ABSTRACT
Two new limonoids, 12-ethoxynimbolinins G and H (compounds 1 and 2), and one known compound, toosendanin (Chuanliansu) (compound 3), were isolated from the bark of Melia toosendan. Their structures were elucidated by spectroscopic analysis and X-ray techniques. The absolute configuration of toosendanin (3) was established by single-crystal X-ray diffraction. Compounds 1-3 were evaluated for their cytotoxicity against five tumor cell lines.
Subject(s)
Humans , Cell Line, Tumor , Cell Proliferation , Limonins , Melia , Chemistry , Molecular Structure , Plant Bark , Chemistry , Plant Extracts , Chemistry , Pharmacology , X-Ray DiffractionABSTRACT
Two new limonoids, 12-ethoxynimbolinins G and H (compounds 1 and 2), and one known compound, toosendanin (Chuanliansu) (compound 3), were isolated from the bark of Melia toosendan. Their structures were elucidated by spectroscopic analysis and X-ray techniques. The absolute configuration of toosendanin (3) was established by single-crystal X-ray diffraction. Compounds 1-3 were evaluated for their cytotoxicity against five tumor cell lines.
Subject(s)
Humans , Cell Line, Tumor , Cell Proliferation , Limonins , Melia , Chemistry , Molecular Structure , Plant Bark , Chemistry , Plant Extracts , Chemistry , Pharmacology , X-Ray DiffractionABSTRACT
<p><b>OBJECTIVE</b>Myanmar has a long history of using medicinal plants for treatment of various diseases. To the best of our knowledge there are no previous reports on antiglycation activities of medicinal plants from Myanmar. Therefore, this study was aimed to evaluate the antioxidant, antiglycation and antimicrobial properties of 20 ethanolic extracts from 17 medicinal plants indigenous to Myanmar.</p><p><b>METHODS</b>In vitro scavenging assays of 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), superoxide (SO) radicals were used to determine the antioxidant activities. Folin-Ciocalteu's method was performed to determine the total phenolic content. Antiglycation and antimicrobial activities were detected by bovine serum albumin-fluorescent assay and agar well diffusion method.</p><p><b>RESULTS</b>Terminalia chebula Retz. (Fruit), containing the highest total phenolic content, showed high antioxidant activities with inhibition of 77.98% ± 0.92%, 88.95% ± 2.42%, 88.56% ± 1.87% and 70.74%± 2.57% for DPPH, NO, SO assays and antiglycation activity respectively. It also showed the antimicrobial activities against Staphylococcus aureus, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans with inhibition zone of 19, 18, 17, 25 and 15 mm, respectively. Garcinia mangostana Linn. showed the strongest activities for SO and antiglycation assays with inhibition of 93.68% ± 2.63% and 82.37% ± 1.78%. Bark of Melia sp. was the best NO radical scavenger with inhibition rate of 89.39%± 0.60%.</p><p><b>CONCLUSION</b>The results suggest that these plants are potential sources of antioxidants with free radical-scavenging and antiglycation activities and could be useful for decreasing the oxidative stress and glycation end-product formation in glycation-related diseases.</p>
Subject(s)
Humans , Anti-Bacterial Agents , Pharmacology , Anti-Infective Agents , Pharmacology , Antioxidants , Pharmacology , Bacteria , Biphenyl Compounds , Metabolism , Candida albicans , Fruit , Garcinia , Chemistry , Glycation End Products, Advanced , Metabolism , Magnoliopsida , Chemistry , Medicine, Traditional , Melia , Chemistry , Myanmar , Nitric Oxide , Metabolism , Oxidative Stress , Phenols , Pharmacology , Phytotherapy , Picrates , Metabolism , Plant Bark , Plant Extracts , Chemistry , Pharmacology , Plants, Medicinal , Superoxides , Terminalia , ChemistryABSTRACT
In the present study, two new limonoids, 1α, 7α-dihydroxyl-3α-acetoxyl-12α-ethoxylnimbolinin (1) and 1α-tigloyloxy-3α-acetoxyl-7α-hydroxyl-12β-ethoxylnimbolinin (2), together with other four known limonoids (3-6), were isolated from the fruits of Melia toosendan. Their structures were elucidated by means of extensive spectroscopic analyses (NMR and ESI-MS) and comparisons with the data reported in the literature. The isolated compounds were evaluated for their antibacterial activities. Compound 4 exhibited significant antibacterial activity against an oral pathogen, Porphyromonas gingivalis ATCC 33277, with an MIC value of 15.2 μg·mL(-1). Compound 2 was also active against P. gingivalis ATCC 33277, with an MIC value of 31.25 μg·mL(-1). In conlcusion, our resutls indicate that these compounds may provide a basis for future development of novel antibiotics.
Subject(s)
Anti-Bacterial Agents , Chemistry , Pharmacology , Drugs, Chinese Herbal , Chemistry , Fruit , Chemistry , Limonins , Chemistry , Magnetic Resonance Spectroscopy , Melia , Chemistry , Molecular Structure , Porphyromonas gingivalis , Spectrometry, Mass, Electrospray IonizationABSTRACT
<p><b>OBJECTIVE</b>To investigate the anti-cancer effects of crude extract from Melia toosendan Sieb. et Zucc and its possible molecular mechanisms in vitro and in vivo.</p><p><b>METHODS</b>Transonic alcohol-chloroform extraction method was used to extract toosendanin from the bark of Melia toosendan Sieb. et Zucc, and the content of toosendanin in the crude extract was measured by high performance liquid chromatography (HPLC). Anti-cancer effects of crude extract from Melia toosendan Sieb. et Zucc were investigated in in vivo and in vitro studies. In the in vitro experiment, human hepatocellular carcinoma cell lines SMMC-7721 and Hep3B were co-incubated with toosendanin crude extract of different concentrations, respectively. In the in vivo experiment, BALB/c mice were subcutaneously inoculated with mouse hepatocellular carcinoma H22 cells and treated with crude extract.</p><p><b>RESULTS</b>HPLC revealed the content of toosendanin was about 15%. Crude extract from Melia toosendan Sieb. et Zucc inhibited cancer cells growth in a dose- and time-dependent manner. The 50% inhibitory concentration (IC50, 72 h) was 0.6 mg/L for SMMC-7721 cells and 0.8 mg/L for Hep3B cells. Both high-dose [0.69 mg/(kg d)] and low-dose [0.138 mg/(kg d)] crude extract could markedly suppress cancer growth, and the inhibition rate was greater than 50%. Hematoxylin and eosin staining showed necrotic area in cancers and transmission electron microscopy displayed necrotic and apoptotic cancer cells with apoptotic bodies. Immunohistochemistry showed that the expression of Bax and Fas increased and the expression of Bcl-2 reduced.</p><p><b>CONCLUSIONS</b>Toosendanin extract has potent anti-cancer effects via suppressing proliferation and inducing apoptosis of cancer cells in vivo and in vitro. The mechanism of apoptosis involves in mitochondrial pathway and death receptor pathway.</p>
Subject(s)
Animals , Female , Male , Antineoplastic Agents , Pharmacology , Therapeutic Uses , Apoptosis , Carcinoma, Hepatocellular , Drug Therapy , Pathology , Cell Proliferation , Drugs, Chinese Herbal , Chemistry , Pharmacology , Therapeutic Uses , Immunohistochemistry , Liver Neoplasms , Drug Therapy , Pathology , Melia , Chemistry , Mice, Inbred BALB C , Mitochondria , Metabolism , Neoplasm Transplantation , Plant Extracts , Therapeutic Uses , Reference Standards , bcl-2-Associated X Protein , Metabolism , fas Receptor , MetabolismABSTRACT
Toxoplasmosis is an important cause of foodborne, inflammatory, as well as congenital abnormalities. There is an urgent need for safe and effective therapies to eliminate or treat this cosmopolitan infectious disease. A medicinal herbal plant, Meliae fructus, has been used to soothe the liver and kills worms in Chinese medicine. In this study, Meliae fructus ethanol extract was examined and screened for its anti-T. gondii activity. For anti-T. gondii activity screening, in vitro study of Meliae fructus extract using tachyzoit of T. gondii RH strain-infected HeLa cells was performed. Further, in vivo anti-T. gondii study using a mouse infection model was conducted. Safety of herbal compounds was evaluated in SD rats by treatment with Meliae fructus extract for 28 days. As a result, selectivity of Meliae fructus ethanol extract was 5.85, which was higher than sulfadiazine selectivity (2.06). We also performed an in vivo study to evaluate the anti-T. gondii activity of Meliae fructus extract in a mouse model. The inhibition rate of Meliae fructus extract was as high as that of sulfadiazine. These results demonstrate that Meliae fructus can successfully cure T. gondii infection and could be a promising native herb treatment for prevention of T. gondii infection.
Subject(s)
Animals , Humans , Mice , Rats , Asian People , Communicable Diseases , Congenital Abnormalities , Ethanol , HeLa Cells , Liver , Mass Screening , Melia , Plants , Plants, Medicinal , Sulfadiazine , Toxoplasma , ToxoplasmosisABSTRACT
Fluorescein diacetate-labeled HepG2 cells model and flouresence automatic microscopy screening assay were used for fast screening 23 components from Toosendan Fructus, in which 5 components showed significant toxicity on HepG2 cells. The 10 compounds in the 2 components were tentatively identified with LC-MS(n), and 3 of them (meliasenin B, trichilinin D and 1-O-tigloy-1-O-debenzoylohchinal) were prepared and identified. Further experiments showed that the 3 compounds displayed dose-dependent toxicity on HepG2 cells, suggesting that these compounds in Toosendan Fructus may cause hepatotoxicity.
Subject(s)
Humans , Chromatography, High Pressure Liquid , Drug-Related Side Effects and Adverse Reactions , Drugs, Chinese Herbal , Chemistry , Toxicity , Fruit , Chemistry , Hep G2 Cells , Liver , Melia , ChemistryABSTRACT
Infection with Helicobacter (H.) pylori is strongly associated with duodenal and gastric ulcers. Substantial epidemiological data has revealed that high rates of H. pylori infection might be related to high rates of gastric cancer. In this study, a medicinal herbal extracts were examined and screened for anti-H. pylori activity. Seventy percent ethanol was used for herbal extraction. For anti-H. pylori activity study, the inhibitory zone tests with 74 herbal compounds were conducted. As the results, thirteen compounds including Cinnamomi Cortex, Magnoliae Cortex and Meliae Fructus were revealed strong anti-H. pylori activities.
Subject(s)
Drugs, Chinese Herbal , Ethanol , Helicobacter , Helicobacter pylori , Magnolia , Melia , Plants, Medicinal , Stomach Neoplasms , Stomach UlcerABSTRACT
Colorectal cancer is one of the leading causes of death in the world. Plant-derived products have proven to be valuable sources for discovery and development of unique anticancer drugs. In this study, the inhibitory effects of ethanolic extract of Melia toosendan fruit (EMTF), a traditional medicine in the Chinese Pharmacopeia were evaluated in vitro and in vivo against colon cancer. Human colon cancer cells SW480 and murine colorectal adenocarcinoma cells CT26 were used to investigate cell proliferation. The results showed that EMTF inhibited cell proliferation of SW480 and CT26 by promoting apoptosis as indicated by nuclear chromatin condensation and DNA fragmentation. Through increasing mitochondrial membrane permeability and cytochrome c release from mitochondria, EMTF induced caspase-9 activity which further activated caspase-3 and poly(ADP-ribose) polymerase cleavage, leading the tumor cells to apoptosis. The in vivo results confirmed reduction of tumor volume and apoptotic effects and the side effects were not induced by EMTF. Therefore, EMTF may be an effective chemotherapeutic agent for colon cancer treatment.
Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/enzymology , Adenocarcinoma/pathology , Animals , Apoptosis/drug effects , Caspase 3/metabolism , Caspase 9/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Colonic Neoplasms/drug therapy , Colonic Neoplasms/enzymology , Colonic Neoplasms/pathology , Cytochromes c/metabolism , Female , Fruit/metabolism , Humans , Melia/chemistry , Membrane Potential, Mitochondrial/drug effects , Mice , Mice, Inbred BALB C , Mitochondria/drug effects , Mitochondria/metabolism , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Poly(ADP-ribose) Polymerases/metabolism , Xenograft Model Antitumor AssaysABSTRACT
El trabajo tuvo como objetivo evaluar la actividad antibacteriana de extractos de hojas de Melia azedarach L. sobre seis bacterias patógenas. Inicialmente mediante extracción por el método Soxhlet se obtuvo extracto total en etanol y a partir de éste se prepararon fracciones líquido-líquido con éter de petróleo y acetato de etilo. El extracto total y las dos fracciones fueron diluidos a diferentes concentraciones (ppm) para evaluar in vitro su actividad antibacteriana. Las bacterias de mayor susceptibilidad fueron las patógenas de humanos Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa y Klebsiella oxytoca, en relación a la fitopatógena Burkholderia glumae quien mostró resistencia a todos los tratamientos. Las bacterias patógenas fueron más susceptibles a la fracción éter de petróleo a concentración mínima de 25 ppm. El screen fitoquímico de la planta indicó presencia de metabolitos secundarios tipo alcaloides, terpenos/esteroles, saponinas, taninos y antocianinas. Estos resultados evidencian el posible uso de M. azederach como alternativa de control biológico sobre las bacterias analizadas.
The work was objective to evaluate the antibacterial activity of extracts from leaves of Melia azedarach (L) on six pathogenic bacteria. Total ethanol extract was obtained initially by extraction with method Soxhlet and from this prepared liquid-liquid fractions with petroleum ether and ethyl acetate. The total extract and the two fractions were diluted at different concentrations (ppm) to evaluate its antibacterial activity in vitro. More susceptible bacteria were the pathogenic human Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa and Klebsiella oxytoca, in relation to the plant pathogen Burkholderia glumae who showed resistance to all treatments. Pathogenic bacteria were more susceptible to the fraction of petroleum ether to the minimum concentration of 25 ppm. Screen plant phytochemical indicated presence of secondary metabolites type alkaloids, terpenes/sterols, saponins, tannins and anthocyanins. These results demonstrate the potential use of M. azederach as biological control alternatively on analysed bacterial.
Subject(s)
Azadirachta , Melia , Melia azedarach , Bacterial Growth , Burkholderia Infections , Enterococcus faecalis , Escherichia coli , Klebsiella oxytoca , Plant Leaves , Pseudomonas aeruginosaABSTRACT
<p><b>OBJECTIVE</b>To establish an absorption-metabolic model suitable for studying the complex traditional Chinese medicine (TCM) system, with the classic Jinlingzi Powder formula as the example, in order to explore the correlation among absorption behavior and absorption-metabolism behavior of different Jinlingzi Powder formulas and their compound compatibility.</p><p><b>METHOD</b>An absorption-metabolic model suitable for TCM study was established according to in vivo characteristics of drugs, to combine the intestinal absorption model with the liver microsomal metabolism model. A quantitative analysis was conduced for absorbable components of Jinlingzi Powder and its absorption-metabolism components by HPLC.</p><p><b>RESULT</b>The model could be used for studies on the absorption-metabolism process of TCM. Among the 15 main components which were derived from Jinlingzi Powder extracts, 10 could be absorbed by intestinal tract. A new component peak was shown after metabolism with the A-M model. The absorbable components of Jinlingzi Powder were related to its compatibility. Toosendan was found to be the major factor impacting the main component-absorption ratio (Ar) and absorption-metabolism ratio (Mr), followed by Rhizoma Corydalis.</p><p><b>CONCLUSION</b>The absorption-metabolism model suitable for studying the complex traditional Chinese medicine system was established and used for the study on compound compatibility of Jinglingzi Powder. The compatibility of the formula has an impact on absorbable component ratio of Jinlingzi Powder, which helps interpret the theory of formula compatibility from the angle of in vitro compound pharmacokinetics (the difference between absorption and metabolism). Toosendan is the main factor impacting overall absorption and absorption-metabolism, while Rhizoma Corydalis is the minor factor.</p>
Subject(s)
Animals , Humans , Male , Rats , Corydalis , Chemistry , Drugs, Chinese Herbal , Metabolism , Pharmacokinetics , Intestinal Absorption , Intestines , Metabolism , Melia , Chemistry , Models, Animal , Powders , Pharmacokinetics , Rats, WistarABSTRACT
In this study, the 4-week oral toxicity and anti-cancer activity of the hexane layer of Melia azedarach L. var. japonica Makino's bark extract were investigated. We carried out a hollow fiber (HF) assay and 28-day repeated toxicity study to confirm the anti-cancer effect and safety of the hexane layer. The HF assay was carried out using an A549 human adenocarcinoma cell via intraperitoneal (IP) site with or without cisplatin. In the result, the 200 mg/kg b.w of hexane layer with 4 mg/kg b.w of cisplatin treated group, showed the highest cytotoxicity aginst A549 carcinoma cells. For the 28-day repeated toxicity study, 6 groups of 10 male and female mice were given by gavage 200, 100, or 50 mg/kg b.w hexane layer with or without 4 mg/kg b.w of cisplatin against body weight, and were then sacrificed for blood and tissue sampling. The subacute oral toxicity study in mice with doses of 200, 100, and 50 mg/kg b.w hexane layer showed no significant changes in body weight gain and general behavior. The cisplatin-treated group significantly decreased in body weight compared to the control group but regained weight with 100 and 200 mg/kg b.w of hexane layer. The biochemical analysis showed significant increase in several parameters (ALT, total billirubin, AST, creatinine, and BUN) in cisplatin-treated groups. However, in the group given a co-treatment of hexane layer (200 mg/kg b.w), levels of these parameters decreased. In hematological analysis, cisplatin induced the reduction of WBCs and neutrophils but co-treatment with hexane layer (100 and 200 mg/kg b.w) improved these toxicities caused by cisplatin. The histological profile of the livers showed eosinophilic cell foci in central vein and portal triad in cisplatin treated mice. These results show that hexane layer might have an anti-cancer activity and could improve the toxicity of cisplatin.
Subject(s)
Animals , Female , Humans , Male , Mice , Adenocarcinoma , Body Weight , Cisplatin , Creatinine , Eosinophils , Liver , Melia , Melia azedarach , Neutrophils , VeinsABSTRACT
In this study, a medicinal herbal plant, Meliae fructus, was examined and screened for anti-Helicobacter (H.) pylori activity. Seventy percent ethanol was used for herbal extraction. For anti-H. pylori activity screening, inhibitory zone tests as an in vitro assay and in vivo study using a Mongolian gerbil (Meriones unguiculatus) model were performed. Also, the safety of herbal compounds was evaluated by animal study. As a result of inhibitory zone test, Meliae fructus extract demonstrated strong anti-H. pylori activities. Also, as results of in vivo animal studies, Meliae fructus demonstrated strong therapeutic effects against H. pylori infection according to the criteria of histological examination and rapid urease test. As results of the safety study, after 28 days treatment of the Meliae fructus extract, the animals were not detected any grossly and histological changes. These results demonstrate that it can be successfully cured against H. pylori infection and protected from H. pylori-induced pathology with Meliae fructus. It could be a promising native herbal treatment for patients with gastric complaints including gastric ulcer caused by H. pylori.
Subject(s)
Animals , Humans , Ethanol , Gerbillinae , Helicobacter , Helicobacter pylori , Mass Screening , Melia , Plants , Plants, Medicinal , Stomach Ulcer , UreaseABSTRACT
To study the chemical constituents of the fruits of Melia toosendan, three limonoids were isolated and purified by repeated silica gel column chromatography and preparative HPLC from the EtOAc extract of M. toosendan. Their structures were determined by their physico-chemical properties and spectroscopic data (1D-NMR, 2D-NMR) as: 24, 25, 26, 27-tetranorapotirucalla-(apoeupha)-1alpha-tigloyloxy-3alpha, 7alpha-dihydroxyl-12alpha-acetoxyl-14, 20, 22-trien-21, 23-epoxy-6, 28-epoxy (1), nimbolinin B (2), and trichilinin D (3), separately. Compound 1 is a new compound, and compound 2 is obtained from this plant for the first time.
Subject(s)
Fruit , Chemistry , Limonins , Chemistry , Melia , Chemistry , Molecular Structure , Plants, Medicinal , ChemistryABSTRACT
The gram-negative bacterium Helicobacter pylori [H. pylori], identified in 1982, is now recognized as the primary etiological factor associated with the development of gastritis and peptic ulcer disease. The growing problem of antibiotic resistance by the organism demands the search for novel compounds from plant based sources. The present study is aimed at evaluating the anti-Helicobacter pylori activity of 10 Iranian plant extracts on clinical isolates of H. pylori. Gastric biopsy samples were obtained from patients presenting with gastroduodenal complications. H. pylori was isolated from the specimens following standard microbiology procedures. The disk diffusion method was used to determine the susceptibility of 12 isolates to methanol plant extracts [Fruit and leaves of Melia azedarach, Melia indica and aerial parts of Stachys setifera, Stachys turcomanica, Stachys trinervis, Stachys subaphylla, Stachys byzanthina, Stachys persica, Stachys inflata, Stachys laxa]. The plants tested at 8 mg/disc concentration demonstrated anti-Helicobacter pylori activity with zone diameters of inhibition ranging from 12-38 mm. Of these, Stachys setifera [aerial parts], Melia indica [Fruit] and Melia azedarach [leaves] showed the most potent anti -H. pylori activity on the isolates. Due to the rise in antibiotic resistance, new sources of anti-H. pylori drugs are needed. The use of medicinal plants may have potential benefit in eradicating such problems. According to the results of this study, further studies will be necessary to investigate the effects of other plants of Iran against H. pylori infectio