Neuroprotective Effects of 7-Geranyloxycinnamic Acid from Melicope lunu ankenda Leaves

Abstract

Neurodegenerative diseases (NDDs) are chronic conditions that have drawn robust interest from the scientific community. Phytotherapeutic agents are becoming an important source of chemicals for the treatment and management of NDDs. Various secondary metabolites have been isolated from Melicope lunu-ankenda plant leaves, including phenolic acid derivatives. However, their neuroprotective activity remains unclear. Thus, the aim of this study is to elucidate the in vitro neuroprotective activity of 7-geranyloxycinnamic acid isolated from Melicope lunu-ankenda leaves. The neuroprotective activity was evaluated in differentiated human neuroblastoma (SH-SY5Y) cells by monitoring cell viability using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Moreover, the potential to impair apoptosis in differentiated cells was investigated employing the Annexin V-FITC assay, acridine orange and propidium iodide (AO/PI) staining, and fluorescence microscopy. Morphological assessment and ultrastructural analysis were performed using scanning and transmission electron microscopy to evaluate the effect of 7-geranyloxycinnamic acid on surface morphology and internal features of the differentiated cells. Pre-treatment of neuronal cells with 7-geranyloxycinnamic acid significantly protected the differentiated SH-SY5Y cells against H2O2-induced apoptosis. Cytoskeleton and cytoplasmic inclusion were similarly protected by the 7-geranyloxycinnamic acid treatment. The present findings demonstrate the neuroprotective potential of 7-geranyloxycinnamic acid against H2O2-induced neurotoxicity in neuronal cells, which is an established hallmark of neuronal disorders.

A Review of the Ethnomedicinal, Phytochemical, and Anticancer Properties of Melicope Species

“…[28][29][30] These compounds have been demonstrated to exert neuroprotective, antioxidant, antiinflammatory, and anticancer activity. [27,31] The ethanolic extract (60 %) obtained from the leaves of M. lunu-ankenda demonstrated significant efficacy against HepG2 hepatocarcinoma cells, displaying an IC 50 of 20.33 � 1.5 μg/mL and 13.7 � 2.1 μg/ mL after exposure for 48 h and 72 h, respectively. [32] A phytochemical investigation of the leaves of this species revealed nine benzopyrans.…”

“…[12] Melibarbichromen B exhibited an IC 50 of 30 μM (NSA assay) and > 100 μM (MTT assay) towards ovarian (A2780) cancer cells. [31] 2.9. Melicope xanthoxyloides M. xanthoxyloides is one of the endemic plants in Papua Island, Indonesia.…”

“…This species is rich in secondary metabolites such as phenolic acid, alkaloids, benzopyran, flavonoids, and coumarins [28–30] . These compounds have been demonstrated to exert neuroprotective, antioxidant, anti‐inflammatory, and anticancer activity [27,31] . The ethanolic extract (60 %) obtained from the leaves of M. lunu‐ankenda demonstrated significant efficacy against HepG2 hepatocarcinoma cells, displaying an IC 50 of 20.33±1.5 μg/mL and 13.7±2.1 μg/mL after exposure for 48 h and 72 h, respectively [32] …”

“…The acetophenones were melibarbinon A and melibarbinon B while the three chromenes were boesenbergin A, melibarbichromen B, and alloevodionol [12] . Melibarbichromen B exhibited an IC 50 of 30 μM (NSA assay) and >100 μM (MTT assay) towards ovarian (A2780) cancer cells [31] …”

Biological Activities of Natural Products

“…Some articles concentrate on the neuroprotective and hepatoprotective activity of plant-derived substances. Mohamed et al [10] evidenced the neuroprotective effect of 7-geranyloxycinnamic acid, isolated from Melicope lunu-ankenda leaves, against H 2 O 2 -induced neurotoxicity in human neuroblastoma cells. This compound protected the cells against H 2 O 2 -induced apoptosis.…”