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

Abstract

Mulinum crassifolium Phil. (Apiaceae) is an endemic shrub from Chile commonly used as infusion in traditional medicine to treat diabetes, bronchial and intestinal disorders and stomach ailments, including ulcers. From the EtOAc extract of this plant, the new mulinane-type diterpenoids 3 and 5 were isolated along with three known diterpenoids. The gastroprotective effect of the infusion of the plant was assayed to support the traditional use and a fast HPLC analysis using high resolution techniques was performed to identify the bioactive constituents. The EtOAc extract and the edible infusion showed gastroprotective effect at 100 mg/kg in the HCl/EtOH induced gastric ulcer model in mice, reducing lesions by 33% and 74%, respectively. Finally, a metabolomic profiling based on UHPLC-ESI-MS/HRMS of the edible infusion was performed and thirty-five compounds were tentatively identified including quercetin, caffeic acid, apigenine glucoside, p-coumaric acid, chlorogenic acids, and caffeoylquinic acids, which have been associated previously with gastroprotective and antiulcer properties. This scientific evidence can support the contribution of polyphenols in the gastroprotective activity of the edible infusion of this plant, and can validate at least in part, its ethnopharmacological use.

Advances in Azorella glabra Wedd. Extract Research: In Vitro Antioxidant Activity, Antiproliferative Effects on Acute Myeloid Leukemia Cells and Bioactive Compound Characterization

“…Upon fragmentation by collision–induced dissociation (CID), these compounds produced the ions at m/z 289, 287, 271, 253, 229, 135, 113, 95, 87, 83, 69, 57. In particular, Areche et al, in 2019, reported the ion fragment at m/z 135 for 14 α -hydroxymulin-12-en-11-one-20-oic acid, a mulinane diterpenoid [ 30 ]. The signal at 16.61 min in IV sub-fraction ( 5 ) with m/z 497.27 indicated the presence of an extra hexose sugar unit with respect to m/z 333.20 and it was putatively identified as mulinic acid hexoside derivative.…”

“…and other species belonging to the Apiaceae family [ 64 ]. Many studies have been reported the different biological activities of these terpenoid compounds, including their antibacterial [ 31 ], antituberculosis [ 65 ], gastroprotective [ 30 ] and antitumor activity [ 34 , 36 ]. In particular, many of the putatively compounds present in AG have important cytotoxic activity; for examples, Bórquez et al showed cytotoxic effect of azorellanes on human breast carcinoma cells; their activity was dependent on their beta acetate group at position C -7 in the skeleton [ 34 ].…”

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

“…In addition, the presence of different functional groups, which include hydroxyl, carboxyl, acetoxy, and double bond, in the mulinane skeleton has allowed the preparation of a significant number of semisynthetic derivatives using dehydration, alkylation, hydrolysis, and oxidation reactions ( Table 3, and Figure 5). To date, only one semisynthetic azorellane derivative, 7β-deacetylazorellanol (16), has been reported; this can be explained by the fact that the cyclopropane ring in the azorellane skeleton can be easily open under weak acidic conditions, to produce semisynthetic derivatives having a mulinane skeleton [54]. However, the limited number of functionalized positions, and the type of functional groups, found in the chemical structures of natural azorellane and mulinane diterpenoids limit the number and type of semisynthetic derivatives that can be prepared through chemical modification [55]; because of this, in recent years, biotransformation using filamentous fungi such as Mucor plumbeus and M. circinelloides has been explored as a new strategy to obtain novel mulinane and azorellane derivatives [51,55,56] (Table 4, Figure 6).…”

“…A search for bioactive metabolites with anti-inflammatory and analgesic properties produced by A. compacta, A. yareta, and L. acaulis resulted in the identification of azorellanol (9), azorellanone (17), and 7β-deacetylazorellanol (16); azorellanol (9) showed anti-inflammatory activity when tested on arachidonic acid (AA) and 12-deoxyphorbol-13-Tetradecanoate (TPA)-induced edemas. The fact that (9) showed a higher activity on the TPA than in the AA-induced edema assays (dose: 15 × 10-7 mol/ear) and that the dermal anti-inflammatory activity was of 70.8%, suggests that the mechanism of action of (9) could involve the inhibition of cyclo-oxygenase activity.…”

“…Other activities reported for mulinanes and azorellanes include cytotoxic activity on human breast adenocarcinoma cells (MCF-7); mulin-11,13-dien-20-oic acid (6), azorellanol (9), 7β-deacetylazorellanol (16), 13β-epiazorellanol (24), and 7β-acetoxy-mulin-9,12-diene (35) displayed good cytotoxic activity (less than 50% cell viability at 100 µM), with azorellanol (9) being the most active (IC 50 = 25.64 µM). The results obtained in this investigation suggested that the beta acetate group at C-7 was required to increase the cytotoxic effect.…”