Sidharth Mehan, Sanjeev Kalra, Raghuvir Singh, Mohit Mehta and Deepa Khanna
Accepted Abstracts: J Neurol Neurophysiol
Huntington?s disease (HD) is an autosomal dominantly inherited progressive neurodegenerative disorder, characterized by progressively worsening chorea, psychiatric disturbances, cognitive impairment and weight loss. The degenerative process primarily involves medium spiny striatal neurons (MSN) and to a lesser extent cortical neurons. Importantly, γ-amino butyric acid (GABA)ergic projection neurons of the striatum, which make up roughly 90% of the striatal neurons are the most vulnerable in HD and their early dysfunction is responsible for the development of chorea. Fruits of G. mangostana are the most treasured part of this plant and are famous for the remarkably pleasant flavour. Over the past decades, it is shown that mangosteen contains high amounts of xanthones, a class of polyphenolic compounds which are shown to have significant biological activities in in-vitro systems. Dried and powdered fruit hull is used as antimicrobial agents and for the anti-parasitic treatments in dysentery as well as externally for healing wounds, suppurations and chronic ulcers. 1,2-Dihydro-1,8,10- trihydroxy-2- (2-hydroxypropan-2-yl)-9-(3-methylbut-2-enyl)furo[3,2-a] xanthen-11-one, 6-deoxy-7-demethylmangostanin, 1,3,7-trihydroxy-2,8-di-(3-methylbut-2-enyl)-xanthone and mangostanin induced quinone reductase in the Hepa 1c1c7 cell line in an in vitro screening assay (IC50, 0.68-2.2 μg/mL) whereas γ-mangostin exhibited hydroxyl radical-scavenging activity (IC50, 0.20 μg/mL). Antioxidant activities are also shown for 8-hydroxycudraxanthone, gartanin, α-mangostin, γ-mangostin and smeathxanthone A using authentic and morpholinosydnonimine-derived peroxynitrite methods. An extract of G. mangostana is reported to have very good antioxidant action in the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) assay. The extract inhibited 50% of free radicals at a concentration of 6.13 μg/mL. In addition, this extract showed high inhibition on TNF-α production generated from peripheral blood mononuclear cells (PBMC) stimulated with Propionibacterum acnes. Therefore this plant is claimed to have a remarkable antiinflammatory effect and to reduce cell damage. A vast number of studies have demonstrated the anti-inflammatory properties of mangosteen. In a clinical study, mangosteen juice exhibited potential anti-inflammatory potential. Primary human adipocytes treated with xanthones, the major bioactive compounds found in mangosteen, demonstrated reduced LPS-induced expression of pro-inflammatory genes (i.e. TNF-α, IL-6, IFN-γ and IL-10) In RAW264.7 macrophage cells, mangosteen extract, α-mangostin and γ-mangostin demonstrated a clear ability to inhibit NO and PGE2 release, along with the gene encoding iNOS and COX-2. Anti-inflammatory mechanism of γ-Mangostin via inhibition of spontaneously PGE(2) release in a concentration-dependent manner as well as inhibit of lipopolysaccharide (LPS)-induced expression of COX-2 protein and its mRNA. γ-Mangostin also inhibits cyclooxygenase and prostaglandin E2 synthesis. Where, both α-Mangostin & γ-Mangostin showed anti-inflammatory activity by inhibition of inducible NO synthase. Currently available drugs provide symptomatic relief but do not stop progression of disease. Thus, the development of new therapeutic strategies remains an unmet medical need. Failure of current drug therapy may be due to their action at only one of many neurotransmitters involved or their inability to upregulate signaling messengers reported to have important role in neuronal functioning, neurotransmitter biosynthesis and release neuronal growth and differentiation, synaptic plasticity and cognitive functioning. Therefore, as already mentioned above, one of the alternatives to restore the anti-oxidant defence mechanism as well to inhibit inflammatory cytokines which are mainly involved in the preogression of Huntington?s diseases. Based on important and versatile role of Mangosteen in prevention of oxidation and inflammation, it may be possible protective strategies of Mangosteen: Garcinia Mangostana in Huntington?s disease and to find out if both complications are equally implicated in the disease pathogenesis or progression.
