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A novel cytotoxic aryltetraline lactone from Bupleurum marginatum (Apiaceae)

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Abstract

A detailed phytochemical study of the aerial parts of Bupleurum marginatum Wall. ex DC revealed a novel aryltetraline lactone lignan identified as 9-(benzo[d][1,3]dioxol-5-yl)-6,7,8-trimethoxy-3a,4,9,9a-tetrahydronaphtho[2,3-c]furan-1(3H)-one (marginatoxin) along with nine known compounds and characterization of five other compounds either by GLC/MS or LC/MS techniques. Chemical structures of the isolated compounds were unambiguously elucidated by both 1D, 2D NMR and mass spectrometry techniques.The in vitro cytotoxic activity of both methanol and dichloromethane extracts as well as the isolated compounds was assessed in two human cancer cell lines HepG2 and HeLa using the MTT assay. The new aryltetraline lactone lignan exhibited a potent cytotoxic activity with IC50 values of 12.14 and 16.90 μM after 24 h treatment for HepG2 and HeLa cells, respectively.

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... Moreover, in an attempt to elucidate the probable mode of action of the extracts, we carried out for the first time an in silico molecular modelling study. This was carried out for the major secondary metabolites that were identified from the plant in our laboratory using LC/MS technique [19] on the active sites of 5-lipoxygenase (5-LOX) and cyclooxygenase (COX-II), the key enzymes of the inflammation process. ...
... Hydrogen atoms were added, and then protein structure was cleaned from any unwanted interactions. The binding site was detected based on the reported data beside the catalytic domain of the enzyme just near the cofactor metal ion Fe. [29] Then, the structures of the previously identified compounds from B. marginatum aerial parts [19,21] were docked within the active site using C-docker protocol in which CHARMm force field was allocated and the binding energies for the best docking poses were computed as described before applying both pH-based and rule-based ionization modes. [30] Statistical analysis ...
... Meanwhile, DCM extract revealed a more similar pattern of secondary metabolites with greater amounts of lignans and terpenoids relative to the methanol extract. [19,31] as illustrated in Figure 2. Both the methanol and DCM extracts were selected for this study aiming to better understand the mechanism of the anti-inflammatory activity and in correlating this activity with the secondary metabolites predominating in the extracts that could further consolidate its ethnopharmacological uses in relieving inflammatory conditions. ...
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Objectives To explore the potential anti‐inflammatory activity of Bupleurum marginatum extracts using in vitro and in vivo studies supported by virtual screening. Methods Antioxidant activity was assessed using the DPPH˙ and inhibition of 2‐deoxyribose degradation assays. Anti‐inflammatory activity was determined in vitro by measuring the suppression of prostaglandin E2 release (PGE2) in pancreatic cancer cells (MIA‐PaCa‐2) and the inhibition of 5‐lipoxygenase whereas the rat paw oedema was used in vivo. The major constituents were docked in 5‐lipoxygenase and cyclooxygenase‐II active sites. Key findings Methanol and dichloromethane (DCM) extracts showed IC50 of 46.99 and 162.99 μg/ml in the DPPH˙, 1.52 and 2.12 μg/ml in inhibition of 2‐deoxyribose degradation assays, respectively. They reduced PGE2 release by 41.33 and 52.85% at 25 μg/ml and inhibited 5‐lipoxygenase with IC50 of 45.28 and 25.92 μg/ml, respectively. 50 and 70% reduction in the diameter of the carrageenan‐induced rat paws with methanol and DCM extracts, respectively, with a marked decline in the inflammation score was observed. Rutin, a predominating compound, showed a strong interaction with the key amino acids in 5‐LOX active site with interaction energy of −74.59 kcal/mol. Conclusions Our study provides evidence for an interesting anti‐inflammatory activity of B. marginatum aerial parts offering a natural anti‐inflammatory agent.
... Specifically, saikosaponins were found in small amounts [10], while flavonoid glycosides and aglycones such as rutin, narcissin, isoquercetrin, isorhamnetin, and quercetin were commonly found in the plant [11]. In addition, lignans such as marginatoxin [11-13] and many phytosterols (stigmasterol, α-spinasterol, β-sitosterol, and daucosterol) have been described from both the aerial and subterranean parts [6,12]. ...
... The chromatographic profiles were established by HPLC/MS (Figure 1). The ME extract (Figure 1A) revealed the presence of high contents of flavonoids, and to lesser extents lignans, sterols, and triterpenoid saponins, as previously reported by the authors [11]. The DCM extract (Figure 1B) showed a similar pattern of secondary metabolites with higher yields of lignans and terpenoids compared with those detected in the ME extract. ...
... The secondary metabolites of B. marginatum have been investigated previously, and various classes of compounds were identified. Specifically, saikosaponins were found in small amounts [10], while flavonoid glycosides and aglycones such as rutin, narcissin, isoquercetrin, isorhamnetin, and quercetin were commonly found in the plant [11]. In addition, lignans such as marginatoxin [11-13] and many phytosterols (stigmasterol, α-spinasterol, β-sitosterol, and daucosterol) have been described from both the aerial and subterranean parts [6,12]. ...
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Bupleurum marginatum Wall. ex DC (Apiaceae) is a perennial herb widely used in traditional Chinese and Kampo medicine for the treatment of various infectious diseases. The biological activities of B. marginatum have not been fully investigated. This study aims to investigate the antitrypanosomal, antimicrobial and antiviral activities of methanol (ME) and dichloromethane (DCM) extracts of B. marginatum aerial parts and the ability of both extracts to inhibit the growth of different cancer cell lines. Phytochemical characterization of the extracts was performed by LC-MS profiling. The antitrypanosomal activity was evaluated using the resazurin method. The antimicrobial activity was assessed using agar diffusion and microdilution methods, and the minimum inhibitory concentration (MIC) values were determined. The antiviral activity was determined for 6.25, 12.5, and 50 mug/mL doses using a plaque reduction assay. Cytotoxicity was investigated in eight cancer cell lines (Caco-2, CCL-81, CCRF-CEM, COS-7, HL-60, MIA PaCa-2, MCF-7, and PANC-1) using the MTT assay and the caspase 3/7 activity was determined over the range of 62.5-1000 mug/mL. Phytochemical analyses resulted in the characterization of 15 components, mainly flavonoids and lignans. The DCM extract showed significant antitrypanosomal activity (IC50: 36.21 mug/mL) and moderate activity against Streptococcus pyogenes (MIC value: 0.25 mg/mL). At a dose of 12.5 mug/mL, the DCM extract inhibited 73.6% of the plaque production by hepatitis A virus. CCRF-CEM cells were the most sensitive to both extracts (IC50: 12.5-22.7 mug/mL). The cytotoxicity was mediated by induction of apoptosis (19-fold increase in the cellular caspase 3/7 level after treatment with the DCM extract at 1 mg/mL). ME and DCM extract of B. marginatum showed anti-infective and antiproliferative effects.
... A detailed phytochemical study of the aerial parts of B. marginatum Wall. ex DC revealed a novel aryltetralin lactone lignan identified as 9-(benzo[d][1,3]dioxol-5-yl)- 6,7,8-trimethoxy-3a,4,9, 9a-tetrahydronaphtho[2,3-c]furan-1(3H)-one (trivially named marginatoxin) 325 (Fig. 13) (Ashour et al. 2012). One arylnaphthalene lignan, saurunarin 326 (Fig. 13), was isolated from Saururus chinensis (Tsai et al. 2014). ...
... The in vitro cytotoxic activity of the isolated compound was assessed against two human cancer cell lines, HepG2 and HeLa, using the MTT assay. The new aryltetraline lactone lignan exhibited potent cytotoxic activity with IC 50 values of 12.14 and 16.90 lM against HepG2 and HeLa cells, respectively, after 24 h of treatment (Ashour et al. 2012). ...
Article
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Arylnaphthalene compounds, also called cyclolignolides, are lignans and have been extensively studied and documented, especially podophyllotoxin and its derivatives. Great progress has been made in phytochemical studies on arylnaphthalenes in the last 20 years (1999–2019), and arylnaphthalenes have been reported to have various biological activities. A total of 338 new arylnaphthalene compounds from over 60 families, including Acanthaceae, Phyllanthaceae, Lamiaceae, Lauraceae, Schisandraceae, Berberidaceae, and Boraginaceae, have been discovered. This paper will highlight their structural features, sources, and biological activities and briefly discuss their structure–activity relationships.
... Previous studies [34,51] also reported that epicatechin (19) had no effect or a weak effect on the A549, liver cancer (HepG2), and gastric carcinoma (MGC-803) cell lines, supporting the results found in the present study. It has also been previously reported [52] that catechin (18) [13,34,53]. Although myricetin 3-O-rutinoside (37) showed no or weak anti-tumor activity against A549, HepG2, MGC-803, and murine foregastric carcinoma (MFC) cell lines (as shown in Figures 3 and 4), it was firstly investigated in the present study. ...
... Previous studies [34,51] also reported that epicatechin (19) had no effect or a weak effect on the A549, liver cancer (HepG2), and gastric carcinoma (MGC-803) cell lines, supporting the results found in the present study. It has also been previously reported [52] that catechin (18) had a weak effect on HepG2 and MGC-803 cell lines. Figures 3 and 4 evidence that rutin (35) exhibited no or weak effects on A549, HepG2, and MGC-803 cell lines, in agreement with previous reports [13,34,53]. ...
Article
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Xanthoceras sorbifolia Bunge. is used in traditional medicine in North China. To evaluate the anti-tumor and radical-scavenging activities of X. sorbifolia husks polyphenols and determine their structure-activity relationships, 37 polyphenols 1-37 were obtained by bioassay-guided fractionation. Two new compounds 1-2, and compounds 5, 6, 8, 9, 11, 14-17, 21-25, 27-29, 31, 33, 34, 36, and 37 were isolated from the genus Xanthoceras for the first time. Compounds 1-37 did not show strong cytotoxicity against the four tested tumor cell lines (A549, HepG2, MGC-803, and MFC) compared to paclitaxel and under the conditions tested in the anti-tumor assay, but compounds 3, 4, 7, 8, 10, 18-20, 25, 26, 29, 30, 32, and 35 exhibited stronger radical-scavenging activity than ascorbic acid in a 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt assay. This was the first report on the anti-tumor and radical-scavenging activities of the polyphenols isolated from X. sorbifolia husks. Overall, the present study contributed valuable information concerning X. sorbifolia husks use in medicine and pharmacology.
... [43,44] Artemisia capillaris Coumarins: coumarin, scopoletin [45,46] Belamcanda chinensis (Iridaceae) P6843/Rhizome Phenolic compounds: Belalloside A, belalloside B, belamphenone, resveratrol, iriflophenone, irisflorentin, tectorigenin, irilin D, tectoridin, iristectorin A, iristectorin B, hispiduloside, androsin, irigenin, iridin, and jaceoside, [47] Bupleurum marginatum (Apiaceae) P6845/ Herb Flavonoids and steroids: Rutin, isoquercetrin, isorhamnetin, quercetin, β-sitosterol, α-spinasterol, daucosterol, α-spinasterol glucoside. [34] Cassia tora (Fabaceae) P6847/ Seeds Anthraquinones and anthraquinones derivatives: Chrysophanol, naphtho-α-pyrone-toralactune, physcion, rubrofusarin, chrysophonic acid -9 -anthrone, dianthrone glycosides (sennoside A, B). [48,49] Centella asiatica (Apiaceae) P6849/ Herb Triterpenes: madecassic acid, brahmic acid and asiatic acid. ...
... [33] The difference in B. marginatum extracts activity could be attributed to the presence of large quantities of flavonoids, mainly rutin, isoquercetrin, quercetin, and isorhamnetin. [34] However, the high solubility of these flavonoids, mainly rutin, in water explains the higher activity of water his valuable support in authentication and DNA-profiling of most of the plant samples. ...
Article
Background: Herbal medicine is widely used all over the world for treating various health disorders. It is employed either alone or in combination with synthetic drugs or plants to be more effective. Objective: The assessment of the effect of both water and methanol extracts of 57 widely used plants from Traditional Chinese Medicine (TCM) against the main phase I metabolizing enzyme CYP3A4 in vitro for the first time. Materials and methods: The inhibition of cytochrome P450 activity was evaluated using a luminescence assay. The principal component analysis (PCA) was used to correlate the inhibitory activity with the main secondary metabolites present in the plant extracts. Molecular modeling studies on CYP3A4 (PDB ID 4NY4) were carried out with 38 major compounds present in the most active plant extracts to validate the observed inhibitory effect. Results: Aqueous extracts of Acacia catechu, Andrographis paniculata, Arctium lappa, Areca catechu, Bupleurum marginatum, Chrysanthemum indicum, Dysosma versipellis, and Spatholobus suberectus inhibited CYP3A4 is more than 85% (at a dose of 100 μg/mL). The corresponding methanol extracts of A. catechu, A. paniculata, A. catechu, Mahonia bealei, and Sanguisorba officinalis inhibited the enzyme by more than 50%. Molecular modeling studies revealed that two polyphenols, namely hesperidin and rutin, revealed the highest fitting scores in the active sites of the CYP3A4 with binding energies equal to -74.09 and -71.34 kcal/mol, respectively. Conclusion: These results provide evidence that many TCM plants can inhibit CYP3A4, which might cause a potential interference with the metabolism of other concomitantly administered herbs or drugs. Summary: In this study, the inhibitory activity of the aqueous and methanol extracts of 57 widely used plants from Traditional Chinese Medicine (TCM) against the main phase I metabolizing enzyme CYP3A4 was tested in vitro for the first time.Aqueous extracts of Acacia catechu, Andrographis paniculata, Arctium lappa, Areca catechu, Bupleurum marginatum, Dysosma versipellis, and Spatholobus suberectus inhibited CYP3A4 by more than 85% (at a dose of 100 μg/mL).The activity could be attributed to the presence of polyphenolics as revealed from the multivariate chemometric analysis and molecular modeling study.These results provide evidence that many TCM plants can inhibit CYP3A4, which might cause a potential interference with the metabolism of other concomitantly administered herbs or drugs. Abbreviation used: CHARMm: Chemistry at HARvard Macromolecular Mechanics, CYP: Cytochrome P450, DMSO: Dimethyl Sulfoxide, PCA: Principal Component Analysis, PDB: Protein Data Bank, TCM: Traditional Chinese Medicine.
... [3] There is evidence that medicinal plants could lower the risk of HCC and liver cirrhosis. [4][5][6][7] Rheum palmatum, commonly known as Chinese rhubarb, belongs to the family Polygonaceae. Rheum palmatum is rich in anthraquinones and tannins, and its extracts exhibit a wide array of pharmacological properties including laxative, hepatoprotective, antiviral, antibacterial, antidiabetic and antimetastatic effects. ...
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Objectives: The aim of this study was to investigate the potential anticancer properties of a methanol extract of Rheum palmatum roots against diethylnitrosamine (DENA)-induced hepatocellular carcinoma (HCC) in rats and to characterize its phytoconstituents. Methods: HPLC-PDA-MS/MS was used to profile the secondary metabolites in R. palmatum root extract. HCC was induced using diethylnitrosamine (DENA). The activity of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT), alpha-fetoprotein (AFP), total proteins, serum albumin and serum globulin was determined. DNA fragmentation and histopathological examination and GST-P immunostaining were also studied. Key findings: LC-MS/MS analysis identified 16 compounds belonging to anthraquinones, flavonoids and tannins. The root extract significantly reduced the elevated liver enzymes ALT and AST and increased total proteins, albumin and globulin in HCC-rats. Also, the tumour markers AFP and GGT levels were significantly reduced in HCC-rats treated with the extract. In addition, the extract significantly reduced elevated DNA fragmentation and decreased the numbers and areas of GST-P positive putative foci in HCC-rats. Conclusions: Rheum palmatum is a potential candidate to be explored for the treatment of hepatocellular carcinoma.
... Recently, the cytotoxicity of lignans and the anti-inflammatory and anti-proliferative qualities of many herbal extracts on the two cell lines have been reported. [12][13][14][15][16][17][18][19] As S. chinensis is a well-known traditional herbal medicine that is believed to have hepatoprotective effects, [20] it is of interest to determine whether its extracts can inhibit hepatocellular carcinoma in the lab. The aim of this study was to investigate a method of purifying schisandrol A using an ODS column, combined with preparative high-performance liquid chromatography (HPLC). ...
Article
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Schisandrol A, a lignan with anticancer effects, is one of the representative components that identifies Schisandra chinensis. A method for purifying schisandrol A from the stems of S. chinensis was established using an octadecylsilyl (ODS) column combined with preparative high-performance liquid chromatography (HPLC). Crude extracts obtained from the stems of S. chinensis using 70% ethanol were separated on an AB-8 macroporous resin column and then eluted with a graded ethanol series. After 70% methanol was used in an ODS column separation, preparative HPLC was used for subsequent purification. The structure was identified by electrospray ionization-mass spectrometry, (1)H-nuclear magnetic resonance, and (13)C-nuclear magnetic resonance. HepG2 and Bel-7402 hepatocellular carcinoma cell lines were used for toxicological evaluation. 21.4 mg of schisandrol A with a purity of 95.2% were collected. The cytotoxicity of the ODS-purified sample and schisandrol A were significantly stronger than that of a resin-purified sample. Schisandrol A was successfully extracted from the stems of S. chinensis and separated with an ODS column combined with preparative HPLC. The samples obtained during the purification process showed different levels of cytotoxicity on the HepG2 and Bel-7402 hepatocellular carcinoma cell lines.
... Some Bupleurum members are used in the treatment of various ailments, such as influenza, fever, and malaria, in folk medicine (Ashour and Wink, 2011;Pan, 2006;Saraço glu et al., 2012). Many biological and chemical studies were performed on both these genera due to the wide variety of well-known uses (Anvari et al., 2016;Ashour et al., 2012Ashour et al., , 2014Hichri et al., 2015;Nan et al., 2014;Radulovi c et al., 2015;Turkmenoglu et al., 2015;Tu sek et al., 2016;Villanueva-Bermejo et al., 2017;Zengin et al., 2017a). However, no information is available on the biological and chemical fingerprints of Achillea phrygia Boiss. ...
Article
This study presents the effects of the Achillea phrygia Boiss. et Bal. and Bupleurum croceum Fenzl. extracts obtained by different solvents (ethyl acetate, methanol and water) on selected enzyme inhibitory effects and antioxidant ability with screening bioactive compounds. Total and individual bioactive compounds were detected by spectrophotometric and HPLC-DAD techniques. Antioxidant abilities were evaluated by different methods including free radical scavenging (ABTS and DPPH), reducing power (CUPRAC and FRAP), phosphomolybdenum and metal chelating. Enzyme inhibitory effects were tested against cholinesterases, tyrosinase, amylase, glucosidase and lipase. Total phenolic contents were ranged from 20.52 mgGAE/g extract (B. croceum methanol extract) to 41.13 mgGAE/g extract (A. phrygia methanol extract). Generally, methanol and water extracts showed the strongest antioxidant abilities, while the ethyl acetate extracts had the most promising enzyme inhibitory effects. HPLC analysis revealed the abundance of some phenolics including rutin, quercetin, sinapic acid and chlorogenic acid, respectively. These components were also assessed using molecular modelling with the aim to study their docking properties on a set of six enzymes used in this study. Overall, these species could be suggested as valuable sources of natural-bioactive agents for developing new functional, pharmacological and health-promoting ingredients.
... Unfortunately, the effects of environmental conditions on the growth of wild Bupleurum species are unknown because there has been little research on these effects. In the past decade, research has focused on the pharmacological functions, taxonomy, chemical composition, and extraction and isolation of chemical components (Kusakari et al., 2011;Wang et al., 2011;Akın et al., 2012;Ashour et al., 2012;Benahmed et al., 2014). ...
Article
Bupleurum chinense DC. is one of the most important traditional Chinese medicines. Among its primary pharmacologically active components, saikosaponins play a vital role. We investigated the ecophysiological characteristics, accumulation of secondary metabolites, and antioxidant system of wild plants at low light intensity in the forest understory at shady and sunny sites. Compared with plants at sunny sites, plants at the shady site were more abundant, had higher specific leaf area (SLA), a lower maximum electron transport rate (Jmax), higher triose phosphate utilization (TPU), and higher chlorophyll b content (Chlb), but lower net photosynthesis (Pn), root and aboveground biomass, dark respiration rate (Rd), light compensation point (LCP), chlorophyll a to b ratio, carotenoid content, and nonphotochemical quenching (NPQ). These features suggest that under low light conditions, the species developed larger leaves to catch more light energy through light-harvesting complex II to increase its photosynthetic efficiency (its ability to use weak light) and photosynthetic electron transport, thereby improving carbon metabolism and survival. The maximum quantum efficiency of photosystem II was about 0.8 at both sites; thus, photoinhibition was not a major problem. Contents of saikosaponins a and d and the total saikosaponin content (SSa, SSd, and SStotal) were much higher at the shady site, accompanied by increased superoxide dismutase (SOD), catalase(CAT), and peroxidases (POD) activity and decreased malondialdehyde (MDA). This suggested that low light activates antioxidant stress-response pathways, leading to increased SSa, SSd, and SStotal. Our results suggest that B. chinense has strong shade tolerance and would be suitable for cultivation in an agroforestry system.
... Lignans that could mediate anticancer activity via a variety of mechanisms, including induction of apoptosis, have been isolated from African medicinal plants. p0185 Studies on aerial parts of the Egyptian plant Bupleurum marginatum revealed a novel aryltetralin lactone lignan identified as marginatoxin [9-(benzo[d][1,3] dioxol-5-yl)-6,7,8-trimethoxy-a,4,9,9-atetrahydronaphtho[2,3-c]furan-1(3H)-one] (42) (Figure 12.11) and lignan [(3,4-dimethoxybenzyl)-2-(3,4-methylenedioxybenzyl) butyrolactone] (43), which exhibited cytotoxic activity, with IC 50 values of 41.3 and 52.7 mM on HeLa and HepG2 cells, respectively[69]. Anolignan B (28), isolated from the roots of T. sericea and Anogeissus acuminate, exhibited cytotoxic effects against fibrosarcoma cell lines[70]. ...
Chapter
Lignans and stilbenes are two groups of related secondary metabolites widely distributed in the plant kingdom. They have been found in roots, rhizomes, stems, bark, leaves, seeds, and fruits of more than 100 species of African medical plants belonging to various families. Lignans are biosynthesized by oxidative dimerization of two phenylpropanoid units; they possess an enormous structural diversity originating from various linkage patterns. Stilbenes are also biosynthesized from phenylpropanoids that can be further oxidized to form oligomers. Both lignans and stilbenes from African medicinal plants have attracted intense interest because of their structural diversity and biological functions, specifically for their anticancer, antiplasmodial, and antibacterial properties. This is exemplified by many clinical studies that have been performed on the use of schweinfurthins, combretastatins, and steganolides to treat cancer. This chapter provides information on the biosynthesis, subclasses, and structural diversity of lignans and stilbenes, as well as their biological activity. Selected data are presented for those molecules with biological information.
... Their structures were fully elucidated by comparing their 1D and 2D NMR data with those reported in literature for previously isolated compounds (Fig. S4). They were identified as daucasterol (1) and stigmasterol glucoside (2) (Ashour et al., 2012) in addition to D-pinitol (4) (Sharma et al., 2016) from A. turkestanus whereas an oleanane type triterpenoidal saponin, azukisaponin V (5) (Gromova et al., 2001), and a flavonoid glycoside, 7-methoxy kaempferol-3-O-β-D-glucopyranoside (7) (Khalfallah et al., 2014) were isolated from A. xапthomeloides ( Fig. 1) The structures of the two new compounds were comprehensively elucidated using UV, NMR and HR-ESI-MS techniques (Table 1). ...
Article
Phytochemical investigation of the methanol extracts of the aerial parts of Astragalus turkestanus and A. xапthomeloides using various chromatographic techniques resulted in the isolation and structural elucidation of two new flavonoid glycosides, namely, 7-methoxy kaempferol-3-O-α-l-arabinosyl-(1 → 6)-β-d-galactopyranoside (3) from the former and kaempferol-3-O-α-l-rhamnopyranosyl-7-O-α-l-rhamnopyranosyl-(1 → 6)-β-d- galactopyranoside (6) from the latter. In addition five other known compounds were isolated for the first time from these species. In silico molecular modeling study was carried out on α-glucosidase (PDB ID 3TOP; 2.88 A°) to assess the α-glucosidase inhibitory activity of the isolated compounds. Both compounds 3 and 6 displayed the highest fitting score with ΔG equals to −82.10 and −67.66 Kcal/mol in the pH-based ionization method and −68.55 and −67.83 Kcal/mol in the rule-based ionization method, respectively. α-Glucosidase inhibitory activity was further asserted in vitro using an ELISA assay that is measured colorimetrically at 405 nm. Compound 3 showed a significant α-glucosidase inhibitory activity displaying IC50 of 50.31 μg/mL approaching that of acarbose (IC50 = 30.57 μg/mL). All the tested samples showed no significant cytotoxic activity against Caco-2 (human epithelial colorectal adenocarcinoma) cells using the MTT assay (IC50 > 400 μg/mL). Thus; both new compounds could offer promising natural antihyperglycaemic entities without any marked toxicity, which could be useful in the pharmaceutical industry.
... Recently, an aryltetraline lactone lignan has found to exhibit the cytotoxic activity with IC 50 values of 12.14 and 16.90 mmol/L after 24 h treatment for HepG2 and HeLa cells, respectively (Ashour et al, 2012). ...
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Many species of genus Bupleurum L. have been pharmaceutically used mainly in Asia and Europe for thousand years. Their roots are the most popular ingredients in Chinese materia medica prescriptions for the treatment of inflammatory diseases and auto-immune diseases. A plenty of chemical constituents have been isolated and identified from the species in Bupleurum L., such as saikosaponins, polysaccharides, volatile oils, flavonoids, polyacetylenes, lignins, and coumarins, most of which possess a variety of biological activities, especially for the hepatoprotective effect, antitumor activity, immunoregulation, and febrifuge efficacy. Therefore, the species in genus Bupleurum L. could be potential herbs of immunomodulator, antineoplastic, anti-oxidant, etc. Meanwhile, as potential toxicities have been discovered in some constituents, it is urgent to establish a comprehensive quality evaluation system to ensure the safety and efficiency of herbs. This paper reviews on the phytochemical and pharmacological studies, especially for the toxicology and quality control of the species in Bupleurum L., which is a reference for the species in this genus for safe usage and further development.
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Two new triterpenoid saponins (1 and 2), together with two known saponins (3 and 4) were isolated from Bupleurum marginatum Wall. ex DC. Their structures were elucidated by the comprehensive spectroscopic analysis. Compounds 1 and 2 represented the rare example of an oleanane-type triterpenoid with two sugar moieties at C-3 and C-28. The cytotoxic activity of four compounds was evaluated against normal heptocell BRL-3A in vitro.
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Liver fibrosis is a common pathological feature of many chronic liver diseases. Bupleurum marginatum Wall.ex DC (ZYCH) is a promising therapeutic for liver fibrosis. In this study, 25 compounds were isolated from ZYCH, and the effects of ZYCH on DMN-induced liver fibrosis in rats were evaluated. The optimal effect group (H-ZYCH group) was selected for further proteomic analysis, and 282 proteins were altered in comparison to the DMN model group (FC > 1.2 or < 0.83, p < 0.05). Based on GO annotation analysis, clusters of drug metabolism, oxidative stress, biomolecular synthesis and metabolism, positive regulation of cell growth, extracellular matrix deposition, and focal adhesion were significantly regulated. Then networks of the altered proteins and compounds was generated by Cytoscape. Importantly, triterpenoid saponins and lignans had possessed high libdock scores, numerous targets, important network positions, and strong inhibitory activity. These findings may suggest that triterpenoid saponins and lignans are important active compounds of ZYCH in liver fibrosis and targeted by proteins involved in liver fibrosis. The combination of network pharmacology with proteomic analysis may provide a forceful tool for exploring the effect mechanism of TCM and identifying bioactive ingredients and their targets.
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In order to discover the bioactive metabolites of Pyrus ussuriensis Maxim, the systematic chemical and pharmacological investigations were performed. The ethyl acetate extract of the plant displayed activities against ear edema in mice, with an inhibition rate of 17.1%, at a dose of 400mg/kg in vivo. Meanwhile, the ethyl acetate extract showed the best apophlegmatic (inhibition: 49.9%) and antitussive effects (inhibition: 34%) at 800mg/kg in vivo tests, and inhibition of NO production (IC50=0.06 μg/mL). Subsequently, twelve compounds were isolated from the ethyl acetate extract and identified as friedelin (1), daucosterol (2), β‐sitosterol (3), betulinic acid (4), oleanolic acid (5), ursolic acid (6), 2‐O‐buty‐1‐O’‐(2‐ethylhexyl) benzene‐1,8‐dicarboxylate (7), Narcissin (8), 3‐hydroxy‐3‐carboxyl‐glutaric acid dimethyl ester (9), 2‐hydroxyl ‐butanediol icacid‐4‐methyleste (10), myristic acid (11), and (Z)‐11‐hexadecen‐1‐ol acetate (12). Among them, compounds 1, 2, 4, 5, 6, and 11 exhibited moderate indirect inhibitory effects on lipopolysaccharide‐induced NO and TNF‐α production. Practical applications Pyrus ussuriensis Maxim is an edible and medical fruit with many functional properties. Unfortunately, few literatures about bioactive components of this fruit have been investigated. The result indicated that P. ussuriensis have obvious anti‐inflammatory, antitussive, and apophlegmatic activities, which were associated with the folk uses of this fruit. Furthermore, this work also suggests a potential use of P. ussuriensis as an important source of natural anti‐inflammatory agents and they may also be considered as a functional food.
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The present study designed to investigate the quantitative distributions in the secondary metabolites and biological activity of sub-fractions obtained successively from water and methanol: dichloromethane (rate 1:1; v:v) solvent decoction of Diplotenia bingolensis aerial parts. The crude extracts were obtained from the aerial parts of the endemic D. bingolensis species refluxing with water and organic solvents. Sub-fractions of water extract were obtained by successive fractionation of the water extract with hexane (WH), dichloromethane (WD), ethyl acetate (WE) and n-butanol (WB), respectively. Sub-fractions of organic solvent were obtained by fractionation of the organic crude extract with hexane (OH), dichloromethane (OD), ethyl acetate (OE), n-butanol (OB) and water (OW), respectively. The total amount of phenols and flavonoids contained in each sub-fraction was analyzed by UV-VIS spectrophotometer, analysis of lipophilic components by GC-MS spectrometer, and quantitative analysis of hydrophilic components by HPLC-TOF/MS spectrophotometer. Furthermore, the biological activity of each sub-fraction was compared with different antioxidant activities such as DPPH radical scavenging activity and ferric ion reduction capacity. Sub-fraction WD (137.1 ± 2.1 μg QE/mg DI) and OE (127.1 ± 5.2 μg QE/mg DI) in terms of flavonoid content, sub-fraction WD (665.8 ± 47.6 μg GAE/mg DI) and OE (724.6 ± 43.6 μg GAE/mg DI) were the richest isolates in terms of total phenol content. Sub-fractions OH and OD contained linoleic acid (17.0 and 11.0%, respectively) and linolenic acid (22.1 and 18.5%, respectively). It was revealed that sub-fractions were rich in terms of rutin (1.2-47.2 μg HC/mg DI) and chlorogenic acid (0.1-12.1 μg HC/mg DI). Sub-fractions WD and OE were showed the highest DPPH radical scavenging activity with 46.4 ± 1.4 and 47.6 ± 10.0 μg/mL EC50 values, respectively. This study is the first to demonstrate biological insight of the potential antioxidant activity of D. bingolensis. These findings warrant the popular use of the endemic D. bingolensis and highlight the potential of its active constituents in the development of new antioxidative drugs.
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In the present study, the total phenol contents and in vitro antioxidant activities of two extracts obtained from herb of Bifora radians were investigated. The phenol contents of the samples were determined using Folin-Ciocalteu's phenol reagent. The antioxidant activity of diethyl ether and methanol extracts were examined by two different techniques: qualitative and quantitative DPPH• (1,1-diphenyl-2-picrylhydrazyl radical) assays to detect the free radical scavenging effect and the TBA (thiobarbituric acid) assay to detect their liposome lipid peroxidation.
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A new aryltetralin lignan, bupleroid A (1), along with ten known analogues (2-11) were isolated from Bupleurum marginatum. The structures of these isolates were determined by 1D and 2D NMR, HRESIMS, and ECD data analysis. In addition, the DPPH radical scavenging capacities of all compounds were evaluated. Compound 6 exhibited good DPPH radical scavenging activity at a concentration of 50 μM.
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Diabetes is an urgent health issue characterized by ethnic and regional variations, and is inseparable from the different dietary habits. It is worthy to note that the incidence of diabetes in Bai nationality has been reported to be much lower than Han in China. As a daily vegetable of Bai, the phytochemical and antidiabetic study of Ottelia acuminata var. acuminata had not been carried out. In this study, 41 metabolites with diverse diarylheptanoid (six new ones, Otteacumienes A–F), flavone, sesquiterpenoid, coumarin, lignan, polyacetylene, and alkaloid skeletons were characterized from O. acuminata var. acuminata . Among them, the racemic nature of 3 was characterized by chiral resolution and calculated ECD methods. The biological study revealed diarylheptanoids showed significant α -glucosidase inhibitory activities with 5 as the most effective one (60-fold stronger than acarbose). Molecular docking studies indicated that these structures have different binding cavities with acarbose. This study demonstrated that O. acuminata var. acuminata might correlated with the low incidence diabetes of Bai and the diarylheptanoids may have potential therapeutic value for diabetes mellitus. Graphical Abstract
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Plants use complex mixtures of secondary compounds (SM) of different structural classes to protect themselves against herbivores, bacteria, fungi and viruses. These complex mixtures may contain SM, which are specific for a single target (monotarget SM). A majority of SM, however, can interfere with several targets (multitarget SM) in a pleiotropic fashion. The composition of such extracts appears to be optimised, since the components are not only additive but apparently synergistic in their bioactivity. Synergism can be achieved by inhibiting the xenobiotics inactivating activities of animals and microbes (MDR, CYP), by facilitating the uptake of polar SM across biomembranes and/or by affecting several important organs in animals concomitantly. Phytotherapy employs equally complex extracts of medicinal plants. Arguments were put together that the utilisation of complex mixtures with pleiotropic agents presents a unique therapeutic approach with many advantages over monotarget compounds. Mixtures of multitarget SM, used in phytotherapy include phenolics, tannins, mono- and sequiterpenes, saponins, iridoid glucosides and anthraquinones, but only few of them alkaloids or other toxic monotarget SM.Multitarget effects are caused by SM, which can modulate the three-dimensional structure of proteins (and thus their function), by interfering with DNA/RNA (especially gene expression) or membrane permeability. In addition, complex extracts may contain synergists, which can inhibit MDR, cytochrome P450 or enhance absorption and thus bioavailability of active metabolites. The molecular modes of action are reviewed for the main groups of secondary metabolites.
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Fifteen flavonoids, 1-7 and 9-16, and a polyacetylene, 8, were isolated from the ethanol extract of the dried whole plant of Bidens parviflora Willd. by various chromatographic techniques. Their structures have been elucidated on the basis of spectroscopic analyses and chemical studies. Compound 8 is new and was identified as 3-(R),8(E)-decene-4,6-diyne-1,3,10-triol. All the flavonoid compounds were isolated for the first time from this plant species. © 2008 by the authors; licensee Molecular Diversity Preservation International.
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Two lignans rel-(8R, 8'R)-3,4:3',4'-bis-(methylenedioxy)-7.7'-dioxo-lignan and (7'R,8'S,8S)-2'-hydroxy-3,4:4',5'-bis-(methylenedioxy)-7-oxo-2,7'-cyclolignan were isolated from seeds of Virola sebifera. The cyclolignan showed two atropisomers as determined by 1H NMR spectroscopy at low temperature.
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The methanol extract obtained from the aerial parts of Aceriphyllum rossii (Saxifragaceae) was fractionated into ethyl acetate (EtOAc), n-BuOH and H2O layers through solvent fractionation. Repeated silica gel column chromatography of EtOAc and n-BuOH layers afforded six flavonol glycosides. They were identified as kaempferol 3-O-beta-D-glucopyranoside (astragalin, 1), quercetin 3-O-beta-D-glucopyranoside (isoquercitrin, 2), kaempferol 3-O-alpha-L-rhamnopyranosyl (1-->6)-beta-D-glucopyranoside (3), quercetin 3-O-alpha-L-rhamnopyranosyl (1-->6)-beta-D-glucopyranoside (rutin, 4), kaempferol 3-O-[alpha-L-rhamnopyranosyl (1-->4)-alpha-L-rhamnopyranosyl (1-->6)-beta-D-glucopyranoside] (5) and quercetin 3-O-[alpha-L-rhamnopyranosyl (1-->4)-alpha-L-rhamnopyranosyl (1-->6)-beta-D-glucopyranoside] (6) on the basis of several spectral data. The antioxidant activity of the six compounds was investigated using two free radicals such as the ABTS free radical and superoxide anion radical. Compound 1 exhibited the highest antioxidant activity in the ABTS [2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)] radical scavenging method. 100 mg/L of compound 1 was equivalent to 72.1+/-1.4 mg/L of vitamin C, and those of compounds 3 and 5 were equivalent to 62.7+/-0.5 mg/L and 54.3+/-1.3 mg/L of vitamin C, respectively. And in the superoxide anion radical scavenging method, compound 5 exhibited the highest activity with an IC50 value of 17.6+/-0.3 microM. In addition, some physical and spectral data of the flavonoids were confirmed.
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The details of the conjugate addition of aryl dithiane anions to 2-butenolide are discussed. The results of the trapping of the resultant lactone enolates with an aryl halide and aryl aldehyde are detailed. The transformation of these intermediates into podorhizol (4a) and isopodophyllotoxone (12a) is also explored. The structures of products from attempted intramolecular Ullmann couplings in the stegnane series are established.
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The volatile composition of the root oils of ten Bupleurum species (B.chinense DC., B.scorzonerifolium Willd., B.microcephalum Diels., B.malconense Shan et Y. Li, B.longicaule Wall. et DC. var. giraldii Wolff, B.marginatum Wall. ex DC, B.bicaule Helm, B.yinchowense Shan et Y. Li, B.wenchuanense Shan et Y. Li, B.smithii Wolff. var. parvifolium Shan et Y. Li) have been studied. The species were collected in their typical habitats of China. The oils were obtained by hydrodistillation and their analyses were performed by GC/FID and GC/MS. Fifty constituents of the oils were identified. The major components of the root oil of B.chinense were hexanal (29.5%), furfural (7.3%), hexanoic acid (7.4%), 2-amylfuran (5.5%) and (E,E)-2,4-decadienal (5.9%). The main components of the root oil of B.scorzonerifolium were hexanal (12.4%), furfural (8.1%), heptanal (9.3%) and dodecanoic acid (5.7%). Sixteen compounds were characterized in the root oil of B.microcephalum, with cyperol (15.6%), heptanal (6.4%) as main constituents. The major components were furfural (13.2%) and p-tolyl-2-propene (7.5%) in the oil of B.malconense. Nineteen compounds were characterized in the root oil of B.longicaule, with hexanal (15.1%), furfural (15.6%) and p-tolyl-2-propene (7.2%) as main constituents. The main constituents were p-tolyl-2-propene (9.2%), p-cymene (8.4%) and cis-linalool oxide (5.4%) in the root oil of B.marginatum. Nineteen compounds were characterized in the root oil of B.bicaule, with 4-tridecen-6-yne (42.6%) as the main constituent. The main compounds were hexanal (30.5%), furfural (11.9%) and hexanoic acid (11.7%) in the root oil of B.yinchowense. The main components were undecane (19.9%), p-tolyl-2-propene (8.5%) and hexanal (6.1%) in the root oil of B.wenchuanense. Twenty-two compounds were characterized in the root oil of B.smithii var. parvifolium, with hexanal (10.8%) and methyl thymol (6.2%). A comparison of the root oil compositions from the ten Bupleurum species showed that the concentration of major compounds was different, but almost all samples were found to contain a series aliphatic derivatives.
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A new lignan, sylvestrin (1), was isolated from the MeOH-soluble fraction of the roots of Anthriscus sylvestris HOFFM. (Umbelliferae), along with six lignans (2—7), three coumarins (8—10), and a polyacetylene (11). The structure of sylvestrin was determined to be 2-(3′,4′,5′-trimethoxybenzylidene)-3-(3″,4″-methylendioxybenzyl)-γ-butyrolactone (1) by spectroscopic means, including 2D-NMR. The eleven compounds were assessed for their abilities to activate a caspase-3 in human promyeloid leukemic HL-60 cells. The intracellular caspase-3 activity of (−)-deoxypodophyllotoxin (3), angeloyl podophyllotoxin (5), deoxypicropodophyllin (6), picropodophyllotoxin (7), and falcarindiol (11) increased approximately 4.6, 3.6, 3.7, 3.9, and 3.9-fold, at 0.001, 1, 1, 1, and 20 μM, respectively, over that of the untreated control. In addition, compounds 3, 5, 6, and 7 showed apoptosis-inducing activities that were measured by DNA fragmentation in HL-60 cells.
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The colorimetric MTT assay based on the selective ability of living cells to reduce 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide into formazan was adapted for measuring antibody independent monocyte mediated cytotoxicity. In view of the suggested application of adoptive immunotherapy we studied the anti leukaemic effects of activated human monocytes and macrophages against U 937 cells in vitro. Purified monocytes (greater than 98%) isolated by centrifugal elutriation and activated with interferon-gamma (IFN) were incubated with U 937 cells for 24 h at effector-to-target cell ratios (E/T) of 0.1-10. We assayed cytotoxicity by relating the optical density (OD) of residual metabolically active U 937 cells after exposure to effector cells to the OD of the initially inoculated U 937 cells. MTT reduction of effector cells was dependent on monocyte activation and differentiation into macrophages but did not interfere with the target cell signal up to an E/T ratio of 10. Improved signals could be obtained by dissolving formazan in DMSO with the addition of glycine instead of using propanol as solvent. Maximum cytostasis (95%, conventional [3H] incorporation assay) and cytotoxicity (80%, modified MTT assay) was reached with IFN activated monocytes at an E/T ratio of 10. In conclusion these data show that the modified MTT assay is a useful method of measuring monocyte mediated cytotoxicity in a sensitive, rapid, semi-automatic manner without the use of radioactive isotopes.
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As a follow-up to Dr Markham's highly successful publication, The Systematic Identification of Flavonoids (1970) co-authored with T.J. Mabry and M.B. Thomas, this book presents a more extensive, up-to-date and thorough guide to techniques used in flavonoid research. The techniques are discussed in the approximate order in which they are normally needed by the researcher and extensive cross-referencing is used throughout to guide the reader to the next recommended technique. Tech- niques covered include: chromatography, recrystallization, UV-visible spectroscopy, hydrolysis and product analysis, derivation degradation, 1 H-NMR, 13 C-NMR, and mass spectroscopy. The book, as a self-contained laboratory manual, contains extensive tabulations of reference data, discusses examples of a wide range of spectra, and features diagrams of flavonoid structures, reaction schemes and appara- tus. Of special interest and importance to the beginner are the tables of trivial names, the list of sources of flavonoid standards and a discussion of the means for proving a new flavonoid identical to a known standard.
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Atom transfer cyclization reactions (ATRC) provide rapid access to functionalized γ-butyrolactones.
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Three new arylnaphthalide lignans, 5-(4-hydroxy-3-methoxyphenyl)furo[3′,4′: 6,7]naphtho[2,3-d]-1,3-dioxol-6(8H)-one (1), 10-(4-hydroxy-3-methoxyphenyl)furo[3′,4′: 6,7]naphtho[1,2-d]-1,3-dioxol-9(7H)-one (2), and 10-(3,4-dimethoxyphenyl)-6-hydroxyfuro[3′,4′: 6,7]naphtho[1,2-d]-1,3-dioxol-9(7H)-one (3), together with two known ones, chinensin (4) and isodiphyllin (5), were isolated from the aerial parts of Bupleurum marginatumWall. ex DC. The structures of the three new lignans were established by means of NMR spectroscopic studies, including HQSC, HMBC, and ROESY.
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Lignans are widely distributed in angiosperms and gymnosperms. The range of their structures and biological activities is broad. Various lignans are known to have anti-tumour, antimitotic and antiviral activity and to specifically inhibit certain enzymes. Toxicity to fungi, insects and vertebrates is observed for some lignans and a variety of physiological activities have been documented. This review summarizes what is presently known about the biological activities of lignans.
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The fresh peel of Citrus jambhiri was extracted with aqueous methanol and the residue was fractionated using light petroleum, chloroform and ethyl acetate. The constituents of the extracts were separated by column chromatography employing solvents of different polarity. The chemical structure of the isolated compounds was then identified by MS and NMR. Column chromatography of the petroleum fraction resulted in the isolation of nobiletin, 5-O-demethylnobiletin, tangeretin, 5-hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone, 3,5,6,7,8,3′,4′-heptamethoxyflavone, and a mixture of β-sitosterol and stigmasterol. The chloroform fraction afforded 6-demethoxynobiletin, 5,4′-dihydroxy-6,7,8,3′-tetramethoxyflavone, limonin and nomilin. The flavonoid glycosides naringin, hesperidin and neohesperidin were isolated from the ethyl acetate fraction. The chemical structure of the isolated compounds was established by MS and NMR (APT, COSY, HSQC, HMBC, and NOESY). LC–ESI-MS analysis of the ethyl acetate fraction afforded eight flavonoid glycosides, while the dichloromethane fraction of the defatted seeds contained seven limonoid aglycones. The chloroform fraction exerted the strongest DPPH∗ free radical scavenging activity in comparison to other fractions. The petroleum fraction showed a significant inhibition of lipoxygenase indicating an anti-inflammatory action (IC50 29 ± 1 μg/mL). Some of the isolated polymethoxyflavones exhibited strong cytotoxicity against COS7, HeLa and Caco-2 cell lines.Research highlights► Nomilin and limonin from Citrus jambhiri peel. ► C. jambhiri extracts with strong DPPH∗ scavenging activity. ► Lipoxygenase inhibition indicates anti-inflammatory activity of C. jambhiri. ► Cytotoxicity of polymethoxyflavones against COS7, HeLa and Caco-2 cell lines.
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Radix Bupleuri represents one of the most successful and widely used herbal drugs in Asia for treatment of many diseases over the past 2000 years. Thorough studies have been carried out on many species of this genus and have generated immense data about the chemical composition and corresponding biological activity of extracts and isolated secondary metabolites. In this work, we review the chemistry and pharmacology of the genus Bupleurum and explore the relationships between the pharmacological effects and the chemical composition of these drugs. Early studies on the genus Bupleurum had focused only on the traditional uses of the plants in the treatment of inflammatory disorders and infectious diseases. After chemical profiling, several groups of secondary metabolites were characterized with relevant biological activity: triterpene saponins (saikosaponins), lignans, essential oils and polysaccharides. As a result, present interest is now focused on the bioactivity of the isolated triterpene saponins acting as immunomodulatory, anti-inflammatory and antiviral agents, as well as on the observed ant-iulcer activity of the polysaccharides and anti-proliferative activity of different lignans. Many saikosaponins exhibited very potent anti-inflammatory, hepatoprotective and immunomodulatory activities both in vivo and in vitro. Further investigations and screenings are required to explore other Bupleurum species, to evaluate the clinical safety and possible interactions with other drugs or herbs. Standardization of Bupleuri extracts is crucial for them being integrated into conventional medicine due to large chemical and biological variations between different species and varieties.
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The aim was to determine the chemical composition of the essential oil of Kadsura longipedunculata and the biological activity of the oil and its major components. The essential oil from stem bark of Kadsura longipedunculata was analysed by capillary gas chromatography (GLC/FID) and gas chromatography-mass spectrometry (GLC/MS). The ability of the oil to reduce diphenylpicrylhydrazine (DPPH(*)) was used to evaluate the antioxidant activity. Inhibition of both lipoxygenase and prostaglandin E(2) was used to assess the anti-inflammatory activity. Antimicrobial activity was studied in vitro against a range of bacteria and fungi using diffusion and microdilution methods. Inhibition of trypanosome proliferation was assessed using resazurin as vital stain. The in-vitro cytotoxicity of the essential oil on six human cancer cell lines (HepG2, MIA PaCa-2, HeLa, HL-60, MDA-MB-231 and SW-480) was examined using the MTT assay. Fifty compounds, representing 97.63% of total oil, were identified. delta-Cadinene (21.79%), camphene (7.27%), borneol (6.05%), cubenol (5.12%) and delta-cadinol (5.11%) were found to be the major components of the oil. The oil exerted a good antimicrobial activity against all Gram-positive bacteria tested, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis. Streptococcus pyogenes and S. agalactiae were the most sensitive bacteria with a minimal inhibitory concentration (MIC) of 60 microg/ml oil. The essential oil showed a moderate fungicidal activity against yeasts, but it did not show any activity against Gram-negative bacteria. The essential oil showed a good trypanocidal activity in Trypanosoma b. brucei with an IC50 value of 50.52 +/- 0.029 microg/ml. Radical scavenging activity had an IC50 value of 3.06 +/- 0.79 mg/ml. 5-Lipoxygenase inhibition (IC50 = 38.58 microg/ml) and prostaglandin E(2) production inhibition (28.82% at 25 microg/ml) accounted for anti-inflammatory activity of the oil. The oil exhibited some degree of cytotoxic activity against MIA PaCa-2, HepG-2 and SW-480 cell lines with IC50 values of 133.53, 136.96 and 136.62 microg/ml, respectively. The oil increased caspase 3/7 activity (an indicator of apoptosis) 2.5-4 fold in MIA Paca-2 cells. Camphene and borneol did not show antioxidant activity. However, both compounds exhibited some degree of antimicrobial, trypanocidal, anti-inflammatory and cytotoxic activity. This investigation provided evidence for, and confirmed the efficacy of, K. longipedunculata, a traditionally used Chinese medicinal plant for the treatment of inflammation and infection.
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A LC-diode array detection (DAD)-ESI-MS/MS method was established for the online characterization and identification of saikosaponins (SSs) from extracts of roots of Bupleurum scorzonerifolium Willd, B. marginatum var. stenophyllum and B. komarovianum. In ESI-MS/MS spectra of SSs, [M-H](- )ions were subjected to the cleavage of glycosidic bonds and produced Y type ions, which can be used to elucidate the structures of saccharide chains and aglycones. Fragmentation of aglycones provided mass information about their major substitutions. For three structural types of SSs, type III can be easily identified by their fragmentation behaviors; while type I and II often occur as isomers and they can be discriminated by their typical UV absorption data. The only sugar ring-cross cleavage corresponding to 76 Da took place at a furanose sugar moiety. As a result, more than 75 SSs, including eight novel compounds, were identified or tentatively characterized based on their UV and mass spectra and retention times. The approach established here allows a comprehensive analysis of the SSs in the genus of Bupleurum and will be helpful for quality control of the crude materials and their related preparations.
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Phytochemical works on the aerial parts of Aster oharai (Compositae) led to the isolation of a new sesquiterpene hydroperoxide, 7alpha-hydroperoxy-3,11-eudesmadiene (2) and seven known compounds, teucdiol B (1), alpha-spinasterol (3), oleanolic acid (4), alpha-spinasterol 3-O-beta-D-glucopyranoside (5), methyl 3,5-di-O-caffeoyl quinate (6), 3,5-di-O-caffeoylquinic acid (7), 3,4-di-O-caffeoylquinic acid (8). The chemical structures of 1-8 were established by chemical and spectroscopic methods. Compound 2 showed cytotoxicity against cultured human tumor cell lines in vitro, SK-OV-3 (ovarian), SK-MEL-2 (skin melanoma), and HCT15 (colon) with ED50 values ranging from 3.86-17.21 microg/mL.
Article
Anti-estrogenic activity of (-)-sesamin (1), helioxanthin (2), savinin (3), taiwanin C (4), and 3-(3,4-dimethoxybenzyl)-2-(3,4-methylenedioxybenzyl)butyrolactone (5) isolated from the root of Acanthopanax chiisanensis was tested using Ishikawa cells. Among them, compound 3 exhibited anti-estrogenic activity (IC50 = 4.86 microM).
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From the roots of Securidaca inappendiculata, one new sterol glycoside securisteroside (1) has been isolated, along with two known sterols, spinasterol (2) and 3-O-beta-D-glucopyranosyl-spinasterol (3). The new sterol was characterized by chemical and spectrometric methods, including EIMS, FABMS and one- and two-dimensional NMR experiments.
Article
A new lignan, sylvestrin (1), was isolated from the MeOH-soluble fraction of the roots of Anthriscus sylvestris HOFFM. (Umbelliferae), along with six lignans (2-7), three coumarins (8-10), and a polyacetylene (11). The structure of sylvestrin was determined to be 2-(3',4',5'-trimethoxybenzylidene)-3-(3'',4''-methylendioxybenzyl)-gamma-butyrolactone (1) by spectroscopic means, including 2D-NMR. The eleven compounds were assessed for their abilities to activate a caspase-3 in human promyeloid leukemic HL-60 cells. The intracellular caspase-3 activity of (-)-deoxypodophyllotoxin (3), angeloyl podophyllotoxin (5), deoxypicropodophyllin (6), picropodophyllotoxin (7), and falcarindiol (11) increased approximately 4.6, 3.6, 3.7, 3.9, and 3.9-fold, at 0.001, 1, 1, 1, and 20 microM, respectively, over that of the untreated control. In addition, compounds 3, 5, 6, and 7 showed apoptosis-inducing activities that were measured by DNA fragmentation in HL-60 cells.
Article
Isorhamnetin is a flavanoid present in plants of the Polygonaceae family and is also an immediate metabolite of quercetin in mammals. Since the plasma level of isorhamnetin is maintained longer than quercetin, isorhamnetin may be a key metabolite to mediate the anti-tumor effect of quercetin. In the present study, we investigated the apoptotic mechanism of isorhamnetin in Lewis lung cancer (LLC) cells in vitro and established its in vivo anti-cancer efficacy. In cell culture, isorhamnetin significantly increased DNA fragmentation, and TUNEL positive apoptotic bodies and sub-G(1) apoptotic population in time- and dose-dependent manners. Western blot analyses revealed increased cleavage of caspase-3, and caspase-9 and PARP and increased cytosolic cytochrome C in isorhamnetin-treated cells. These events were accompanied by a reduced mitochondrial potential. Apoptosis was blocked by a general caspase inhibitor or the specific inhibitor of caspase-3 or -9. These in vitro results support mitochondria-dependent caspase activation to mediate isorhamnetin-induced apoptosis. Furthermore, an animal study revealed for the first time that isorhamnetin given by i.p. injection at a dose that is at least one order of magnitude lower than quercetin significantly suppressed the weights of tumors excised from LLC bearing mice. The in vivo anti-tumor efficacy was accompanied by increased TUNEL-positive and cleaved-caspase-3-positive tumor cells. Our data therefore support isorhamnetin as an active anti-cancer metabolite of quercetin in part through caspase-mediated apoptosis.
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