María Elena Sánchez-Mendoza

Bioassay-Guided Isolation of an Anti-Ulcer Compound, Tagitinin C, from Tithonia diversifolia: Role of Nitric Oxide, Prostaglandins and Sulfhydryls

Tithonia diversifolia is a medicinal plant from the Municipality of Suchiapa, Chiapas, Mexico, that according to local folk medicine is considered useful in the treatment of gastric ulcers. The aim of the present study was to investigate the gastroprotective activity of T. diversifolia by using an ethanol-induced gastric ulcer experimental model in male Wistar rats. The results showed that T. diversifolia had gastroprotective activity, and that the dichloromethane extract had the highest protective activity (close to 90% when using doses between 10 to 100 mg/kg), and that further the compound tagitinin C isolated from this extract was the main active gastroprotective agent. Rats treated with tagitinin C suspended in Tween 80 at 1, 3, 10 and 30 mg/kg showed 37.7, 70.1, 100, and 100% gastroprotection, respectively. The effect elicited by tagitinin C (30 mg/kg) was not attenuated by pretreatment with either NG-nitro-L-arginine methyl ester (70 mg/kg, i.p.), a nitric oxide (NO) synthase inhibitor, N-ethylmaleimide (10 mg/kg, s.c.), a blocker of sulfhydryl groups, or indomethacin (10 mg/kg, s.c.), a blocker of prostaglandin synthesis, which suggests that the gastroprotective mechanism of action of this sesquiterpene lactone does not involve NO, sulfhydryl groups or prostaglandins.

Gastroprotection of Suaveolol, Isolated from Hyptis suaveolens, against Ethanol-Induced Gastric Lesions in Wistar Rats: Role of Prostaglandins, Nitric Oxide and Sulfhydryls

Hyptis suaveolens is a medicinal plant that is, according to traditional medicine, considered useful in the treatment of gastric ulcers. Although its gastroprotective activity was reported, the active compounds have not been identified. Therefore, the aim of the present study was to identify at least one active compound potentially responsible for the gastroprotective activity of H. suaveolens by using a bioassay guided study with an ethanol-induced gastric ulcer experimental model in rats. The results show that the hexane extract had protective activity (close to 70% when using doses between 10 and 100 mg/kg), and that the compound suaveolol, isolated from this extract, was one of the active gastroprotective agents. This is the first report about the gastroprotective activity of suaveolol. Rats treated with this compound at 3, 10, 30 and 100 mg/kg showed 12.6, 21.3, 39.6 and 70.2% gastroprotection respectively. The effect elicited by suaveolol (at 100 mg/kg) was attenuated by pretreatment with either NG-nitro-L-arginine methyl ester (70 mg/kg, i.p.), a nitric oxide (NO) synthase inhibitor, indomethacin (10 mg/kg, s.c.), a blocker of prostaglandin synthesis, or N-ethylmaleimide (10 mg/kg, s.c.), a blocker of sulfhydryl groups. This suggests that the gastroprotective mechanism of action of this compound involves NO, prostaglandins and sulfhydryl groups.

Gastroprotection and effect of the simultaneous administration of Cuachalalate (Amphipterygium adstringens) on the pharmacokinetics and anti‐inflammatory activity of diclofenac in rats

This work aimed to study the effect of Cuachalalate methanol extract (CME) on the anti‐inflammatory activity and pharmacokinetics of diclofenac sodium, a frequently prescribed non‐steroidal antiinflammatory drug (NSAID). The gastroprotective effect of CME on the gastric injury induced by diclofenac was studied in rats. CME showed a gastroprotective effect of 15.7% at 1 mg kg−1 and 72.5% at dose of 300 mg kg−1. Omeprazole, used as anti‐ulcer reference drug, showed gastroprotective effects of 50–89.7% at doses tested (1–30 mg kg−1). The value of the 50% effective dose for the anti‐inflammatory effect of diclofenac sodium (ED50 = 1.14 ± 0.23 mg kg−1) using carrageenaninduced rat paw oedema model, was not modified by the concomitant administration of 30 or 100 mg kg−1 of CME. The effect of CME (30, 100 and 300 mg kg−1, p.o.) on the pharmacokinetics of diclofenac sodium was studied. It was observed that the simultaneous administration of diclofenac sodium and 300 mg kg−1 of CME decreased significantly the values of Cmax (7.08 ± 1.42 μg mL−1) and AUC (12.67 ± 2.97 μg h mL−1), but not the value of tmax (0.13 (0.1–0.25) h) obtained with the administration of diclofenac alone. The simultaneous administration of 30 or 100 mg kg−1 of CME did not modify the pharmacokinetic parameters of diclofenac. The experimental findings in rats suggest that CME at doses lower than 100 mg kg−1 protects the gastric mucosa from the damage induced by diclofenac sodium without altering either the anti‐inflammatory activity or the pharmacokinetics of this NSAID.

Dillapiole, Isolated from Peperomia pellucida, Shows Gastroprotector Activity against Ethanol-Induced Gastric Lesions in Wistar Rats

Peperomia pellucida is a plant used in traditional medicine to treat gastric ulcers. Although this gastroprotective activity was reported, the active compounds have not been identified. Therefore, the aim herein was to identify the most active compound in the gastroprotective activity of P. pellucida using an ethanol-induced gastric ulcer experimental rat model. A gastroprotective effect was observed when the hexane and dichloromethane extracts were tested, with the higher effect being obtained with the dichloromethane extract (82.3 ± 5.6%) at 100 mg/kg. Dillapiole was identified as the most active compound in this extract. Although there have been previous reports on dillapiole, this is the first on its gastroprotective activity. Rats treated with this compound at 3, 10, 30 and 100 mg/kg showed 23.1, 56.1, 73.2 and 85.5% gastroprotection, respectively. The effect elicited by dillapiole at 100 mg/kg was not attenuated by pretreatment with indomethacin (10 mg/kg, s.c.), a prostaglandin synthesis blocker, NG-nitro-l-arginine methyl ester (70 mg/kg, i.p.), a nitric oxide (NO) synthase inhibitor, or N-ethylmaleimide (10 mg/kg, s.c.), a blocker of sulfhydryl groups. This suggests that the gastroprotective mechanism of action of dillapiole does not involve prostaglandins, NO or sulfhydryl groups.

Relaxant action mechanism of berberine identified as the active principle of Argemone ochroleuca Sweet in guinea‐pig tracheal smooth muscle

In this study we investigated the relaxant effect of the aerial parts of Argemone ochroleuca (Papaveraceae), which is used in Mexican traditional medicine for the treatment of various respiratory diseases such as cough, bronchitis and asthma. The alkaloid berberine was identified as one of the active relaxant principles (EC50 = 118.50 ± 3.91 μM) in the dichloromethane extract of A. ochroleuca (EC50 = 78.03 ± 2.15 μg mL−1 with 95.12 ± 3.56% of relaxation). Berberine concentration‐dependently relaxed the carbachol‐induced precontractions but not histamine‐ or KCl‐induced precontraction. The relaxant effect of berberine was unaffected by the presence of propranolol (3 μM), glibenclamide (10 μM) or ODQ (10 μM). However, 2′, 5′‐dideoxyadenosine (10 μM) blocked the log concentration‐response curves of berberine. On the other hand, berberine produced a leftward shift of the log concentration‐response curves of isoproterenol, forskolin and nitroprusside. Additionally, berberine produced a parallel rightward shift of the concentration‐response curve of carbachol in a competitive manner with a pA2 of 3.87 ± 0.045. The above results suggest that the relaxant effect of berberine on tracheal muscle is due to its antagonistic effect on muscarinic acetylcholine receptors.

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.