A new mulinane diterpenoid from the cushion shrub Azorella compacta growing in Perú

Abstract

Background:Azorella compacta is a rare yellow-green compact resinous cushion shrub growing from the high Andes of southern Perú to northwestern Argentina, and which is a producer of biologically active and unique diterpenoids.Objective:This study investigated the secondary metabolites present in a Peruvian sample of Azorella compacta and the evaluation of gastroprotective activity of the isolated compounds in a gastric- induced ulcer model in mice.Material and Methods:Six secondary metabolites (diterpenoids 1-6) present in the dichloromethane (DCM) extract of A. compacta growing in Perú were isolated by a combination of Sephadex LH-20 permeation and silica gel chromatography and their chemical structures were elucidated by spectroscopic methods (NMR) and molecular modeling. The gastroprotective activity of the new compound 1 was evaluated on the HCl/EtOH-induced gastric lesion model in mice and compared to the activity showed by the known compounds.Results:A new mulinane diterpene along with five known diterpenoids have been isolated from a Peruvian sample of A. compacta and the gastroprotective results show that compound 1 is less active than the other known mulinane diterpenoids isolated.Conclusions:A. compacta growing in Perú showed the presence of the new mulinane 1, which was poorly active in the HCl/EtOH-induced gastric lesion model in mice. Indeed, the activity was lower than other diterpenoids (2-6) showing an oxygenated function at C-16 or/and C-20, which confirm the role of an oxygenated group (OH or carboxylic acid) for the gastroprotective activity of mulinane compounds.

Mulinum crassifolium Phil; Two New Mulinanes, Gastroprotective Activity and Metabolomic Analysis by UHPLC-Orbitrap Mass Spectrometry

“…The same study demonstrated that the mulinane diterpenoids have increased the activity due to the presence of an additional carboxylic acid [32]. In another study, the hydro-carbonated compounds mulin-11,13-diene, mulin-11,13-dien-20-ol, and mulin-11,13-dien-20-oic acid were less active than lansoprazole reducing the gastric lesions by 18%, 26% and 39%, respectively [32,33]. Regarding the mode of gastroprotective action for mulin-11,13-dien-20-oic acid evaluated at 55 mg/kg, its effect was reduced by pre-treatment with indomethacin and N -ethylmaleimide, suggesting that prostaglandins and sulfhydryl compounds are positively involved in the gastroprotective activity of this mulinane diterpenoid [11].…”

Ancestral knowledge on the use of wild plants for the treatment of diseases in alpacas

“…A. absinthium contiene metabolitos secundarios (e.g. terpenoides, fenilpropanoides, timol y eugenol) con propiedades antihelmínticas, antibacteriales y antiprotozoarios (Hussain et al, 2017), B. tricuneata tiene terpenos (nerolidol) con efectos bactericidas y fungicidas (Abad y Bermejo, 2007), A. compacta contiene diterpenoides con propiedades acaricidas (Salgado et al, 2014;Tello et al, 2014) y antiplasmódicas (Loyola et al, 2004). Respecto a L. daucifolia aún no se ha caracterizado sus metabolitos secundarios, a pesar de su amplio uso para el control de la sarna y parasitosis entérica.…”

Mulinane- and Azorellane-Type Diterpenoids: A Systematic Review of Their Biosynthesis, Chemistry, and Pharmacology

“…A number of azorellanes ( 9 , 11 , and 15 ) and mulinanes ( 1 , 5 , 6 , 28 , 29 , 31 , and 40 ) isolated from A. compacta exhibited gastroprotective activity in HCl/EtOH-induced gastric lesions in mice, at a dose of 20 mg/kg. The best activity was caused by mulin-11,13-dien-18-acetoxy-16,20-dioic acid ( 31 ), azorellanol ( 9 ), and 13 β -hydroxyazorellane ( 15 ), with values (73–69%) similar to those observed for the positive control Lansoprazole (78–68%) at the same dose [ 24 , 26 ]. Similarly, mulin-11,13-dien-20-oic acid ( 6 ) isolated from A. trifurcata also demonstrated a gastroprotective effect (ED 50 = 55 mg/kg); the possible mode or gastroprotective action of 6 was evaluated in mice using a pre-treatment with various blockers such as Indomethacin (inhibitor of prostaglandin synthesis), N-ethylmaleimide (blocker of sulfhydryl compounds), N-nitro-L-arginine methyl ester (inhibitor of nitric oxide), and ruthenium red (vanilloid receptor antagonist).…”