Anti-inflammatory and diuretic effects of the diterpene ent-dihydrotucumanoic acid
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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%25) and IL-1β (36%25) 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. © 2019 Wiley Periodicals, Inc.
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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%25) and IL-1β (36%25) 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%2b (ED50 = 66.7 mg/kg), and K%2b (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. © 2019 Wiley Periodicals, Inc.
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anti-inflammatory; dihydrotucumanoic acid; diuretic antiinflammatory agent; dihydrotucumanoic acid; diterpene; diuretic agent; furosemide; indometacin; interleukin 1beta; n(g) nitroarginine methyl ester; nitric oxide; nitric oxide synthase; potassium ion; sodium ion; tumor necrosis factor; unclassified drug; 1,1-diphenyl-2-picrylhydrazyl; 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid; antiinflammatory agent; antioxidant; benzothiazole derivative; biphenyl derivative; carrageenan; cytokine; diuretic agent; lipopolysaccharide; nitric oxide; picric acid; sulfonic acid derivative; ABTS radical scavenging assay; animal cell; animal experiment; animal model; antiinflammatory activity; antioxidant activity; Article; Asteraceae; carrageenan-induced paw edema; comet assay; controlled study; cytokine release; diuretic activity; DPPH radical scavenging assay; ferric reducing antioxidant power assay; genotoxicity; Gymnosperma glutinosum; IC50; in vivo study; male; mouse; nonhuman; otorhinolaryngology; peritoneum macrophage; potassium urine level; sodium urine level; urinary excretion; urine pH; animal; Bagg albino mouse; chemistry; drug effect; edema; human; macrophage; metabolism; mononuclear cell; Animals; Anti-Inflammatory Agents; Antioxidants; Asteraceae; Benzothiazoles; Biphenyl Compounds; Carrageenan; Comet Assay; Cytokines; Diuretics; Edema; Humans; Leukocytes, Mononuclear; Lipopolysaccharides; Macrophages; Male; Mice, Inbred BALB C; Nitric Oxide; Picrates; Sulfonic Acids
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