Toxicological and Pharmacological Activities of Leptohyptis macrostachys (Benth.) Harley and J.F.B.Pastore (Lamiaceae) on Intestinal Smooth Muscle.

Leptohyptis macrostachys, previously known as Hyptis macrostachys Benth., is used in folk medicine to relieve the symptoms of asthma, cough, and bronchitis. Recently, we showed that the ethanol extract obtained from Leptohyptis macrostachys has selective spasmolytic activity on guinea pig ileum. Therefore, the aim of this study was to characterize the spasmolytic mechanism of this extract, investigated whether it presents toxicological and antidiarrheal activities. Therefore, the crude ethanolic extract of Leptohyptis macrostachys was analyzed by high-performance liquid chromatographic-diode array detection (HPLC-DAD). The spasmolytic effect was evaluated on guinea pig ileum, toxicological activity using rats and antidiarrheal activity using male and female mice. In HPLC-DAD analysis, Rosmarinic acid (5.44%) was the most abundant phenolic compound, being considered as a chemical marker. The spasmolytic potency of the extract on histamine-induced contraction was reduced in the presence of 1 mM TEA+, a selective big-conductance K+ channels blocker (BKCa). The extract produces a dose-dependent antidiarrheal activity, inhibiting equipotently defecation frequency and liquid stool formation. In addition, the extract has inhibited in a dose-dependent manner both castor oil-induced intestinal transit and intestinal fluid content. Thus, the spasmolytic activity of the extract involves positive modulation of BKCa and its antidiarrheal activity is related to inhibition of intestinal motility and secretion.

Dolichocarpols A-F, Unprecedented Macrocyclic Humulene-Type Sesquiterpenoids from Anaxagorea dolichocarpa.

Six sesquiterpenoids with unprecedented macrocyclic humulene-type structures, namely, dolichocarpols A-E (1-5) with ether-bridged bicyclic rings between C-10 and C-2, C-10 and C-7, C-10 and C-6 (×2), and C-6 and C-3 and dolichocarpol F (6) cyclized between C-7 and C-2 and with an ether bridge between C-10 and C-3, were isolated from Anaxagorea dolichocarpa roots. The structures of the compounds were elucidated by NMR, MS, and IR data. Absolute configurations of compounds 1-3 and 6 were established on the basis of data from electronic circular dichroism, whereas relative configurations of compounds 4 and 5 were suggested by the NOESY spectrum. In addition, a putative biosynthetic pathway of the compounds is proposed. Furthermore, the cytotoxicity of 3, 4, and 6 against HCT-116 (human colorectal carcinoma) and L929 (murine fibroblast) was evaluated.