Diversity of Adenostemma lavenia, multi-potential herbs, and its kaurenoic acid composition between Japan and Taiwan

Adenostemma lavenia (L.) Kuntze (Asteraceae) is widely distributed in tropical regions of East Asia, and both A. lavenia and A. madurense (DC) are distributed in Japan. In China and Taiwan, A. lavenia is used as a folk medicine for treating lung congestion, pneumonia, and hepatitis. However, neither phylogenic nor biochemical analysis of this plants has been performed to date. We have reported that the aqueous extract of Japanese A. lavenia contained high levels of ent-11 alpha-hydroxy-15-oxo-kaur-16-en-19-oic acid (11 alpha OH-KA; a kaurenoic acid), which is a potent anti-melanogenic compound. Comparison of chloroplast DNA sequences suggested that A. lavenia is originated from A. madurense. Analyses of kaurenoic acids revealed that Japanese A. lavenia and A. madurense contained high levels of 11 alpha OH-KA and moderate levels of 11 alpha,15OH-KA, while Taiwanese A. lavenia mainly contained 9,11 alpha OH-KA. The diverse biological activities (downregulation of Tyr, tyrosinase, gene expression [anti-melanogenic] and iNOS, inducible nitric oxide synthase, gene expression [anti-inflammatory], and upregulation of HO-1, heme-oxygenase, gene expression [anti-oxidative]) were associated with 11 alpha OH-KA and 9,11 alpha OH-KA but not with 11 alpha,15OH-KA. Additionally, 11 alpha OH-KA and 9,11 alpha OH-KA decreased Keap1 (Kelch-like ECH-associated protein 1) protein levels, which was accompanied by upregulation of protein level and transcriptional activity of Nrf2 (NF-E2-related factor-2) followed by HO-1 gene expression. 11 alpha OH-KA and 9,11 alpha OH-KA differ from 11 alpha,15OH-KA in terms of the presence of a ketone (alpha beta-unsaturated carbonyl group, a thiol modulator) at the 15(th) position; therefore, thiol moieties on the target proteins, including Keap1, may be important for the biological activities of 11 alpha OH-KA and 9,11 alpha OH-KA and A. lavenia extract. [GRAPHICS] .

Automated summary

Adenostemma lavenia is a widely distributed traditional herbal medicine in East Asia, with different chemical compositions and diverse biological activities in different regions. Chemical analysis revealed high levels of specific compounds in Japanese A. lavenia that showed potent anti-melanogenic effects, while Taiwanese A. lavenia contained different compounds with various biological properties such as anti-inflammatory and anti-oxidative effects. The presence of thiol moieties on target proteins may be crucial for the biological activities of specific compounds found in A. lavenia.