Aqueous Extract of Dendropanax morbiferus Leaves Effectively Alleviated Neuroinflammation and Behavioral Impediments in MPTP‐Induced Parkinson’s Mouse Model

Abstract

Parkinson's disease (PD) is a commonly reported age-related neurodegenerative disorder. Microglial-mediated neuroinflammation is one of the cardinal hallmarks of various neurodegenerative disorders, including PD progression. Inadequate therapeutic strategies and substantial adverse effects of well-established drug candidates demand new therapeutic leads to treat PD. Dendropanax morbifera (DM) is an endemic plant species of South Korea, and it has been used extensively as traditional medicine to treat numerous clinical complications. In this study, we conducted an initial profiling of the few major phytoconstituents of aqueous DM leaf extracts (DML) and quantified the same using high-performance liquid chromatography tandem mass spectrometry with electrospray ionization (HPLC-ESI-MS/MS). We subsequently evaluated the antineuroinflammatory activity and ameliorative potential of DML in both in vitro and in vivo experimental PD models. The prophylactic treatment of DML effectually improved the behavioral deficits, curbed the microglial-mediated neuroinflammation, and protected dopaminergic (DA) neuronal loss by restoring tyrosine hydroxylase (TH) levels in brain tissue of the MPTP-induced PD mouse model. We conducted chromatographic profiling and identified chlorogenic acid (CA) as a major constituent (19.5 mg/g of BuOH fraction), which has been well documented as an antioxidant and anti-inflammatory agent. This was found to be in harmony with our in vitro results, where DML suppressed the level of inflammatory mediators and allied the signaling pathway in LPS-stimulated microglial cells. The results of our study indicate that DML and its bioactive constituents can be developed as potential therapeutic candidates against progressive PD complications.

Neurobehavioral and neuroprotective role of captopril in the rotenone model of rat Parkinsonism

“…(Carvalho et al, 2013) Captopril has shown signi icant improvement in motor coordina- tion, as evidenced through the rotarod test. Similarly improved motor co-ordination preventing the rat or mice from falling from the rotarod has been recorded after the administration of Dendropanax morbiferus leaves (Park et al, 2018) Apium graveolens (Chonpathompikunlert et al, 2018) (MPTP model), Juniperus communis (Bais et al, 2015) (CPZ model), caffeine (Khadrawy et al, 2017) (rotenone model) and with many other chine herbal medicines. (Kum et al, 2011;Pan et al, 2011) However, in the present study, captopril has not shown signi icant improvement in spontaneous locomotor activity in the rotenone model.…”

Metal Chelation Therapy and Parkinson’s Disease: A Critical Review on the Thermodynamics of Complex Formation between Relevant Metal Ions and Promising or Established Drugs

“…Creatine [179,180] Cudraflavone B [181] Curcumin [89,117,[182][183][184] Cyanidin [185,186] D-512 [187] D-607 (bipyridyl-D2R/D3R agonist hybrid) [12,188,189] DA-2 (8D) [12,89] DA-3 [12] DA-4 [12] Dabigatran etexilate [190] Dabrafenib [191] (S)-3,4-DCPG [115] Deferasirox [24] Deferricoprogen [192] Delphinidin [160,185,193,194] Demethoxycurcumin [195] Dendropanax morbifera active compound [196] Desferrioxamine (Desferoxamine, Desferal, DFO) [112] (S)-N-(3-(3,6-Dibromo-9H -carbazol-9-yl)-2-fluoropropyl)-6-methoxypyridin-2-amine [197] 4,5-O-Dicaffeoyl-1-O-(malic acid methyl ester)-quinic acid derivatives (R1, R2, R3, R4, or R5 = caffeoyl) [198] Dihydromyricetin [199]…”

Anti-Melanogenic Effect of Dendropanax morbiferus and Its Active Components via Protein Kinase A/Cyclic Adenosine Monophosphate-Responsive Binding Protein- and p38 Mitogen-Activated Protein Kinase-Mediated Microphthalmia−Associated Transcription Factor Downregulation

“…Dendropanax morbiferus H. Lev, an endemic species in South Korea, has been used as an alternative traditional medicine for several diseases, such as headache, dysmenorrhea, infectious disorders, and skin disorders, for a long time (Jeong et al, 1995;Park et al, 2004;Lim et al, 2015). There are some reports that D. morbiferus shows anti-hyperuricemic, antiamnesic, anti-obesity, immunomodulatory, and antiinflammatory activities (Birhanu et al, 2018;Cho et al, 2018;Park et al, 2018a;Park et al, 2018b;Song et al, 2018;Sun et al, 2018b;Choo et al, 2019). The corresponding ingredients isolated from D. morbiferus leaves, such as 1-tetradecanol, dendropanoxide, rutin, gentisic acid, or oleifoliosides, have been reported to have diverse therapeutic potentials (Yu et al, 2012;Lee et al, 2013;Park et al, 2014;Park et al, 2017;Sun et al, 2018a).…”