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Lycopodium Attenuates Loss of Dopaminergic Neurons by Suppressing Oxidative Stress and Neuroinflammation in a Rat Model of Parkinson's Disease.
Molecules. 2019 Jun 10; 24(11)M

Abstract

Parkinson's disease, a chronic, age related neurodegenerative disorder, is characterized by a progressive loss of nigrostriatal dopaminergic neurons. Several studies have proven that the activation of glial cells, presence of alpha-synuclein aggregates, and oxidative stress, fuels neurodegeneration, and currently there is no definitive treatment for PD. In this study, a rotenone-induced rat model of PD was used to understand the neuroprotective potential of Lycopodium (Lyc), a commonly-used potent herbal medicine. Immunohistochemcial data showed that rotenone injections significantly increased the loss of dopaminergic neurons in the substantia nigra, and decreased the striatal expression of tyrosine hydroxylase. Further, rotenone administration activated microglia and astroglia, which in turn upregulated the expression of α-synuclein, pro-inflammatory, and oxidative stress factors, resulting in PD pathology. However, rotenone-injected rats that were orally treated with lycopodium (50 mg/kg) were protected against dopaminergic neuronal loss by diminishing the expression of matrix metalloproteinase-3 (MMP-3) and MMP-9, as well as reduced activation of microglia and astrocytes. This neuroprotective mechanism not only involves reduction in pro-inflammatory response and α-synuclein expression, but also synergistically enhanced antioxidant defense system by virtue of the drug's multimodal action. These findings suggest that Lyc has the potential to be further developed as a therapeutic candidate for PD.

Authors+Show Affiliations

Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates. richardlj@uaeu.ac.ae.Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates. rbeiram@uaeu.ac.ae.Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates. azim.sheikh@uaeu.ac.ae.Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates. nagoormeeran1985@uaeu.ac.ae.Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates. shreeshojha@uaeu.ac.ae.Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates. abdu.adem@uaeu.ac.ae.Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates. fakhreya@uaeu.ac.ae.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31185705

Citation

Jayaraj, Richard L., et al. "Lycopodium Attenuates Loss of Dopaminergic Neurons By Suppressing Oxidative Stress and Neuroinflammation in a Rat Model of Parkinson's Disease." Molecules (Basel, Switzerland), vol. 24, no. 11, 2019.
Jayaraj RL, Beiram R, Azimullah S, et al. Lycopodium Attenuates Loss of Dopaminergic Neurons by Suppressing Oxidative Stress and Neuroinflammation in a Rat Model of Parkinson's Disease. Molecules. 2019;24(11).
Jayaraj, R. L., Beiram, R., Azimullah, S., Meeran, M. F. N., Ojha, S. K., Adem, A., & Jalal, F. Y. (2019). Lycopodium Attenuates Loss of Dopaminergic Neurons by Suppressing Oxidative Stress and Neuroinflammation in a Rat Model of Parkinson's Disease. Molecules (Basel, Switzerland), 24(11). https://doi.org/10.3390/molecules24112182
Jayaraj RL, et al. Lycopodium Attenuates Loss of Dopaminergic Neurons By Suppressing Oxidative Stress and Neuroinflammation in a Rat Model of Parkinson's Disease. Molecules. 2019 Jun 10;24(11) PubMed PMID: 31185705.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lycopodium Attenuates Loss of Dopaminergic Neurons by Suppressing Oxidative Stress and Neuroinflammation in a Rat Model of Parkinson's Disease. AU - Jayaraj,Richard L, AU - Beiram,Rami, AU - Azimullah,Sheikh, AU - Meeran,Mohamed Fizur Nagoor, AU - Ojha,Shreesh K, AU - Adem,Abdu, AU - Jalal,Fakhreya Yousuf, Y1 - 2019/06/10/ PY - 2019/05/02/received PY - 2019/05/26/revised PY - 2019/06/04/accepted PY - 2019/6/13/entrez PY - 2019/6/13/pubmed PY - 2019/11/30/medline KW - Parkinson’s disease KW - lycopodium KW - matrix metalloproteinase KW - neurodegeneration KW - neuroinflammation KW - oxidative stress JF - Molecules (Basel, Switzerland) JO - Molecules VL - 24 IS - 11 N2 - Parkinson's disease, a chronic, age related neurodegenerative disorder, is characterized by a progressive loss of nigrostriatal dopaminergic neurons. Several studies have proven that the activation of glial cells, presence of alpha-synuclein aggregates, and oxidative stress, fuels neurodegeneration, and currently there is no definitive treatment for PD. In this study, a rotenone-induced rat model of PD was used to understand the neuroprotective potential of Lycopodium (Lyc), a commonly-used potent herbal medicine. Immunohistochemcial data showed that rotenone injections significantly increased the loss of dopaminergic neurons in the substantia nigra, and decreased the striatal expression of tyrosine hydroxylase. Further, rotenone administration activated microglia and astroglia, which in turn upregulated the expression of α-synuclein, pro-inflammatory, and oxidative stress factors, resulting in PD pathology. However, rotenone-injected rats that were orally treated with lycopodium (50 mg/kg) were protected against dopaminergic neuronal loss by diminishing the expression of matrix metalloproteinase-3 (MMP-3) and MMP-9, as well as reduced activation of microglia and astrocytes. This neuroprotective mechanism not only involves reduction in pro-inflammatory response and α-synuclein expression, but also synergistically enhanced antioxidant defense system by virtue of the drug's multimodal action. These findings suggest that Lyc has the potential to be further developed as a therapeutic candidate for PD. SN - 1420-3049 UR - https://www.unboundmedicine.com/medline/citation/31185705/Lycopodium_Attenuates_Loss_of_Dopaminergic_Neurons_by_Suppressing_Oxidative_Stress_and_Neuroinflammation_in_a_Rat_Model_of_Parkinson's_Disease_ DB - PRIME DP - Unbound Medicine ER -