Antihyperglycemic Sesquiterpenes fromPsacaliumdecompositum

Abstract

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 1a and 1b was assigned 3R,5S and 3S,5S, respectively, based on ROESY data, 3J H-H values, and molecular mechanics calculations. Complete 13C and 1H NMR chemical shifts were assigned for 1a, 1b, 2a, 2b, and 3, and several revisions in 13C 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 H3-12 in a pseudoaxial position.

Modified eremophilanes and anti-inflammatory activity of Psacalium cirsiifolium

“…The molecular formula C 17 H 20 O 5 , determined by HRESIMS, showed eight degrees of insaturation. The 1 H NMR spectrum (Table 1) was similar to those of cacalone (5) and epi-cacalone (6) 6 with two additional signals at d H 5.13 (tt, 1H, J 6.0, 5.0 Hz) and 2.05 (s, 3H). The first one was attributed to H-2 by its correlations with the H 2 -1 and H 2 -3 methylene groups observed in the COSY experiment.…”

“…1 They are disseminated from the south of the United States to Guatemala and some of them are used in folk medicine to cure diabetes and renal, hepatic, gastrointestinal and dermatological problems. 2,3 The hypoglycemic, anti-inflammatory and antioxidant activities of P. decompositum, [4][5][6] P. peltatum 7,8 and P. radulifolium 9 extracts have been reported. The antimicrobial effects of P. radulifolium 10 and the antiinflammatory properties of P. sinuatum 11 have also been determined.…”

“…The antimicrobial effects of P. radulifolium 10 and the antiinflammatory properties of P. sinuatum 11 have also been determined. Sesquitepenes mainly of eremophilane and modified eremophilane types are the main secondary metabolites isolated from the eight species of the genus chemically studied so far: P. decompositum [4][5][6] (also studied as Cacalia decomposita), 12,13 P. tussilaginoides (studied as Cacalia ampulacea), 13 P. peltatum, 7,8 P. sinuatum,…”

“…17,18 As continuation of our research on Senecioneae we studied the chemical composition of P. cirsiifolium which to the best of our knowledge has no previous studies. We report the isolation of fourteen modified eremophilane derivatives (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14), of which four (1-4) are described for the first time. Two known caryophyllenes (16,18), one aromadendrene (17) and one flavonoid (15) were also isolated ( Figure 1).…”

Discovery of a Small Molecule Insulin Receptor Activator

“…Moreover, the antifungal lipopeptide known as caspofungin acetate (MK0991, CANCIDASTM), a semisynthetic derivative of the mngal metabolite pneumocandin Bs, is now in phase III clinical trials. In the particular case of diabetes, a number of plant-derived secondary metabolites have been described to possess antidiabetic activity in a variety of model systems (Cignarella et al, 1996;Perez et al, 1997;Carney et al, 1999;Inman et al;, 1999).…”