Chemical analysis and antioxidant, anti-inflammatory and toxicological evaluations of the hydromethanolic extract of Psidium guineense Swartz leaves

Psidium guineense, popularly known as “araçá-do-campo”, is used in popular medicine for the treatment of inflammatory diseases. Our research group studied an essential oil obtained from its leaves and reported anti-inflammatory and analgesic properties. However, to date, the anti-inflammatory actions of the leaf extract have not been evaluated although the traditional folk use of this plant has these indications. The current study was designed to evaluate the antioxidant and anti-inflammatory effects and toxicity of the hydromethanolic extract of the leaves from P. guineense (HME-PG), as well as to investigate the chemical composition. HME-PG was chemically investigated by Ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). The antioxidant activity was evaluated with 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and malondialdehyde (MDA). Swiss mice were orally (p.o.) pretreated with HME-PG (30, 100 and 300 mg/kg), and after 1 h received carrageenan via paw injection (edema, cold sensitivity and mechanical hyperalgesia were analyzed) or pleural injection (leukocyte migration was analyzed after 4 h) and for nociception using the formalin model. Acute (14 days) and subacute (28 days) toxicity was assessed with female Wistar rats orally treated with 500 and 2000 mg/kg HME-PG. HME-PG showed high levels of phenolic and flavonoid compounds. Six compounds were identified based on UHPLC-MS/MS analysis, including gallic acid, quercetin, 3′-formyl-2′,4′,6′-trihydroxy-5′-methyldihydrochalcone, vanillic acid, ursolic acid and corilagin. HME-PG exhibited an IC50 of 48.14 μg/mL in the MDA assay and an IC50 of 45.15 μg/mL in the DPPH test. The treatment with HME-PG (100 and 300 mg/kg) significantly inhibited edema at all time points evaluated, mechanical hyperalgesia after 4 h and the response to cold 3 and 4 h after carrageenan injection and anti-nociceptive effects in both phases of formalin nociception. All oral HME-PG treatments significantly inhibited leukocyte migration and plasma extravasation in the pleurisy model. Toxicity tests did not cause signs of toxicity in the treated animals. The present study showed that HME-PG has antioxidant and anti-inflammatory properties, and no toxicity was detected after acute or subacute treatment with HME-PG, showing the possibility for the safe traditional use of P. guineense. [Display omitted]