Neuroprotective Potential of Secondary Metabolites from Melicope lunu-ankenda (Rutaceae)

Abstract

Plant natural compounds have great potential as alternative medicines for preventing and treating diseases. Melicope lunu-ankenda is one Melicope species (family Rutaceae), which is widely used in traditional medicine, consumed as a salad and a food seasoning. Consumption of different parts of this plant has been reported to exert different biological activities such as antioxidant and anti-inflammatory qualities, resulting in a protective effect against several health disorders including neurodegenerative diseases. Various secondary metabolites such as phenolic acid derivatives, flavonoids, coumarins and alkaloids, isolated from the M. lunu-ankenda plant, were demonstrated to have neuroprotective activities and also exert many other beneficial biological effects. A number of studies have revealed different neuroprotective mechanisms for these secondary metabolites. This review summarizes the most significant and recent studies for neuroprotective activity of M. lunu-ankenda major secondary metabolites in neurodegenerative diseases.

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

“…Similarly, in another study, the neuroprotective effect of caffeoylquinic acid (CQA) derivatives was established against H 2 O 2 -induced neurotoxicity in SH-SY5Y cells via inhibition of oxidative stress and activation of antioxidant defence [37]. Caffeic acid is a cinnamic acid, its neuroprotective effect at dose 222 µM was demonstrated in the pheochromocytoma (PC12) cell line against H 2 O 2 -induced cytotoxicity [17]. A further study revealed that caffeic acid at concentrations of 55.5 and 111 µM exerts neuroprotective activity against Aβ-induced neurotoxicity in pheochromocytoma (PC12) cells via impaired tau phosphorylation and phosphorylation of GSK-3β (glycogen synthase kinase-3β), impaired oxidative stress and a decrease in intracellular calcium levels [34].…”

“…The M. lunu-ankenda plant is widely used as a medicinal plant to treat diabetes mellitus, hypertension, menstrual disorders, fever, and as a tonic [15]. Hydroxycinnamic acids are secondary metabolites isolated from M. lunu-ankenda leaves and exhibit antioxidant, anti-inflammatory and neuroprotective activities via impaired H 2 O 2 -mediated oxidative damage [17]. Neuronal cells exposed to H 2 O 2 displayed enhanced intracellular defense mechanisms, including a rise in endogenous antioxidants [33].…”

“…Neuroprotective effects of caffeic acid were also reported in primary mouse cortical neurons against 5-S-cysteinyl-dopamine (CysDA)-induced cell injury at dose 1 µM of caffeic acid [19]. Ferulic acid is a hydroxycinnamic acid reported to suppress lipid peroxidation in the synaptosomal system and inhibit free radical damage in cultured neuronal cells at a concentration of 50 µM; in a study conducted in a synaptosome model and in a hippocampal neuronal cell culture, ferulic acid protected against cytotoxicity induced by hydroxyl-and peroxyl radicals [17]. Sinapic acid was studied to evaluate its free radical scavenging ability as exemplified by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay.…”

“…Phytochemicals have been used to alleviate and treat symptoms of neuronal disorders; some of these exert antioxidant and anti-inflammatory effects [13,14]. A number of secondary metabolites have been isolated from Melicope lunu-ankenda (Rutaceae), known locally in Malaysia as "tenggek burung" [15,16], such as polyphenols including hydroxycinnamic acid derivatives and hydroxybenzoic acid derivatives [17]. Polyphenols, including phenolic acids, have been demonstrated to exert neuroprotective activity through the prevention of protein oxidation, ROS generation and lipid peroxidation as well as anti-apoptotic and anti-inflammatory activities [18][19][20].…”

Cinnamic Acid Conjugates in the Rescuing and Repurposing of Classical Antimalarial Drugs

“…These acids are frequently found in a conjugated form, constituting key building blocks of complex polyphenols, such as acylated derivatives of flavonoid glycosides [5], and they have a number of biological roles in plants, from protection against microbes long been explored for their potential therapeutic applications, most of which related to their antioxidant, antimicrobial, and antineoplastic properties [4,[7][8][9][10][11][12][13][14]. The potential of CA-based compounds as therapeutic agents for other conditions, including Alzheimer's Disease [15], other nervous system disorders [16,17], acute pain [18], inflammation [19], diabetes [20,21], viral infections [22], tuberculosis [23][24][25][26], and malaria [26][27][28][29], among others, has also been addressed. Depending on their therapeutic targets, different modes of action seem to be exerted by CA and their derivatives or analogues.…”