Narudol Teerapattarakan1, Hattaya Benya-Aphikul2, Rossarin Tansawat3, Oraphan Wanakhachornkrai4, Mayuree H Tantisira5, Ratchanee Rodsiri6. 1. Inter-Disciplinary Program of Pharmacology, Graduate School, Chulalongkorn University, Bangkok 10330, Thailand; Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand. 2. Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand. 3. Department of Food and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand. 4. Physiology Unit, Department of Medical Sciences, Faculty of Sciences, Rangsit University, Pathumthani 12000, Thailand. 5. Faculty of Pharmaceutical Sciences, Burapha University, Chonburi 20131, Thailand. 6. Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand. Electronic address: ratchanee.r@pharm.chula.ac.th.
Abstract
BACKGROUND: Mitochondrial dysfunction and reactive oxygen species (ROS) generation cause dopaminergic neurodegeneration in Parkinson's disease. The neuroprotective approach is a promising strategy to slow disease progression in Parkinson's disease. A standardized extract of Centella asiatica ECa233 has been previously reported to have pharmacological effects in the central nervous system. PURPOSE: This study aimed to determine the neuroprotective effect and mechanisms of ECa233 in rotenone-induced parkinsonism rats. METHODS: Rats were orally given either vehicle or ECa233 (10, 30 and 100 mg/kg) for 20 consecutive days. Rotenone (2.5 mg/kg i.p.) was given to parkinsonism (PD) and ECa-treated rats from day 15 to 20. Locomotor activity was recorded on day 1, 14, 17 and 20. Tyrosine-hydroxylase (TH) immunohistological staining was used to determine dopaminergic neurons in the substantia nigra and striatum. Furthermore, mitochondrial complex I activity, malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase protein expression were measured in brain tissue. RESULTS: Rats receiving ECa233 30 mg/kg showed a significant increase in distances (p < 0.01) together with a higher number and intensity of dopaminergic neurons in the substantia nigra and striatum (p < 0.001) compared to PD rats. ECa233 (30 mg/kg) protected against mitochondrial complex I inhibition, decreased MDA levels (p < 0.05) and increased SOD (p < 0.01) and catalase (p < 0.05) expression. CONCLUSION: ECa233 can protect against rotenone-induced motor deficits and dopaminergic neuronal death. These effects are mediated through the protection of mitochondrial complex I activity, the effects of antioxidants and the enhancement of antioxidant enzyme expression.
BACKGROUND:Mitochondrial dysfunction and reactive oxygen species (ROS) generation cause dopaminergic neurodegeneration in Parkinson's disease. The neuroprotective approach is a promising strategy to slow disease progression in Parkinson's disease. A standardized extract of Centella asiatica ECa233 has been previously reported to have pharmacological effects in the central nervous system. PURPOSE: This study aimed to determine the neuroprotective effect and mechanisms of ECa233 in rotenone-induced parkinsonismrats. METHODS:Rats were orally given either vehicle or ECa233 (10, 30 and 100 mg/kg) for 20 consecutive days. Rotenone (2.5 mg/kg i.p.) was given to parkinsonism (PD) and ECa-treated rats from day 15 to 20. Locomotor activity was recorded on day 1, 14, 17 and 20. Tyrosine-hydroxylase (TH) immunohistological staining was used to determine dopaminergic neurons in the substantia nigra and striatum. Furthermore, mitochondrial complex I activity, malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase protein expression were measured in brain tissue. RESULTS:Rats receiving ECa233 30 mg/kg showed a significant increase in distances (p < 0.01) together with a higher number and intensity of dopaminergic neurons in the substantia nigra and striatum (p < 0.001) compared to PDrats. ECa233 (30 mg/kg) protected against mitochondrial complex I inhibition, decreased MDA levels (p < 0.05) and increased SOD (p < 0.01) and catalase (p < 0.05) expression. CONCLUSION: ECa233 can protect against rotenone-induced motor deficits and dopaminergic neuronal death. These effects are mediated through the protection of mitochondrial complex I activity, the effects of antioxidants and the enhancement of antioxidant enzyme expression.
Authors: Jose Ivo A Beserra-Filho; Amanda Maria-Macêdo; Suellen Silva-Martins; Ana Cláudia Custódio-Silva; Beatriz Soares-Silva; Sara Pereira Silva; Rafael Herling Lambertucci; Adriano Antunes de Souza Araújo; Angélica Maria Lucchese; Lucindo J Quintans-Júnior; José Ronaldo Santos; Regina H Silva; Alessandra M Ribeiro Journal: Metab Brain Dis Date: 2022-07-02 Impact factor: 3.655