Oleanane-type triterpene saponins from the bark of Aralia elata and their NF-κB inhibition and PPAR activation signal pathway

• Published in: Bioorganic & medicinal chemistry letters 2011-10, Vol.21 (20), p.6143-6147
• Main Authors: Nhiem, Nguyen Xuan, Lim, Ho Young, Kiem, Phan Van, Minh, Chau Van, Thu, Vu Kim, Tai, Bui Huu, Quang, Tran Hong, Song, Seok Bean, Kim, Young Ho
• Format: Article
• Language: English
• Subjects: Anti-Infective Agents - chemistry; Anti-Infective Agents - isolation & purification; Anti-Infective Agents - pharmacology; anti-inflammatory activity; Aralia - chemistry; Aralia elata; Araliaceae; bark; Biological and medical sciences; chemical structure; COX-2; Elatoside L; General pharmacology; Hep G2 Cells; human cell lines; Humans; inducible nitric oxide synthase; inhibitory concentration 50; iNOS; luciferase; Medical sciences; messenger RNA; NF-kappa B - antagonists & inhibitors; NF-kappa B - immunology; NF-κB; Oleanane-type saponin; Oleanolic Acid - chemistry; Oleanolic Acid - isolation & purification; Oleanolic Acid - pharmacology; Peroxisome Proliferator-Activated Receptors - immunology; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Plant Bark - chemistry; PPAR; Saponins - chemistry; Saponins - isolation & purification; Saponins - pharmacology; signal transduction; Tarasaponin IV; transcription factor NF-kappa B; transcriptional activation; triterpenoid saponins; tumor necrosis factor-alpha
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.08.024

Phytochemical investigation resulted in isolation two new oleanane-type triterpene saponins, tarasaponin IV ( 1) and elatoside L ( 2), and four known compounds from the bark of Aralia elata. Their NF-κB and activation of PPARs in HepG2 cells inhibitory activities were evaluated for using luciferase reporter system. As results, compounds 2 and 4 were found to inhibit NF-κB activation stimulated by TNFα in a dose-dependent manner with IC 50 values of 4.1 and 9.5 μM, respectively, when compared with that of positive control, sulfasalazine (0.9 μM). Compounds 2 and 4 also inhibited TNFα-induced expression of iNOS and COX-2 mRNA. Compounds 4– 6 significantly increased PPARγ transactivation. However, compounds ( 4– 6) did not activate in any other PPAR subtypes. Two new oleanane-type triterpene saponins, tarasaponin IV ( 1) and elatoside L ( 2), and four known; stipuleanoside R 2 ( 3), kalopanax-saponin F ( 4), kalopanax-saponin F methylester ( 5), and elatoside D ( 6) were isolated from the bark of Aralia elata. Kalopanax-saponin F methyl ester was isolated from nature for the first time. Their chemical structures were elucidated using the chemical and physical methods as well as good agreement with those of reported in the literature. Oleanane-type triterpene saponins are the main component of A. elata. All compounds were investigated the anti-inflammatory activity. We measured their inhibition of NF-κB and activation of PPARs activities in HepG2 cells using luciferase reporter system. As results, compounds 2 and 4 were found to inhibit NF-κB activation stimulated by TNFα in a dose-dependent manner with IC 50 values of 4.1 and 9.5 μM, respectively, when compared with that of positive control, sulfasalazine (0.9 μM). Compounds 2 and 4 also inhibited TNFα-induced expression of iNOS and COX-2 mRNA. Furthermore, compounds 1– 6 were evaluated PPAR activity using PPAR subtype transactivation assays. Among of them, compounds 4– 6 significantly increased PPARγ transactivation. However, compounds 4– 6 did not activate in any other PPAR subtypes.