Benito Reyes-Trejo

Bioassay‐guided isolation of an anti‐ulcer diterpenoid from Croton reflexifolius: role of nitric oxide, prostaglandins and sulfhydryls

Croton reflexifolius H. B. K (Euphorbiaceae) is a very common medicinal plant in the Huastecan region of Mexico that, according to local folk medicine, is considered useful in the treatment of gastritis and gastric ulcer. We have aimed to test the validity of this practice by using the experimental model of an ethanol‐induced gastric ulcer in male Wistar rats. The results showed that C. reflexifolius had gastroprotector activity, that the hexane extract had the highest protective activity (64.38 ± 7.72%), and that polyalthic acid isolated from this extract was the main active gastroprotector agent. Rats treated orally with polyalthic acid showed a gastroprotective effect similar to that elicited by carbenoxolone. As with carbenoxolone, the effect elicited by polyalthic acid was attenuated by pretreatment with either NG‐nitro‐l‐arginine methyl ester (70 mgkg−1, i.p.), a nitric oxide (NO) synthase inhibitor, or N‐ethylmaleimide (10 mgkg−1, s.c.), a blocker of sulfhydryl groups. This suggested that the gastroprotective mechanism of this diterpenoid involved the participation of both NO and endogenous sulfhydryl groups. Contrary to carbenoxolone, the gastroprotective effect of polyalthic acid was not affected by the inhibition of prostaglandin synthesis with indometacin (10 mgkg−1, s. c.). In conclusion, Croton reflexifolius contains compounds with gastroprotector activity. Polyalthic acid, which was isolated from this plant, was the main compound with gastroprotector activity, having effectiveness similar to that found with the use of carbenoxolone. Whereas NO and sulfhydryl groups were involved in the mechanisms of gastroprotective action of polyalthic acid, prostaglandins were not.

Bioassay-guided isolation of an anti-ulcer chromene from Eupatorium aschenbornianum: Role of nitric oxide, prostaglandins and sulfydryls

Eupatorium aschenbornianum is considered useful in the treatment of gastric ulcer. In the current study the validity of this practice was tested by using the experimental model of an ethanol induced gastric ulcer in rats. The results show that E. aschenbornianum had gastroprotective activity, that the hexane extract had the highest protective activity (85.65+/-4.76%), and that encecanescin isolated from this extract was the main active gastroprotective agent. The effect elicited by encecanescin was attenuated by N(G)-nitro-L-arginine methyl ester, N-ethylmaleimide and indomethacin, which suggests that NO, prostaglandins and sulfydryl groups are involved in the mechanisms of gastroprotective action.

Relaxant Effect of the Extracts of Crataegus mexicana on Guinea Pig Tracheal Smooth Muscle

a B S t r a c t Crataegus sp. has been used in the traditional medicine of Mexico as well as other countries for the treatment of several respiratory diseases, such as flu, cough and asthma. The tracheal relaxant effect of the leaves of C. mexicana is investigated here for the first time, through a bioassay-guided study by using isolated tracheal rings of guinea-pig as an experimental model. the hexane extract was the most active compared to dichloromethane and methanol. an active fraction was obtained from the hexane extract. Assays by HPLC-MS reveal that at least 14 compounds may exist in it. In addition, the results suggest that relaxant effect of the effective fraction was in part related to the activity of β-adrenergic receptors and not to K + atP channels. This study represents the first in which the relaxant effect of leaves of C. mexicana on tracheal rings of guinea pig was clearly demonstrated. More studies are required to correctly identify the bioactive compounds that contribute to the relaxant effects of Crataegus mexicana, and to know the mechanisms of action of these compounds.

Modhephene derivatives from Pluchea sericea

Abstract The roots of Pluchea sericea (Compositae) afforded the known compoundsboehmerol acetate and P-sitosterol together with two new sesquiterpenes14-hydroxymodhephene and its acetate. Their structures were determined by 1 H and 13 C NMRspectroscopy including the use of a lanthanide shift reagent and trichloroacetyl isocyanate.

Polyalthic Acid Isolated from Croton reflexifolius has Relaxing Effect in Guinea Pig Tracheal Smooth Muscle

The relaxing activity of Croton reflexifolius H.B.K (Euphorbiaceae) leaves was assessed in isolated guinea pig tracheal rings. The dichloromethane extract of C. reflexifolius was the most active relaxant (EC50 = 118.98 ± 5.927 μ g/mL), and within this extract polyalthic acid was identified as the main active relaxing agent. Polyalthic acid showed a relaxing effect on tracheal rings precontracted with carbachol (EC50 = 183.71 ± 3.28 μM), histamine (6.24 ± 0.28 μM), and KCl (195.79 ± 10.36 μM). The pretreatment with polyalthic acid did not affect the concentration response curve to histamine, and it reduced the Emax of carbachol without affecting its EC50, thus suggesting that polyalthic acid produces a mild antimuscarinic activity. In addition, neither glibenclamide, l-NAME nor propranolol modified the effect of polyalthic acid, although the latter enabled isoproterenol activity. In conclusion, this study represents the first in which the relaxing effect of C. reflexifolius on tracheal rings of guinea pig was clearly demonstrated. Polyalthic acid, which was the main active agent in this relaxing action, produced a mild antimuscarinic activity in a noncompetitive manner. Its relaxing effect was independent of the contractile agent employed and was not related with β -adrenergic receptors, K channels, or nitric oxide. Further experiments are needed to clarify the mechanism of action of polyalthic acid.

Molecular Disorder in (‒)-Encecanescin

(‒)-Encecanescin (1) has been isolated from the leaves of Eupatorium aschembornianum. Two conformers are present in the crystal structure as a result of molecular disorder. The structure of 1 was established by 1H- and 13C-NMR spectroscopy in CDCl3 solution using 2D NMR techniques (gHSQC, gHMBC and NOESY). A Monte Carlo random search using molecular mechanics followed by the geometry optimization of each minimum energy structure using density functional theory (DFT) calculations at the B3LYP/6–31G* level and a Boltzmann analysis of the total energies generated accurate molecular models describing the conformational behavior of 1. The three most stable conformers 2–4 of compound 1 were reoptimized at the B3LYP/6-311++G(d,p) level of theory using CHCl3 as a solvent. Correlations between the experimental 1H- and 13C-NMR chemical shifts (δexp) have been found, and the GIAO/B3LYP/6-311++G(d,p) calculated magnetic isotropic shielding tensors (σcalc) for conformers 2 and 3, δexp = a + b σcalc, are reported. A good linear relationship between the experimental and calculated NMR data has been obtained for protons and carbon atoms.