Antinociception of petroleum ether fraction derived from crude methanol extract of Melastoma malabathricum leaves and its possible mechanisms of action in animal models

The antinociceptive property of Centella asiatica extracts is known but the analgesic activity of its bioactive constituent asiaticoside has not been reported. We evaluated the antinociceptive activity of orally (p. o.) administered asiaticoside (1, 3, 5, and 10 mg/kg) in mice using the 0.6% acetic acid-induced writhing test, the 2.5% formalin-induced paw licking test, and the hot plate test. The capsaicin- and glutamate-induced paw licking tests were employed to evaluate the involvement of the vanilloid and glutamatergic systems, respectively. Asiaticoside (3, 5, and 10 mg/kg, p. o.) reduced the rate of writhing (p < 0.0001) by 25.3, 47.8, and 53.9%, respectively, and increased the latency period (p < 0.05) on the hot plate at 60 min post-treatment until the end of the experiment. Moreover, asiaticoside (3, 5, and 10 mg/kg, p. o.) shortened the time spent in licking/biting the injected paw (p < 0.0001) in the early phase of the formalin test by 45.7, 51.4, and 52.7%, respectively, and in the late phase (p < 0.01) by 23.6, 40.5, and 50.6%, respectively. Antinociception induced by asiaticoside (10 mg/kg) was not antagonized by naloxone in both the 2.5% formalin-induced nociception and the hot plate test, indicating a nonparticipation of the opioidergic system. Asiaticoside (1, 3, 5, and 10 mg/kg, p. o.) reduced the duration of biting/licking the capsaicin-injected paw (p < 0.0001) by 40.5, 48.2, 59.5, and 63.5%, respectively. Moreover, asiaticoside (5 and 10 mg/kg) shortened the time spent in biting/licking the glutamate-injected paw (p < 0.01) by 29.9 and 48.6%, respectively. Therefore, asiaticoside (5 and 10 mg/kg, p. o.) induces antinociception possibly through the vanilloid and glutamatergic systems.

We recognize the chemical composition of the acetonic extract of Rhizophora mangle barks (AERM) using mass spectrometry analysis [liquid chromatography (LC)–ESI–IT-MS/MS and matrix-assisted laser desorption/ionization-time of flight-MS (MALDI-TOF)]. Analgesic activity was evaluated by formalin and tail-flick experimental assays. Anti-inflammatory activity was performed by paw edema test induced by carrageenan and 48/80 compounds. The first series of experiments involved [LC]–FIA–IT-MS/MS with 11 separated catechins derivatives until degree of polymerization 3 (DP3). The spectra obtained by MALDI-TOF analysis of the AERM presented two homologous series: one based on polymers of m/z 288 Da increments (up to DP12) and another series based on polymers of m/z [288 + 162] Da increments (up to DP11). In addition to these series of flavan-3-ol, each DP had a subset of masses with a variation of − 16 Da (homologous series of afzelechins—m/z 873–3465 Da) and + 16 Da (homologous series of gallocatechins—m/z 905–3497 Da). A similar pattern with homologous series of gallocatechins and afzelechins could also be observed for a fifth and a sixth monohexoside series: glucogallocatechins (m/z 779–3371) and glucoafzelechins (m/z 747–3339). The intraperitoneal administration of different doses of AERM (50, 150 and 300 µg mL−1) have a morphine-like effect and intense anti-inflammatory activity. Graphical Abstract

Phytochemically the leaves of M. malabathricum contained amides, flavonoid, triterpenes, saponins, tannins, steroids, glycosides and phenolic compounds. [1][2][3] Leaves extract of M. malabathricum contained quercetin, quercitrin and kaempferol-3-O-(2′,6′-di-Op-trans-kumaroyl)-β-glucoside. 4 Besides that, other components also found in the leaves extracts such as 5-hydroxymethylfurfural, palmitic acid, stearic acid methyl ester, trans-squalene and tocopherol. 5 M. malabathricum is an important ethnomedicine and used by tribes in Malaysia, China, India and Indonesia as traditional medicine. 1 Leaves and roots were used as wound healing and prevent scarring from smallpox by