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

• Published in: Drug development research Vol. 80; no. 6; pp. 800 - 806
• Main Authors: Alonso‐Castro, Angel Josabad, Arana‐Argáez, Víctor E., Deveze‐Alvarez, Martha Alicia, Chan‐Zapata, Ivan, Torres‐Romero, Julio Cesar, Carranza‐Álvarez, Candy, Luna‐Rubio, Sarahí, González‐Chávez, Marco M., Zapata‐Morales, Juan R., Aragón‐Martínez, Othoniel H., Ramírez‐Morales, Marco Antonio
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-09-2019; Wiley Subscription Services, Inc
• Subjects: Acids; Animals; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Anti-Inflammatory Agents - toxicity; Antioxidants; Antioxidants - chemistry; Antioxidants - pharmacology; Antioxidants - therapeutic use; Antioxidants - toxicity; anti‐inflammatory; Asteraceae; Benzothiazoles - chemistry; Bioassays; Biphenyl Compounds - chemistry; Carrageenan; Comet Assay; Cytokines - metabolism; Damage detection; dihydrotucumanoic acid; Diterpenes - chemistry; Diterpenes - pharmacology; Diterpenes - therapeutic use; Diterpenes - toxicity; diuretic; Diuretics; Diuretics - chemistry; Diuretics - pharmacology; Diuretics - therapeutic use; Diuretics - toxicity; Edema; Edema - chemically induced; Edema - drug therapy; Excretion; Genotoxicity; Humans; In vivo methods and tests; Leukocytes, Mononuclear - drug effects; Lipopolysaccharides; Macrophages; Macrophages - drug effects; Macrophages - metabolism; Male; Medical treatment; Mice, Inbred BALB C; Nitric oxide; Nitric Oxide - metabolism; Nitric-oxide synthase; Peritoneum; Picrates - chemistry; Sulfonic Acids - chemistry; Tumor necrosis factor; Urine; anti-inflammatory; dihydrotucumanoic acid; diuretic
• ISSN: 0272-4391; 1098-2299
• DOI: 10.1002/ddr.21561

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.