Cytotoxic and Nitric Oxide Production‐Inhibitory Activities of Limonoids and Other Compounds from the Leaves and Bark of Melia azedarach |
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| Authors: | Xin Pan Masahiro Matsumoto Yuki Nishimoto Eri Ogihara Jie Zhang Motohiko Ukiya Harukuni Tokuda Kazuo Koike Momoko Akihisa Toshihiro Akihisa |
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| Affiliation: | 1. College of Science and Technology, Nihon University, 1‐8‐14 Kanda Surugadai, Chiyoda‐ku, Tokyo 101‐8308, Japan;2. Graduate School of Medical Science, Kanazawa University, 13‐1 Takara‐machi, Kanazawa 920‐1980, Japan;3. School of Pharmaceutical Sciences, Toho University, 2‐2‐1 Miyama, Funabashi‐shi, Chiba 274‐8510, Japan;4. Department of Endocrinology and Metabolism, Medical Hospital of Tokyo Medical and Dental University, 1‐5‐45 Yushima, Bunkyo‐ku, Tokyo 113‐8519, Japan;5. Akihisa Medical Clinic, 1086‐3 Kamo, Sanda‐shi, Hyogo 669‐1311, Japan, (fax: +81‐79‐5671980) |
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| Abstract: | Nine limonoids, 1 – 9 , one apocarotenoid, 11 , one alkaloid, 12 , and one steroid, 13 , from the leaf extract; and one triterpenoid, 10 , five steroids, 14 – 18 , and two flavonoids, 19 and 20 , from the bark extract of Melia azedarach L. (Chinaberry tree; Meliaceae) were isolated. Among these compounds, three compounds, 4 – 6 , were new, and their structures were established as 3‐deacetyl‐28‐oxosalannolactone, 3‐deacetyl‐28‐oxosalanninolide, and 3‐deacetyl‐17‐defurano‐17,28‐dioxosalannin, respectively, on the basis of extensive spectroscopic analyses and comparison with literature data. All of the isolated compounds were evaluated for their cytotoxic activities against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK‐BR‐3) cancer cell lines. 3‐Deacetyl‐4′‐demethyl‐28‐oxosalannin ( 3 ) against HL60 and AZ521 cells, and methyl kulonate ( 10 ) against HL60 cells exhibited potent cytotoxicities with IC50 values in the range of 2.8–5.8 μM . In addition, upon evaluation of compounds 1 – 13 against production of nitric oxide (NO) in mouse macrophage RAW 264.7 cells induced by lipopolysaccharide (LPS), seven, i.e., trichilinin B ( 1 ), 4 , ohchinin ( 7 ), 23‐hydroxyohchininolide ( 8 ), 21‐hydroxyisoohchininolide ( 9 ), 10 , and methyl indole 3‐carboxylate ( 12 ), inhibited production of NO with IC50 values in the range of 4.6–87.3 μM with no, or almost no, toxicity to the cells (IC50 93.2–100 μM ). Western blot analysis revealed that compound 7 reduced the expression levels of the inducible NO synthase (iNOS) and COX‐2 proteins in a concentration‐dependent manner. Furthermore, compounds 5, 6, 13 , and 18 – 20 exhibited potent inhibitory effects (IC50 299–381 molar ratio/32 pmol TPA) against Epstein? Barr virus early antigen (EBV‐EA) activation induced by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) in Raji cell line. |
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| Keywords: | Melia azedarach Limonoids Triterpenoids Cytotoxic activity NO Production‐inhibitory activity Epstein Barr virus early antigen |
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