Search for


TEXT SIZE

search for



CrossRef (0)
Natural Products as Potential Therapeutic Strategies for Parkinson's Disease
Biomed Sci Letters 2023;29:121-129
Published online September 30, 2023;  https://doi.org/10.15616/BSL.2023.29.3.121
© 2023 The Korean Society For Biomedical Laboratory Sciences.

Hae-Rim Cha1,*, Mi-Ran Lee2,** and Hyun-Jeong Cho1,†,**

1Department of Biomedical Laboratory Science, College of Medical Science, Konyang University, Daejeon 35365, Korea
2Department of Biomedical Laboratory Science, Jungwon University, Chungcheongbuk-do 28024, Korea
Correspondence to: Hyun-Jeong Cho. Department of Biomedical Laboratory Science, College of Medical Science, Konyang University, Daejeon 35365, Korea.
Tel: +82-42-600-8433, Fax: +82-42-600-8408, e-mail: hjcho@konyang.ac.kr
*Graduate student, **Professor.
Received July 21, 2023; Accepted September 5, 2023.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
 Abstract
Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects millions of people worldwide. The conventional treatment model for PD have harmful side effects, such as dyskinesia, hallucinations, nausea, and fatigue, and are expensive. As a result, natural products derived from medicinal herbs, fruits, and vegetables have emerged as potential therapeutic strategies for PD. These natural products have been traditionally used to treat various diseases and have been shown to possess anti-oxidative and anti-inflammatory properties, as well as inhibitory roles in protein misfolding, mitochondrial homeostasis, neuroinflammation and other neuroprotective processes. In addition, they have fewer side effects and are generally less expensive than conventional drugs. It also discusses the limitations of current treatments and the potential of natural remedies derived from plants to treat PD in new ways or as supplements to existing treatments. The multifunctional mechanisms of medicinal plants that may be utilized to treat PD are also discussed, including the modulation of neurotransmitter systems, the enhancement of neurotrophic factors, and the inhibition of apoptosis. While more research is needed to fully understand their mechanisms of action and efficacy, natural products have the potential to provide safer and more effective treatment options for patients with PD.
Keywords : Parkinson's disease, Natural products, Mitochondria dysfunction, α-synuclein, Neuroinflammation, Autophagy
1. 꽌濡

뙆궓뒯蹂(Parkinson's disease, PD) 슦슱利, 遺덉븞 諛 젙떊蹂묎낵 媛숈 젙떊怨쇱쟻 利앹긽쓣 룷븿븯뿬 슫룞셿꽌, 븞젙 떆 뼥由, 洹쇱쑁 寃쎌쭅 諛 遺덇퇏삎 벑 떎닔쓽 슫룞옣븷 利앹긽 쑀諛쒖쓣 듅吏뺤쑝濡 븯뒗 쟾 꽭怨꾩뿉꽌 몢 踰덉㎏濡 쓷븳 떊寃 눜뻾꽦 옣븷씠떎(Goetz, 2011). 뙆궓뒯蹂묒쓽 쑀蹂묐쪧 굹씠媛 뱾닔濡 利앷븯硫 룊깮 룞븞 諛쒕퀝븷 쐞뿕꽦 궓꽦쓽 寃쎌슦 2.0%, 뿬꽦쓽 寃쎌슦 1.3%씠떎(Schneider et al., 2017). 씠 吏덊솚 씪諛섏쟻쑝濡 以묎컙뇤쓽 쓳깋吏 移섎遺(substantia nigra pars compacta, SNpc)뿉꽌 룄뙆誘쇱꽦 떊寃쎌꽭룷(DA neuron)쓽 議곌린 궗硫멸낵 Lewy 냼泥 諛 Lewy 떊寃쎈룎湲곗쓽 썝씤씠 릺뒗 慣-synuclein 떒諛깆쭏쓽 鍮꾩젙긽쟻씤 쓳吏묒껜 利앷瑜 듅吏뺤쑝濡 븳떎(Kalia and Lang, 2015). 吏덈퀝쓽 紐낇솗븳 썝씤 븘吏 븣젮吏吏 븡븯吏留 궛솕뒪듃젅뒪, 誘명넗肄섎뱶由ъ븘 湲곕뒫옣븷, 鍮꾩젙긽쟻씤 떒諛깆쭏 쓳吏 諛 옄媛룷떇 옣븷 벑씠 蹂묒씤씠 맆 닔 엳떎.

吏湲덇퉴吏 뙆궓뒯蹂묒쓽 二쇱슂 移섎즺踰뺤 Levodopa 媛숈 룄뙆誘 泥댁슂踰뺤씠吏留 옣湲 궗슜 떆 援ъ뿭, 援ы넗, 뼱吏읆利, 씠긽슫룞利 벑쓽 遺옉슜쓣 쑀諛쒗븯硫 뙆궓뒯蹂 옱諛 솗瑜좎씠 넂 떒젏씠 엳怨(Aquino and Fox, 2015), 솚옄뿉寃 쁺援ъ쟻씤 移섎즺쟻 씠젏씠 쟻떎. 쁽옱 留롮 뿰援ъ옄뱾씠 뙆궓뒯蹂묒쓽 떊寃 눜뻾 怨쇱젙쓣 뒭異붽린 쐞빐 끂젰븯怨 엳쑝굹, 엫긽 뙆궓뒯蹂 솚옄뿉寃 떊寃쎈낫샇 삉뒗 吏덈퀝 議곗젅 슚怨쇨 엳뒗 寃껋쑝濡 엯利앸맂 빟臾쇱 뾾떎.

븳렪 愿묐쾾쐞븳 泥쒖뿰 솕븰臾쇱쭏뱾씠 뙆궓뒯蹂 移섎즺瑜 쐞븳 泥 쓽빟뭹쑝濡 몢릺怨 엳쑝硫(Sharma et al., 2018), 쁺뼇遺꾩빞 怨쇳븰옄뱾 뙆궓뒯蹂 利앹긽쓣 셿솕븯怨 빆뙆궓뒯 愿젴 빟臾쇱쓽 슜웾 諛 湲곌컙뿉 뵲瑜 遺옉슜쓣 以꾩씠湲 쐞븯뿬 湲곗〈 빟臾쇱슂踰뺤쓽 蹂댁“쟻씤 移섎즺踰뺤쑝濡 泥쒖뿰臾쇱쓣 젣븞븳떎. 洹 삁濡 泥쒖뿰 뿀釉뚯젣뭹怨 빆뙆궓뒯 빟臾쇱쓽 蹂묒슜슂踰뺤 Levodopa濡 옣湲곌컙 移섎즺븳 썑쓽 빀蹂묒쬆쓣 셿솕븯뒗뜲 긽떦븳 씠젏씠 엳뒗 寃껋쑝濡 굹궗떎(Rao et al., 2006). 뵆씪蹂대끂씠뱶(flavonoid) 諛 븣移쇰줈씠뱶(alkaloid) 媛숈 떇臾쇱쓽 깮泥댄솢꽦 쑀룄泥대뒗 빆궛솕 諛 빆뿼利앹쓽 듅꽦씠 엳쑝硫, 씠윭븳 옄뿰諛쒖깮 솕빀臾쇱 誘명넗肄섎뱶由ъ븘 湲곕뒫쓣 媛뺥솕븯怨 媛뺣젰븳 씤吏 媛뺥솕젣 뿭븷쓣 븷 닔 엳떎(Essa et al., 2012).

뵲씪꽌 빀꽦솕빀臾쇱쓽 궗쉶寃쎌젣쟻씤 遺떞怨 뿬윭 遺옉슜쓣 怨좊젮뻽쓣 븣, 泥쒖뿰臾 궗슜 뙆궓뒯蹂 移섎즺뿉 엳뼱 쑀留앺븳 諛⑸쾿쑝濡 젣떆릺怨 엳떎.

2. 뙆궓뒯蹂묒쓽 蹂묐━ 쁽긽

以묒텛떊寃쎄퀎(CNS)뿉꽌 떊寃 빆긽꽦쓽 쑀吏뒗 以묒슂븯硫, 룄뙆誘쇱꽦 떊寃쎌꽭룷쓽 궗硫몄 뙆궓뒯蹂묎낵 媛숈 떊寃쏀눜뻾 긽깭쓽 썝씤씠 릺硫(MacMahon Copas et al., 2021), 뙆궓뒯蹂묒쓽 蹂묐━븰쟻 듅吏뺤씠 굹굹뒗 SNpc뿉꽌 룄뙆誘쇱꽦 돱윴쓽 젏吏꾩쟻씤 눜뻾쑝濡 꽑議곗껜(striatum) 諛 뵾媛(putamen)쓽 룄뙆誘 닔移섎뒗 젏李 媛먯냼븳떎. 吏덈퀝쓽 二쇱슂 슫룞 利앹긽 룄뙆誘쇱꽦 떊寃쎌꽭룷媛 50~60% 뙆愿대릺怨, 꽑議곗껜쓽 룄뙆誘 닔移섍 80~85% 媛먯냼뻽쓣 븣 굹굹湲 떆옉븳떎(Agid, 1991; Obeso et al., 2017). 삉븳, 뙆궓뒯蹂 솚옄쓽 궗썑 뇤 議곗쭅쓽 쓳깋吏덉 깉깋릺뼱 엳뒗뜲(Lees et al., 1988), 쟻떦븳 닔以쓽 硫쒕씪땶쓣 룷븿븯怨 엳뒗 룄뙆誘쇱꽦 돱윴쓽 궗硫몃줈 씤빐 諛쒖깮븳떎(Hacker et al., 2012; Luo et al., 2014; Prodoehl et al., 2014). 씠윭븳 蹂묐━쟻 利앹긽쓣 굹궡뒗 뙆궓뒯蹂묒 떊寃 蹂꽦쓣 쑀諛쒗븯뒗 븘옒 媛숈 떎뼇븳 썝씤뿉 쓽빐 諛쒖깮븳떎.

2.1 뙆궓뒯蹂묒쓽 誘명넗肄섎뱶由ъ븘 湲곕뒫옣븷

룄뙆誘쇱꽦 돱윴 넂 誘명넗肄섎뱶由ъ븘 뿉꼫吏 슂援 궗濡 留ㅼ슦 솢룞쟻씠硫, 넀긽릺硫 湲곕뒫옣븷濡 씠뼱吏寃 맂떎(Haddad and Nakamura, 2015). 誘명넗肄섎뱶由ъ븘 湲곕뒫옣븷 궛솕뒪듃젅뒪쓽 利앷뒗 洹쇰낯쟻씤 硫붿빱땲利섏씠 紐낇솗븯吏 븡吏留 뙆궓뒯蹂묒쓽 蹂묒씤뿉 以묒슂븳 뿭븷쓣 븯뒗 寃껋쑝濡 엯利앸릺뿀떎. 誘명넗肄섎뱶由ъ븘 湲곕뒫옣븷뒗 二쇰줈 諛섏쓳꽦 궛냼 醫(ROS)쓽 깮꽦, 誘명넗肄섎뱶由ъ븘 蹂듯빀泥 I 슚냼 솢꽦쓽 媛먯냼, Cytochrome C 諛⑹텧, ATP 怨좉컝 諛 caspase 3 솢꽦솕瑜 듅吏뺤쑝濡 븳떎. 誘명넗肄섎뱶由ъ븘 蹂듯빀泥 I 寃고븤 듅諛쒖꽦 뙆궓뒯蹂묒쓽 蹂묒씤怨 愿젴븯뿬 쓳깋吏덉뿉꽌 ROS瑜 삎꽦븯怨, ROS뒗 돱윴쓽 셿쟾꽦쓣 넀긽떆耳 돱윴쓽 눜솕瑜 媛냽븳떎(Engelhardt, 1999). 誘명넗肄섎뱶由ъ븘 궗 以묐떒쓽 媛옣 吏곸젒쟻씤 利앷굅뒗 遺寃 議곗쭅 諛 洹 쇅 議곗쭅 깦뵆쓣 궗슜븳 뿰援ъ 솚옄濡쒕꽣 쑀옒븳 泥댁쇅 꽭룷 諛곗뼇뿉꽌 李얠쓣 닔 엳떎(Henchcliffe and Beal, 2008). 삉븳 뙆궓(Parkin) 寃고븤 伊먯 뙆궓뒯蹂 珥덊뙆由 紐⑤뜽뿉꽌룄 誘명넗肄섎뱶由ъ븘 씠긽씠 蹂닿퀬릺뿀떎(Palacino et al., 2004; Shim et al., 2011). 궗썑 뿰援ъ뿉꽌뒗 궛솕쟻 넀긽쓽 紐 媛吏 marker 닔以씠 利앷뻽쓬쓣 솗씤븯怨, 듅엳 吏吏, 떒諛깆쭏 諛 DNA뿉 븳 궛솕쟻 넀긽씠 궛諛쒖쟻 뙆궓뒯蹂 솚옄쓽 뇤쓽 SNpc뿉꽌 愿李곕릺뿀떎(Jenner, 2007).

2.2 뙆궓뒯蹂묒쓽 Lewy 냼泥 諛 慣-synuclein

뇤以꾧린 諛 以묎컙뇤빑뿉꽌쓽 吏꾪뻾꽦 떊寃쎌꽭룷 넀떎怨 Lewy 냼泥 諛 Lewy 떊寃쎈룎湲 삎깭쓽 慣-synuclein 떒諛깆쭏쓽 愿묐쾾쐞븳 쓳吏묒 뙆궓뒯蹂묒쓽 떊寃쎈퀝由ы븰쟻 듅吏뺤씠떎(Spillantini et al., 1997). Lewy 떊寃쎈룎湲곕뒗 Lewy 냼泥댁뿉꽌 諛쒓껄릺뒗 쑀궗븳 怨쇰┰臾쇱쭏怨 慣-synuclein 꽟쑀吏덉쓣 룷븿븯뒗 鍮꾩젙긽쟻씤 떊寃쎈룎湲곕줈 Lewy 떊寃쎈룎湲곕뒗 Lewy 냼泥대낫떎 쓳吏묐맂 삎깭씠硫 遺遺꾩쓽 뙆궓뒯蹂 궗濡뿉꽌 렪룄泥댁 꽑議곗껜뿉 異뺤쟻맂떎(Duda et al., 2002; Braak et al., 2003). Lewy 떊寃쎈룎湲곕뒗 異뺤궘 닔넚 諛 湲고 以묒슂븳 꽭룷 怨쇱젙쓣 諛⑺빐븯뿬 떊寃 湲곕뒫 諛 꽭룷깮議댁쓣 넀긽떆궗 닔 엳떎(Morfini et al., 2009; Perlson et al., 2010). 떎닔쓽 룞臾 紐⑤뜽 諛 깮솕븰쟻 뿰援ъ뿉꽌 慣-synuclein쓽 꽟쑀 삎깭媛 뙆궓뒯蹂묒쓽 떊寃 蹂꽦 怨쇱젙뿉 湲곗뿬븯뒗 珥덇린 룆꽦엫씠 븣젮졇 엳떎(Emmanouilidou et al., 2010; Winner et al., 2011; Choi et al., 2013; Roberts et al., 2015).

2.3 뙆궓뒯蹂묒쓽 떊寃쎌뿼利

뿼利앹 넀긽쓣 쑀諛쒗븯뒗 씤옄濡쒕꽣 닕二쇰 蹂댄샇븯怨 議곗쭅蹂듦뎄瑜 珥됱쭊븯뒗 寃껋쓣 紐⑺몴濡 議곗젅릺뒗 硫붿빱땲利섏씠떎. 씠 愿젴빐 以묒텛떊寃쎄퀎(CNS)뿉꽌뒗 蹂묒썝泥 愿젴 遺꾩옄 뙣꽩(PAMP)怨 넀긽 愿젴 遺꾩옄 뙣꽩(DAMP)뿉 븳 媛뺣젰븳 꽑泥 硫댁뿭諛섏쓳씠 쑀룄맆 닔 엳떎. 삉븳 誘몄꽭븘援먯꽭룷(microglia) 蹂꾩븘援먯꽭룷(astrocyte) 媛숈 떊寃쎌븘援먯꽭룷뒗 넀긽맂 돱윴 삉뒗 떒諛깆쭏 쓳吏묒껜쓽 遺꾨퉬씤옄씤 PAMP DAMP뿉 쓽빐 솢꽦솕릺뼱 吏냽쟻씤 떊寃쎌뿼利앹쓣 쑀諛쒗븷 닔 엳떎. 留뚯꽦 떊寃쎌뿼利앹 뙆궓뒯蹂묒뿉꽌 吏덈퀝 吏꾪뻾쓽 蹂댁“씤옄濡 諛앺議뚯쑝硫(Chen and Trapp, 2016), 뿼利앹 꽭룷궗硫몄쓽 寃곌낵씪 닔룄 엳吏留, 慣-synuclein 쓳吏묒쓽 吏곸젒쟻씤 뿭븷씪 닔룄 엳떎. 慣-synuclein怨 媛숈 옒紐 젒엺 떒諛깆쭏쓽 쓳吏묒 誘몄꽭븘援먯꽭룷瑜 M1 쟾 뿼利앹꽦 몴쁽삎쑝濡 쟾솚븯怨(von Bernhardi et al., 2015), 씠 몴쁽삎 떥씠넗移댁씤, TNF-慣, IL6, IL1棺 벑쓽 뿼利 쑀諛쒕ℓ媛쒖껜쓽 깮꽦쓣 利앷떆궓떎(Wang et al., 2015). 씠윭븳 뿼利 쑀諛쒕ℓ媛쒖껜뒗 떎떆 꽭룷궗硫몄쓣 珥덈옒븳떎. 떎젣濡 뙆궓뒯蹂묒뿉꽌 誘몄꽭븘援 몴쁽삎 M1씠 솗씤릺뿀怨, TNF-慣, IL6, IL1棺쓽 긽듅씠 꽑議곗껜 肉먮쭔 븘땲씪 궗썑 깦뵆쓽 쓳깘吏덉뿉꽌룄 寃異쒕릺뿀떎(Nagatsu et al., 2000).

2.4 뙆궓뒯蹂묒쓽 옄媛룷떇 옣븷

옄媛룷떇 寃쎈줈뒗 썑냽 룆꽦 諛 꽭룷궗硫몄쓣 諛⑹븯湲 쐞빐 吏꾪빑꽭룷뿉꽌 닔紐낆씠 湲 떒諛깆쭏 諛 湲곕뒫옣븷 냼湲곌쓣 쟻떆뿉 젣嫄고븯뒗뜲 븘닔쟻씠떎. 뵲씪꽌 옄媛룷떇 諛 由ъ냼醫 湲곕뒫옣븷 媛숈 遺꾪빐寃쎈줈쓽 삤옉룞룄 뙆궓뒯蹂묒쓽 蹂묒씤씠 맂떎(Zhu et al., 2003; Tanji et al., 2011). 慣-synucelin 쓳吏 諛 lewy 냼泥대룄 autophagic-lysosomal 湲곕뒫옣븷쓽 寃곌낵씠떎(Moors et al., 2016). 慣-synucelin 誘명넗肄섎뱶由ъ븘 autophagic-lysosomal 湲곕뒫옣븷뿉 쁺뼢쓣 二쇱뼱 寃고븿씠 엳뒗 誘명넗肄섎뱶由ъ븘媛 遺꾪빐릺吏 紐삵븯怨 異뺤쟻릺硫댁꽌 二쇰쓽 嫄닿컯븳 誘명넗肄섎뱶由ъ븘源뚯 넀긽떆궎뒗 ROS媛 깮꽦릺뼱 븙닚솚쓣 珥덈옒븳떎(Ryan et al., 2015; Xilouri et al., 2016). 뙆궓뒯蹂 솚옄쓽 궗썑 쓳깋吏덉뿉꽌 autophagic vacuoles쓽 異뺤쟻씠 泥섏쓬쑝濡 諛쒓껄맂 썑(Anglade et al., 1997), autophagosomes쓽 留덉빱씤 microtubule-associated protein 1 light chain 3 (LC3)쓽 利앷媛 뙆궓뒯蹂 솚옄쓽 쓳깋吏덉뿉꽌 諛쒓껄릺뿀떎(Tanji et al., 2011). 삉븳, 由ъ냼醫 怨좉컝 뙆궓뒯蹂 솚옄쓽 쓳깋吏덉뿉꽌 lysosome쓽 留덉빱씤 lysosomal-associated membrane protein type 1 (LAMP1)쓽 媛먯냼濡 굹궗떎(Dehay et al., 2010).

3. 뙆궓뒯蹂묒뿉꽌 泥쒖뿰臾쇱쓽 뿭븷

뙆궓뒯蹂묒뿉 븳 뿬윭 醫낅쪟쓽 떊寃쎈낫샇 移섎즺젣 以 泥쒖뿰臾쇱씠 쑀젰븳 썑蹂대Ъ吏덉씠 맆 닔 엳떎. 泥쒖뿰臾(natural product) 떇臾쇱텛異쒕Ъ, 닔궛臾, 泥대궡쓽 誘몄깮臾 議곗꽦, 궗궛臾 삉뒗 궗엺怨 룞臾쇱쓽 궡씤꽦 솕븰議곗꽦 벑 궡븘엳뒗 쑀湲곗껜媛 깮궛븯뒗 紐⑤뱺 寃껋쓣 留먰븳떎. 뙆궓뒯蹂묒뿉 빐 뿬윭 泥쒖뿰臾 쓽빟뭹씠 룄뙆誘 떊寃쎌꽭룷쓽 눜뻾쓣 諛⑹븯뒗 빆궛솕 諛 빆뿼利 솢꽦쓣 젣怨듯븳떎뒗 寃껋씠 諛앺졇 엳쑝硫, 洹 쇅뿉룄 옒紐 젒엺 떒諛깆쭏쓣 뼲젣븯뒗 벑쓽 빆뙆궓뒯 듅꽦씠 엳떎怨 븣젮졇 엳떎(Table 1). 삉븳 吏湲덇퉴吏 닔留롮 꽭룷 諛 룞臾쇱떎뿕뿉꽌 泥쒖뿰臾쇱씠 뙆궓뒯蹂묒뿉 빐 蹂댄샇 諛 移섎즺 슚怨쇱뿉 엳뼱 쑀留앺븳 썑蹂대Ъ吏덉엫씠 븣젮졇 엳떎(Solayman et al., 2017).

Their chemical structures and functions in Parkinson's disease-related natural products

Molecules Structural formula Plant of origin Function References
Baicalein Scutellaria baicalensis, Scutellaria lateriflora
  • Attenuates dopamine depletion in the striatum

  • Increased dopaminergic neurons

  • Inhibit α-syn and α-syn oligomer formation

  • Reduce mitochondrial stress and apoptosis.

(Wang et al., 2005; Cheng et al., 2008; Lu et al., 2011)
Resveratrol Fruits (grape etc.)
  • Antioxidant and radical scavenging

  • Protect dopaminergic neurons

(Mudo et al., 2012)
Madecassoside Centella asiatica
  • Attenuates striatal dopamine decline

  • Increased BDNF protein expression rate

  • ROS reduction

  • Downregulation of pro-inflammatory protein expression

(Xu et al., 2013; Sasmita et al., 2018)
Berberine Berberis vulgaris, Berberis aristata etc.
  • Attenuates of oxidative stress, inhibition of apoptosis in hippocampus

  • Attenuates of dopaminergic neurodegeneration

  • Improvement of memory

  • Increase of motor balance

  • Neuroprotective effect

(Bae et al., 2013; Kim et al., 2014; Zhang et al., 2017)
EGCG (epigallocatechin gallate) Camelia Sinesis (Green tea)
  • Attenuates DA depletion in the SNpc

  • Survival and protection of dopaminergic neurons

  • Blocking the absorption of MPP+

  • Decreased DAT

(Levites et al., 2001; Loder and Melikian, 2003)
Ginkgolides Ginkgo biloba
  • Reduce behavioral disorders

  • Reduce oxidative stress

  • Protect striatum

  • Prevent dopamine depletion

(Kim et al., 2004; Rojas et al., 2008)
Bilobalide

α-syn; alpha-synucelin, BDNF; brain-derived neurotrophic factor, ROS; reactive oxygen species, DA; dopamine, SNpc; substantia nigra pars compacta, MPP+; 1-methyl-4-phenylpyridinium, DAT; dopamine transpoter



3.1 Baicalein

Baicalein Scutellaria baicalensis Bupleurum scorzonerifolfium (S/B)쓽 肉뚮━뿉꽌 怨좊냽룄濡 諛쒓껄릺뒗 뵆씪蹂대끂씠뱶씠떎(Wang et al., 2005). 씠 솕빀臾쇱 꽑議곗껜뿉꽌 룄뙆誘 怨좉컝쓣 빟솕떆궎怨, 룄뙆誘쇱꽦 돱윴쓽 닔瑜 利앷떆궓떎(Cheng et al., 2008). 삉븳 GSH (glutathione) 닔以쓣 利앷떆궎怨, 慣-synuclein怨 慣-synuclein oligomer 삎꽦쓣 뼲젣븯硫(Lu et al., 2011), 誘명넗肄섎뱶由ъ븘 뒪듃젅뒪 꽭룷궗硫몄쓣 媛먯냼떆궗 닔 엳떎(Kuang et al., 2017). SH-SY5Y 꽭룷뿉꽌 phspho-JNK 諛 caspase 솢꽦쓣 媛먯냼떆耳 6-OHDA濡 쑀룄맂 룆꽦쓣 셿솕떆궓 뿰援ш껐怨쇨 議댁옱븳떎(Lee et al., 2005).

3.2 Resveratrol

Resveratrol 뿴留ㅼ 룷룄 벑 떎뼇븳 떇臾쇱뿉 議댁옱븯뒗 뤃由ы럹 솕빀臾쇱씠떎(Fr챕mont, 2000). P. quinquefolia (L.) Planch, Paeonia lactifloraMorus alba 媛숈 떎뼇븳 떇臾쇨낵(Wu et al., 2013) 뵺湲곕쪟, 븙肄, 씤, 쟻룷룄 벑 紐 媛吏 씪諛섏떇뭹뿉룄 議댁옱븳떎(Oliveira et al., 2017). Resveratrol 빆궛솕 諛 씪뵒移 젣嫄 뒫젰쓣 媛吏怨 엳뼱 뙆궓뒯 伊먯뿉꽌 룄뙆誘쇱꽦 돱윴쓣 蹂댄샇븳떎. 뿰援ш껐怨 PGC-1慣 (peroxisome proliferator-activated receptor-gamma coactivator-1慣)뒗 誘명넗肄섎뱶由ъ븘 솢꽦뿉 以묒슂븳 뿭븷쓣 븯뒗뜲, resveratrol SIRT1쓽 깉븘꽭떥솕瑜 넻빐 PGC-1慣瑜 怨쇰컻쁽븯뒗 슚怨쇰줈 MPTP濡 쑀룄맂 꽭룷궗硫몄쓣 寃щ뵒硫 誘명넗肄섎뱶由ъ븘 湲곕뒫옣븷瑜 셿솕븯怨 떊寃쎈낫샇 뿭븷쓣 븯뒗 寃껋쑝濡 굹궗떎(Mudo et al., 2012). 삉븳 GSH 諛 GPx (glutathione peroxidase)쓽 솢꽦쓣 媛뺥솕븷 肉 븘땲씪 SOD (superoxide dismutase) 諛 CAT (catalase) 닔移섎 媛먯냼떆궓떎(Khan et al., 2010).

3.3 Madecasoside

Madecasoside뒗 Centella asictica쓽 異붿텧臾쇰줈 諛뺥뀒由ъ븘 媛먯뿼, 嫄댁꽑, 沅ㅼ뼇뿉 쓽븳 긽泥섏 솕긽쑝濡 씤븳 뵾遺뿼利 諛 떎뼇븳 뵾遺吏덊솚쓣 移섎즺븯湲 쐞빐 닔諛 뀈 룞븞 븘쑀瑜대쿋떎 諛 以묎뎅 쟾넻 쓽븰뿉꽌 愿묐쾾쐞븯寃 궗슜릺뿀떎(Thomas et al., 2010; Kwon et al., 2011). 理쒓렐 madecasoside쓽 떊寃쎈낫샇 슚怨 삉븳 諛앺吏怨 엳뒗뜲, MPTP濡 쑀룄맂 꽑議곗껜쓽 룄뙆誘 媛먯냼瑜 쁽븯寃 빟솕떆궎硫, MDA 닔以 媛먯냼븯怨, GSH 닔以 諛 Bcl-2/Bax 鍮꾩쑉, BDNF 떒諛깆쭏 諛쒗쁽 鍮꾩쑉씠 madecasoside 泥섎━ 援곗뿉꽌 쁽븯寃 利앷뻽떎(Xu et al., 2013). 삉븳 LPS뿉 쓽빐 쑀룄맂 떊寃쎌뿼利 紐⑤뜽뿉꽌 ROS 깮꽦쓣 쁽븯寃 媛먯냼떆궎怨, 쟾 뿼利앹꽦 떒諛깆쭏 諛쒗쁽쓣 븯뼢議곗젅 뻽떎(Sasmita et al., 2018).

3.4 Berberine

Berberine 떇臾쇱쓽 肉뚮━, 猿띿쭏 諛 뿴留ㅼ뿉꽌 異붿텧릺뒗 븘씠냼대由 븣移쇰줈씠뱶濡 빆뿼利, 빆궛솕 벑뿉 슚怨쇨 엳뼱 誘쇨컙슂踰뺤쑝濡 궗슜릺뼱 솕떎(Imanshahidi and Hosseinzadeh, 2008). Berberine PI3K/AKT/Bcl-2 諛 Nrf2/ HO-1 寃쎈줈뿉꽌 궛솕뒪듃젅뒪瑜 빟솕떆궎硫, 怨좎슜웾蹂대떎뒗 슜웾뿉꽌 떊寃쎈낫샇 슚怨쇨 엳떎(Bae et al., 2013; Zhang et al., 2017). 삉븳 룞臾쇱떎뿕 寃곌낵 berberine쓽 蹂듦컯 궡 닾뿬뒗 빆슦슱뿉룄 슚뒫씠 엳뒗 寃껋쑝濡 諛앺議뚯쑝硫(Kulkarni and Dhir, 2008), 떎瑜 룞臾쇱떎뿕뿉꽌뒗 berberine쓽 寃쎄뎄닾뿬뒗 빐留덉뿉꽌쓽 꽭룷궗硫몄쓣 뼲젣븯怨, 룄뙆誘쇱꽦 떊寃 蹂꽦쓣 빟솕떆궎硫 湲곗뼲젰뼢긽 諛 슫룞 洹좏삎쓣 利앷떆耳곕떎(Kim et al., 2014).

3.5 Epigallocatechin gallate (EGCG)

Epicatechin-3-gallate (EGCG)뒗 끃李⑥쓽 異붿텧臾쇰줈 빆궛솕 諛 떊寃 깮꽦 슚怨쇰 젣怨듯븯뒗 李⑥쓽 媛옣 뭾遺븳 뤃由ы럹씠떎(Salah et al., 1995; Nanjo et al., 1996). 湲곗〈뿉 떎떆맂 뿭븰 뿰援щ 넻빐 EGCG瑜 룷븿븯뒗 끃李⑤ 留덉떆뒗 吏묐떒뿉꽌 議곌뎔怨 鍮꾧탳빐꽌 뙆궓뒯蹂묒쓽 쐞뿕 셿솕 諛 궙 쑀蹂묐쪧쓣 蹂댁뿬二쇨퀬 엳뼱, 끃李⑥쓽 떊寃쎈낫샇 슚怨쇰 뮮諛쏆묠븯怨 엳뿀떎(Checkoway et al., 2002; Tan et al., 2003). 삉븳, 룞臾쇱떎뿕뿉꽌 MPTP濡 쑀諛쒕맂 뙆궓뒯蹂 留덉슦뒪뿉꽌 끃李⑥텛異쒕Ъ 뇤쓽 쓳깋吏 쁺뿭쓽 DA 怨좉컝쓣 빟솕떆궎怨 룄뙆誘쇱꽦 돱윴쓣 깮議댄븷 닔 엳寃 븯떎(Levites et al., 2001). 삉븳 EGCG쓽 移댄뀒肄 쑀궗 援ъ“뒗 떊寃쎈룆씤 MPP+ (1-methyl-4-phenylpyridinium)쓽 씉닔瑜 李⑤떒븯怨, MPP+뿉 쓽븳 넀긽쑝濡쒕꽣 룄뙆誘쇱꽦 돱윴쓣 蹂댄샇븯硫, 룞떆뿉 룄뙆誘쇱닔넚泥(DAT)瑜 15%뿉꽌 60%源뚯 媛먯냼떆耳곕떎(Loder and Melikian, 2003).

3.6 Ginkgolides & Bilobalidae

Ginkgolides Bilobalidae뒗 뻾굹臾(Ginkgo biloba)뿉 議댁옱븯뒗 깮由ы솢꽦 꽦遺꾩쑝濡 뵆씪蹂대끂씠뱶, 뀒瑜댄렂 諛 씫넠쓽 삎깭씠硫, 궛솕뒪듃젅뒪濡쒕꽣 돱윴蹂댄샇 슚怨쇨 엳뼱 떇臾쇱쑀옒 빆궛솕젣濡 뿬寃⑥쭊떎(Oyama et al., 1996). Ginkgolides Bilobalde媛 룷븿맂 솕빀臾 EGb761 6-OHDA濡 쑀룄맂 뙆궓뒯蹂 紐⑤뜽 留덉슦뒪뿉꽌 뻾룞옣븷瑜 媛먯냼떆耳곗쑝硫(Kim et al., 2004), MPTP濡 쑀룄맂 뙆궓뒯 留덉슦뒪 紐⑤뜽뿉꽌 궛솕뒪듃젅뒪瑜 媛먯냼떆궎怨, 꽑議곗껜瑜 蹂댄샇븯硫 룄뙆誘(DA) 怨좉컝쓣 諛⑹븯뒗 슚怨쇰줈 떊寃쎈낫샇 슚怨쇰 蹂댁떎(Rojas et al., 2008).

4. 寃곕줎

씠 끉臾몄 떒諛깆쭏 쓳吏, 誘명넗肄섎뱶由ъ븘 湲곕뒫옣븷, 떊寃쎌뿼利앷낵 媛숈 뙆궓뒯蹂묒쓽 蹂묒씤 諛 以묒슂븳 援ъ꽦슂냼뿉 빐 꽕紐낇븯硫, 씠윭븳 硫붿빱땲利섏쓣 몴쟻쑝濡 옞옱쟻씤 移섎즺쟾왂씤 떎뼇븳 泥쒖뿰臾쇱쓽 떊寃쎈낫샇 슚怨쇰 젣떆븯怨좎옄 븯떎. 룄뙆誘(DA) 옉슜젣, 젅蹂대룄뙆, 移대퉬룄뙆, 紐⑤끂븘誘 삦떆떎븘젣 B삎 뼲젣젣 諛 빆肄쒕┛젣 媛숈 湲곗〈쓽 빆뙆궓뒯 빟臾쇱 룄뙆誘 泥댁슂踰뺤쑝濡쒖꽌 뙆궓뒯蹂 移섎즺쓽 二쇰쪟濡 궗슜릺뼱 솕吏留, 쑀빐븳 遺옉슜怨 넂 移섎즺鍮꾩슜 벑쑝濡 씤빐 솚옄 鍮꾩튇솕쟻씤 삎깭씠떎. 理쒓렐뿉뒗 씠윭븳 븳怨꾩젏쓣 洹밸났븯湲 쐞빐 뙆궓뒯蹂묒뿉 븳 泥 삉뒗 蹂댁셿슂踰뺤쑝濡 泥쒖뿰젣뭹뿉 愿븳 愿떖씠 넂븘吏怨 엳떎.

떎뼇븳 떇臾쇱쑀옒 泥쒖뿰臾쇱 뙆궓뒯蹂 移섎즺瑜 쐞븳 빟臾쇰줈 궗슜맆 媛뒫꽦씠 엳떎. Baicalein, Resveratrol, Madecasoside, Berberine, Epigallocatechhin gallate (EGCG), Ginkgolides 諛 Bilobalide 벑怨 媛숈 泥쒖뿰臾쇰뱾 떒諛깆쭏쓽 옒紐삳맂 젒옒 諛 쓳吏묒쓣 뼲젣븯怨, 誘명넗肄섎뱶由ъ븘 湲곕뒫쓣 媛뺥솕븯硫, 떊寃쎌뿼利앹쓣 셿솕븯怨, 떊寃 湲곕뒫쓣 쑀吏븯뒗 뜲 以묒슂븳 뿭븷쓣 븯뒗 옄媛룷떇쓣 珥됱쭊븳떎. 씠윭븳 떊寃쎈낫샇 슚怨 쇅뿉룄 泥쒖뿰젣뭹 湲곗〈 빟臾쇨낵 鍮꾧탳빐 씪諛섏쟻쑝濡 졃븯怨 遺옉슜씠 쟻떎뒗 옣젏씠 엳떎. 삉븳 泥쒖뿰臾쇱 湲곗〈 슂踰뺤쓽 蹂댁땐젣濡 궗슜븯뿬 슚뒫쓣 넂씠怨, 蹂묒슜닾뿬쓽 삎깭濡 移섎즺 슚怨쇰 넂씪 닔 엳떎뒗 옣젏씠 엳쓣 닔 엳떎.

븯吏留 씠윭븳 泥쒖뿰젣뭹뿉 븳 엫긽 뿰援щ뒗 留ㅼ슦 遺議깊븯硫, 솚옄뿉 쟻슜릺湲 쐞빐꽌뒗 빆뙆궓뒯 슚뒫쓣 엯利앺븯湲 쐞븳 留롮 뿰援ш 吏꾪뻾맆 븘슂媛 엳떎怨 궗猷뚮맂떎. 떎뿕뿉 궗슜맂 紐⑤뜽 以 씪遺뒗 遺쟻젅븯嫄곕굹 遺덉땐遺꾪븯硫, 뀒뒪듃븳 솕빀臾 삉뒗 異붿텧臾쇱쓽 떊寃쎈룆꽦 옉슜쓽 궗 옣븷뿉 븳 젙蹂대뒗 젣怨듯븯吏留, 紐낇솗븳 떊寃쎈낫샇 슚怨쇰뒗 젣怨듯븯吏 븡뒗 寃쎌슦룄 엳뿀떎. 삉븳 삁븸-뇤 옣踰(Blood-brain barrier) 닾怨쇱꽦뿉 븳 利앷굅媛 遺議깊븯떎. 뵲씪꽌 뙆궓뒯蹂 移섎즺뿉 엳뼱 泥쒖뿰臾쇱쓽 옞옱젰 쑀留앺븯吏留, 옉슜 硫붿빱땲利섍낵 슚뒫쓣 셿쟾엳 씠빐븯젮硫 뜑 留롮 뿰援ш 븘슂븯떎怨 궗猷뚮맂떎.

泥쒖뿰臾쇱쓣 솢슜븳 移섎즺젣 媛쒕컻 諛 뿰援щ뒗 쁽옱룄 솢諛쒗븯寃 吏꾪뻾릺怨 엳쑝硫, 떎뼇븳 깮由 湲곕뒫쓣 媛吏뒗 泥쒖뿰臾쇱씠빞留먮줈 蹂듭옟븳 蹂묐━ 쁽긽쓣 媛吏 뙆궓뒯蹂묒쓽 移섎즺諛⑸쾿뿉 븳 븞씠 맆 닔 엳쓬쓣 씠 끉臾몄쓣 넻빐 젣떆븯怨좎옄 븳떎.

ACKNOWLEDGEMENT

This research was supported by the National Research Foundation (NRF) funded by the Korean government (No. 2022R1F1A10651621230882063400102).

CONFLICT OF INTEREST

The authors declare no competing interests.

References
  1. Agid Y. Parkinson's disease: Pathophysiology. The Lancet. 1991. 337: 1321-1324.
    Pubmed CrossRef
  2. Anglade P, Vyas S, Javoy-Agid F, Herrero Ezquerro MT, Michel P, Marquez J, Mouatt-Prigent A, Ruberg M, Hirsch E, Agid Y. Apoptosis and autophagy in nigral neurons of patients with parkinson's disease. Histology and Histopathology. 1997.
  3. Aquino CC, Fox SH. Clinical spectrum of levodopa-induced complications. Mov Disord. 2015. 30: 80-89.
    Pubmed CrossRef
  4. Bae J, Lee D, Kim YK, Gil M, Lee JY, Lee KJ. Berberine protects 6-hydroxydopamine-induced human dopaminergic neuronal cell death through the induction of heme oxygenase-1. Mol Cells. 2013. 35: 151-157.
    Pubmed KoreaMed CrossRef
  5. Braak H, Del Tredici K, R체b U, De Vos RA, Steur ENJ, Braak E. Staging of brain pathology related to sporadic parkinson's disease. Neurobiology of Aging. 2003. 24: 197-211.
    Pubmed CrossRef
  6. Checkoway H, Powers K, Smith-Weller T, Franklin GM, Longstreth W Jr, Swanson PD. Parkinson's disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake. American Journal of Epidemiology. 2002. 155: 732-738.
    Pubmed CrossRef
  7. Chen Z, Trapp BD. Microglia and neuroprotection. J Neurochem. 2016. 136 Suppl 1: 10-17.
    Pubmed CrossRef
  8. Cheng Y, He G, Mu X, Zhang T, Li X, Hu J, Xu B, Du G. Neuroprotective effect of baicalein against mptp neurotoxicity: Behavioral, biochemical and immunohistochemical profile. Neurosci Lett. 2008. 441: 16-20.
    Pubmed CrossRef
  9. Choi BK, Choi MG, Kim JY, Yang Y, Lai Y, Kweon DH, Lee NK, Shin YK. Large alpha-synuclein oligomers inhibit neuronal snare-mediated vesicle docking. Proc Natl Acad Sci U S A. 2013. 110: 4087-4092.
    Pubmed KoreaMed CrossRef
  10. Dehay B, Bove J, Rodriguez-Muela N, Perier C, Recasens A, Boya P, Vila M. Pathogenic lysosomal depletion in parkinson's disease. J Neurosci. 2010. 30: 12535-12544.
    Pubmed KoreaMed CrossRef
  11. Duda JE, Giasson BI, Mabon ME, Lee VM, Trojanowski JQ. Novel antibodies to synuclein show abundant striatal pathology in lewy body diseases. Ann Neurol. 2002. 52: 205-210.
    Pubmed CrossRef
  12. Emmanouilidou E, Stefanis L, Vekrellis K. Cell-produced alpha-synuclein oligomers are targeted to, and impair, the 26s proteasome. Neurobiol Aging. 2010. 31: 953-968.
    Pubmed CrossRef
  13. Engelhardt JF. Redox-mediated gene therapies for environmental injury: Approaches and concepts. Antioxidants &. Redox Signaling. 1999. 1: 5-27.
    Pubmed CrossRef
  14. Essa MM, Vijayan RK, Castellano-Gonzalez G, Memon MA, Braidy N, Guillemin GJ. Neuroprotective effect of natural products against alzheimer's disease. Neurochemical Research. 2012. 37: 1829-1842.
    Pubmed CrossRef
  15. Fr챕mont L. Biological effects of resveratrol. Life Sciences. 2000. 66: 663-673.
    Pubmed CrossRef
  16. Goetz CG. The history of parkinson's disease: Early clinical descriptions and neurological therapies. Cold Spring Harb Perspect Med. 2011. 1: a008862.
    Pubmed KoreaMed CrossRef
  17. Hacker CD, Perlmutter JS, Criswell SR, Ances BM, Snyder AZ. Resting state functional connectivity of the striatum in parkinson's disease. Brain. 2012. 135: 3699-3711.
    Pubmed KoreaMed CrossRef
  18. Haddad D, Nakamura K. Understanding the susceptibility of dopamine neurons to mitochondrial stressors in parkinson's disease. FEBS Lett. 2015. 589: 3702-3713.
    Pubmed KoreaMed CrossRef
  19. Henchcliffe C, Beal MF. Mitochondrial biology and oxidative stress in parkinson disease pathogenesis. Nat Clin Pract Neurol. 2008. 4: 600-609.
    Pubmed CrossRef
  20. Imanshahidi M, Hosseinzadeh H. Pharmacological and therapeutic effects of berberis vulgaris and its active constituent, berberine. Phytother Res. 2008. 22: 999-1012.
    Pubmed CrossRef
  21. Jenner P. Current concepts on the etiology and pathogenesis of parkinson disease. Principles and Practice of Movement Disorders: Churchill Livingstone. 2007. 672.
  22. Kalia LV, Lang AE. Parkinson's disease. Lancet. 2015. 386: 896-912.
    Pubmed CrossRef
  23. Khan MM, Ahmad A, Ishrat T, Khan MB, Hoda MN, Khuwaja G, Raza SS, Khan A, Javed H, Vaibhav K, Islam F. Resveratrol attenuates 6-hydroxydopamine-induced oxidative damage and dopamine depletion in rat model of parkinson's disease. Brain Res. 2010. 1328: 139-151.
    Pubmed CrossRef
  24. Kim M, Cho K-H, Shin M-S, Lee J-M, Cho H-S, Kim C-J, Shin D-H, Yang HJ. Berberine prevents nigrostriatal dopaminergic neuronal loss and suppresses hippocampal apoptosis in mice with parkinson's disease. International Journal of Molecular Medicine. 2014. 33: 870-878.
    Pubmed CrossRef
  25. Kim MS, Lee JI, Lee WY, Kim SE. Neuroprotective effect of Ginkgo biloba l. Extract in a rat model of parkinson's disease. Phytother Res. 2004. 18: 663-666.
    Pubmed CrossRef
  26. Kuang L, Cao X, Lu Z. Baicalein protects against rotenone-induced neurotoxicity through induction of autophagy. Biological and Pharmaceutical Bulletin. 2017. 40: 1537-1543.
    Pubmed CrossRef
  27. Kulkarni SK, Dhir A. On the mechanism of antidepressant-like action of berberine chloride. Eur J Pharmacol. 2008. 589: 163-172.
    Pubmed CrossRef
  28. Kwon H-J, Park J-H, Kim G-T, Park Y-D. Determination of madecassoside and asiaticoside contents of c. Asiatica leaf and c. Asiatica-containing ointment and dentifrice by hplc-coupled pulsed amperometric detection. Microchemical Journal. 2011. 98: 115-120.
    CrossRef
  29. Lee HJ, Noh YH, Lee DY, Kim YS, Kim KY, Chung YH, Lee WB, Kim SS. Baicalein attenuates 6-hydroxydopamine-induced neurotoxicity in sh-sy5y cells. Eur J Cell Biol. 2005. 84: 897-905.
    Pubmed CrossRef
  30. Lees AJ, Blackburn NA, Campbell VL. The nighttime problems of parkinson's disease. Clinical Neuropharmacology. 1988. 11: 512-519.
    Pubmed CrossRef
  31. Levites Y, Weinreb O, Maor G, Youdim MB, Mandel S. Green tea polyphenol (-)릂pigallocatechin3릆allate prevents n-methyl-4-phenyl-1, 2, 3, 6릘etrahydropyridine릋nduced dopaminergic neurodegeneration. Journal of Neurochemistry. 2001. 78: 1073-1082.
    Pubmed CrossRef
  32. Loder MK, Melikian HE. The dopamine transporter constitutively internalizes and recycles in a protein kinase c-regulated manner in stably transfected pc12 cell lines. J Biol Chem. 2003. 278: 22168-22174.
    Pubmed KoreaMed CrossRef
  33. Lu JH, Ardah MT, Durairajan SS, Liu LF, Xie LX, Fong WF, Hasan MY, Huang JD, El-Agnaf OM, Li M. Baicalein inhibits formation of alpha-synuclein oligomers within living cells and prevents abeta peptide fibrillation and oligomerisation. Chembiochem. 2011. 12: 615-624.
    Pubmed CrossRef
  34. Luo C, Song W, Chen Q, Zheng Z, Chen K, Cao B, Yang J, Li J, Huang X, Gong Q. Reduced functional connectivity in early-stage drug-naive parkinson's disease: A resting-state fmri study. Neurobiology of Aging. 2014. 35: 431-441.
    Pubmed CrossRef
  35. MacMahon Copas AN, McComish SF, Fletcher JM, Caldwell MA. The pathogenesis of parkinson's disease: A complex interplay between astrocytes, microglia, and t lymphocytes?. Frontiers in Neurology. 2021. 12: 666737.
    Pubmed KoreaMed CrossRef
  36. Moors T, Paciotti S, Chiasserini D, Calabresi P, Parnetti L, Beccari T, van de Berg WD. Lysosomal dysfunction and alpha-synuclein aggregation in parkinson's disease: Diagnostic links. Mov Disord. 2016. 31: 791-801.
    Pubmed CrossRef
  37. Morfini GA, Burns M, Binder LI, Kanaan NM, LaPointe N, Bosco DA, Brown RH Jr, Brown H, Tiwari A, Hayward L, Edgar J, Nave KA, Garberrn J, Atagi Y, Song Y, Pigino G, Brady ST. Axonal transport defects in neurodegenerative diseases. J Neurosci. 2009. 29: 12776-12786.
    Pubmed KoreaMed CrossRef
  38. Mudo G, Makela J, Di Liberto V, Tselykh TV, Olivieri M, Piepponen P, Eriksson O, Malkia A, Bonomo A, Kairisalo M, Aguirre JA, Korhonen L, Belluardo N, Lindholm D. Transgenic expression and activation of pgc-1alpha protect dopaminergic neurons in the mptp mouse model of parkinson's disease. Cell Mol Life Sci. 2012. 69: 1153-1165.
    Pubmed CrossRef
  39. Nagatsu T, Mogi M, Ichinose H, Togari A. Changes in cytokines and neurotrophins in parkinson's disease. Advances in Research on Neurodegeneration. 2000. 277-290.
    Pubmed CrossRef
  40. Nanjo F, Goto K, Seto R, Suzuki M, Sakai M, Hara Y. Scavenging effects of tea catechins and their derivatives on 1, 1-diphenyl-2-picrylhydrazyl radical. Free Radical Biology and Medicine. 1996. 21: 895-902.
    Pubmed CrossRef
  41. Obeso J, Stamelou M, Goetz C, Poewe W, Lang A, Weintraub D, Burn D, Halliday GM, Bezard E, Przedborski S. Past, present, and future of parkinson's disease: A special essay on the 200th anniversary of the shaking palsy. Movement Disorders. 2017. 32: 1264-1310.
    Pubmed KoreaMed CrossRef
  42. Oliveira ALB, Monteiro VVS, Navegantes-Lima KC, Reis JF, Gomes RS, Rodrigues DVS, Gaspar SLF, Monteiro MC. Resveratrol role in autoimmune disease-a mini-review. Nutrients. 2017. 9.
    Pubmed KoreaMed CrossRef
  43. Oyama Y, Chikahisa L, Ueha T, Kanemaru K, Noda K. Ginkgo biloba extract protects brain neurons against oxidative stress induced by hydrogen peroxide. Brain Research. 1996. 712: 349-352.
    Pubmed CrossRef
  44. Palacino JJ, Sagi D, Goldberg MS, Krauss S, Motz C, Wacker M, Klose J, Shen J. Mitochondrial dysfunction and oxidative damage in parkin-deficient mice. J Biol Chem. 2004. 279: 18614-18622.
    Pubmed CrossRef
  45. Perlson E, Maday S, Fu MM, Moughamian AJ, Holzbaur EL. Retrograde axonal transport: Pathways to cell death?. Trends Neurosci. 2010. 33: 335-344.
    Pubmed KoreaMed CrossRef
  46. Prodoehl J, Burciu RG, Vaillancourt DE. Resting state functional magnetic resonance imaging in parkinson's disease. Current Neurology and Neuroscience Reports. 2014. 14: 1-8.
    Pubmed CrossRef
  47. Rao SS, Hofmann LA, Shakil A. Parkinson's disease: Diagnosis and treatment. American Family Physician. 2006. 74: 2046-2054.
  48. Roberts RF, Wade-Martins R, Alegre-Abarrategui J. Direct visualization of alpha-synuclein oligomers reveals previously undetected pathology in parkinson's disease brain. Brain. 2015. 138: 1642-1657.
    Pubmed KoreaMed CrossRef
  49. Rojas P, Serrano-Garcia N, Mares-Samano JJ, Medina-Campos ON, Pedraza-Chaverri J, Ogren SO. Egb761 protects against nigrostriatal dopaminergic neurotoxicity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in mice: Role of oxidative stress. Eur J Neurosci. 2008. 28: 41-50.
    Pubmed CrossRef
  50. Ryan BJ, Hoek S, Fon EA, Wade-Martins R. Mitochondrial dysfunction and mitophagy in parkinson's: From familial to sporadic disease. Trends Biochem Sci. 2015. 40: 200-210.
    Pubmed CrossRef
  51. Salah N, Miller NJ, Paganga G, Tijburg L, Bolwell GP, Riceevans C. Polyphenolic flavanols as scavengers of aqueous phase radicals and as chain-breaking antioxidants. Archives of Biochemistry and Biophysics. 1995. 322: 339-346.
    Pubmed CrossRef
  52. Sasmita AO, Ling APK, Voon KGL, Koh RY, Wong YP. Madecassoside activates anti-neuroinflammatory mechanisms by inhibiting lipopolysaccharide멼nduced microglial inflammation. International Journal of Molecular Medicine. 2018. 41: 3033-3040.
    Pubmed CrossRef
  53. Schneider RB, Iourinets J, Richard IH. Parkinson's disease psychosis: Presentation, diagnosis and management. Neurodegenerative Disease Management. 2017. 7: 365-376.
    Pubmed CrossRef
  54. Sharma R, Kabra A, Rao M, Prajapati P. Herbal and holistic solutions for neurodegenerative and depressive disorders: Leads from ayurveda. Current Pharmaceutical Design. 2018. 24: 2597-2608.
    Pubmed CrossRef
  55. Shim JH, Yoon SH, Kim KH, Han JY, Ha JY, Hyun DH, Paek SH, Kang UJ, Zhuang X, Son JH. The antioxidant trolox helps recovery from the familial parkinson's disease-specific mitochondrial deficits caused by pink1- and dj-1-deficiency in dopaminergic neuronal cells. Mitochondrion. 2011. 11: 707-715.
    Pubmed CrossRef
  56. Solayman M, Islam MA, Alam F, Khalil I, Amjad Kamal M, Hua Gan S. Natural products combating neurodegeneration: Parkinson's disease. Current Drug Metabolism. 2017. 18: 50-61.
    Pubmed CrossRef
  57. Spillantini MG, Schmidt ML, Lee VM-Y, Trojanowski JQ, Jakes R, Goedert M. -synuclein in lewy bodies. Nature. 1997. 388: 839-840.
    Pubmed CrossRef
  58. Tan EK, Tan C, Fook-Chong SM, Lum SY, Chai A, Chung H, Shen H, Zhao Y, Teoh ML, Yih Y, Pavanni R, Chandran VR, Wong MC. Dose-dependent protective effect of coffee, tea, and smoking in parkinson's disease: A study in ethnic chinese. J Neurol Sci. 2003. 216: 163-167.
    Pubmed CrossRef
  59. Tanji K, Mori F, Kakita A, Takahashi H, Wakabayashi K. Alteration of autophagosomal proteins (lc3, gabarap and gate-16) in lewy body disease. Neurobiol Dis. 2011. 43: 690-697.
    Pubmed CrossRef
  60. Thomas MT, Kurup R, Johnson AJ, Chandrika SP, Mathew PJ, Dan M, Baby S. Elite genotypes/chemotypes, with high contents of madecassoside and asiaticoside, from sixty accessions of centella asiatica of south india and the andaman islands: For cultivation and utility in cosmetic and herbal drug applications. Industrial Crops and Products. 2010. 32: 545-550.
    CrossRef
  61. von Bernhardi R, Eugenin-von Bernhardi L, Eugenin J. Microglial cell dysregulation in brain aging and neurodegeneration. Front Aging Neurosci. 2015. 7: 124.
    Pubmed KoreaMed CrossRef
  62. Wang J-Y, Chiu J-H, Tsai T-H, Tsou A-P, Hu C-P, Chi C-W, Yeh S-F, Lui W-Y, Wu C-W, Chou C-K. Gene expression profiling predicts liver responses to a herbal remedy after partial hepatectomy in mice. International Journal of Molecular Medicine. 2005. 16: 221-231.
    CrossRef
  63. Wang WY, Tan MS, Yu JT, Tan L. Role of pro-inflammatory cytokines released from microglia in alzheimer's disease. Ann Transl Med. 2015. 3: 136.
  64. Winner B, Jappelli R, Maji SK, Desplats PA, Boyer L, Aigner S, Hetzer C, Loher T, Vilar M, Campioni S, Tzitzilonis C, Soragni A, Jessberger S, Mira H, Consiglio A, Pham E, Masliah E, Gage FH, Riek R. In vivo demonstration that alpha-synuclein oligomers are toxic. Proc Natl Acad Sci U S A. 2011. 108: 4194-4199.
    Pubmed KoreaMed CrossRef
  65. Wu C-F, Yang J-Y, Wang F, Wang X-X. Resveratrol: Botanical origin, pharmacological activity and applications. Chinese Journal of Natural Medicines. 2013. 11: 1-15.
    CrossRef
  66. Xilouri M, Brekk OR, Stefanis L. Autophagy and alpha-synuclein: Relevance to parkinson's disease and related synucleopathies. Mov Disord. 2016. 31: 178-192.
  67. Xu CL, Qu R, Zhang J, Li LF, Ma SP. Neuroprotective effects of madecassoside in early stage of parkinson's disease induced by mptp in rats. Fitoterapia. 2013. 90: 112-118.
    Pubmed CrossRef
  68. Zhang C, Li C, Chen S, Li Z, Jia X, Wang K, Bao J, Liang Y, Wang X, Chen M, Li P, Su H, Wan JB, Lee SMY, Liu K, He C. Berberine protects against 6-ohda-induced neurotoxicity in pc12 cells and zebrafish through hormetic mechanisms involving pi3k/akt/bcl-2 and nrf2/ho-1 pathways. Redox Biol. 2017. 11: 1-11.
    Pubmed KoreaMed CrossRef
  69. Zhu JH, Guo F, Shelburne J, Watkins S, Chu CT. Localization of phosphorylated erk/map kinases to mitochondria and autophagosomes in lewy body diseases. Brain Pathology. 2003. 13: 473-481.
    Pubmed KoreaMed CrossRef