Effect of metformin and indole-3-carbinol on a rat model of Parkinson’s disease induced by 6-hydroxydopamine

Abstract

Parkinson's disease (PD) is a motor system disorder caused by factors that lead to depletion of dopamine from the dopaminergic neurons in the substantia nigra. Mechanisms of PD include mitochondrial dysfunction, oxidative stress and neuroinflammation. Metformin is an old antidiabetic drug that has recently been shown to offer protective effects against many types of cancer, cardiovascular and neurodegenerative diseases. Indole-3-carbinol (I3C) is a phytochemical derived from the cruciform vegetables. Recently, I3C was proven to have antioxidant, anti-inflammatory and neuroprotective properties. The aim of this work was to study the effect of metformin and/or I3C on 6-hydroxydopamine (6-OHDA)-induced PD in rats. Sixty male Wistar rats were divided into 6 equal groups: Control; 6-OHDA, metformin + 6-OHDA; I3C + 6-OHDA; carboxymethyl cellulose + 6-OHDA and metformin + I3C + 6-OHDA group. Striatal dopamine, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), transforming growth factor beta1 (TGF-β1), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione reductase (GR), mitochondrial complex 1 activity, total swim score and catalepsy score were measured. The striatum was subjected to immunohistochemical examination. The combination between metformin and I3C induced significant increase in striatal SOD, GR, mitochondrial complex 1 activity and dopamine with significant decrease in striatal TNF-α, IL-6, TGF-β1, MDA and nuclear factor kappa-B expression with significant improvement in catalepsy and total swim scores better than the groups that received either I3C or metformin alone. So, metformin/I3C combination may represent a beneficial therapeutic modality for amelioration of 6-OHDAinduced PD in rats..

Current understanding and future directions of cruciferous vegetables and their phytochemicals to combat neurological diseases

“…Further, metformin and I3C combination therapy to 6‐hydroxydopamine (6‐OHDA) induced PD rats substantially ameliorated the oxidative stress, and inflammation (TNF‐α, IL‐6, TGF‐β1, and NF‐kB) and significantly elevated the mitochondrial complex I activity and striated dopamine levels. This research, therefore, demonstrated that metformin and I3C administration together protected rats from 6‐OHDA‐induced PD better than the metformin treatment alone and increased the mitochondrial complex I activity that was decreased in metformin‐treated PD rats (Borg et al, 2020). In vitro, studies revealed that I3C treatment delayed the amyloid beta (Aβ) formation (nucleation and elongation phase) (Morshedi et al, 2007) and inhibited Aβ 1‐140 aggregates and its mediated cytotoxicity (Cohen et al, 2006).…”

A New Method for the Synthesis of 1-Methyl-1H-indole-3-carboxylate Derivatives, Employing Copper(II)

“…13 C NMR (125 MHz, CDCl 3 ):  = 163. 23 50 Synthesized according to the procedure for 3a. Yield: 2.25 g (85%); white solid; mp 86-87 °C.…”

“…11 The indole ring is one of the most important structural classes in marketed drugs, such as indomethacin, 12 pravadoline, 13 delavirdine, 14 yohimbine, 15 apaziquone, 16 umifenovir, 17 and panobinostat. 18 In addition, indoles are one of the most important structural motifs among biologically active materials, such as antimicrobial agents, 19 antitumor agents, 20 anticancer agents, 21 antidiabetic agents, 22 anti-Parkinson agents, 23 antiviral agents, 24 anti-inflammatory agents, 25 anti-Alzheimer agents, 26 antibacterial agents, 27 and compounds with analgesic and antioxidant activities. 28 Furthermore, several bioactive indole-based molecules, such as tryptamine, serotonin derivatives, 29 bufotenine, 29a ergot, and vinca alkaloids, 30 have been isolated from plants, fungi, and bacteria.…”

A Brief Review of the Medicinally Important Indole Derivatives

“…Indoles are promising scaffolds in the medicinal world. Due to versatile applications of natural and synthetic indole derivatives in biological and pharmacological fields, they are being used as drugs, e.g., anti-HIV [4], anticancer [5][6], antimicrobial [7], antioxidant [8][9], anti-inflammatory [10], anticholinesterase [11], antidepressant [12], antihistaminic [13], antiparkinson [14], antitumor [15,16], tubulin inhibitors [17] and receptor inhibitors [18].…”