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Xanthine Oxidase-Inhibitory Activity and Antioxidant Properties of the Methanol Extract and Flavonoids of Artemisia Asiatica
Abstract
The MeOH extract of the aerial parts of Artemisia asiatica significantly inhibited the xanthine oxidase (XO) induced uric acid production. Flavonoids were isolated from the active extract and identified as eupatilin (1), hispidulin (2), jaceosidin (3), cirsilineol (4), 5,7,4',5'-tetrahydroxy-6,3'-dimethoxyflavone (5), 6- methoxytricin (6) and chrysosplenetin (7). With the exception of cirsilineol and chrysoplenetin, all these flavonoids exerted marked XO-inhibitory effects, with IC50 values in the range 1.33-6.13 μM. The degree of XO inhibition by 1-3, 5 and 6 suggests the importance of the free OH group on C-7. Evaluation of the isolated compounds 1-7 for their free radical scavenging activity in DPPH tests, revealed the substantial antioxidant activity of 5,7,4',5'-tetrahydroxy-6,3'-dimethoxy-flavone (5), which contains orthodihydroxy and 5-hydroxy groups. In summary, the flavonoid-containing MeOH extract of A. asiatica exhibits dual action, inhibiting XO (1-3, 5, 6) and resulting in a reduced generation of reactive oxygen species, and additionally scavenging free radicals (5).
... From A. asiatica, 22 known phytochemical compounds have been identified including flavonoids, coumarins, terpenes, sesquiterpene lactones, monoterpenes, guaianolide, secoguianolide lignans, phenylpropanoids, and steroids (Table 1) (Hajdú et al., 2014). Some of these compounds exhibit variety of bioactivities in vivo and in vitro, as mentioned in Table 2. ...
... Flavonoids are the most common and important secondary metabolites found in many plants. To date, seven flavonoids have been identified from aerial parts of A. asiatica: (a) eupatilin, (b) jaceosidin, (c) hispidulin, (d) 5,7,4′,5′-tetrahydroxy-6,3′-dimethoxy-flavone, (e) 6methoxytricin, (f) cirsilineol, and (g) chrysosplenetin (Hajdú et al., 2014;Lee et al., 2015). Among these flavonoids, eupatilin and jaceosidin are regarded as the main phytochemical components in this plant. ...
... These compounds are 15-carbon compounds with three isoprene units followed by a cisor trans-fused lactone. To date, seven sesquiterpene lactones ( Fig. 1) have been reported in the A.asiatica: (h) artecanin, (i) ridentin, (j) 3β-chloro-4α,10α-dihydroxy-1α,2α-epoxy-5α,7αH-guaia-11,en-12,6α-olide, (k) 4β,15-dihydro-3-dehydrozaluxanin, (l) isoseco-tanapartholide 3-O-methyl ether, (m) artemiloside, and (n) artemisinin (Hajdú et al., 2014;Ivanescu et al., 2015). ...
... The extract of Artemisia asiatica herb with antiproliferative activity against four human tumor cell lines (A2780, A431, HeLa, and MCF7) was analyzed by the MTT assay, and bioassay-directed fractionation was carried out in order to identify the compounds responsible for the cytotoxic activity. Guaianolide (1-4), seco-guianolide (5), germacranolide (6) and eudesmanolide sesquiterpenes (7), monoterpenes (8,9), including the new compound artemisia alcohol glucoside (8), and flavonoids (10)(11)(12)(13)(14)(15)(16) were isolated as a result of a multistep chromatographic procedure (CC, CPC, PLC, and gel filtration). The compounds were identified by means of UV, MS, and NMR spectroscopy, including 1 H-and 13 C-NMR, 1 H-1 H COSY, NOESY, HSQC, and HMBC experiments. ...
... The isolated compounds 1-16 were evaluated for their tumor cell growth-inhibitory activities on a panel of four adherent cancer cell lines, and different types of secondary metabolites were found to be responsible for the cytotoxic effects of the extract. Especially cirsilineol (13), 3β-chloro-4α,10α-dihydroxy-1α,2α-epoxy-5α,7αH-guai-11(13)-en-12,6α-olide (3), and iso-seco-tanapartholide 3-Omethyl ester (5) exerted marked cytotoxic effects against the investigated cell lines, while jaceosidin (12), 6-methoxytricin (15), artecanin (2), and 5,7,4′,5′-tetrahydroxy-6,3′-dimethoxyflavone (14) were moderately active. All the sesquiterpenes and monoterpenes are reported here for the first time from this species, and in the case of artecanin (2), 3α-chloro-4β,10α-dihydroxy-1β, 2β-epoxy-5α,7αH-guai-11(13)-en-12,6α-olide (4), ridentin (6), and ridentin B (7), previously unreported NMR spectroscopic data were determined. ...
... Compound 9 was identical in all of its spectral characteristics with dehydrolinalool oxide [13]. Furthermore, flavonoids were isolated in pure form from the active fractions II and III and identified as eupatilin (10), hispidulin (11), jaceosidin (12), cirsilineol (13), 5,7,4′,5′-tetrahydroxy-6,3′-dimethoxy-flavon (14), 6-methoxytricin (15), and chrysoplenetin (16) [14]. Some of the isolated compounds were subjected to an antiproliferative assay on human adherent cell lines (HeLa, A431, MCF7, and A2780; l " Table 3). ...
... The extract of Artemisia asiatica herb with antiproliferative activity against four human tumor cell lines (A2780, A431, HeLa, and MCF7) was analyzed by the MTT assay, and bioassay-directed fractionation was carried out in order to identify the compounds responsible for the cytotoxic activity. Guaianolide (1-4), seco-guianolide (5), germacranolide (6) and eudesmanolide sesquiterpenes (7), monoterpenes (8,9), including the new compound artemisia alcohol glucoside (8), and flavonoids (10)(11)(12)(13)(14)(15)(16) were isolated as a result of a multistep chromatographic procedure (CC, CPC, PLC, and gel filtration). The compounds were identified by means of UV, MS, and NMR spectroscopy, including 1 H-and 13 C-NMR, 1 H-1 H COSY, NOESY, HSQC, and HMBC experiments. ...
... The isolated compounds 1-16 were evaluated for their tumor cell growth-inhibitory activities on a panel of four adherent cancer cell lines, and different types of secondary metabolites were found to be responsible for the cytotoxic effects of the extract. Especially cirsilineol (13), 3β-chloro-4α,10α-dihydroxy-1α,2α-epoxy-5α,7αH-guai-11(13)-en-12,6α-olide (3), and iso-seco-tanapartholide 3-Omethyl ester (5) exerted marked cytotoxic effects against the investigated cell lines, while jaceosidin (12), 6-methoxytricin (15), artecanin (2), and 5,7,4′,5′-tetrahydroxy-6,3′-dimethoxyflavone (14) were moderately active. All the sesquiterpenes and monoterpenes are reported here for the first time from this species, and in the case of artecanin (2), 3α-chloro-4β,10α-dihydroxy-1β, 2β-epoxy-5α,7αH-guai-11(13)-en-12,6α-olide (4), ridentin (6), and ridentin B (7), previously unreported NMR spectroscopic data were determined. ...
... Compound 9 was identical in all of its spectral characteristics with dehydrolinalool oxide [13]. Furthermore, flavonoids were isolated in pure form from the active fractions II and III and identified as eupatilin (10), hispidulin (11), jaceosidin (12), cirsilineol (13), 5,7,4′,5′-tetrahydroxy-6,3′-dimethoxy-flavon (14), 6-methoxytricin (15), and chrysoplenetin (16) [14]. Some of the isolated compounds were subjected to an antiproliferative assay on human adherent cell lines (HeLa, A431, MCF7, and A2780; l " Table 3). ...
The extract of Artemisia asiatica herb with antiproliferative activity against four human tumor cell lines (A2780, A431, HeLa, and MCF7) was analyzed by the MTT assay, and bioassay-directed fractionation was carried out in order to identify the compounds responsible for the cytotoxic activity. Guaianolide (1-4), seco-guianolide (5), germacranolide (6) and eudesmanolide sesquiterpenes (7), monoterpenes (8, 9), including the new compound artemisia alcohol glucoside (8), and flavonoids (10-16) were isolated as a result of a multistep chromatographic procedure (CC, CPC, PLC, and gel filtration). The compounds were identified by means of UV, MS, and NMR spectroscopy, including (1)H-and (13)C-NMR, (1)H-(1)H COSY, NOESY, HSQC, and HMBC experiments. The isolated compounds 1-16 were evaluated for their tumor cell growth-inhibitory activities on a panel of four adherent cancer cell lines, and different types of secondary metabolites were found to be responsible for the cytotoxic effects of the extract. Especially cirsilineol (13), 3β-chloro-4α,10α-dihydroxy-1α,2α-epoxy-5α,7αH-guai-11(13)-en-12,6α-olide (3), and iso-seco-tanapartholide 3-O-methyl ester (5) exerted marked cytotoxic effects against the investigated cell lines, while jaceosidin (12), 6-methoxytricin (15), artecanin (2), and 5,7,4',5'-tetrahydroxy-6,3'-dimethoxyflavone (14) were moderately active. All the sesquiterpenes and monoterpenes are reported here for the first time from this species, and in the case of artecanin (2), 3α-chloro-4β,10α-dihydroxy-1β,2β-epoxy-5α,7αH-guai-11(13)-en-12,6α-olide (4), ridentin (6), and ridentin B (7), previously unreported NMR spectroscopic data were determined.
... For compound 2, the 1 H and 13 C NMR showed similar pattern like the compound 1 ( Table 1) In addition to 1D NMR data, 2D NMR data confirmed the predicted three methoxylated flavone structure for compound 2. The analysis of HMBC data of compound 2 showed the following correlations: (a) H-8 with C-10, C-6, C-9, C-7, C-4 in A ring, (b) H-3 with C-1', C-2, C-10, C-4, (c) H-2' with C-3', C-4', C-2, and C-6' in B ring, (d) H-5' with C-3', C-4', and C-6' in B ring, © H-6, H-7, and H-3' of methoxyl groups with C-6, C-7, and C-2, respectively, in A ring ( Table 1) H-2'. Based on these information in addition to the TOCSY, COSY, HSQC, and NOSEY data ( Table 1 and the supporting information uploaded as a supplementary file compound 2 was identified as cirsilineol (30)(31)(32)(33). ...
... However, the in-silico methods could be an open valuable line for purposeful assays on natural compounds. class of compounds don't have high toxicity against normal cells, numerous investigations showed their cytotoxic potential against various carcinogenic cell lines (33). These anticancer potentials of the various flavonoids have attracted huge attention for finding natural or synthetic flavonoids related compounds as lead anticancer compounds. ...
In this study, methoxylated flavonoids and volatile constitutions of Agrostis gigantea Roth (Poaceae) were investigated for the first time. The flavonoids were identified by spectroscopic methods (¹H-NMR, ¹³C-NMR, COSY, NOSEY, TCOSY, and HMBC). The volatile constitutions of aerial parts and seeds were analyzed by gas chromatography–mass spectrometry (GC-MS). Two methoxylated flavonoids, luteolin 5-methyl ether (1), and cirsilineol (2) were isolated from the aerial parts of this plant. According to the GC-MS data the main constitutions of these volatile oils belong to the simple phenolic category which include coniferyl alcohol (18.80%) and eugenol (12.19%) in aerial parts and seeds, respectively. By using the computer- aided molecular modeling approaches, the binding affinity of these compounds was predicted in the catalytic domains of aryl hydrocarbon receptor (AhR).
These two isolated flavonoids were investigated in-vitro for their inhibitory activity on 4T1 breast carcinoma cells. It was predicted that these compounds could be well-matched in aryl hydrocarbon receptor (3H82) active site, but based on the in-vitro assay, the IC50 values on cytotoxicity were 428.24 ±3.21 and 412.7±3.02 μg/mL for luteolin 5-methyl ether and cirsilineol, respectively. Thus, it can be concluded that these flavonoids exhibit low cytotoxicity against 4T1 breast carcinoma cell line.
... The genus Artemisia is a plentiful supplier of flavonoids [10]. Although A. annua-from which over 50 flavonoids have been found-has received the most attention among the Artemisia species, other species, such as A. absinthium L. [11], A. asiatica [12], and A. herba-alba [13] have also been found to contain a number of flavonoids. ...
Secondary metabolites have been shown to possess a range of biological functions. Flavonoids, due to their ability to scavenge ROS, are famous antioxidants. The plants of Artemisia species are rich sources of flavonoids; however, the amount of these metabolites is less. In the current study, the flavonoid content was detected and then enhanced by genetically modifying the Artemisia carvifolia Buch with Agrobacterium tumefaciens strain GV3101 carrying rol A gene. The transformation of rol A gene was confirmed with PCR and the gene copy number was confirmed by Southern blot analysis. The HPLC analysis revealed the presence of catechin (3.19 ug/mg DW) and geutisic acid (2.22 ug/mg DW) in transformed plants, unlike wild-type plants. In transformed plants, all detected flavonoids (vanillic acid, rutin, catechine, gallic acid, syringic acid, caffeic acid, coumaric acid, geutisic acid, ferulic acid, and cinnamic acid) were increased up to several folds. Real-time qPCR revealed the higher expression levels of the genes for flavonoid biosynthesis enzymes phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS) in plants transformed with rol A genes, as the expression levels were increased up to 9–20-fold and 2–6-fold, respectively. The rol A transgenic lines T3 and T5 carrying two copies of rol A gene, particularly showed higher expression of both PAL and CHS gene, with the highest expression in T3 line. The transgenic lines demonstrated an average increase of 1.4-fold in the total phenolic content and 1–2-fold in the total flavonoid content as compared to wild-type plants. Total antioxidant capacity and total reducing power were increased up to an average of 1–2-fold and 1.5–2-fold respectively, along with increased free radical scavenging ability. Furthermore, the rol A gene transgenics were found to have much greater cytotoxic capacity than the A. carvifolia wild-type plant against the MCF7, HeLA, and HePG2 cancer cell lines. Current findings show that the rol A gene effectively increases the flavonoid content of A. carvifolia Buch, boosting the plant’s capacity as an antioxidant and an anticancer. This is the first-ever report, demonstrating the genetic transformation of Artemisia carvifolia Buch with rol A gene.
... This species is widely known for its medicinal properties and their essential oil is commonly used in medicine and food products (Oh et al. 2005;Ryu et al. 1998;Ahuja et al. 2018). Characteristic secondary metabolites of A. asiatica include flavonoids, coumarins, terpenes, sesquiterpene lactones, monoterpenes, guaianolidem secoguianolide, lignans, phenylpropanoids and steroids (Hajdú et al. 2014). Despite the broad-spectrum bioactivity of A. asiatica, its endophytic fungal community and their bioactive compounds has not been investigated. ...
Endophytic fungi produce a plethora of secondary metabolites, which may open new avenues to study their applicability in pharmaceuticals. Therefore, the present study focuses on the fungal endophytic community of Artemisia asiatica. During our work, fungal endophytes were isolated from a medicinal plant, A. asiatica. The culturable endophytic fungi were identified using molecular techniques and biodiversity, richness and tissue specificity were examined. As these microorganisms have been generally identified as an abundant reservoir of novel antimicrobial compounds, the antimicrobial (i.e. antibacterial and antifungal) activities of the metabolites produced by the isolated fungi were studied. Numerous extracts containing the endophytic metabolites proved to be active against the applied test microorganisms including Gram-positive and Gram-negative bacteria, as well as yeasts and filamentous fungi, which can be examined in detail in the future and, based on the the chemical nature of these active metabolites, allow to discover novel bioactive metabolites.
... The genus Artemisia consists of more than 300 species and is one of the richest sources of these flavonoids [145]. Within this genus, A. annua is the most extensively studied species from which around 50 flavonoids have been isolated, however, several flavonoids have been detected in other species too like A. absinthium L. [152,153], A. asiatica [154], A. herba-alba [155], A. abrotanum [156], A. lactiflora [157] and A. sphaerocephal [130,131]. Phenolics isolated from A. annua have been summarized in the scheme shown in Fig. 4. ...
The world is experiencing a cancer epidemic and an increase in the prevalence of the disease. Cancer remains a major killer, accounting for more than half a million deaths annually. There is a wide range of natural products that have the potential to treat this disease. One of these products is artemisinin; a natural product from Artemisia plant. The Nobel Prize for Medicine was awarded in 2015 for the discovery of artemisinin in recognition of the drug’s efficacy. Artemisinin produces highly reactive free radicals by the breakdown of two oxygen atoms that kill cancerous cells. These cells sequester iron and accumulate as much as 1000 times in comparison with normal cells. Generally, chemotherapy is toxic to both cancerous cells and normal cells, while no significant cytotoxicity from artemisinin to normal cells has been found in more than 4000 case studies, which makes it far different than conventional chemotherapy. The pleiotropic response of artemisinin in cancer cells is responsible for growth inhibition by multiple ways including inhibition of angiogenesis, apoptosis, cell cycle arrest, disruption of cell migration, and modulation of nuclear receptor responsiveness. It is very encouraging that artemisinin and its derivatives are anticipated to be a novel class of broad-spectrum antitumor agents based on efficacy and safety. This review aims to highlight these achievements and propose potential strategies to develop artemisinin and its derivatives as a new class of cancer therapeutic agents.
... The mass spectrum exhibited peaks for the deprotonated molecule with m/z 491 and a fragment with m/z 329 TABLE 1. PMR (500 MHz) and 13 C NMR Spectra (125 MHz) of 1 and 2 (DMSO-d 6 , 298 K, δ, ppm, J/Hz) that lost a hexose, indicating that 2 was an O-glycosylflavone [18]. Acid hydrolysis of 2 produced D-glucose and jaceosidin (5,7,4′-trihydroxy-6,3′-dimethoxyflavone) that was identified using UV and NMR spectroscopy and mass spectrometry [24]. PMR and 13 C NMR spectra of 2 showed sets of resonances characteristic of jaceosidin and the added β-glucopyranose (Table 1). ...
New flavonoids were isolated from the aerial part of Artemisia frigida Willd. (Asteraceae). Their structures were elucidated using UV, IR, and NMR spectroscopy and mass spectrometry as chrysoeriol-7-O-(2′′-Oacetyl)-β-D-glucopyranoside (2′′-O-acetylthermopsoside), jaceosidin-4′ -O-β-D-glucopyranoside (isojaceoside), and 13 known flavonoids. The influence of the isolated compounds on α-glucosidase activity and triglyceride accumulation in 3T3-L1 preadipocytes was studied. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.
... Thus, it was subjected to a phytochemical investigation, which resulted in the isolation of a new sesquiterpene named vulgaric acid (1), together with eight previously reported compounds. The known compounds were identified as 2a-chloro-3b,9b-dihydroxy-1b,10b-epoxy-4a,6aH-guai-11(13)-en-12,5-olide (2) (Mahmoud et al. 2012), apigenin (3) (da Silva et al. 2015), jaceosidin (4) (Hajd u et al. 2014), 5,7,3'-trihydroxy-6,4'-dimethoxyflavone (5) (Wang et al. 2016), 5,7,3',5'-tetrahydroxy-6,4'-dimethoxyflavone (6) (Song et al. 2013), eupatilin (7) (Deng et al. 2004), umbelliferone (8) (Kim et al. 2006), and isoscopoletin (9) (Zhao et al. 2014) (Figure 1). Herein, we describe the isolation, structure elucidation of the new compound, along with preferential cytotoxicity screening of all isolated compounds against PANC-1 cells. ...
The 70% ethanolic extract of Artemisia vulgaris showed preferential cytotoxicity against PANC-1 human pancreatic cancer cells under a nutrient-deprived condition with PC50 12.5 μg/mL. A phytochemical investigation of this extract yielded a new bicyclic [4:3:0] sesquiterpene named (+)-vulgaric acid (1), together with eight previously reported compounds. The structural elucidation of 1 was achieved by HRFABMS and NMR analysis. The absolute configuration of 1 was deduced by computational calculations of ECD data. All isolated compounds were tested for preferential cytotoxicity against PANC-1 cells, and apigenin (3) showed the strongest activity with PC50 30.7 μM.
... HPLC separation of fraction 4 (and also 5) afforded the previously reported verbascoside (11) [12,14] as the major compound (Fig. 5). Fraction 11 yielded the known flavonoids hispidulin (12) [21], and jaceosidin (13) [22], which are reported for the first time from E. glabra. Fraction 13 yielded a previously undescribed serrulatane, 18-acetoxy-8, 20-dihydroxyserrulat-14-en-19-oic acid (14), along with the known 8,18,20-trihydroxyserrulat-14-en-19oic acid (5) [8] and the flavonoid cirsimaritin (15) that are also reported for the first time from E. glabra [23]. ...
Recent reports of Eremophila glabra (R.Br.) Ostenf. (Scrophulariaceae) displaying antibacterial activity has led us to investigate the bioactive secondary metabolites responsible for this activity. Bioassay-directed fractionation of solvent extracts prepared from the leaves of E. glabra led to the isolation of seven serrulatane diterpenes, three flavonoids and the caffeoyl ester disaccharide verbascoside. Among these, four serrulatanes, namely 18-acetoxy-8, 20-dihydroxyserrulat-14-en-19-oic acid (14), 18,20-diacetoxy-8-hydroxyserrulat-14-en-19-oic acid (16), 8,18,20-triacetoxyserrulat-14-en-19-oic acid (17) and 18-acetoxy-8-hydroxyserrulat-14-en-19-oic acid (18) are described for the first time, while 8,20-diacetoxyserrulat-14-en-19-oic acid (3), 8,18,20-trihydroxyserrulat-14-en-19-oic acid (5) and 20-acetoxy-8-hydroxyserrulat-14-en-19-oic acid (19) were previously reported. All three flavonoids hispidulin (12), jaceosidin (13) and cirsimaritin (15) are known but reported for the first time in E. glabra. All compounds were tested in an agar diffusion antimicrobial assay against Staphylococcus aureus (NCTC 10442) and Staphylococcus epidermidis (ATCC 14990). Compounds 12, 13, 17, 18 and 19 exhibited moderate activity, with minimum inhibitory concentrations (MICs) ranging from 32 to 512μg/mL. Compound 19 demonstrated the highest activity against S. epidermidis ATCC 14990 with MIC of 32μg/mL, while 13 demonstrated the highest activity against S. aureus NCTC 10442 with MIC of 128μg/mL.
... Liu et al. studied the methanol extracts of Euonymus laxiflorus, Rubia lanceolata, and Gardenia jasminoides for XO inhibitory activity. Rinelori-The flavonoid-containing methanolic extract of A. asiatica has a dual effect, resulting in the reduced generation of ROS, and by scavenging free radicals.188 Hashim et al. demonstrated that methanolic extract of Morinda elliptica leaves, under the optimized conditions, showed 88.93% XO inhibition. ...
Almost all drug molecules become the substrates for oxidoreductase enzymes, get metabolized into more hydrophilic products and eliminated from the body. These metabolites sometime may be more potent, active, inactive, or toxic in nature compared to parent molecule. Xanthine oxidoreductase and aldehyde oxidase belong to molybdenum containing family and are well characterized for their structures and functions, in particular to their ability to oxidize/hydroxylate the xenobiotics. Their upregulated clinical levels causing oxidative stress are associated with pathways either directly involved in the progression of diseases, gout, or indirectly with the succession of other diseases such as diabetes, cancer, etc. Herein, we have put forth a comprehensive review on the xanthine and aldehyde oxidases pertaining to their structures, functions, pathophysiological role, and a comparative analysis of structural insights of xanthine and aldehyde oxidases' binding domains with endogenous ligands or inhibitors. Though both the enzymes are molybdenum containing and are likely to share some common pathways and interact with inhibitors in a similar manner but we have focused on structural prerequisites for inhibitor specificity to both the enzymes keeping in view of the existing X-ray structures. This review also provides futuristic implications in the design of inhibitors derived from inorganic complexes or small organic molecules considering the spatial features and structural insights of both the enzymes.
... The known compounds were characterized as calceolarioside A (2) [8], scutellarein 7-O-β-D-glucopyranoside (3) [9], hispidulin 7-O-β-D-glucopyranoside (4) [10], cleroindicins B (5) and F (6) [11], and adenosine (7) [12] by comparing their spectroscopic data with those published previously. Moreover, a mixture of β-glucopyranosyl-(16)-4-O-caffeoyl-α/β-glucopyranose and 3,4-dihydroxyphenylethanol, which could be an artefact formed during the isolation procedure, was characterized. ...
A new phenylethanoid glycoside, named digiviridifloroside (1), was isolated from the leaves of Digitalis viridiflora Lindley along with a known phenylethanoid glycoside, calceolarioside A (2), two flavonoid glycosides, scutellarein 7-O-beta-D-glucopyranoside (3) and hispidulin 7-O-beta-D-glucopyranoside (4), two cleroindicins, cleroindicins B (5) and F (6), a nucleoside, adenosine (7), as well as a mixture of beta-glucopyranosyl-(1 -> 6)-4-O-caffeoyl-alpha/beta-glucopyranose and 3,4-dihydroxyphenylethanol. The structure of the new compound was established as 3,4-dihydroxy-beta-phenylethoxy-6-O-(E)-feruloyl-beta-glucopyranosyl-(1 -> 6)-4-O-(E)-caffeoyl-beta-glucopyranoside (1) based on extensive 1D- and 2D-NMR spectroscopy, as well as BR-BSI-MS. Digiviridifloroside represents a rare type of phenylethanoid glycoside which bears two aromatic acyl units in its structure. In addition to phytochemical studies, the isolates were evaluated for their in vitro antimicrobial activities against three pathogenic bacteria and three yeast strains using a microdilution method. Among the tested compounds, 5 exhibited moderate antibacterial activity against Bacillus cereus NRRLB 3711 with a MIC value of 25 mu g/mL, whereas compounds 5 and 6 showed relatively high anticandidal activity against Candida strains with MIC values down to 12.5 mu g/mL, in comparison to the standard antimicrobial compounds.
... Apigenin (4), hispidulin (5), salvigenin (6), eupatorin (7), 3'-methyleupatorin (8) and isokaempferide (9): yellow or pale yellow crystals. 1 H and 13 C NMR and MS data were identical with those published in the literature [4][5][6]. ...
Background:
Centaurea virgata Lam. is a species widely used in the traditional medicine in Turkey for the treatment of diabetes, allergy and gastric ulcers. The rationale of its use in the therapy has not been studied previously, therefore the present work aimed at the chemical-pharmacological evaluation of the plant.
Objective:
The xanthine oxidase (XO) inhibitory activity of the MeOH extract and its subextracts (n-hexane, CHCl3 and remaining MeOH-H2O) prepared from C. virgata was investigated in vitro. Moderate activity was exerted in case of the CHCl3 extract (98.9 ± 15.8 µg/mL), therefore constituents of this extract were analysed.
Method:
Different purification steps, such as VLC, CPC, PLC and crystallization were used for the isolation, and ESIMS, NMR, LC-MS and authentic standards were applied for identification of the compounds. XO inhibitory and DPPH assays were used for evaluation of the bioactivities.
Results:
Sesquiterpenes [8α-hydroxysonchucarpolide, 8α-(3,4-dihydroxy-2-methylene-butanoyloxy)-dehydromelitensine, and cnicin], flavones (apigenin, hispidulin, salvigenin, eupatorin, 3'-methyleupatorin), and the flavonol isokaempferide were isolated from the active extract. The XO-inhibitory activity of these compounds was analyzed using allopurinol as a positive control (IC50 7.49 ± 0.29 μM). It was found that sesquiterpenes and flavonoids, containing 7-OMe group, are inactive.
Conclusion:
7-Hydroxyflavones (apigenin and hispidulin) exerted significant XO inhibitory effect with IC50 values of 0.99 ± 0.33 μM and 4.88 ± 1.21 μM, respectively. Therefore these compounds are responsible for the XO-inhibitory effect of the extract. The free radical scavenging activity of the isolated flavonoids were determined by DPPH assay, and it was stated that none of the compounds have substantial antioxidant activity, therefore the reduced generation of reactive oxygen species may be the consequence only of XO inhibition.
... The Artemisia genus is a particularly rich source of flavonoids [8]. While A. annua is the most extensively studied species, resulting in the isolation of around 50 flavonoids, these antioxidants have also been detected in other species, including A. absinthium L [9], A. asiatica [10], A. Herba-Alb [11]. However, the flavonoid concentration is usually very low and highly variable, not only among different chemotypes but also in the same plant at different growth stages [12]. ...
Background
The secondary metabolites of the Artemisia genus are well known for their important therapeutic properties. This genus is one of the valuable sources of flavonoids and other polyphenols, but due to the low contents of these important metabolites, there is a need to either enhance their concentration in the original plant or seek alternative sources for them. The aim of the current study was to detect and enhance the yield of antioxidant compounds of Artemisia carvifolia Buch. HPLC analysis was performed to detect the antioxidants. With the aim of increasing flavonoid content, Rol gene transgenics of A. carvifolia were established. Two genes of the flavonoid biosynthetic pathway, phenylalanine ammonia-lyase and chalcone synthase, were studied by real time qPCR. Antioxidant potential was determined by performing different antioxidant assays. ResultsHPLC analysis of wild-type A. carvifolia revealed the presence of flavonoids such as caffeic acid (30 μg/g DW), quercetin (10 μg/g DW), isoquercetin (400 μg/g DW) and rutin (300 μg/g DW). Compared to the untransformed plants, flavonoid levels increased 1.9–6-fold and 1.6–4-fold in rol B and rol C transgenics, respectively. RT qPCR analysis showed a variable expression of the flavonoid biosynthetic genes, including those encoding phenylalanine ammonia-lyase and chalcone synthase, which were found to be relatively more expressed in transformed than wild-type plants, thus correlating with the metabolite concentration. Methanolic extracts of transgenics showed higher antioxidant capacity, reducing power, and protection against free radical-induced DNA damage. Among the transgenic plants, those harboring rol B were slightly more active than the rol C-transformants. Conclusion
As well as demonstrating the effectiveness of rol genes in inducing plant secondary metabolism, this study provides insight into the molecular dynamics of the flavonoid accumulation pattern, which correlated with the expression of biosynthetic genes.
... Artemisia genus is one of the sumptuous sources of the antioxidants like flavonoids and other polyphenols [9]. Within this genus, A. annua is the most extensively studied species from which around 50 flavonoids have been set apart; however, several flavonoids have been found in other species too like A. absinthium L [10], A. asiatica [11], and A. herba-Alb [12]. However, the concentration of these flavonoids and other polyphenols is usually very low, and not only different chemotypes show lots of variability but also fluctuations have been observed in the same plant at different growth stages [13]. ...
Flavonoids are famous for their antioxidant capacity and redox potential. They can combat with cell aging, lipid peroxidation, and cancer. In the present study, Artemisia annua hybrid (Hyb8001r) was subjected to qualitative and quantitative analysis of flavonoids through HPLC. Rol genes transgenics of A. annua were also evaluated for an increase in their flavonoid content along with an increase in antioxidant and cytotoxic potential. This was also correlated with the expression level of flavonoids biosynthetic pathway genes as determined by real-time qPCR. Phenylalanine ammonia-lyase and chalcone synthase genes were found to be significantly more highly expressed in rol B (four to sixfold) and rol C transgenics (3.8-5.5-fold) than the wild-type plant. Flavonoids detected in the wild-type A. annua through HPLC include rutin (0.31 mg/g DW), quercetin (0.01 mg/g DW), isoquercetin (0.107 mg/g DW) and caffeic acid (0.03 mg/g DW). Transgenics of the rol B gene showed up to threefold increase in rutin and caffeic acid, sixfold increase in isoquercetin, and fourfold increase in quercetin. Whereas, in the case of transgenics of rol C gene, threefold increase in rutin and quercetin, 5 fold increase in isoquercetin, and 2.6-fold increase in caffeic acid was followed. Total phenolics and flavonoids content was also found to be increased in rol B (1.5-fold) and rol C (1.4-fold) transgenics as compared to the wild-type plant along with increased free radical scavenging activity. Similarly, the cytotoxic potential of rol gene transgenics against MCF7, HeLA, and HePG2 cancer cell lines was found to be significantly enhanced than the wild-type plant of A. annua. Current findings support the fact that rol genes can alter the secondary metabolism and phytochemical level of the plant. They increased the flavonoids content of A. annua by altering the expression level of flavonoids biosynthetic pathway genes. Increased flavonoid content also enhanced the antioxidant and cytotoxic potential of the plant.
... The previously studied shows that the extracts rich in flavonoids, which have been associated with their antioxidant activities. However, insufficient studies have been conducted on flavonoids from QingLi Cao and its antioxidant activity [1]. ...
An ultrasound-assisted extraction technique was used to extract the total flavonoids from QingLi Cao. The optimal conditions were ethanol concentration 59.20%, liquid-to-solid ratio 31.15 mL/g, extraction time 57.42 min and extraction temperature 58.57°C, which were determined using response surface methodology. The antioxidant activities including reducing power, ABTS+, DPPH, superoxide anion and hydroxyl radical were evaluated, suggested significant antioxidant activities.
Polymethoxyflavonoids (PMFs) are a large group of compounds belonging to the more general class of flavonoids that possess a flavan carbon framework decorated with a variable number of methoxy groups. Hydroxylated polymethoxyflavonoids (HPMFs), instead, are characterized by the presence of both hydroxyl and methoxy groups in their structural unities. Some of these compounds are the aglycone part in a glycoside structure in which the glycosidic linkage can involve the −OH at various positions. These compounds are particular to Citrus genus plants, especially in fruits, and they are present mainly in the peel. A considerable number of PMFs and HPMFs have shown promising biological activities and they are considered to be important nutraceuticals, responsible for some of the known beneficial effects on health associated with a regular consumption of Citrus fruits. Among their several actions on human health, it is notable that the relevant contribution in controlling the intracellular redox imbalance is associated with the inflammation processes. In this work, we aim to describe the status concerning the chemical identification and the anti-inflammatory activity of both PMFs and HPMFs. In particular, all of the chemical entities unambiguously identified by isolation and complete NMR analysis, and for which a biochemical evaluation on the pure compound was performed, are included in this paper.
The mangosteen peels contain biologically active compounds, with antioxidant and anticancer properties. Among these isolated phytochemicals, α-mangostin is one of the most powerful natural antioxidants and anticancer compounds. This study focused on synthesizing novel α-mangostin (α-MG) derivatives at positions of C-3 and C-6 from extracted α-MG of mangosteen peels and investigating antioxidant and anticancer activities. The structures of the synthesized compounds were determined by using MS, ¹H-NMR, ¹³C-NMR, and HPLC. The analysis of the interaction between structure and bioactivity showed that phenol groups on C-3 and C-6 positions play a crucial role in antiproliferative activity to boost both anticancer efficacy and drug-like properties. The antioxidant activity of α-MG and its derivatives were investigated by the DPPH method. Among α-MG derivatives, 1-hydroxy-7-methoxy-2,8-bis(3-methylbut-2-en-1-yl)-9-oxo-9H-xanthene-3,6-diyl bis(2-bromobenzoate) (compound 4) exhibited significant antioxidant property. The in vitro cytotoxicity against various cancer cell lines (HeLa, MCF-7, NCI–H460, and HepG2) was evaluated by the standard sulforhodamine B assay. The anticancer activities (HeLa, MCF-7, NCI–H460, and HepG2) of compound 4 are five to six times higher than those of α-MG and other derivatives. The acetylation at C-3 and C-6 of α-MG by halogen of benzoyl greatly improved cancer cell toxicity. Our results provide new opportunities for further explorations of α-MG derivatives for antioxidant property and promise as drugs in cancer therapy.
Twelve chlorogenic acid derivatives and two flavones were isolated from Moquiniastrum floribundum (Asteraceae). Compounds were evaluated in relation to their cytotoxicity and antiradical properties. Cytotoxicity were not observed for compounds, however chlorogenic acid derivatives showed antiradical activity and were more active than the Trolox standard. Quinic acid esterified with caffeoyl group at C‐4 position showed higher antiradical activity compared to acylation at C‐3 or C‐5 positions. Additional caffeoyl groups esterified in quinic acid increase the antiradical activity observed for 4‐caffeoylquinic acid. Excepted to 3,4‐dicaffeoylquinic acid methyl ester, methyl esters derivatives show higher capacity of trapping radicals than their respective acids. Consequently, the presence of caffeoyl group at C‐4 position of quinic acid is suggested as fundamental to obtain the highest antiradical activity.
The modulation of xanthine oxidase (XO) activity is critical to the treatment of hyperuricemia and oxidative stress-related disease. Although the walnut protein hydrolysates had been reported to inhibit XO, their interaction mechanism remained unclear. Herein, the walnut protein-derived peptides were used to evaluate their in vitro XO-inhibitory activity and their inhibitory mechanism. The results suggested that Trp-containing walnut protein-derived peptides were able to effectively inhibit XO, moreover, the increased number of Trp would significantly enhance the XO-inhibitory activity of Trp-containing peptides. Similar to the allopurinol, Trp had active interaction with the critical residues Glu802, Leu873, Ser876, Arg880, Phe914, Phe1009, Thr1010, Val1011, Leu1014, Ala1078, Ala1079 and molybdopterin MOS3004 of XO, making Trp-containing peptide have high XOI activity. Simultaneously, the Trp-containing walnut protein-derived peptide also had been found to show great potential in antioxidant activity. Present work would introduce functional food-derived peptides for the improvement of hyperuricemia and oxidative stress-related disease.
As a result of complex chemical processing of medicinal raw materials of Artemisia glabella Kar. et Kir., including CO2 extraction and lactones isolation, we have investigated the chemical composition of flavonoids to select the biologically active ones and carry out modifications on their basis. Two flavonoids pectolinaringenin and cirsilineol have been isolated by partition chromatography from the secondary raw materials of Artemisia glabella Kar. et. Kir. and identified. To obtain new biologically active compounds, we have synthesized new amino derivatives of cirsilineol by the Mannich reaction with secondary amines (piperidine and N-methylpiperazine) in isopropanol with the presence of dimethylaminopyridine. In proton NMR spectrum of the synthesized compounds there are proton signals of the initial cirsilineol fragment; however, there is no N-8 proton signal, besides other signals typical for amines’ benzene ring have been observed at 1.53–3.90 ppm. It means that reaction occurred at the C-8 position of carbon in ring A. The synthesized compounds have been studied for various types of biological activity typical for this class, including hepatoprotective and anti-inflammatory activities. Amino derivatives of cirsilineol exhibit a moderate activity against HepG2 cell line, while cirsilineol at a dose of 5 mg/ml expresses a pronounced hepatoprotective activity. Moreover, all samples at a dose of 25 mg/kg show poor anti-inflammatory effects on the model of acute exudative reaction in vivo.
Four flavones were isolated from dried leaves of Artemisia campestris L. 2',4',5,7-tetrahydroxy-5',6-dimethoxyflavone, eupatilin and dimethoxycentaureidin were reported for the first time in this species whereas cirsiliol was previously identified but it was isolated for the first time. Their structures were elucidated by spectroscopic methods, including 1D and 2D NMR experiments and mass spectrometry analysis. In addition, all isolated flavones were evaluated for their antioxidant, anti-inflammatory, anti-superoxide dismutase, anti-xanthine oxidase and cytotoxic activities. The results showed that all isolated compounds exhibited potent anti-xanthine oxidase activity with IC50 ranging from 3.3 to 6.8 μM, which was higher than that of the control compound allopurinol (8.2 ± 0.6 μM). In addition, cirsiliol was found to be the most cytotoxic against OVCAR-3, IGROV-1and HCT-116 cell lines at 15μM, with inhibition percentage values of 53.7, 48.8 and 40.9%, respectively. All compounds also showed weak to moderate anti-inflammatory and anti-superoxide dismutase activities.
Two new 2,2-dimethyl-chromene derivatives and the new pentaisovaleryl sucrose were isolated from the roots of Artemisia asiatica together with the known 1-(5-acetyl-2,4-dihydroxy-phenyl)-3-methyl-butan-1-one, 6-hydroxytremetone and (E)-coniferyl aldehyde. The structures of the compounds were elucidated by extensive 1D (1H, 13C and JMOD) and 2D (1H-1H COSY, HSQC, HMBC and NOESY) NMR studies and APCIMS and HRESIMS investigations. 6-Acetyl-3,7-dihydroxy-2,2-dimethyl-chromene and 6-acetyl-3-hydroxy-2,2-dimethyl-chromene are biogenetically related to 1-(5-acetyl-2,4-dihydroxy-phenyl)-3-methyl-butan-1-one and 6-hydroxytremetone as all having isoprenoid acetophenone origin. All the isolated compounds were described for the first time from this species; interestingly none of them are related to the metabolites identified from the extracts of the aerial part of the plant.
From the MeOH ext. of the flowers of Chrysanthemum sinense, a new flavone glucoside, acacetin 7-O-(3-O-acetyl-beta -D-glucopyranoside) (1), has been isolated together with 27 known compds. including flavonoids, caffeoylquinic acid derivs., phenolics, and a monoterpenoid glucoside. Their structures were elucidated on the basis of spectroscopic data. Compds. 1 - 15, 20 - 24, and 27 displayed significant xanthine oxidase inhibitory activity in a concn.-dependent manner, and compds. 2 - 11 and 22 showed more potent inhibitory activity, with IC50 values ranging from 0.13 to 2.31 micro M, than that of a pos. control allopurinol (IC50 = 2.50 micro M). The kinetic study indicated that 1 - 15 and 20 - 24 displayed competitive-type inhibition like that of allopurinol, while 27 displayed a mixed-type inhibition.
In addition to inhibiting cyclooxygenase and prostaglandin, nonsteroidal anti-inflammatory drugs (NSAIDs) may cause gastroduodenal injuries due to reactive oxygen species produced by recruited inflammatory cells. DA-9601 is a novel antioxidant with anti-inflammatory and cyto-protective effects. This study was conducted to compare the efficacy and safety of DA-9601 with misoprostol for preventing NSAID-associated gastroduodenal injury. In this randomized, double-blind, multicenter, noninferiority trial we compared the extents of protection of gastric and duodenal mucosae by endoscopy after 4 weeks of treatment with DA-9601 60 mg or misoprostol 200 µg three times daily, in subjects with normal baseline endoscopic findings who received an NSAID twice daily for 4 weeks. A total of 266 subjects were randomized to treatment. At week 4, the gastric protection rates with DA-9601 and misoprostol were 85.1% and 95.2%, respectively; the difference between the groups was -10.1% (var = 0.001), which was shown to indicate noninferiority of DA-9601 compared to misoprostol. Adverse events were lower in the DA-9601 group, 56.4% (95% CI, 48.0%-64.8%) than in the misoprostol group, 69.2% (95% CI, 61.3%-77.0%) (P = 0.031). DA-9601 is not inferior to misoprostol for preventing NSAID-associated gastroduodenal injury, and superior to it with respect to treatment-related side effects.
Acute gastric injury by alcohol or indomethacin has been reported to be prevented by DA-9601, an extract of the herb Artemisia asiatica. Ghrelin, an endogenously produced gastrointestinal peptide hormone, has also been demonstrated to play a role in gastric mucosal defense. The aim of this study was to investigate the effects of DA-9601 on ghrelin in an acute gastric injury model induced by alcohol or indomethacin.
A total of 140 Sprague-Dawley rats were divided into two groups, a placebo group and a DA-9601-pretreated group. Thirty minutes later, half of the rats in each group received ethanol injury and the other half received indomethacin injury. Levels of serum ghrelin and gastric mucosal ghrelin mRNA were measured by ELISA and RT-PCR, respectively.
Immediately after ethanol administration, ghrelin increased in both groups pretreated with DA-9601 and placebo. However, the increase occurred more rapidly and was higher in the DA-9601-pretreated rats than in the controls that did not receive DA-9601-pretreatment. Similarly, from 30 minutes to 2 hours after indomethacin administration, the DA-9601-pretreated rats showed a significant increase in serum and gastric mucosal ghrelin concentrations, whereas placebo-pretreated rats showed only a mild increase.
DA-9601 potentiates the endogenous production and secretion of ghrelin in acute gastric injury models induced by ethanol or indomethacin.
To determine the efficacy and safety of DA-9601 on erosive gastritis versus cetraxate as a standard drug by gastrointestinal endoscopy.
Five hundred and twelve patients with erosive gastritis were divided into three groups. The groups received 180 mg or 360 mg of DA-9601, or 600 mg of cetraxate (Neuer) t.i.d. for 2 wk, respectively. Endoscopic observations were performed before and 2 wk after the treatment, and the cure and improvement rates were investigated.
Of the 512 intention-to-treat (ITT) population, 457 patients comprised the per protocol (PP) analysis. Endoscopic cure rate was significantly higher in the DA-9601 group than in the cetraxate group in both the PP (56%, 58% vs 36%; DA-9601 180 mg, 360 mg and cetraxate, respectively) and ITT (52%, 51% vs 35%) populations. Two DA-9601 groups (180 and 360 mg) had significantly higher endoscopic improvement rates than the cetraxate group in both the PP (67%, 65% vs 46%) and ITT (63%, 58% vs 45%) populations. The percentage of symptom relief over the 2 wk was found not significantly different between groups. During the study, both DA-9601 and cetraxate produced no treatment-associated adverse events.
From these results, it appears that DA-9601 has excellent efficacy on erosive gastritis. This study also confirms the safety profile of DA-9601.
To investigate the therapeutic effects of DA-9601 on sodium taurocholate (TCA)-induced chronic reflux gastritis in SD rats.
In this study, we have investigated the therapeutic effects of DA-9601 on chronic erosive and atrophic gastritis induced by 6 mo of TCA administration (5 mmol/L in drinking water) in SD rats.
Four weeks of DA-9601 administration (0.065%, 0.216% in rat chow), following the withdrawal of TCA treatment, resulted in a significant decrease in total length of erosions in rats in a dose-dependent manner. Furthermore, the indicators of atrophic gastritis, such as reduced mucosal thickness and reduction in the number of parietal cells, were improved by the administration of DA-9601 in a dose-related manner. DA-9601 also attenuated inflammatory cell infiltration and the proliferation of collagenous fiber in the gastric mucosa. The improvement in the reduction of the gastric mucus was observed in the rats receiving a high dose of DA-9601 (0.216%). The therapeutic effect of DA-9601 on experimental chronic erosive gastritis was superior to that of rebamipide (1.08% in rat chow). Biochemical analyses showed increased mucosal prostaglandin E2 and reduced glutathione levels by DA-9601 treatment.
We suggest that DA-9601 is a promising agent for the treatment of chronic erosive and atrophic gastritis with an etiological factor of bile reflux. Increased mucosal prostaglandin E2 and reduced glutathione by DA-9601 treatment may be therapeutic mechanisms for chronic erosive and atrophic gastritis.
From the MeOH extract of the flowers of Chrysanthemum sinense, a new flavone glucoside, acacetin 7- O-(3- O-acetyl- beta- D-glucopyranoside), has been isolated together with 27 known compounds including flavonoids, caffeoylquinic acid derivatives, phenolics, and a monoterpenoid glucoside. Their structures were elucidated on the basis of spectroscopic data. Compounds and displayed significant xanthine oxidase inhibitory activity in a concentration-dependent manner, and compounds and showed more potent inhibitory activity, with IC50 values ranging from 0.13 to 2.31 microM, than that of a positive control allopurinol (IC50=2.50 microM). The kinetic study indicated that and displayed competitive-type inhibition like that of allopurinol, while displayed a mixed-type inhibition.
The leaves of Artemisia asiatica are used clinically in Traditional Korean Medicine as the treatment of digestive disorder, abdominal pain, and anorexia. To treat the diseases, A. asiatica is extracted with water at boiling point and administered orally. However, the water extract of A. asiatica was yet to be studied to have the gastroprotective effects, although the ethanol extract was already known. The aim of the present study is to investigate the effects of the clinical remedy, which is water extract, as well as ethanol extract. Gastrohemorrhagic lesion was experimentally created by oral intubation of 80% ethanol containing 0.15mol/L HCl to the rats. The rats were divided into six groups consisting normal group, the water extract treating (100 and 300mg/kg, p.o.) groups, the ethanol extract treating (100 and 300mg/kg, p.o.) groups, and positive control group using cimetidine (100mg/kg, p.o.). Samples were administered 30 minutes before EtOH-HCl. The rats were sacrificed an hour later and the gastrohemorrhagic lesion was measured. The treatment with water extract 300mg/kg significantly reduced the gastrohemorrhagic lesion by 86.0% (p<0.001) as compared to the control group. These results suggest that A. asiatica extracted with water, clinical remedy, is available to treat gastritis as the ethanol extract.
5,7-Dihydroxy-3',4',6'-trimethoxyflavone (eupatilin), the active pharmacological ingredient from Artemisia asiatica Nakai (Asteraceae), is reported to have a variety of anti-inflammatory properties in intestinal epithelial cells. However, little information is known about the molecular mechanism of eupatilin-induced attenuation of bronchial epithelial inflammation. This study investigates the role of eupatilin in the adhesion of inflammatory cells such as monocytes and eosinophils to bronchial epithelial cells. Stimulation of a human bronchial epithelial cell line (BEAS-2B) with tumour necrosis factor-α (TNF-α) increased the expression of surface adhesion molecules, including intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), in which eupatilin significantly inhibited the expression of those adhesion molecules in a dose-dependent manner. Eupatilin suppressed the TNF-α-induced activation of IκBα and nuclear factor-κB (NF-κB) signals in BEAS-2B cells. The IκB kinase (IKK) activation was also significantly reduced in eupatilin-pre-treated BEAS-2B and primary normal human bronchial epithelial (NHBE) cells. However, eupatilin did not influence AP-1 activity in TNF-α-stimulated cells. Suppression of NF-κB signalling induced by eupatilin resulted in the inhibition of the expression of adhesion molecules and the adhesion of monocytes and eosinophils to BEAS-2B cells. Furthermore, eupatilin suppressed the phosphorylation of Akt in TNF-α-stimulated BEAS-2B and NHBE cells, leading to down-regulation of NF-κB activation and adhesion molecule expression and finally to suppression of the inflammatory cell adhesion to epithelial cells. These results suggest that eupatilin can inhibit the adhesion of inflammatory cells to bronchial epithelial cells via a signalling pathway, including activation of Akt and NF-κB, as well as expression of adhesion molecules.
Eupatilin (5,7-dihydroxy-3,4,6-trimethoxyflavone) is a pharmacologically active ingredients in Stillen(TM), a drug for the gastric mucosal ulcers. Eupatilin has been known to possess anti-peptic, anti-cancer, and anti-allergy activity. In this report, we defined the effect of eupatilin on the endotoxin-induced inflammation in lipopolysaccharide (LPS)-stimulated macrophages.
Mouse J774A.1 cell line and mouse peritoneal macrophages were used. Gene expression and production of inflammatory mediators were determined by real-time PCR and Western blot.
Eupatilin dose-dependently suppressed LPS-induced expression of inducible nitric oxide synthase (iNOS) and production of nitric oxide (NO). Eupatilin decreased LPS-induced expression of inflammatory mediators and pro-inflammatory cytokines such as cyclooxygenase-2, monocyte chemoattractant protein-1, tumor necrosis factor-α, interleukin (IL)-1β and IL-6. In addition, this suppression of inflammatory mediators was nuclear factor (NF)-κB dependent.
Our findings imply that eupatilin suppresses inflammatory responses by the inhibition of NF-κB signaling pathway, and downstream inflammatory mediators in endotoxin-stimulated macrophages.
Medicinal plants are nature's gift to human beings to make disease free healthy life, and play a vital role to preserve our health. They are believed to be much safer and proven elixir in the treatment of various ailments. The genus Artemisia (Astraceae) consists of about 500 species, occurring throughout the world. The present review comprises the ethnopharmacological, phytochemical and therapeutic potential of various species of Artemisia.
The aim of this this review is to bring together most of the available scientific research conducted on the genus Artemisia, which is currently scattered across various publications. Through this review the authors hope to attract the attention of natural product researchers throughout the world to focus on the unexplored potential of Artemisia species.
This review has been compiled using references from major databases such as Chemical Abstracts, Medicinal and Aromatic Plants Abstracts, ScienceDirect, SciFinder, PubMed, King's American Dispensatory, Henriette's Herbal Homepage, Dr. Duke's Phytochemical and Ethnobotanical Databases.
An exhaustive survey of literature revealed that the different species of Artemisia have a vast range of biological activities including antimalarial, cytotoxic, antihepatotoxic, antibacterial, antifungal and antioxidant activity. Some very important drug leads have been discovered from this genus, notably artemisinin, the well known antimalarial drug isolated from the Chinese herb Artemisia annua. Terpenoids, flavonoids, coumarins, caffeoylquinic acids, sterols and acetylenes constitute major classes of phytoconstituents of the genus.
Various species of Artemisia seems to hold great potential for in-depth investigation for various biological activities, especially their effects on the central nervous and cardiovascular systems.
The exposure of gastric mucosa to ethanol produces pathological changes such as inflammatory process, hemorrhagic erosions, even acute ulcers. The gastric mucosal lesions accompanied by a significant decrease of gastric blood flow and increase of reactive oxygen species (ROS) implicate a role of xanthine oxidase in ethanol-induced gastric hemorrhagic erosions. DA-9601, a novel antipeptic formulation of extracts of Artemisia asiatica Nakai, was studied for its inhibitory effect on gastric xanthine oxidase activity and type conversion of the enzyme that has a profound role in free radical generation. Intubation of absolute ethanol (4 g/kg) significantly induced gastrohemorrhagic lesions and lipid peroxidation in the rat stomach. Oral administration of DA-9601 at 40 mg/kg body weight significantly reduced ethanol-induced gastric mucosal hemorrhagic lesions and lipid peroxidation, which was proportional to the inhibitory effect of DA-9601 on alcohol-induced xanthine oxidase-type conversion and enzyme activity. The results suggest that alcohol-induced gastric mucosal damage may be, in part, due to the increased activity of xanthine oxidase and type conversion rate of the enzyme and that the preventive effect of DA-9601 on gastrohemorrhagic lesions would result from its inhibitory action against xanthine oxidase and oxidative stress in alcohol-treated rats.
Accelerated Ulcer Healing and Resistance to Ulcer Recurrence with Gastroprotectants in Rat Model of Acetic Acidinduced Gastric Ulcer
- T Y Oh
- C Y Shin
- Y S Sohn
- D H Kim
- B O Ahn
- E B Lee
- C H Park
T.Y. Oh, C.Y. Shin, Y.S. Sohn, D.H. Kim, B.O. Ahn, E.B. Lee and C.H. Park (2005). Accelerated Ulcer
Healing and Resistance to Ulcer Recurrence with Gastroprotectants in Rat Model of Acetic Acidinduced Gastric Ulcer, World J Gastroenterol. 11, 7430-7435