Antihyperglycemic sesquiterpenes from Psacalium decompositum

• Published in: Journal of natural products (Washington, D.C.) Vol. 62; no. 8; pp. 1088 - 1092
• Main Authors: Inman, W.D, Luo, J, Jolad, S.D, King, S.R, Cooper, R
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.08.1999; Amer Chemical Soc; American Society of Pharmacognosy
• Subjects: Animals; Asteraceae; Asteraceae - chemistry; Biological and medical sciences; Blood Glucose - metabolism; Body Weight - drug effects; chemical constituents of plants; chemical structure; Chemistry, Medicinal; Chromatography, High Pressure Liquid; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Eating - drug effects; General pharmacology; hyperglycemia; hypoglycemic agents; Hypoglycemic Agents - isolation & purification; Hypoglycemic Agents - pharmacology; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; Medical sciences; medicinal plants; Mice; Mice, Inbred C57BL; Mice, Obese; Molecular Conformation; Pharmacognosy. Homeopathy. Health food; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Plant Sciences; roots; Science & Technology; Sesquiterpenes - isolation & purification; Sesquiterpenes - pharmacology; sesquiterpenoids; spectral analysis; Mexico; Central America; United States; North America; America; PLANTS; INHIBITION; Endocrinopathy; Relative configuration; Epimer; Oxygen heterocycle; Non insulin dependent diabetes; Medicinal plant; Hypoglycemic agent; Folk medicine; Sesquiterpenes; Aromatic compound; Terpenoid; Root; Pharmacognosy; Rodentia; Oral administration; Lactone; Tricyclic compound; Biological activity; Vertebrata; Chemotherapy; Experimental disease; Mammalia; Treatment; Mouse; Animal; Plant origin; Phenols; Isolation; Structural analysis
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np990023v

Psacalium decompositum was investigated for antihyperglycemic compounds using diabetic ob/ob mice as a model for type 2 diabetes. In vivo bioassay-guided fractionation of an aqueous extract from the roots of P. decompositum led to the isolation of two new eremophilanolides, 3-hydroxycacalolide (1a) and epi-3-hydroxycacalolide (1b). A 1:1 mixture of 1a/1b exhibited antihyperglycemic activity when tested at 1.09 mmol/kg in ob/ob mice. The known furanoeremophilanes, cacalone (2a) and epicacalone (2b), were also isolated from the aqueous extract and were inactive. The known furanoeremophilane, cacalol (3), was isolated from a CH2Cl2 extract of P. decompositum roots and possessed antihyperglycemic activity. The relative stereochemistry in la and 1b was assigned 3R*,5S* and 3S*,5S*, respectively, based on ROESY data, (3)J(H-H) values, and molecular mechanics calculations. Complete C-13 and H-1 NMR chemical shifts were assigned for 1a, 1b, 2a, 2b, and 3, and several revisions in C-13 NMR assignments for 2a and 3 were made. Results from the conformational analysis of 1a, 1b, 2a, and 2b indicate that each compound exists in one major conformation in solution with H-3-12 in a pseudoaxial position.