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. Author manuscript; available in PMC: 2022 May 1.
Published in final edited form as: Pharmacol Ther. 2020 Nov 20;221:107749. doi: 10.1016/j.pharmthera.2020.107749

Table 1.

Neuroprotective natural products targeting mitochondrial dysfunction reported from January 2010 to May 2020

a Mode of action (MOA) on mitochondria
Compound name Structural class Biogenesis Dynamics Bioenergetics ∆Ψm [Ca2+]m Oxytosis/ferroptosis References
PlantSource
Resveratrol Stilbenoid X X X X X X (Ferretta et al., 2014; Ishige et al., 2001; Kesherwani et al., 2013; Liu et al., 2012; Narayanan, Dave, Saul, & Perez-Pinzon, 2015; Peng, Tao, et al., 2016; Porquet et al., 2014; Valenti et al., 2016)
ε-Viniferin Stilbenoid X X (Fu et al., 2012)
Artoindonesianin O Stilbenoid X (Seo et al., 2014)
Pterostilbene Stilbenoid X (Wang, Liu et al., 2016)
Curcumin Diarylheptanoid X X X X X X (Eckert et al., 2013; Liu et al., 2008; Liu et al., 2014; Rajasekar et al., 2013; Reddy et al., 2016; Seo et al., 2010; van der Merwe et al., 2017)
Tetrahydrocurcumin Diarylheptanoid X (Vacek et al., 2018)
Acerogenin A Diarylheptanoid X (Lee et al., 2015)
Juglanin C Diarylheptanoid X (Yang et al., 2011)
Genistein Isoflavone X X X (Atlante et al., 2010; Rasbach & Schnellmann, 2008)
Daidzein Isoflavone X X X (Atlante et al., 2010; Rasbach & Schnellmann, 2008)
Baicalein Flavone X X X X X (Ishige et al., 2001; Li et al., 2012; Wang et al., 2017; Zhang et al., 2017)
Luteolin Flavone X X X (Ishige et al., 2001; Zhao, Yao-Yue, Qin, & Guo, 2012)
Nobiletin Flavone X X (Lee, Amarsanaa, et al., 2018)
7,8-Dihydroxyflavone Flavone X (Chen, Chua, et al., 2011)
Cudraflavone B Flavone X (Lee et al., 2014)
Quercetin Flavonol X X X X X (Ay et al., 2017; Ishige et al., 2001; Liu et al., 2015)
Fisetin Flavonol X X X (Alikatte, Palle, Rajendra Kumar, & Pathakala, 2020; Ishige et al., 2001)
Galangin Flavonol X (Ishige et al., 2001)
Morin Flavonol X (Ishige et al., 2001)
Kaempferol Flavonol X (Ishige et al., 2001)
Myricetin Flavonol X (Zhang et al., 2011)
Epigallocatechin-3-gallate (EGCG) Flavanol X X X X X X (Chen et al., 2017; Chen et al., 2018; He et al., 2019; Valenti et al., 2013; Valenti et al., 2016)
Catechin/epicatechin Flavanol X X (Moreno-Ulloa et al., 2014)
Theaflavic acid Flavanol X (Li, Shi, et al., 2020)
Procyanidin B2 3”-O-gallate Flavanol X (Song et al., 2019)
Procyanidin C1 Flavanol X (Song, Lee, & Kang, 2019)
Naringenin Flavanone X X (de Oliveira, Brasil, & Andrade, 2017)
Sterubin Flavanone X (Fischer et al., 2019; Maher, Fischer, et al., 2020)
Liquiritigenin Flavanone X X (Jo et al., 2016; Yang, Park, & Song, 2013)
Dihydromyricetin Flavanonol X X (Liu et al., 2016)
Xanthohumol Chalconoid (flavonoid) X (Wang, Ho, et al., 2020)
Isoliquiritigenin Chalconoid (flavonoid) X X (Yang et al., 2012)
Morachalcone A Chalconoid (flavonoid) X (Wen et al., 2020)
Morachalcone D Chalconoid (flavonoid) X (Wen et al., 2020)
Silibinin Flavonolignan X X X (Geed et al., 2014; Schramm et al., 2018)
Isoorientin Flavone glycoside X X (Liang et al., 2016; Liang & Li, 2018; Ziqubu et al., 2020)
Orientin Flavone glycoside X (Yu, Wang, et al., 2015)
Palhinoside D Flavone glycoside X (Li et al., 2020)
Puerarin Isoflavone glycoside X X (Zhu et al., 2016)
Rutin Flavonol glycoside X (Yu, Li, et al., 2015)
Icariin Flavonol glycoside X X (Zeng et al., 2019; Zeng, Wang, et al., 2019)
Isoquercitrin Flavonol glycoside X (Carmona et al., 2020)
Naringin Flavanone glycoside X X (Garabadu & Agrawal, 2020)
Chrysanthemin Anthocyanidin glycoside X (Ereminas et al., 2017)
Mulberrofuran K Lignan X (Xia et al., 2019)
Pinoresinol Lignan X (In et al., 2015)
Rasidasin II Neolignan X (Zhou, Yao, et al., 2018)
Obovatol Neolignan X X (Yang, Lee, et al., 2013)
Honokiol Neolignan X X (Yang, Lee, et al., 2013)
Syringaresinol-4-O-β-D-glucopyranoside Lignan glycoside X (Yang et al., 2020)
Casuarinin Ellagitannin X (Song et al., 2017)
Coniferyl ferulate Hydroxycinnamic acid X (Gong et al., 2020)
Ferulic acid Hydroxycinnamic acid X X X (Anis et al., 2020; Zafeer, Firdaus, Anis, & Mobarak Hossain, 2019)
Artepillin C Hydroxycinnamic acid X (Takashima et al., 2019)
Daphnetin Coumarin X (Du et al., 2014)
Auraptene Terpenoid coumarin X (Jang et al., 2019)
Hydroxytyrosol Simple phenol X X (Peng, Hou, et al., 2016; Zheng et al., 2015)
Salidroside Phenolic glycoside X X (Barhwal et al., 2015)
Gastrodin Phenolic glycoside X X (de Oliveira et al., 2018)
α-Arbutin Phenolic glycoside X (Ding et al., 2020)
Butylphthalide Polyketide X (Xiong et al., 2012)
γ-Mangostin Xanthonoid (polyketide) X (Wang, Li, et al., 2016)
β-Lapachone Naphthoquinone (polyketide) X (Lee, Ban, et al., 2018)
Emodin Anthraquinone (polyketide) X (Ahn et al., 2016)
Chrysophanol Anthraquinone (polyketide) X X (Chae et al., 2017)
Hyperforin Polyketidic terpenoid X (Zolezzi et al., 2013)
5-Heptadecylresorcinol Resorcinolic lipid (polyketide) X X (Liu et al., 2020)
∆9-Tetahydrocannabinolic acid
(∆9-THCA)		 Cannabinoid (polyketidic terpenoid) X (Nadal et al., 2017)
∆9-Tetrahydrocannabinol (THC) Cannabinoid (polyketidic terpenoid) X X X (Schubert et al., 2019; Zeissler et al., 2016)
Cannabidiol (CBD) Cannabinoid (polyketidic terpenoid) X X (Schubert et al., 2019; Sun et al., 2017)
Cannabinol (CBN) Cannabinoid (polyketidic terpenoid) X (Schubert et al., 2019)
Cannabichromene (CBC) Cannabinoid (polyketidic terpenoid) X (Schubert et al., 2019)
Linalool Monoterpenoid X X X X (Sabogal-Guáqueta et al., 2019)
Oleuropein Iridoid glycoside (monoterpenoid) X X (Kim et al., 2018; Park et al., 2017)
Geniposide Iridoid glycoside (monoterpenoid) X (Lv et al., 2014)
Artemisinin Sesquiterpenoid X X (Lin et al., 2018; Yan et al., 2017)
Daphne D Sesquiterpenoid X (Wang, Liu et al., 2020)
Linearol Diterpenoid X X X (González-Burgos et al., 2016)
Sidol Diterpenoid X X X (González-Burgos et al., 2016)
Andrographolide Diterpenoid X (Yang & Song, 2014)
Tanshinone I Diterpenoid quinone X X (de Oliveira, Schuck, & Bosco, 2017)
Tanshinone IIa Diterpenoid quinone X X X (Li et al., 2017)
Cryptotanshinone Diterpenoid quinone X (Lee et al., 2020)
Celastrol Triterpenoid X (Deng et al., 2013)
Asiatic acid Triterpenoid X X X X (Ding et al., 2018; Lee et al., 2012; Xu et al., 2012)
Tenuigenin Triterpenoid X (Liang et al., 2011)
Protopanaxadiol Triterpenoid X X (Bak et al., 2016)
Glycyrrhizic acid Triterpenoid saponin X X (Rashedinia, Saberzadeh, Khosravi Bakhtiari, Hozhabri, & Arabsolghar, 2019)
Ginsenoside Rb1 Triterpenoid saponin X X X X (Fernández-Moriano, González-Burgos, et al., 2017; Xu et al., 2019)
Ginsenoside Rg1 Triterpenoid saponin X X X X (Fernández-Moriano, González-Burgos, et al., 2017; Xu et al., 2019)
Bicelaphanol A Trinorditerpenoid X (Wang et al., 2013)
Astaxanthin Carotenoid (tetraterpenoid) X (Lee et al., 2011)
α-Tocopherol (vitamin E) Terpenoid quinone X X X (Sanderson et al., 2015; Schubert, Kimura, & Maher, 1992)
Huperzine A Sesquiterpenoid alkaloid X X (Mao et al., 2016; Yang, Ye, et al., 2012)
Tomatidine Steroidal alkaloid (triterpenoid) X (Taveira et al., 2014)
Berberine Benzylisoquinoline alkaloid X X (Yu et al., 2018)
Neferine Benzylisoquinoline alkaloid X X (Wu et al., 2019)
Fangchinoline Benzylisoquinoline alkaloid X (Bao et al., 2019)
Sanguinarine Benzophenanthridine alkaloid X X (Park et al., 2014)
3,3’-Diindolylmethane Indole alkaloid X (Ito et al., 2017)
Voacamine Indole alkaloid X (Currais et al., 2014)
Geissoschizine methyl ether Indole alkaloid X X (Sun et al., 2016)
3-Alkyl-1,4-benzoquinone Fatty acid benzoquinone X (Madathil et al., 2012)
Embelin Fatty acid benzoquinone X X X (Rao et al., 2020)
AnimalSource
Melatonin Indole hormone X X X X X X (Ansari Dezfouli et al., 2019; Carretero et al., 2009; Chuang et al., 2016; Herrera et al., 2007; Jou et al., 2010)
α-Lipoic acid Fatty acid X X X (Jiang, Yin, Yao, Brinton, & Cadenas, 2013; Mehrotra et al., 2015)
15-Deoxy- ∆12,14-prostaglandin J2 Fatty acid X (Wappler et al., 2013)
Progesterone Steroid (triterpenoid) X (Grimm et al., 2014)
Estradiol Steroid (triterpenoid) X (Grimm et al., 2014)
Allopregnanolone Steroid (triterpenoid) X (Grimm et al., 2014; Wang, Yao, et al., 2020)
Estrone Steroid (triterpenoid) X (Grimm et al., 2014)
Testosterone Steroid (triterpenoid) X (Grimm et al., 2014)
3α-Androstanediol Steroid (triterpenoid) X (Grimm et al., 2014)
Dehydroepiandrosterone Steroid (triterpenoid) X (Grimm et al., 2014)
Ursodeoxycholic acid Steroid (triterpenoid) X X X (Bell et al., 2018)
Ursocholanic acid Steroid (triterpenoid) X X (Mortiboys et al., 2013)
Gracilin A Norditerpenoid X (Leirós, Sánchez, et al., 2014)
Makaluvamine J Iminoquinone alkaloid X (Alonso et al., 2016)
MicrobialSource
Santacruzamate A Peptide X X (Chen, et al., 2019)
Fumarprotocetraric acid Depsidon (polyketide) X X (Fernández-Moriano, Divakar, et al., 2017)
Bikaverin Naphthoquinone (polyketide) X (Nirmaladevi et al., 2014)
Anhydroexfoliamycin Naphthoquinone (polyketide) X (Leirós, Alonso, et al., 2014)
Fusarubin Naphthoquinone (polyketide) X (Choi et al., 2020)
Evariquinone Anthraquinone (polyketide) X (Song et al., 2018)
Polyozellin Terphenylquinone X (Yang & Song, 2015)
Fischerin Pyridone alkaloid X (Bang et al., 2019)
Pontemazine B Phenazine alkaloid X (Cha et al., 2015)
a

“X” denotes reported MOA on mitochondria.