Geraniol Protects Against the Protein and Oxidative Stress Induced by Rotenone in an In Vitro Model of Parkinson’s Disease

Abstract

Dysfunction of autophagy, mitochondrial dynamics and endoplasmic reticulum (ER) stress are currently considered as major contributing factors in the pathogenesis of Parkinson's disease (PD). Accumulation of oxidatively damaged cytoplasmic organelles and unfolded proteins in the lumen of the ER causes ER stress and it is associated with dopaminergic cell death in PD. Rotenone is a pesticide that selectively kills dopaminergic neurons by a variety of mechanism, has been implicated in PD. Geraniol (GE; 3,7-dimethylocta-trans-2,6-dien-1-ol) is an acyclic monoterpene alcohol occurring in the essential oils of several aromatic plants. In this study, we investigated the protective effect of GE on rotenone-induced mitochondrial dysfunction dependent oxidative stress leads to cell death in SK-N-SH cells. In addition, we assessed the involvement of GE on rotenone-induced dysfunction in autophagy machinery via α-synuclein accumulation induced ER stress. We found that pre-treatment of GE enhanced cell viability, ameliorated intracellular redox, preserved mitochondrial membrane potential and improves the level of mitochondrial complex-1 in rotenone treated SK-N-SH cells. Furthermore, GE diminishes autophagy flux by reduced autophagy markers, and decreases ER stress by reducing α-synuclein expression in SK-N-SH cells. Our results demonstrate that GE possess its neuroprotective effect via reduced rotenone-induced oxidative stress by enhanced antioxidant status and maintain mitochondrial function. Furthermore, GE reduced ER stress and improved autophagy flux in the neuroblastomal SK-N-SH cells. The present study could suggest that GE a novel therapeutic avenue for clinical intervention in neurodegenerative diseases especially for PD.

Modulation of Adenosine Receptors and Antioxidative Effect of Beer Extracts in in Vitro Models

“…Rutin, a flavonoid glucoside present in several vegetables, is suggested as a multi-target preventive agent that may act as an adjuvant complementary molecule against oxidative stress in neuroblastoma IMR32 cells [66]. Geraniol has also showed a protective effect in SK-N-SH cells against oxidative stress induced by rotenone [67]. Other studies affirm that dietary flavonoids, specially flavonols, are associated with low rates of dementia in some countries [68].…”

Protective Effect of Geraniol on Oxidative, Inflammatory and Apoptotic Alterations in Isoproterenol-Induced Cardiotoxicity: Role of the Keap1/Nrf2/HO-1 and PI3K/Akt/mTOR Pathways

“…Geraniol was demonstrated to possess numerous pharmacological actions, including neuroprotective [ 13 ], antioxidant [ 13 ], antinociceptive [ 14 ], anti-inflammatory, antifungal [ 15 ], anti-arrhythmic [ 12 ], anti-osteoarthritis [ 9 ], and antitumor [ 16 ] activities. In addition, geraniol is a promising drug candidate for diverse health problems such as ulcerative colitis [ 17 ], non-alcoholic steatohepatitis [ 18 ], hyperlipidemia [ 19 ], cardiac complications of diabetes [ 10 ], and neuropathic pain [ 20 ].…”

“…Clinically, dietary geraniol might be an influential constituent as a food supplement for irritable bowel syndrome (IBS) via ameliorating intestinal dysbiosis and relieving IBS symptoms [ 21 ]. In addition, in an in vitro model of rotenone-induced Parkinson’s disease, geraniol presented a neuroprotective action by improving antioxidant status and maintaining mitochondrial function [ 13 ]. Several lines of experimental evidence addressed the therapeutic or preventive actions of geraniol as well as the underlying mechanisms in diverse types of cancer, such as breast, lung, colon, prostate, pancreatic, and hepatic cancer [ 16 ].…”

Natural Compounds and Autophagy: Allies Against Neurodegeneration

“…Geraniol, an acyclic monotherpene present in several aromatic plants, was effective to protect neurons from rotenone stress, an in vitro PD model, by recovering mitochondria and decreasing α-synuclein and improving autophagic flux (Rekha and Sivakamasundari, 2018).…”