9,9′-tetrahydroxy-3-methoxy-8-O-4′-neolignan-9′-O-β-D-glucopyranoside (10), cedrusin-4-O-β-D-glucopyranoside (11), icariside E3 (12), everlastoside L (13) and rosmarinic acid (14). Their chemical structures were elucidated on the basic of extensive 1D and 2D-NMR experiments, as well as their mass spectroscopic data. The absolute configurations of the compounds 1 and 2 were successfully indicated by both theoretical and calculated CD spectra. Compounds 3–7, 9 and 10 potential inhibited NO production in LPS-activated RAW264.7 cells with IC50 values of 6.71, 8.97, 12.38, 14.27, 16.13, 13.54, 16.27 µM, respectively, compared to that of the positive control of N G-monomethyl-L-arginine acetate (L-NMMA), IC50 = 32.51 µM.

Identification of anti-inflammatory components in Dioscorea nipponica Makino based on HPLC-MS/MS, quantitative analysis of multiple components by single marker and chemometric methods

The rhizome of Dioscorea nipponica Makino (RDN) is a widely used herbal medicine, which has significant anti-inflammatory activities on various inflammatory diseases. However, the bioactive compositions responsible for the anti-inflammatory activity of RDN are still unknown. This study aimed to identify the anti-inflammatory bioactive compounds in RDN using high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q/TOF-MS), quantitative analysis of multiple components by single marker (QAMS) and chemometric methods. Firstly, an HPLC-Q/TOF-MS method was employed for identification of bioactive steroidal saponins in RND, and a total of twelve steroid saponins were identified. Then, QAMS method was employed to determine the contents of seven bioactive steroidal saponins, including protodioscin, protogracillin, methyl protodioscin, pseudoprotodioscin, pseudoprogracillin, dioscin and gracillin in RND samples using dioscin as the reference analyte. The anti-inflammatory effects of RDN samples were then evaluated by inhibition of NO production in LPS-induced RAW264.7 cells. Furthermore, chemometric methods, including Pearson correlation analysis and partial least squares regression (PLSR) were employed to investigate the correlations between chemical components and anti-inflammatory activities, and explore the potential anti-inflammatory bioactive compounds of RDN. The results indicated that protodioscin, dioscin and gracillin were selected as the major anti-inflammatory compounds in RND. The further verification experiments showed that protodioscin, dioscin and gracillin exhibited great inhibition on NO production with IC50 values (the half maximal inhibitory concentration) of 0.712 μM, 0.469 μM and 0.815 μM, respectively. They also significantly reduced the levels of TNF-α, IL-1β, and IL-6 in LPS-induced RAW264.7 cells. The present study provided evidences for the anti-inflammatory activity of RND and identification of the anti-inflammatory components in RDN.

A new lignanamide from the stems of Derris elliptica (Wall.) Benth with antimicrobial and anti‐inflammatory activities

AbstractA new lignanamide, named derristicine A (1), together with ten known compounds, dalbin (2), wistin (3), 3,5‐dimethoxy‐4‐hydroxy‐1‐O‐β‐D‐glucopyranoside (4), 3,4,5‐trimethoxyphenyl‐1‐O‐(4′‐sulfo)‐β‐D‐glucopyranoside (5), vanillic acid glucosyl ester (6), (9R)‐roseoside (7), (9S)‐roseoside (8), pumilaside A (9), (8R,8′R)‐secoisolariciresinol‐9‐O‐β‐D‐glucopyranoside (10), and (8S,8′S)‐secoisolariciresinol‐9‐O‐β‐D‐glucopyranoside (11) were isolated from Derris elliptica (Wall.) Benth stems. Their chemical structures were determined by analysis of HR‐ESI‐MS, NMR spectral data, as well as comparison with previous reports. Compounds 2‐3, 5‐8, and 10 showed potential inhibitory effect on the growth of Candida albicans strain with a MIC value of 37.5 μM. Compounds weakly inhibited NO production in LPS activated RAW264.7 cells.

Synthesis of benzylated amine-substituted xanthone derivatives and their antioxidant and anti-inflammatory activities.

Oxidative stress and its constant companion, inflammation, play a critical part in the pathogenesis of many acute and chronic illnesses. The discovery of new multi-targeted drug candidates with antioxidant and anti-inflammatory properties is deemed necessary. Thus, a series of novel xanthone derivatives with halogenated benzyl (4b-4d, 4f-4h) and methoxylated benzyl groups (4e) attached to the butoxy amine substituent were synthesized in this study. The synthesized xanthone derivatives exhibited stronger antioxidant activity against H2 O2 scavenging than the standard drug, α-tocopherol, but weaker towards DPPH scavenging and ferrous ion chelation. Besides that, 4b-4d, 4f-4h demonstrated good anti-inflammatory activities through NO production inhibition towards lipopolysaccharide (LPS)-induced RAW 264.7 cells and showed 2-4 times stronger effects than the standard drug, diclofenac sodium. Moreover, compound 4b with two brominated benzyl groups attached to the butoxy amine substituent suppressed the production of pro-inflammatory cytokines, TNF-α and IL-1β, significantly. Structure-activity relationship elucidated that the halogenated benzylamine substituent plays an important role in contributing the antioxidant and anti-inflammatory activities of xanthones. In summary, xanthone 4b was identified as a potential lead compound to be further developed into antioxidant and anti-inflammatory drugs. Thus, further studies on the related mechanisms of action of 4b are recommended.