Abstract
Varronia multispicata (Cham.) Borhidi (Cordiaceae), an herbaceous plant distributed in tropical and subtropical regions is native of Brazil and widely used in folk medicine to treat respiratory and digestive diseases, inflammation, and some types of infections. Thus, this study aimed to investigate acute oral toxicity, antinociceptive, and anti-inflammatory activities of dry aqueous extract of V. multispicata (AEVm) and to identify its compounds. Extract was obtained by lyophilized leaf infusion and its composition was analyzed by ultra-performance liquid chromatography-high resolution mass spectrometry (LC-MS). Acute oral toxicity was evaluated in female rats treated with AEVm (2,000 mg/kg) in a single oral dose. Mortality, body weight changes, feed and water intake, organ weights, histological and biochemical parameters were screened for 14 days. Antinociceptive activity was evaluated by writhing (WT), formalin (FT), and hot plate (HP) tests in male mice while anti-inflammatory activity was performed by carrageenan (CPE) and dextran (DPE)-induced paw edema tests and carrageenan-induced peritonitis (CP) test in male rats. Additionally, spontaneous open-field (OF) locomotion was evaluated. LC-MS analysis revealed the presence of flavonoids with biological activity. In toxicity evaluation, extract did not cause deaths in dose of 2,000 mg/kg, and there were no significant behavioral or biochemical alterations. Additionally, evidence of hepatoprotective and antioxidant activity was observed. In pharmacological evaluation AEVm showed dose-dependent antinociceptive activity in WT, with a median effective dose of 146.89 mg/kg, which showed selectivity by inflammatory base processes (FT first phase; p < 0.001), showing no activity in neuropathic nociception components (FT second phase and HP) or about consciousness and locomotion in OF. AEVm also showed significant anti-inflammatory activity, inhibiting CPE (p < 0.001) and cell migration (p < 0.05) and nitric oxide (NO) production (p < 0,01) in CP test. These data demonstrate that AEVm has low oral toxicity—with evidence of hepatoprotective and antioxidant properties—antinociceptive and anti-inflammatory activity, supporting V. multispicata traditional use, possibly related to flavonoids present in its constitution.
Highlights
Inflammation and pain are clinical conditions present in most pathologies, being among main sources of dysfunctional and disabling conditions, requiring pharmacological intervention (Nathan and Ding, 2010; Henschke et al, 2015)
The liquid chromatography coupled to mass spectrometry (UPLC-electrospray ionization (ESI)-HRMS) analysis of the sample of aqueous extract of V. multispicata (AEVm) used in the present investigation allowed the identification of nine constituents
Little is known about its chemical constitution, toxicity, and pharmacological properties, evidencing the relevance of elucidating its therapeutic potential
Summary
Inflammation and pain are clinical conditions present in most pathologies, being among main sources of dysfunctional and disabling conditions, requiring pharmacological intervention (Nathan and Ding, 2010; Henschke et al, 2015). The most commonly used medications are steroidal and nonsteroidal anti-inflammatory drugs (NSAIDs), and central-acting analgesics (Conforti et al, 2009; Kunanusorn et al, 2009). NSAIDs are among most widely used medications due to their efficacy for a wide range of pain and inflammatory conditions. Their long-term administration may induce several adverse effects such gastro-intestinal ulcers, hepatotoxicity, bleeding, renal disorders, and immunosuppression (Henzen, 2003; Wirtha et al, 2006). Development of more powerful and safe anti-inflammatory and analgesic drugs is still needed as alternatives to these drugs limitations (Dharmasiri et al, 2003; Kumara, 2001)
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