Anti‐inflammatory and diuretic effects of the diterpene ent‐dihydrotucumanoic acid

Abstract

Gymnosperma glutinosum (Spreng) Less (Asteraceae) is a shrub used in traditional medicine for the treatment of inflammatory and renal diseases. The ent‐dihydrotucumanoic acid (DTA) is a diterpene obtained from G. glutinosum. This study evaluated the antioxidant, genotoxic, and diuretic properties of DTA, as well as its in vitro and in vivo anti‐inflammatory actions. The antioxidant actions of DTA were assessed with the 2,2′‐azino‐bis (3‐ethylbenzothiazoline‐6‐sulphonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and 2,2′‐diphenyl‐1‐picrylhydrazyl (DPPH) assays, the genotoxic action was assessed with the comet assay, and the diuretic effects of DTA were assessed using metabolic cages. The anti‐inflammatory actions were evaluated using primary murine peritoneal macrophages stimulated with LPS and the λ‐carrageenan‐induced hind paw edema test. DTA lacked antioxidant (IC50 > 25,000 μg/mL) activity in the ABTS, FRAP, and DPPH assays. DTA at 500–1,000 μg/mL showed moderate genotoxicity. In LPS‐stimulated macrophages, DTA showed IC50 values of 74.85 μg/mL (TNF‐α) and 58.12 μg/mL (NO), whereas the maximum inhibition of IL‐6 (24%) and IL‐1β (36%) was recorded at 200 μg/mL. DTA induced in vivo anti‐inflammatory effects with ED50 = 124.3 mg/kg. The in vitro anti‐inflammatory activity of DTA seems to be associated with the decrease in the release of TNF‐α and NO. DTA promoted the excretion of urine (ED50 = 86.9 mg/kg), Na+ (ED50 = 66.7 mg/kg), and K+ (ED50 = 8.6 mg/kg). The coadministration of DTA with L‐NAME decreased the urinary excretion shown by DTA alone. Therefore, the diuretic activity is probably associated with the participation of nitric oxide synthase. In conclusion, DTA exerted anti‐inflammatory and diuretic effects, but lacked antioxidant effects.

TSA-1-C4 plus Tc24-C4 recombinant protein stimulation induce immunomodulatory activity by activation of macrophages

“…On the other hand, some studies, suggest that, ROS and NO molecules are essential for parasite proliferation and growth, due to provide ideal conditions (e.g., iron availability in macrophages) for parasite-replication 52,53 . In the present study, the amounts of NO and H 2 O 2 molecules reported are similar to those reported in previous studies 36,54,55 , which peritoneal murine macrophages were stimulated with extracts of plants or microorganisms with antiparasitic activity. According to those data, toxic effects were not detected, therefore, we believe that the amounts of molecules produced by the TSA-1-C4 plus Tc24-C4 bivalent recombinant strategy is appropriate.…”

Rapid and Simultaneous Extraction of Bisabolol and Flavonoids from Gymnosperma glutinosum and Their Potential Use as Cosmetic Ingredients

“…Most of the compounds isolated from G. glutinosum are methoxylated flavones such as 5,7-dihydroxy 3,6,8-trimethoxyflavone and 5,7-dihydroxy 3,6,8,2 ,4 ,5 -hexamethoxyflavone, and some ent-labdane-type diterpene [20][21][22][23]. More recent studies showed the isolation of a diterpene ent-labdene-type: ent-dihydrotumanoic acid (DTA) with antidiarrheal and antinociceptive effects [24][25][26]. However, even when this plant is used in the treatment of some skin problems, there are no studies about the relation between the isolated compounds and these diseases.…”

Efectos sobre la peroxidación de mitocondrias y microsomas hepáticas de ratas Wistar, análisis fitoquímico y genotoxicidad de Cestrum parqui L’Her (“duraznillo negro”, Solanaceae) y Pascalia glauca Ortega (“sunchillo”, Asteraceae)

“…Extractos a base de hexano y etanol de Gimnosperma glutinosum (Spreng) Less. ensayados con células mononucleares de sangre periférica demostraron genotoxicidad moderada ante el uso un diterpeno extraído (ácido ent-dihidrotucumanoico)(Alonso Castro et al, 2019). Altamirano (2019) menciona la capacidad genotóxica de extractos de Acanthospermum australe (Loefl.)…”