ABSTRACT
This is the first study to analyze the anti-inflammatory and antinociceptive effect of withanicandrin, isolated from Datura Ferox leaves, and the possible mechanism of action involved in adult zebrafish (ZFa). To this end, the animals were treated intraperitoneally (i. p.) with withanicandrin (4; 20 and 40â mg/kg; 20â µL) and subjected to locomotor activity and acute toxicity. Nociception tests were also carried out with chemical agents, in addition to tests to evaluate inflammatory processes induced by κ-Carrageenan 1.5 % and a Molecular Docking study. As a result, withanicandrin reduced nociceptive behavior by capsaicin at a dose of 40â mg/kg and by acid saline at doses of 4 and 40â mg/kg, through neuromodulation of TRPV1 channels and ASICs, identified through blocking the antinociceptive effect of withanicandrin by the antagonists capsazepine and naloxone. Furthermore, withanicandrin caused an anti-inflammatory effect through the reduction of abdominal edema, absence of leukocyte infiltrate in the liver tissue and reduction of ROS in thel liver tissue and presented better affinity energy compared to control morphine (TRPV1) and ibuprofen (COX-1 and COX-2).
ABSTRACT
This study reports the biotechnological importance of seven Lippia albaspecimens collected in different places in Brazil, and evaluation of some activities as larvicidal against Aedes spp., antifungal against dermatophytes; cytotoxicity against SNB-19 (astrocytoma), HCT-116 (human colon) and PC-3 (human prostate) cancer cell lines, and inhibition of the enzyme acetylcholinesterase (AChE). The essential oils, whose extraction yield was about 1.24 w/w ± 0.9%, showed differences in their chemical composition and considered as chemotypes. The essential oils containing neral and geranial as main constituents showed better action against HCT-116 cell lines (IC50 value was 9.22 µg/mL), larvicidal activity against arbovirus vectors (LC50 value against A. aegypti was 1.59 µg/mL) and inhibition of AChE (halo inhibition zone was 1 cm). The essential oils containing mainly monoterpenoids showed better antifungal action with MIC values range from 0.15 to 1.25 mg/mL. This chemical and biological characterization may be useful for biotechnological applications.
Este estudio reporta la importancia biotecnológica de siete especímenes de Lippia alba recolectados en diferentes lugares de Brasil, y evaluación de algunas actividades como larvicida contra Aedes spp., Antifúngico contra dermatofitos; citotoxicidad contra líneas celulares de cáncer SNB-19 (astrocitoma), HCT-116 (colon humano) y PC-3 (próstata humana), e inhibición de la enzima acetilcolinesterasa (AChE). Los aceites esenciales, cuyo rendimiento de extracción fue de aproximadamente 1,24 p/p ± 0,9%, mostraron diferencias en su composición química y se consideraron quimiotipos. Los aceites esenciales que contienen neral y geranial como constituyentes principales mostraron una mejor acción contra las líneas celulares HCT-116 (el valor de CI50 fue de 9.22 µg/mL), actividad larvicida contra los vectores de arbovirus (el valor de LC50 contra A. aegypti fue de 1.59 µg/mL) e inhibición de AChE (la zona de inhibición del halo era de 1 cm). Los aceites esenciales que contienen principalmente monoterpenoides mostraron una mejor acción antifúngica con valores de CMI en el rango de 0.15 a 1.25 mg/mL. Esta caracterización química y biológica puede ser útil para aplicaciones biotecnológicas.
Subject(s)
Oils, Volatile/chemistry , Lippia/chemistry , Plants, Medicinal/chemistry , Medicine, Traditional , Antineoplastic Agents/pharmacologyABSTRACT
Ouratea fieldingiana (Gardner) Engl is popularly used for wound healing. This study describes the main chemical compounds present in extracts of O. fieldingiana and evaluates their biological potential by investigating antifungal, antioxidant, and anticholinesterase activities. The action mechanism of main antifungal compound was investigated by molecular docking using the enzyme sterol 14-α demethylase, CYP51, required for ergosterol biosynthesis. The seeds and leaves were extracted with ethanol in a Soxhlet apparatus and by maceration, respectively. Both extracts were subjected to silica gel column chromatography for isolation of main constituents, followed by purification in sephadex. The structures of compounds were established by 1H and 13C-NMR spectroscopy and identified by comparison with literature data as amentoflavone and kaempferol 3-O-rutinoside, respectively. The antioxidant activities of the extracts were determined by the DPPH and ABTS free radical inhibition methods. In general, the extracts with the highest antioxidant activity corresponded to those with higher content of phenolic compounds and flavonoids. The ethanol extracts and two isolated compounds presented relevant antifungal activity against several Candida strains. The in silico findings revealed that the compound amentoflavone coupled with the CYP450 protein due to the low energy stabilization (-9.39 kcal/mol), indicating a possible mechanism of action by inhibition of the ergosterol biosynthesis of Candida fungi.
