PMID- 31185705 OWN - NLM STAT- MEDLINE DCOM- 20191128 LR - 20200225 IS - 1420-3049 (Electronic) IS - 1420-3049 (Linking) VI - 24 IP - 11 DP - 2019 Jun 10 TI - Lycopodium Attenuates Loss of Dopaminergic Neurons by Suppressing Oxidative Stress and Neuroinflammation in a Rat Model of Parkinson's Disease. LID - 10.3390/molecules24112182 [doi] LID - 2182 AB - 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 alpha-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 alpha-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. FAU - Jayaraj, Richard L AU - Jayaraj RL AD - Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates. richardlj@uaeu.ac.ae. FAU - Beiram, Rami AU - Beiram R AD - Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates. rbeiram@uaeu.ac.ae. FAU - Azimullah, Sheikh AU - Azimullah S AD - 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. FAU - Meeran, Mohamed Fizur Nagoor AU - Meeran MFN AD - Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates. nagoormeeran1985@uaeu.ac.ae. FAU - Ojha, Shreesh K AU - Ojha SK AD - Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates. shreeshojha@uaeu.ac.ae. FAU - Adem, Abdu AU - Adem A AD - 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. FAU - Jalal, Fakhreya Yousuf AU - Jalal FY AD - Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates. fakhreya@uaeu.ac.ae. LA - eng GR - UPAR 31M234/United Arab Emirates University/ PT - Journal Article DEP - 20190610 PL - Switzerland TA - Molecules JT - Molecules (Basel, Switzerland) JID - 100964009 RN - 0 (Antioxidants) RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 0 (Nitrites) RN - 0 (Plant Extracts) RN - 0 (alpha-Synuclein) RN - 03L9OT429T (Rotenone) RN - 31C4KY9ESH (Nitric Oxide) RN - 4Y8F71G49Q (Malondialdehyde) RN - EC 1.11.1.6 (Catalase) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 3.4.24.- (Matrix Metalloproteinases) RN - GAN16C9B8O (Glutathione) SB - IM MH - Animals MH - Antioxidants/metabolism MH - Brain/*pathology MH - Catalase/metabolism MH - Cyclooxygenase 2/metabolism MH - Cytokines/metabolism MH - Disease Models, Animal MH - Dopaminergic Neurons/drug effects/*pathology MH - Glutathione/metabolism MH - Inflammation/*pathology MH - Inflammation Mediators/metabolism MH - Lipid Peroxidation/drug effects MH - Lycopodium/*chemistry MH - Male MH - Malondialdehyde/metabolism MH - Matrix Metalloproteinases/metabolism MH - Microglia/drug effects/metabolism MH - Nerve Degeneration/pathology MH - Neuroprotection/drug effects MH - Nitric Oxide/metabolism MH - Nitric Oxide Synthase Type II/metabolism MH - Nitrites/metabolism MH - *Oxidative Stress/drug effects MH - Parkinson Disease/*drug therapy/*pathology MH - Plant Extracts/pharmacology/*therapeutic use MH - Rats, Wistar MH - Rotenone MH - Superoxide Dismutase/metabolism MH - alpha-Synuclein/metabolism PMC - PMC6600474 OTO - NOTNLM OT - Parkinson's disease OT - lycopodium OT - matrix metalloproteinase OT - neurodegeneration OT - neuroinflammation OT - oxidative stress COIS- The authors declare no conflict of interest. EDAT- 2019/06/13 06:00 MHDA- 2019/11/30 06:00 PMCR- 2019/06/10 CRDT- 2019/06/13 06:00 PHST- 2019/05/02 00:00 [received] PHST- 2019/05/26 00:00 [revised] PHST- 2019/06/04 00:00 [accepted] PHST- 2019/06/13 06:00 [entrez] PHST- 2019/06/13 06:00 [pubmed] PHST- 2019/11/30 06:00 [medline] PHST- 2019/06/10 00:00 [pmc-release] AID - molecules24112182 [pii] AID - molecules-24-02182 [pii] AID - 10.3390/molecules24112182 [doi] PST - epublish SO - Molecules. 2019 Jun 10;24(11):2182. doi: 10.3390/molecules24112182.