Further mulinane diterpenoids from Azorella compacta Carlos Areche a , Francisca Rojas-Alvarez a , Carolina Campos-Briones a , Carlos Lima a , Edwin G. Pérez b and Beatriz Sepúlveda c a Departamento de Química, Facultad de Ciencias, Universidad de Chile, b Facultad de Química, Pontificia Universidad Católica de Chile, Santiago and c Departmento de Química, Universidad Andrés Bello, Viña del Mar, Chile Keywords Azorella compacta; diterpenoid; gastric ulcer; llareta; mulinane Correspondence Carlos Areche, Faculty of Sciences, Universidad de Chile, Casilla 653, Santiago, Chile. E-mail: areche@uchile.cl Received November 30, 2012 Accepted April 11, 2013 doi: 10.1111/jphp.12083 Abstract Objectives The chemical study of a dichloromethane extract from Azorella com- pacta was directed to the isolation of characteristic mulinane and azorellane diter- penoids in order to determine their gastroprotective activity. Methods Usual chromatographic techniques on the extract led to the isolation of 12 compounds, which were identified by their spectroscopic properties. The HCl/ ethanol-induced gastric lesions model in mice was used to determine the gastro- protective activity. Key findings The new diterpenoids, 13b-hydroxymulinane (1), mulin-11, 13-dien-20-ol (2), 13a-methoxyazorellanol (3) and mulin-11,13-dien-18- acetoxy-16,20-dioic acid (12) were isolated from A. compacta. The known diterpenoids mulin-11,13-dien-20-oic acid (4), 13a-hydroxyazorellane (5), 13b- hydroxyazorellane (6), mulinic acid (7), mulinolic acid (8) and azorellanol (9), and the aromatic compounds 5,7-dihydroxychromone (10) and isoflavonoid biochanin A (11), were also obtained from the extract. Compounds 6, 9 and 12 at 20 mg/kg reduced gastric lesions by 69%, 71% and 73%, respectively, being statistically similar to lansoprazole at the same dose. Conclusions The results corroborate the intraspecific chemical variations detected previously in specimens of A. compacta collected at different Chilean lati- tudes. A high concentration of azorellanol (9) could account in part for some of the therapeutic properties attributed to this species, in particular in ulcer treat- ment. Most of the mulinane and azorellane diterpenoids isolated in this study showed relevant gastroprotective activity at a low dose in the bioassay. Introduction Azorella compacta Phil. (Apiaceae, Umbelliferae), locally known as ‘llareta’, is a tiny evergreen flowering shrub dis- tributed throughout the high Andean regions (3000– 4500 m) of Peru, Bolivia, Chile and Argentina. Previous chemical studies on this species [1–8] suggest striking varia- tions in the concentration of diterpenoids in extracts obtained from specimens growing at different latitudes in northern and central Chile. Thus, plants collected at Tatio (Atacama Desert, Chile) were reported to produce mainly mulin-11,13-dien-20-oic acid, mulinol, 11,12-epoxy-mulin- 13-en-20-oic acid, azorellanol, mulinolic acid, mulinic acid and desacetylazorellanol. [1–6] On the other hand, specimens of A. compacta collected at Vallenar (III region, Chile) afforded 20-hydroxymulin-11,13-dienyl acetate and 13,14- dihydroxymulin-11-en-20-oic acid. [7] Finally, the extract of plants collected at Farellones (Santiago, Chile), led to the isolation of mulin-12,14-dien-11-on-20-oic acid and mulin-12-ene-11,14-dion-20-oic acid. [8] The local reputation of llareta as an antidiabetic, antiul- cer, anticholesterol, anti-inflammatory and antiseptic, among other curative properties attributed to the species, has led to several bioactivity studies that report interesting results with some of the unique diterpenoids found in the extract. [5–9] Mulinolic acid and azorellanol were reported to decrease glycaemia [6] in streptozotocin diabetic rats at a similar level as chlorpropamide. Azorellanol, found in high concentrations in most specimens of A. compacta studied, has been reported to display high tripanocidal, And Pharmacology Journal of Pharmacy Research Paper © 2013 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology, 65, pp. 1231–1238 1231 Downloaded from https://academic.oup.com/jpp/article/65/8/1231/6132928 by guest on 17 November 2022