Inhibition of pro-inflammatory enzymes by medicinal plants from the Argentinean highlands (Puna)

Abstract

Ethnopharmacological relevance: Human groups in the Argentinean Andes highlands (Puna) selected native plants as anti-inflammatory agents. The indications of use are mainly to relieve pain, as infusions, ethanolic extracts or plasters.

Aim of the study: The objective of the study was to assess the effect of hydroalcoholic extracts from native highland plants as anti-inflammatory agents according to the traditional indications of use. The chemical profile of the three most active species was analyzed by HPLC-ESI-MS to get an insight into the constituents and the effects observed according to the ethnopharmacological information.

Materials and methods: Hydroalcoholic extracts from 13 Argentinean Puna plants used as anti-inflammatory were evaluated as inhibitors of the pro-inflammatory enzymes phospholipase A₂ (sPLA₂), lipoxygenase (LOX), hyaluronidase, and for their capacity to stabilize red blood cells membrane. In addition, the extracts were evaluated to determine their reducing power, iron chelating capacity and ABTS^•+ radical scavenging effect. The chemical profiles of the most active species were analyzed by HPLC-ESI-MS.

Results: Among the species investigated, Ephedra multiflora was the most active as LOX inhibitor (IC₅₀:132µg/mL), by reducing the non-heme iron group and by scavenging radicals. The IC₅₀ values of the reference compounds caffeic acid and naproxen were 57.0 and 14.0µg/mL, respectively. Parastrephia lucida showed the highest sPLA₂ inhibitory effect (63% of inhibition at 200µg/mL). Under the same experimental conditions, the IC₅₀ of the reference compound acetylsalicylic acid was 65±1µg/mL. Tessaria absinthioides exhibited the best inhibition towards hyaluronidase with an IC₅₀ of 93.2±4.3µg/mL. Under the same experimental conditions, the reference compounds quercetin and indomethacin presented IC₅₀ values of 340.0±17.0 and 502.0±10.0µg/mL, respectively. Among the most active species, 13 compounds were tentatively identified by HPLC-ESI-MS in E. multiflora and P. lucida, and 12 compounds in T. absinthioides. The constituents included caffeoyl- and feruloylquinic acid derivatives, flavonoids, simple phenolics and sesquiterpene glycosides.

Conclusions: Six out of the 13 species investigated showed a moderate to strong effect towards the enzyme sPLA₂ (>40% inhibition at 200µg/mL) while three species presented a strong activity against LOX with IC₅₀<250µg/mL and three were very active against hyaluronidase. Most of the crude drug extracts were able to stabilize the red blood cells membrane, preventing their lysis. The compounds identified in the extracts explain, at least in part, the activity found in the samples. The effect observed for the most active species supports their traditional use as anti-inflammatory agents. However, more studies should be undertaken to disclose the potential of the Puna plants as anti-inflammatory crude drugs.

Keywords: Anti-inflammatory In vitro; Argentinean highlands; Ephedra multiflora; Parastrephia lucida; Tessaria absinthioides.