Search Results (13)

The progression of type 2 diabetes is associated with multiple complications, one of which is diabetic nephropathy (DN). This study aimed at investigating the nephroprotective potential of two doses 150 mg/kg and 300 mg/kg of Tanacetum balsamita leaf extract (ETB) on metabolic-induced renal injury (MIRI) in rats. Markers of renal oxidative stress and antioxidant defense, histopathology, serum biochemistry, and urinalysis were measured. Blood glucose level and arterial blood pressure were assessed weekly for the experimental period of eight weeks. ETB at a high dose significantly decreased the blood glucose levels and mildly lowered systolic pressure in diabetic rats. In the kidney, ETB restored the antioxidant marker malondialdehyde, reduced glutathione, and markedly increased enzymatic activity related to GSH turnover by 46% (GPx), 22% (GR), 32% (GST), and 96% (SOD). ETB reduced elevated urea and creatinine levels and alleviated the proteinuria along with other urinalysis parameters. Histopathological examination of the kidney supported the observed protective effects. Both doses of the ETB ameliorated most of the investigated parameters similarly to positive controls enalapril and acarbose. ETB benefits on MIRI-induced damages could be associated with high levels of mono- and dicaffeoylquinic acids together with a series of methoxylated flavones and flavonols, which may hold significance for its antidiabetic and nephroprotective activity. Full article

The cytotoxic and apoptotic properties of four bioactive natural compounds, the prenylated α-pyronephloroglucinol heterodimer arzanol (ARZ), the methoxylated flavones eupatilin (EUP) and xanthomicrol (XAN), and the sesquiterpene zerumbone (ZER), were compared in SH-SY5Y human neuroblastoma cells to assess their potential as neuroblastoma-specific therapeutics. EUP, XAN, and ZER (2.5–100 μM) exerted marked significant cytotoxicity (MTT assay) and morphological changes after 24 h of incubation, following the order XAN > ZER > EUP > ARZ (no toxic effect). The propidium iodide fluorescence assay (PI, red fluorescence) and NucView^® 488 assay (NV, green fluorescence) evidenced a significant increase in the apoptotic cell number, vs. controls, in SH-SY5Y cells pre-incubated for 2 h with the compounds, in the following order of apoptotic potency: XAN > EUP > ZER > ARZ. The PubChem database and freely accessible web tools SwissADME, pkCSM-pharmacokinetics, and SwissTargetPrediction were used to assess the physicochemical/pharmacokinetic properties and potential protein targets of the compounds. At 50 μM, a positive correlation (r = 0.917) between values of % viability reduction and % human intestinal absorption (bioavailability) was observed, indicating a marked contribution of compound membrane permeability to cytotoxicity in SH-SY5Y cells. The capacity of compounds to induce apoptosis emerged as inversely correlated to the computed lipophilicity (r = −0.885). Full article

Melanoma is a skin cancer caused by the malignant transformation of melanocytes and cutaneous melanoma represents the most aggressive and deadliest type of skin cancer with an increasing incidence worldwide. The main purpose of the present research was to evaluate the anticancer effects of the natural bioactive compounds xanthomicrol (XAN) and eupatilin (EUP) in human A375 malignant skin melanoma cells, a cell line widely used as an in vitro model of cutaneous melanoma. XAN and EUP are lipophilic methoxylated flavones with antioxidant, anti-inflammatory, and antitumor properties. The effects of XAN and EUP on cell viability, morphology, lipid profile, oxidative status, apoptosis, and mitochondrial membrane polarization were determined and compared in A375 cells. At 24 h-incubation (MTT assay), XAN significantly reduced viability at the dose range of 2.5–200 μM, while EUP showed a significant cytotoxicity from 25 μM. Moreover, both methoxylated flavones induced (at 10 and 25 μM, 24 h-incubation) marked cell morphological alterations (presence of rounded and multi-nucleated cells), signs of apoptosis (NucView 488 assay), and a noteworthy mitochondrial membrane depolarization (MitoView 633 assay), coupled to a marked lipid profile modulation, including variations in the ratio of phospholipid/cholesterol and a decrease in the oleic, palmitic, and palmitoleic acid amounts. Moreover, a remarkable time-dependent ROS generation (2′,7′-dichlorodihydrofluorescein diacetate assay) was observed during 3 h-incubation of A375 cancer cells in the presence of XAN and EUP (10 and 25 μM). Our results confirm the potential antitumor effect of natural EUP and XAN in cutaneous melanoma by the activation of multiple anticancer mechanisms. Full article

Internal parasitic diseases of swine constitute a major welfare and health concern in low-input livestock farming. Due to an increase in chemical resistance, phytotherapeutic remedies have become an alternative for the prophylaxis and therapy of digestive parasitosis, albeit few remedies have been subjected to scientific validation. Low-input swine farming in Romania has adopted the traditional use of phytotherapy for controlling pathogens in livestock. The current study aimed to assess the antiparasitic potential of Calendula officinalis and Satureja hortensis against digestive parasites of swine in two low-input farms. The fecal samples were collected from sows, fatteners, and weaners, and were tested using the following coproparasitological methods: centrifugal sedimentation, flotation (Willis, McMaster egg counting technique), Ziehl–Neelsen stain modified by Henricksen, modified Blagg method, and in vitro nematode larvae/protozoan oocyst cultures. Six species of digestive parasites were diagnosed, namely Ascaris suum, Trichuris suis, Oesophagostomum spp., Balantioides coli, Eimeria spp., and Cryptosporidium spp., in various combinations, dependent on the swine category. A dose of 140 mg/kg bw/day of C. officinalis and 100 mg/kg bw/day of S. hortensis powders administered for 10 consecutive days revealed a strong antiprotozoal and anthelmintic activity on the aforementioned parasites. The curative efficacy can be attributed to the presence of polyphenols, sterols, tocopherols, and methoxylated flavones. In conclusion, our results indicate that S. hortensis and C. officinalis are promising alternatives to the commercially available antiparasitics, enabling their use as natural antiparasitic products against gastrointestinal parasites in pigs. Full article

Gymnosperma glutinosum is a plant popularly known as “popote”, “tatalencho”, “tezozotla” or “pegajosa”, and it is used in traditional medicine in the region of Tehuacán, Puebla (Mexico), for the treatment of jiotes and acne and to cure diarrhea using the aerial parts in infusions. To analyze the phytochemical composition, we have developed a rapid protocol for the extraction and separation of the components of the aerial parts of G. glutinosum. After a maceration process, chloroformic and methanolic extracts were obtained and analyzed. Extracts were evaluated by GC-MS (gas chromatography-mass spectrometry), and their composition revealed the presence of (−)-α-bisabolol (BIS) as the main component in the chloroformic extract, which was isolated and analyzed by ¹H NMR to confirm its presence in the plant. The analysis of methanolic extracts by UPLC-MS (ultra-performance liquid chromatography-mass spectrometry) revealed the occurrence of six methoxylated flavones with m/z 405.08 (C₁₉H₁₈O₁₀), m/z 419.09 (C₂₀H₂₀O₁₀) and m/z 433.11 (C₂₁H₂₂O₁₀), and a group of C20-, C18-hydroxy-fatty acids, which give the plant its sticky characteristic. The presence of BIS, an important sesquiterpene with therapeutic skin effects, as well as some antioxidant compounds such as methoxylated flavones and their oils, could play an important role in cosmetology and dermatology formulations. Full article

The methoxylated flavone xanthomicrol represents an uncommon active phenolic compound identified in herbs/plants with a long application in traditional medicine. It was isolated from a sample of Achillea erba-rotta subsp. moschata (musk yar-row) flowering tops. Xanthomicrol promising biological properties include antioxidant, anti-inflammatory, antimicrobial, and anticancer activities. This study mainly focused on the evaluation of the xanthomicrol impact on lipid metabolism in cancer HeLa cells, together with the investigation of the treatment-induced changes in cell growth, morphology, and apoptosis. At the dose range of 5–100 μM, xanthomicrol (24 h of incubation) significantly reduced viability and modulated lipid profile in cancer Hela cells. It induced marked changes in the phospholipid/cholesterol ratio, significant decreases in the levels of oleic and palmitic acids, and a marked increase of stearic acid, involving an inhibitory effect on de novo lipogenesis and desaturation in cancer cells. Moreover, marked cell morphological alterations, signs of apoptosis, and cell cycle arrest at the G2/M phase were observed in cancer treated cells. The bioactivity profile of xanthomicrol was compared to that of the anticancer methoxylated flavones eupatilin and artemetin, and structure–activity relationships were underlined. Full article

The Artemisia L. genus comprises over 500 species with important medicinal and economic attributes. Our study aimed at providing a comprehensive metabolite profiling and bioactivity assessment of five Artemisia species collected from northeastern Romania (A. absinthium L., A. annua L., A. austriaca Jacq., A. pontica L. and A. vulgaris L.). Liquid chromatography–tandem high-resolution mass spectrometry (LC-HRMS/MS) analysis of methanol and chloroform extracts obtained from the roots and aerial parts of the plants led to the identification of 15 phenolic acids (mostly hydroxycinnamic acid derivatives), 26 flavonoids (poly-hydroxylated/poly-methoxylated flavone derivatives, present only in the aerial parts), 14 sesquiterpene lactones, 3 coumarins, 1 lignan and 7 fatty acids. Clustered image map (CIM) analysis of the phytochemical profiles revealed that A. annua was similar to A. absinthium and that A. pontica was similar to A. austriaca, whereas A. vulgaris represented a cluster of its own. Correlated with their total phenolic contents, the methanol extracts from both parts of the plants showed the highest antioxidant effects, as assessed by the DPPH and ABTS radical scavenging, CUPRAC, FRAP and total antioxidant capacity methods. Artemisia extracts proved to be promising sources of enzyme inhibitory agents, with the methanol aerial part extracts being the most active samples against acetylcholinesterase and glucosidase. All Artemisia samples displayed good antibacterial effects against Mycobacterium tuberculosis H37Ra, with MIC values of 64–256 mg/L. In conclusion, the investigated Artemisia species proved to be rich sources of bioactives endowed with antioxidant, enzyme inhibitory and anti-mycobacterial properties. Full article

The O-methylation of specialized metabolites in plants is a unique decoration that provides structural and functional diversity of the metabolites with changes in chemical properties and intracellular localizations. The O-methylation of flavonoids, which is a class of plant specialized metabolites, promotes their antimicrobial activities and liposolubility. Flavonoid O-methyltransferases (FOMTs), which are responsible for the O-methylation process of the flavonoid aglycone, generally accept a broad range of substrates across flavones, flavonols and lignin precursors, with different substrate preferences. Therefore, the characterization of FOMTs with the physiology roles of methoxylated flavonoids is useful for crop improvement and metabolic engineering. In this review, we summarized the chemodiversity and physiology roles of methoxylated flavonoids, which were already reported, and we performed a cross-species comparison to illustrate an overview of diversification and conserved catalytic sites of the flavonoid O-methyltransferases. Full article

Several medical plants, such as Passiflora incarnata L., contain C-glycosylated flavonoids, which may contribute to their efficacy. Information regarding the bioavailability and metabolism of these compounds is essential, but not sufficiently available. Therefore, the metabolism of the C-glycosylated flavones orientin, isoorientin, schaftoside, isoschaftoside, vitexin, and isovitexin was investigated using the Caco-2 cell line as an in vitro intestinal and epithelial metabolism model. Isovitexin, orientin, and isoorientin showed broad ranges of phase I and II metabolites containing hydroxylated, methoxylated, and sulfated compounds, whereas schaftoside, isoschaftoside, and vitexin underwent poor metabolism. All metabolites were identified via UHPLC-MS or UHPLC-MS/MS using compound libraries containing all conceivable metabolites. Some structures were confirmed via UHPLC-MS experiments with reference compounds after a cleavage reaction using glucuronidase and sulfatase. Of particular interest is the observed cleavage of the C–C bonds between sugar and aglycone residues in isovitexin, orientin, and isoorientin, resulting in unexpected glucuronidated or sulfated luteolin and apigenin derivatives. These findings indicate that C-glycosidic flavones can be highly metabolized in the intestine. In particular, flavonoids with ortho-dihydroxy groups showed sulfated metabolites. The identified glucuronidated or sulfated aglycones demonstrate that enzymes expressed by Caco-2 cells are able to potentially cleave C–C bonds in vitro. Full article

Cytotoxic flavonoids of Murraya tetramera were investigated in this study. A novel flavonoid and twelve known flavonoids, including seven flavones (1–7), three flavanones (8–10), and three chalcones (11–13) were isolated from the leaves and twigs of Murraya tetramera. Chemical structures were elucidated by NMR combined with MS spectral analysis, and the new compound (6) was confirmed as 3′,5′-dihydroxy-5,6,7,4′-tetramethoxyflavone. Furthermore, all the isolated flavonoids were evaluated for their cytotoxicities against murine melanoma cells (B16), and human breast cancer cells (MDA-MB-231) by CCK-8 assay. Among them, compounds 7, 13, and 5 exhibited potent cytotoxic activities against B16 cell lines (IC₅₀ = 3.87, 7.00 and 8.66 μg/mL, respectively). Compounds 5, 13, and 12 displayed potent cytotoxicities against MDA-MB-231 cell lines (IC₅₀ = 3.80, 5.95 and 7.89 μg/mL, respectively). According to the correlation of the structure and activity analysis, 5-hydroxyl and 8-methoxyl substituents of the flavone, 8-methoxyl substituent of the flavanone, and 3′,5′-methoxyl substituents of the chalcone could be critical factors of the high cytotoxicity. The results indicated that the active flavonoids have potential to be developed as leading compounds for treating cancers. Full article

We investigated the effect of 21 flavonoids in a three-dimensional in vitro system for their ability to inhibit gap formation by MCF-7 breast cancer spheroids in monolayers of lymphendothelial cells. Different representatives of the classes of flavones, flavonols, and flavanones were tested in the circular chemorepellent-induced defects (CCID)-assay. Bay11-7082, a known inhibitor of CCID formation served as the positive control. This study provides the first comparison of the potential of flavonoids to suppress features influencing the intravasation of MCF-7 breast cancer cells aggregates through the lymph endothelial barrier. The most significant effects were seen after incubation with the flavones luteolin, chrysin, and apigenin. Additional hydroxylation or methoxylation in positions 6 or 8, as expected, resulted in decreased activity. The tested flavanones remained without or low efficacy. Full article

Various flavonoid derivatives including methoxylated flavones display remarkable biological activities. Chrysoeriol is a methoxylated flavone of great scientific interest because of its promising anti-microbial activities against various Gram-negative and Gram-positive bacteria. Sustainable production of such compounds is therefore of pronounced interest to biotechnologists in the pharmaceutical and nutraceutical industries. Here, we used a sugar O-methyltransferase enzyme from a spinosyn biosynthesis gene cluster of Saccharopolyspora spinosa to regioselectively produce chrysoeriol (15% conversion of luteolin; 30 µM) in a microbial host. The biosynthesized chrysoeriol was structurally characterized using high-resolution mass spectrometry and various nuclear magnetic resonance analyses. Moreover, the molecule was investigated against 17 superbugs, including thirteen Gram-positive and four Gram-negative pathogens, for anti-microbial effects. Chrysoeriol exhibited antimicrobial activity against nine pathogens in a disc diffusion assay at the concentration of 40 µg per disc. It has minimum inhibitory concentration (MIC) values of 1.25 µg/mL against a methicillin-resistant Staphylococcus aureus 3640 (MRSA) for which the parent luteolin has an MIC value of sixteen-fold higher concentration (i.e., 20 µg/mL). Similarly, chrysoeriol showed better anti-microbial activity (~1.7-fold lower MIC value) than luteolin against Proteus hauseri, a Gram-negative pathogen. In contrast, a luteolin 4′-O-methylated derivative, diosmetin, did not exhibit any anti-microbial activities against any tested pathogen. Full article

Chemical studies of Praxelis clematidea R.M. King & Robinson resulted in the isolation of six flavones: Apigenine, genkwanine, 7,4’-dimethylapigenin, trimethylapigenin,cirsimaritin and tetramethylscutellarein, which were tested for their toxicity against Staphylococcus aureus SA-1199B, a strain possessing the NorA efflux pump. Efflux pumps are integral proteins of the bacterial membrane and are recognized as one of the main causes of bacterial drug resistance, since they expel antibiotics from the cell. The inhibition of this transporter is one form of modulating bacterial resistance to antimicrobial drugs. The flavones tested did not show any significant antibacterial activity against the Staphylococcus aureus strain used, but were able to modulate bacterial drug resistance. This property might be related to the degree of lipophilicity of the flavones conferred by the methoxyl groups, since 4’,5,6,7 tetramethoxyflavone the most methoxylated compound, reduced the minimal inhibitory concentration of the drug 16-fold. Full article