Diarylheptanoid glycosides from Tacca plantaginea and their effects on NF-κB activation and PPAR transcriptional activity

• Published in: Bioorganic & medicinal chemistry letters 2012-11, Vol.22 (21), p.6681-6687
• Main Authors: Quang, Tran Hong, Ngan, Nguyen Thi Thanh, Minh, Chau Van, Kiem, Phan Van, Yen, Pham Hai, Tai, Bui Huu, Nhiem, Nguyen Xuan, Thao, Nguyen Phuong, Anh, Hoang Le Tuan, Luyen, Bui Thi Thuy, Yang, Seo Young, Choi, Chun Whan, Kim, Young Ho
• Format: Article
• Language: English
• Subjects: Antimetabolites - chemistry; Antimetabolites - pharmacology; Biological and medical sciences; chemistry; chromatography; Diarylheptanoid glycoside; Diarylheptanoids - chemistry; Diarylheptanoids - pharmacology; Dioscoreaceae - chemistry; Enzyme Activation - drug effects; fractionation; GAL-4-PPAR chimera assay; General pharmacology; glycosides; Glycosides - chemistry; Glycosides - pharmacology; Hep G2 Cells; human cell lines; Humans; inhibitory concentration 50; Magnetic Resonance Spectroscopy; Medical sciences; medicinal plants; metabolic diseases; methanol; Methanol - chemistry; Molecular Structure; NF-kappa B - metabolism; NF-κB-luciferase assay; Peroxisome Proliferator-Activated Receptors - metabolism; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Plantagineoside; PPRE-luciferase assay; screening; spectroscopy; Tacca; Tacca plantaginea; transcription (genetics); transcription factor NF-kappa B; Transcription, Genetic - drug effects
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2012.08.099

Three new diarylheptanoid glycosides, plantagineosides A–C (1–3), and three known compounds (4–6) were isolated from the whole plant of Tacca plantaginea. Compounds 3–6 significantly inhibited TNFα-induced NF-κB transcriptional activity in HepG2 cells with IC50 values ranging from 0.9 to 9.4μM. Compounds 1–6 significantly activated the transcriptional activity of PPARs with EC50 values ranging from 0.30 to 10.4μM. In addition, the transactivational effects of compounds 1–6 were evaluated on three individual PPAR subtypes, including PPARα, γ, and β(δ). In the screening search for NF-κB inhibitory and PPAR transactivational agents from medicinal plants, a methanol extract of the whole plant of Tacca plantaginea and its aqueous fraction showed the significant activities. Bioassay-guided fractionation combined with repeated chromatographic separation of the aqueous fraction of the methanol extract of T. plantaginea resulted in the isolation of two new diarylheptanoid glycosides, plantagineosides A (1) and B (2), an unusual new cyclic diarylheptanoid glycoside, plantagineoside C (3), and three known compounds (4–6). Their structures were determined by extensive spectroscopic and chemical methods. Compounds 3–6 significantly inhibited TNFα-induced NF-κB transcriptional activity in HepG2 cells in a dose-dependent manner, with IC50 values ranging from 0.9 to 9.4μM. Compounds 1–6 significantly activated the transcriptional activity of PPARs in a dose-dependent manner, with EC50 values ranging from 0.30 to 10.4μM. In addition, the transactivational effects of compounds 1–6 were evaluated on three individual PPAR subtypes, including PPARα, γ, and β(δ). Compounds 1–6 significantly enhanced the transcriptional activity of PPARβ(δ), with EC50 values in a range of 11.0–30.1μM. These data provide the rationale for using T. plantaginea and its components for the prevention and treatment of inflammatory and metabolic diseases.