A New Anti‐Inflammatory Alkaloid from Roots of Heracleum dissectum

Using various chromatographic methods, a new piperidinone alkaloid, (3S)‐3‐{4‐[(1E)‐3‐hydroxyprop‐1‐en‐1‐yl]‐2‐methoxyphenoxy}piperidin‐2‐one ( 1 ), together with 10 known compounds, bergapten ( 2 ), xanthotoxol ( 3 ), isopimpinellin ( 4 ), isobergapten ( 5 ), heratomol‐6‐O‐β‐d ‐glucopyranoside ( 6 ), scopoletin ( 7 ), apterin ( 8 ), 3‐methoxy‐4‐β‐d ‐glucopyranosyloxypropiophenone, (praeroside; 9 ), tachioside ( 10 ) and coniferin ( 11 ), were isolated from roots of Heracleum dissectum Ledeb . Their structures were elucidated on the basis of physicochemical properties and the detailed interpretation of various spectroscopic data. All the isolated compounds were screened for anti‐inflammatory activity in vitro. As the results, compound 1 and 8 showed significantly inhibitory activity on nitric oxide production in RAW264.7 cells.     

Biphenyl Derivatives from the Aerial Parts of Oenanthe javanica and Their COX‐2 Inhibitory Activities

Four new biphenyl derivatives ( 1 – 4 ), along with six known biphenyl derivatives ( 5 – 10 ) were isolated and elucidated by their detailed analyses of spectroscopic data and references from the aerial parts of Oenanthe javanica for the first time. Compounds ( 1 – 10 ) were assayed for their activities about the inhibition of COX‐2 enzyme in vitro for the first time. Compounds 1 , 2 , 4 , and 6 showed inhibitory activities against COX‐2 with IC₅₀ values ranging from 22.18±0.29 to 108.54±0.42 μm .     

Structure Elucidation of Two New Norlignans from Anemone vitifolia and Their Anti‐Inflammatory Activities

Two new norlignans together with two known phenylpropanoids were isolated from the whole herb of Anemone vitifolia. All compounds were reported from this plant for the first time. The structures of these compounds were identified by comprehensive HR‐ESI‐MS, 1D and 2D NMR spectroscopic data analysis and comparison with literature data. Additionally, bioactivity study results showed that two new compounds have potential anti‐inflammatory activity. The plausible biosynthetic pathway for these compounds were also speculated in this article.     

Synthesis and in Vitro Antimicrobial Activity Screening of New 3‐Acetyl‐2,5‐disubstituted‐1,3,4‐oxadiazoline Derivatives

Thirteen new 3‐acetyl‐2,5‐disubstituted‐1,3,4‐oxadiazoline derivatives were synthesized from corresponding hydrazide‐hydrazones of isonicotinic acid in the reaction with acetic anhydride. The obtained compounds were identified with the use of spectral methods (IR, ¹H‐NMR, ¹³C‐NMR, MS). In vitro antimicrobial activity screening of synthesized compounds against a panel of bacteria and fungi revealed interesting antibacterial and antifungal activity of tested 1,3,4‐oxadiazoline derivatives, which is comparable to that of commonly used antimicrobial agents.     

Three New Phenylpropanoids from the Roots of Piper taiwanense and Their Inhibitory Activities on Platelet Aggregation and Mycobacterium tuberculosis

Bioassay‐guided fractionation of the active AcOEt‐soluble fraction from the roots of Piper taiwanense has led to the isolation of two new phenylpropanoids, taiwanensols A and B ( 1 and 2 , resp.), a new natural product, taiwanensol C ( 3 ), and 3‐acetoxy‐4‐hydroxy‐1‐allylbenzene ( 4 ). The compounds were obtained as two isomer mixtures ( 1 / 2 and 3 / 4 , resp.). Their structures were elucidated by spectroscopic analyses, including 1D‐ and 2D‐NMR spectroscopy and mass spectrometry, and by the comparison of their NMR data with those of related compounds. Compounds 1 – 4 were evaluated for their antiplatelet and antitubercular activities. The mixtures 1 / 2 and 3 / 4 showed potent inhibitory activities against platelet aggregation induced by collagen, with IC₅₀ values of 35.2 and 8.8 μM , respectively. In addition, 1 / 2 and 3 / 4 showed antitubercular activities against Mycobacterium tuberculosis H37Rv, with MIC values of 30.0 and 48.0 μg/ml, respectively.     

α‐Glucosidase Inhibitory Xanthones from the Roots of Garcinia fusca

Two new compounds, fuscaxanthones J ( 1 ) and K ( 2 ), together with eight known xanthones ( 3 – 10 ) were isolated from an ethyl acetate extract of the roots of Garcinia fusca. Their structures were determined using spectroscopic methods, mainly 1D‐ and 2D‐NMR. α‐Glucosidase inhibitory activity of the isolated compounds was evaluated and fuscaxanthone J ( 1 ) showed the most significant effect with an IC₅₀ value of 8.3 ± 1.8 μm (compared with acarbose, IC₅₀ = 214.5 ± 2.3 μm ).     

Valorization of the Green Waste from Two Varieties of Fennel and Carrot Cultivated in Tunisia by Identification of the Phytochemical Profile and Evaluation of the Antimicrobial Activities of Their Essentials Oils

The purpose of this study was to identify the chemical composition and the antibacterial activity of the essential oils (EOs) extracted from the green tops of Daucus carota L. subsp. sativus (Hoffm .) Arcang. plants producing yellow roots (DcsYR) and those producing orange roots (DcsOR) and from two varieties of Foeniculum vulgare subsp. vulgare cultivated in Tunisia. Analyses revealed that the EOs from the two D. carota varieties were rich in constituents belonging to sesquiterpenes. Phenylpropanoids and non‐terpene derivatives were the most abundant classes of compounds in the EOs from the two varieties of F. vulgare, of which compositions were predominated by (E)‐anethole and p‐acetonylanisole. All the tested EOs were significantly more effective against Gram‐negative bacteria, and that obtained from var. azoricum was more active against the yeast Candida albicans than the reference drug. The EOs obtained from these by‐products showed indeed interesting potential to be promoted as natural antimicrobials in food preservation systems, as well as the possibility to be used in flavor industries.     

Green Tea Polyphenol Epigallocatechin Gallate Inhibits Adipogenesis and Induces Apoptosis in 3T3‐L1 Adipocytes

Objective: Green tea catechins have been shown to promote loss of body fat and to inhibit growth of many cancer cell types by inducing apoptosis. The objective of this study was to determine whether epigallocatechin gallate (EGCG), the primary green tea catechin, could act directly on adipocytes to inhibit adipogenesis and induce apoptosis. Research Methods and Procedures: Mouse 3T3‐L1 preadipocytes and mature adipocytes were used. To test the effect of EGCG on viability, cells were incubated for 3, 6, 12, or 24 hours with 0, 50, 100, or 200 μM EGCG. Viability was quantitated by MTS assay. To determine the effect of EGCG on apoptosis, adipocytes were incubated for 24 hours with 0 to 200 μM EGCG, then stained with annexin V and propidium iodide and analyzed by laser scanning cytometry. Both preadipocytes and adipocytes were also analyzed for apoptosis by terminal deoxynucleotidyl transferase dUTP nick‐end labeling assay. To determine the effect of EGCG on adipogenesis, maturing preadipocytes were incubated during the 6‐day induction period with 0 to 200 μM EGCG, then stained with Oil‐Red‐O and analyzed for lipid content. Results: EGCG had no effect on either viability or apoptosis of preconfluent preadipocytes. EGCG also did not affect viability of mature adipocytes; however, EGCG increased apoptosis in mature adipocytes, as demonstrated by both laser scanning cytometry and terminal deoxynucleotidyl transferase dUTP nick‐end labeling assays. Furthermore, EGCG dose‐dependently inhibited lipid accumulation in maturing preadipocytes. Discussion: These results demonstrate that EGCG can act directly to inhibit differentiation of preadipocytes and to induce apoptosis of mature adipocytes and, thus, could be an important adjunct in the treatment of obesity.     

Four New Acylated Iridoid Glycosides from the Aerial Part of Veronicastrum sibiricum and Their Antioxidant Response Element‐Inducing Activity

Four new ( 1 – 4 ) and one known ( 5 ) acylated iridoid glycosides were isolated from the aerial parts of Veronicastrum sibiricum (L.) Pennell . The chemical structures of the isolated compounds were determined to be 3″,4″‐dicinnamoyl‐6‐O‐rhamnopyranosyl‐10‐O‐bergaptol‐5,7‐bisdeoxycynanchoside ( 1 ), 3″,4″‐dicinnamoyl‐6‐O‐rhamnopyranosylpaulownioside ( 2 ), 2″,4″‐dicinnamoyl‐6‐O‐rhamnopyranosylcatalpol ( 3 ), 3″,4″‐dicinnamoyl‐6‐O‐rhamnopyranosylaucubin ( 4 ), and 3″,4″‐dicinnamoyl‐6‐O‐rhamnopyranosylcatalpol ( 5 ) using spectroscopic techniques. Among these compounds, compound 5 increased antioxidant response element (ARE) luciferase activity.     

Structural Characterization and α‐Glucosidase Inhibitory and Antioxidant Activities of Fucoidans Extracted from Saccharina japonica

Two sulfated fucoidan fractions (Lj3 and Lj5) were extracted from Saccharina japonica and then subjected to acid hydrolysis to obtain Lj3h and Lj5h. Lj3h and Lj5h were characterized using IR, methylation analysis, and mass spectrometry. It was found that Lj3h and Lj5h were homogeneous low molecular weight fucoidans. Specifically, Lj3h was composed of the main chain of 1,3‐linked α‐L‐fucopyranose residues with sulfate at C‐2 and/or C‐4 and three different monosaccharides (galactose, glucose, mannose) branched at C‐2 and/or C‐4 of fucose residue. Lj5h contained backbones of alternating galactopyranose residues and fucopyranose residues attached via a 1→3 linkage (galactofucan) and 1→6 linked galactan. The sulfation pattern was mainly located at C2/C4 fucose or galactose residues and more branches occupied at C‐4 of fucose residue and C‐2, C‐3 or/and C‐6 of galactose residue. In vitro assay indicated that, among the four fucoidans tested, only Lj5 showed potent α‐glucosidase inhibitory activity with IC₅₀ of 153.27±22.89 μg/mL, and the two parent fucoidans, Lj3 and Lj5, showed better antioxidant activity than their derivatives. These findings highlight the structure and bioactivity diversity of Saccharina japonica‐derived fucoidans.     

Synthesis of the N‐methyl Derivatives of 2‐Aminothiazol‐4(5H)‐one and Their Interactions with 11βHSD1‐Molecular Modeling and in Vitro Studies

11β‐Hydroxysteroid dehydrogenase type 1 (11β‐HSD1) is an enzyme that affects the body's cortisol levels. The inhibition of its activity can be used in the treatment of Cushing's syndrome, metabolic syndrome and type 2 diabetes. In this study, we synthesized new derivatives of 2‐(methylamino)thiazol‐4(5H)‐one and tested their activity towards inhibition of 11β‐HSD1 and its isoform – 11β‐HSD2. The results were compared with the previously tested allyl derivatives. We found out that methyl derivatives are weaker inhibitors of 11β‐HSD1 in comparison to their allyl analogs. Due to significant differences in the activity of the compounds, molecular modeling was performed, which was aimed at comparing the interactions between 11β‐HSD1 and ligands differing by substituent at the amine group (allyl vs. methyl). Modeling showed that the absence of the allyl group can lead to the rotation of whole ligand molecule which affects its interaction with the enzyme.     

Three New Constituents with Anti-Inflammatory and Antimicrobial Activities in Vitro from the Roots of Capsicum annuum L.

Three new compounds, including two new sesquiterpenes ( 1–2 ), named Annuumine E−F, and one new natural product, 3-hydroxy-2,6-dimethylbenzenemethanol ( 3 ), together with seventeen known compounds ( 4–20 ) were isolated from the ethanol extract of the roots of Capsicum annuum L. Among them, five compounds ( 4 , 5 , 9 , 10 and 20 ) were isolated from this plant for the first time. The structures of new compounds ( 1–3 ) were determined via detailed analysis of the IR, HR-ESI-MS and 1D and 2D NMR spectra. The anti-inflammatory activities of the isolated compounds were evaluated by their ability to reduce NO release by LPS-induced RAW 264.7 cells. Notably, compound 11 exhibited moderate anti-inflammatory activity (IC₅₀=21.11 μM). Moreover, the antibacterial activities of the isolated compounds were also evaluated.     

Design,Synthesis, and Cytotoxic Activity of 3‐Aryl‐N‐hydroxy‐2‐(sulfonamido)propanamides in HepG2, HT‐1080, KB,and MCF‐7 Cells

A new series of (sulfonamido)propanamides ( 6a1 – 6a13 , 6b1 – 6b15 , 7c1 – 7c5 , 6d1 – 6d5 , 6e1 – 6e6 ) was designed and synthesized. All the synthesized compounds were characterized by NMR and mass spectrometry. The target compounds were evaluated for their in vitro cytotoxic activity against hepatocellular carcinoma (HepG2), fibrosarcoma (HT‐1080), mouth epidermal carcinoma (KB), and breast adenocarcinoma (MCF‐7) cell lines with the sulforhodamine B (SRB) assay, with gemcitabine and mitomycin C as positive controls. Most of these compounds exhibit a more potent cytotoxic effect than the positive control group on various cancer cell lines and the most potent compound, 6a7 , shows the IC₅₀ values of 29.78±0.516 μm , 30.70±0.61 μm , and 64.89±3.09 μm in HepG2, HT‐1080, KB, and MCF‐7 cell lines, respectively. Thus, these compounds with potent cytotoxic activity have potential for development as new chemotherapy agents.     

Hormone and pharmaceutical regulation of ASP production in 3T3‐L1 adipocytes

Several studies have demonstrated increases in acylation stimulating protein (ASP), and precursor protein C3 in obesity, diabetes and dyslipidemia, however the nature of the regulation is unknown. To evaluate chronic hormonal and pharmaceutical mediated changes in ASP and potential mechanisms, 3T3‐L1 adipocytes were treated with physiological concentrations of relevant hormones and drugs currently used in treatment of metabolic diseases for 48 h. Medium ASP production and C3 secretion were evaluated in relation to changes in adipocyte lipid metabolism (cellular triglyceride (TG) mass, non‐esterified fatty acid (NEFA) release and real‐time FA uptake). Chylomicrons increased ASP production (up to 411 ± 133% P < 0.05), while leptin, triiodothyronine, and β‐blockers atenolol and propranolol had no effect. Dexamethasone, lovastatin, rosiglitazone and rimonabant decreased ASP production (?53 to ?85%, P < 0.05), associated with a decrease in the precursor protein C3 (?37% to ?65%, P < 0.01). By contrast, epinephrine, progesterone, testosterone, angiotensin II and metformin also decreased ASP (?54% to ?100%, P < 0.05), but without change in precursor protein C3, suggesting a direct effect on convertase activity, possibly mediated by interference (except metformin) due to marked increases in NEFA (5.6–31‐fold, increased P < 0.05). Both lovastatin and metformin induced decreases in ASP were also associated with decreased TG mass (maximal ?60%, P < 0.05) and real‐time FA uptake (maximum ?75%, P < 0.05), suggesting a change in adipocyte differentiation status. These in vitro results are consistent with in vivo ASP profiles in subjects, and suggest that ASP may be regulated through precursor C3 availability, convertase activity and differentiation status. J. Cell. Biochem. 109: 896–905, 2010. © 2010 Wiley‐Liss, Inc.     

Superbanone,A New 2‐Aryl‐3‐benzofuranone and Other Bioactive Constituents from the Tube Roots of Butea superba

Phytochemical investigation from the tube roots of Butea superba, led to the isolation and identification of a new 2‐aryl‐3‐benzofuranone named superbanone ( 1 ), one benzoin, 2‐hydroxy‐1‐(2‐hydroxy‐4‐methoxyphenyl)‐2‐(4‐methoxyphenyl)ethanone ( 2 ), eight pterocarpans ( 3  –  10 ), and eleven isoflavonoids ( 11  –  21 ). Compound 2 was identified for the first time as a natural product. The structure of the isolated compounds was elucidated using spectroscopic methods, mainly 1D‐ and 2D‐NMR. The isolated compounds and their derivatives were evaluated for α‐glucosidase inhibitory and antimalarial activities. Compounds 3 , 7 , 8 , and 11 showed promising α‐glucosidase inhibitory activity (IC₅₀ = 13.71 ± 0.54, 23.54 ± 0.75, 28.83 ± 1.02, and 12.35 ± 0.36 μm , respectively). Compounds 3 and 11 were twofold less active than the standard drug acarbose (IC₅₀ = 6.54 ± 0.04 μm ). None of the tested compounds was found to be active against Plasmodium falciparum strain 94. On the basis of biological activity results, structure–activity relationships are discussed.