Bioassay-Guided Isolation of Constituents of Piper sarmentosum Using a Mitochondrial Transmembrane Potential Assay

• Published in: Journal of natural products (Washington, D.C.) Vol. 74; no. 10; pp. 2193 - 2199
• Main Authors: Pan, Li, Matthew, Susan, Lantvit, Daniel D, Zhang, Xiaoli, Ninh, Tran Ngoc, Chai, Heebyung, Carcache de Blanco, Esperanza J, Soejarto, Djaja D, Swanson, Steven M, Kinghorn, A. Douglas
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society and American Society of Pharmacognosy 28.10.2011; Amer Chemical Soc; American Society of Pharmacognosy
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Biological and medical sciences; Chemistry, Medicinal; Drug Screening Assays, Antitumor; Flavones - chemistry; Flavones - isolation & purification; Flavones - pharmacology; General pharmacology; HL-60 Cells; HT29 Cells; Humans; Inhibitory Concentration 50; Life Sciences & Biomedicine; Medical sciences; Membrane Potentials - drug effects; Mitochondria - drug effects; Pharmacognosy. Homeopathy. Health food; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Piper - chemistry; Plant Sciences; Science & Technology; Vietnam; Asia; Vietnam; UVARIA-CHAMAE; APOPTOSIS; ROXB; ACID; AFRICANA BENTH OLIVER; CHEMICAL-CONSTITUENTS; C-BENZYLATED FLAVANONES; LEAVES; EXTRACT; Human; Piper sarmentosum; Pharmacognosy; Oriental medicine; Piperaceae; Enzyme inhibitor; Cytotoxicity; Flavonoid; Biological activity; Flavanone derivatives; Medicinal plant; Mitochondria; Cell line; Folk medicine; Dicotyledones; Proteasome inhibitor; Angiospermae; Plant origin; Isolation; Spermatophyta; Colon; Membrane potential; Tumor cell; Structural analysis
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np200557e

Bioassay-guided fractionation was conducted on a chloroform-soluble extract of the aerial parts of Piper sarmentosum collected in Vietnam, monitored by a mitochondrial transmembrane potential assay using HT-29 human colon cancer cells. This led to the isolation of four new C-benzylated dihydroflavones, sarmentosumins A–D (1–4), as well as 14 known compounds. The structures of the new compounds were elucidated on the basis of spectroscopic data interpretation. Among these compounds, 1–4 as well as five known C-benzylated dihydroflavones (5–9) and a piperamide, pipercallosine (11), were found to induce apoptosis in HT-29 cells by moderately reducing the mitochondrial transmembrane potential (ΔΨm), with ED50 values ranging from 1.6 to 13.6 μM. Furthermore, 7-methoxydichamanetin (8) and pinocembrin (10) exhibited proteasome inhibitory activities in a human 20S proteasome bioassay with IC50 values of 3.45 ± 0.18 and 2.87 ± 0.26 μM, respectively. This is the first time that C-benzylated dihydroflavones have been reported to demonstrate an apoptotic effect associated with disruption of the mitochondrial transmembrane potential.