Pharmacological and toxicological study of a chemical-standardized ethanol extract of the branches and leaves from Eysenhardtia polystachya (Ortega) Sarg. (Fabaceae)
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Eysenhardtia polystachya is used for the empirical treatment of cancer, infections, diarrhea, inflammation, and pain. This study identified, using GC-MS, the main chemical components in an ethanol extract of E. polystachya branches and leaves (EPE) and tested its cytotoxic, antimicrobial, anti-diarrheal, anti-inflammatory, and antinociceptive effects. The in vitro and in vivo toxicity of EPE was evaluated using the comet assay in human peripheral blood mononuclear cells (PBMC) and the acute toxicity test in mice, respectively. The cytotoxic and the antimicrobial effects were performed using the MTT assay and the minimum inhibitory concentration (MIC) test, respectively. The levels of pro-inflammatory mediators in LPS-stimulated macrophages were measured to evaluate the in vitro anti-inflammatory effects of EPE. The antidiarrheal (castor oil test, small intestine transit, and castor oil-induced enteropooling), and anti-inflammatory activities (TPA and carrageenan) of EPE were also performed. The antinociceptive actions of EPE were carried out with the following tests: acetic acid, formalin, and hot plate. The hypnotic and locomotor effects were analyzed using pentobarbital and a rotarod system, respectively. The main component in EPE was D-pinitol (26.93%25). The antidiarrheal and antinociceptive effects of D-pinitol were also evaluated. EPE showed low in vitro toxicity (DNA damage in PBMC at concentrations higher than 200 µg/ml), and low in vivo toxicity (LD50 > 2000 mg/kg i.p. and p.o.). Furthermore, EPE lacked cytotoxic activity (IC50 > 300 µg/ml) on human cancer cells, but showed good antimicrobial effects in E. coli (MIC=1.56 µg/ml) and S. aureus (MIC = 0.78 µg/ml). In multi-drug resistant microorganisms, EPE showed MIC> 100 µg/ml. EPE exerted in vitro anti-inflammatory effects, mainly, by the decrease in the production of H2O2 (IC50 = 43.9 ± 3.8 µg/ml), and IL-6 (73.3 ± 6.9 µg/ml). EPE (ED50 =7.5 ± 0.9 mg/kg) and D-pinitol (ED50 = 0.1 ± 0.03 mg/kg) showed antidiarrheal activity, and antinociceptive effects in the acetic acid test with ED50 = 117 ± 14.5 mg/kg for EPE and 33 ± 3.2 mg/kg for D-pinitol. EPE showed also antinociceptive activity in the phase 2 of the formalin test (ED50 = 48.9 ± 3.9 mg/kg), without inducing hypnotic effects or altering the locomotor activity in mice. The results here presented corroborate the folk medicinal use of Eysenhardtia polystachya in the treatment of infections, diarrhea, inflammation, and pain. D-pinitol, the main metabolite of EPE, showed antinociceptive and antidiarrheal effects with similar potency compared to standard drugs. © 2018 Elsevier B.V.
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and ondansetron (PubChem CID:4595); Anti-inflammatory; Antidiarrheal; Antinociceptive; clonazepam (PubChem CID:2802); D-pinitol (PubChem CID:164619); dimethyl sulfoxide (PubChem CID:679); Eysenhardtia polystachya; glibenclamide (PubChem CID:3488); loperamide hydrochloride (PubChem CID:71420); naloxone (PubChem CID:5464092); naproxen sodium (PubChem CID: 23681059); pentobarbital (PubChem CID: 4737); Tramadol hydrochloride (PubChem CID:63013) 1h 1,2,4 oxadiazolo[4,3 a]quinoxalin 1 one; 2 furoic acid; analgesic agent; antidiarrheal agent; antiinfective agent; antiinflammatory agent; ceftazidime; cisplatin; clonazepam; cytotoxic agent; dextro pinitol; Eysenhardtia polystachya extract; fumaric acid; glibenclamide; glycerol; indometacin; interleukin 1beta; interleukin 6; lactic acid; loperamide; n(g) nitroarginine methyl ester; naloxone; nitric oxide; ondansetron; oxacillin; pentobarbital; plant extract; succinic acid; tumor necrosis factor; unclassified drug; unindexed drug; alcohol; analgesic agent; antidiarrheal agent; antiinfective agent; antiinflammatory agent; cytokine; nitric oxide; plant extract; solvent; acute toxicity; analgesic activity; animal cell; animal experiment; animal model; antidiarrheal activity; antiinflammatory activity; antimicrobial activity; antineoplastic activity; Article; cancer cell; Candida albicans; carrageenan-induced paw edema; castor oil-induced diarrhea; controlled study; cytokine production; DNA damage; Escherichia coli; Eysenhardtia polystachya; Fabaceae; genotoxicity; hot plate test; human; human cell; in vitro study; in vivo study; intestine transit time; locomotion; male; mass fragmentography; medicinal plant; minimum inhibitory concentration; mouse; multidrug resistance; nonhuman; peritoneum macrophage; plant leaf; Proteus vulgaris; sleep latency; sleep time; Staphylococcus aureus; TPA-induced ear edema; animal; Bagg albino mouse; cell line; cell survival; chemically induced; chemistry; diarrhea; drug effect; edema; gastrointestinal transit; metabolism; mononuclear cell; pain; plant stem; tumor cell line; Analgesics; Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Antidiarrheals; Cell Line; Cell Line, Tumor; Cell Survival; Cytokines; Diarrhea; Edema; Ethanol; Fabaceae; Gastrointestinal Transit; Humans; Leukocytes, Mononuclear; Macrophages, Peritoneal; Male; Mice, Inbred BALB C; Nitric Oxide; Pain; Plant Extracts; Plant Leaves; Plant Stems; Solvents
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