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.
Adenocarcinoma ; Animals ; Body Weight ; Cisplatin ; Creatinine ; Eosinophils ; Female ; Humans ; Liver ; Male ; Melia ; Melia azedarach ; Mice ; Neutrophils ; Veins

OBJECTIVETo investigate the antibacterial potential of the polar and non-polar extracts of the seeds of Melia azedarach (M. azedarach) L. (Meliaceae) against eighteen hospital isolated human pathogenic bacterial strains.

METHODSPetrol, benzene, ethyl acetate, methanol, and aqueous extracts at five different concentrations (1, 2, 5, 10 and 15 mg/mL) were evaluated. Disk diffusion method was followed to evaluate the antibacterial efficacy.

RESULTSAll extracts of the seeds demonstrated significant antibacterial activity against tested pathogens. Among all extracts, ethyl acetate extract revealed the highest inhibition comparatively. The present study also favored the traditional uses reported earlier.

CONCLUSIONSResults of this study strongly confirm that the seed extracts of M. azedarach could be effective antibiotics, both in controlling gram-positive and gram-negative human pathogenic infections.

Anti-Bacterial Agents ; isolation & purification ; pharmacology ; Bacteria ; drug effects ; isolation & purification ; Bacterial Infections ; microbiology ; Cross Infection ; microbiology ; Humans ; Melia azedarach ; chemistry ; Microbial Sensitivity Tests ; Plant Extracts ; isolation & purification ; pharmacology ; Seeds ; chemistry

Two new furan fragment isomerized limonoids, meliazedalides A and B (compounds 1 and 2), were isolated from the fruits of Melia azedarach Linn.. Their chemical structures were elucidated on the basis of HR-ESI-MS and 1D and 2D NMR data, which belonged to nimbolinin- and trichilin-class, respectively. Compound 2 exhibited weak inhibitory effect on NO production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages with IC being 37.41 μmol·L.
Animals ; Anti-Inflammatory Agents ; chemistry ; isolation & purification ; pharmacology ; Drugs, Chinese Herbal ; chemistry ; Fruit ; chemistry ; Limonins ; chemistry ; isolation & purification ; pharmacology ; Macrophages ; drug effects ; metabolism ; Melia azedarach ; chemistry ; Mice ; Molecular Structure ; Nitric Oxide ; metabolism ; RAW 264.7 Cells

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.
Drugs, Chinese Herbal ; Ethanol ; Helicobacter ; Helicobacter pylori ; Magnolia ; Melia ; Plants, Medicinal ; Stomach Neoplasms ; Stomach Ulcer

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.
Animals ; Ethanol ; Gerbillinae ; Helicobacter ; Helicobacter pylori ; Humans ; Mass Screening ; Melia ; Plants ; Plants, Medicinal ; Stomach Ulcer ; Urease

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.
Fruit ; chemistry ; Limonins ; chemistry ; isolation & purification ; Melia ; chemistry ; Molecular Structure ; Plants, Medicinal ; chemistry

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.
Animals ; Asian Continental Ancestry Group ; Communicable Diseases ; Congenital Abnormalities ; Ethanol* ; HeLa Cells ; Humans ; Liver ; Mass Screening ; Melia* ; Mice ; Plants ; Plants, Medicinal ; Rats ; Sulfadiazine ; Toxoplasma ; Toxoplasmosis

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.
Chromatography, High Pressure Liquid ; Drug-Related Side Effects and Adverse Reactions ; Drugs, Chinese Herbal ; chemistry ; toxicity ; Fruit ; chemistry ; Hep G2 Cells ; Humans ; Liver ; drug effects ; Melia ; chemistry

OBJECTIVETo 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.

METHODAn 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.

RESULTThe 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.

CONCLUSIONThe 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.

Animals ; Corydalis ; chemistry ; Drugs, Chinese Herbal ; metabolism ; pharmacokinetics ; Humans ; Intestinal Absorption ; Intestines ; metabolism ; Male ; Melia ; chemistry ; Models, Animal ; Powders ; pharmacokinetics ; Rats ; Rats, Wistar

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.
Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Limonins ; isolation & purification ; Melia ; chemistry ; Molecular Structure ; Plant Bark ; chemistry ; Plant Extracts ; chemistry ; isolation & purification ; pharmacology ; X-Ray Diffraction