Search

This present phytomedicinal study aims at both identifying the variety of the Croton cajucara lead molecule trans-dehydrocrotonin (DCTN), in all parts of 11/2 to 6 year old plants, and perform a general evaluation of its biological efficacy. In addition, the biochemical evaluation of trans-crotonin (CTN), trans-cajucarin B (t-CJC-B), cis-cajucarin B (c-CJC-B), acetyl aleuritolic acid (AAA), cajucarinolide (CJCR) and isocajucarinolide (ICJCR) were performed. The pharmacological action of bioactive extracts and semi-purified fractions of this Croton are discussed herein. The phytochemical investigation proved that only the stem bark of the mature plants (MP) is a rich source of DCTN (1.4% of dry bark), while 3- year-old plants contained only 0.26%. In young plants (YP) the triterpene AAA was the major component and in these the diterpene DCTN was not present. Phytochemical investigation of the C. cajucara stem bark yields AAA, CTN, DCTN, t-CJC-B, c-CJC-B, CJCR, ICJCR, trans-cajucarin A (t-CJC-A) and isosacacarin. In addition, the common metabolites 4-hydroxy-3-methoxy-benzoic acid (vanilic acid), 4- hydroxy-benzoic acid and 2-methylamino-3-(4-hydroxyphenyl)propanoic acid (N-methyltyrosine) were isolated. The structure elucidation of DCTN and CTN was revised using 600MHz NMR (nuclear magnetic resonance) spectrum, confirming their original structure. Synthetic transformation of DCTN afforded great amount of semi-synthetic CTN, CJCR and ICJCR derivatives, which were submitted to pharmacological experiments. Among the pharmacological experiments, DCTN and CTN were studied for their in vivo antitumor activities on Ehrlich carcinoma and Sarcoma 180 (S-180), and in vivo release was evaluated. The in vitro antiproliferative effects of DCTN and CTN were determined on the cultured Ehrlich carcinoma cells. The cytotoxic effects of CJCR, ICJCR, t-CJC-B, c-CJC-B, a tea preparation, and a MeOH extract were evaluated for human K562 leukemia and Ehrlich carcinoma cells. The tea preparation was also studied for its hepatotoxic effects on the weight variations and glutamic pyruvic transaminase (GPT) dosage in mice, in which GPT value variations revealed a dosage-response relation. The genotoxic action of DCTN was examined in Swiss mouse bone marrow cells in vivo, submitted to acute intraperitoneal treatment, by micronucleus (MN) and chromosomal aberration (CA) tests. Statistical analysis indicated that DCTN doses (50% and 75% of the LD50 via intraperitoneal or gavage treatments) were antimutagenic with regard to cyclophosphamide. The oral administration of DCTN and AAA (100 mg/kg) reduced gastrointestinal transit of mice and index of gastric mucosa damage (GMD) induced by cold stress. After pylorus ligature in rats, similar dose of DCTN decreased acid secretion and volume. These compounds (1 μM) also reduced the C-AP uptake induced by histamine (10-5 M); however, uniquely DCTN decreased the uptake induced by bethanechol. [ABSTRACT FROM AUTHOR]