TABLE 1.
Summary a few natural products and their targets of action imparting neuroprotective activity.
| Categories | Natural products | Dosage | Targets/pathway | References |
|---|---|---|---|---|
| Flavonoid | Baicalin | 50, 100, 200 mg/kg (in vivo), 10 μg/ml (in vitro) | MDA, SOD, GSH, GSH-Px, caspase-3, BDNF, NOD2, TNFα, IL-1β, COX-2, iNOS, NO, PGE2, TLR2/4, NF-κB p65, MCL-1, Bcl-2 MRTF-A, PI3K, ERK1/2 | (Cao et al., 2011; Li, F et al., 2010; Tu et al., 2011; Xue et al., 2010; Zheng et al., 2015) |
| Scutellarin/scutellarein | 50, 100 mg/kg (in vivo), 0.54 mM (in vitro) | TNF-α, IL-1β, JNK, ERK, p38, iNOS, eNOS, nNOS, ROS, NOX2, Cx43, SOD, MDA, NO, caspase-3, Notch-1, NICD, HES-1, VEGF, bFGF, ACE, ANG II, AT1R, IL-6 | (Chen, S et al., 2020; Fang et al., 2016; Fang et al., 2015; Hu et al., 2005; Sun, R et al., 2018; Tang et al., 2014; Wang et al., 2016) | |
| Apigenin/Vitexin | 2–40 mg/kg (in vivo), 2.5, 5, 10μM and 0.5, 2.5, 10 nM (in vitro) | IL-1β, IL-6, TNF-α, IL-10, LDH, SOD, MDA, NO, eNOS, iNOS, bax, Bcl-2, Caspase-3, PARP, MMP-2, MMP-9, ROCK2, RhoA, VEGF, BDNF, PI3K/Akt, ERK, JNK, p38, mTOR, PPAR-γ, Caveolin-1, Beclin1, p62, LC3Ⅰ, LC3Ⅱ, NKCC1, Ulk1, Keap1, HO-1, Nrf2, CREB | (Cui et al., 2019; Jiang et al., 2018; Pang et al., 2018; Tu et al., 2017; Wang et al., 2015b; Zhang, X. et al., 2019) | |
| Icariin | 10, 30 mg/kg (in vivo), 0.25, 0.5, 1 mg/L (in vitro) | IL-1 β, IL-6, TNF-α, TGF-β1, NF-κB p65, PPARα, PPARγ, IκB-α, IRE1α, XBP1u, XBP1s, caspase-3, Bcl-2, bax | (Deng et al., 2016; Xiong et al., 2016; Mo et al., 2020; Yang et al., 2020) | |
| Quercetin | 5–25 mg/kg (in vivo), 10 μM (in vitro) | TNF-α, IL-1β, LDH, ERK, akt, EGF, MMP-9, Claudin-5, ZO-1, β-catenin, GSK-3β, Axin, LEF1, MDA, SOD, CAT, caspase-3, Bcl-2, Nrf2, NOX4, IκBα, p65 | (Dai et al., 2018; Jin et al., 2019; Park et al., 2020; Wang, Y et al., 2020) | |
| Calycosin | 5–30 mg/kg | BDNF/TrkB, TNF-α, Bcl-2, NBR1, p62, caveolin-1, claudin-5, NO, ZO-1, MMP-2, MMP-9, ROS, ER-α, RASD1, Bcl-2, SIRT1, FOXO1, Bcl-2, bax, PGC-1α | (Guo et al., 2012; Hsu et al., 2020; Wang, Y et al., 2014; Wang, Y. et al., 2018) | |
| Alkaloid | Berberine | 0.002–100 mg/kg (in vivo), 0.5 μg/ml (in vitro) | PI3K/Akt, p53, cyclin D1, caspase 3, bad, p55γ, BDNF, TrkB, GSK3β, CREB, claudin-5, NF-κB, HIF-1α | (Hu et al., 2012; Song et al., 2012; Zhang et al., 2012; Chai et al., 2013; Zhang et al., 2016b; Yang et al., 2018b) |
| Ligustrazine | 10–100 mg/kg (in vivo), 1, 10, 100 mM (in vitro) | IL-1β, IL-6, TNF-α, IL-10, SOD, GSH-Px, MDA, p53, Caspase-3, Bcl-2, bax, mTOR, ULK1, BNIP3, Beclin1, LC3 II/I, Bax/Bcl-2, HIF-1α, MPO, Nrf2, HO-1, ERK, IFN-γ、TLR4、HMGB1, occludin, JAM-1、AQP4, MMP9, NO, iNOS, eNOS, akt, MCP-1, ICAM-1, TLR-4/NF-κb p65 | (Chang et al., 2015; Chang et al., 2007; Ding et al., 2019; Xu et al., 2017; Yan et al., 2015; Yu, P. et al., 2017; Yu et al., 2016; Zhou et al., 2019) | |
| Daurisoline | 5, 10, 20 mg/kg | Cyt-C, Caspase 3, Caspase 9, SOD, MDA, GSH-Px | (Li and Gong 2004; Yang et al., 2009; Lan and Lianjun 2020) | |
| Tetrahydropalmatine | 10, 20, 40 mg/kg | MPO, NO, ONOO2-, iNOS, p85, eNOS, akt, HIF-1, VEGF, TNF-α, occludin, ZO-1, claudin-5, caveolin-1, MMP-2/9, src, MLCK, p-MLC, p38, bax, caspase-3, Bcl-2, PRAP | (Han et al., 2012; Mao et al., 2015; Sun, R et al., 2018) | |
| Peimine | 1–5 mg/kg | SOD, MDA, LDH, IL-6, IL-10, IL-18, ICAM-1, IL-1β, caspase-9, caspase-3, bax, bcl-2, LC3Ⅱ/LC3Ⅰ, beclin1, p62, PI3K、Akt, mTOR, TNF -α, β-arrestin | (Guo et al., 2019; Duan et al., 2020) | |
| Polyphenols and acids | Curcumin | 30–300 mg/kg (in vivo), 1.25–20 μM (in vitro) | MDA, GSH, GSH-Px, SOD, NF-κB p65, Nrf2, IL-1β, IL-8, JAK2, STAT3, akt, mTOR, LC3-II, LC3-I, p62, TLR4, p-38, IL-1, IL-6, TNF-α, iNOS, caspase-3, bax, Bcl-2, Bcl-XL, COX-2, Nrf2, NO, HO-1, MEK, ERK, CREB, LDH, MnSOD, AIF, caspase-9/-3, Trx-2, MPT, MMP-9, ZO1, occludin, HIF-1α, JNK | (Huang et al., 2018; Li et al., 2015; Li et al., 2016; Lu et al., 2018; Xie, C. J. et al., 2018; Xu, N. et al., 2019) |
| Resveratrol | 20–40 mg/kg (in vivo), 1–50 µM (in vitro) | NF-κb p65, NO, iNOS, eNOS, nNOS, JNK, GFAP, PI3K/Akt, GSK-3β, CREB, PGE, COX-1, COX-2, LDH, Bcl-2, Caspase-3, NQO-1, Sirt1, UCP2, LC3B-II/I, p62, NLRP3, caspase-1, IL-18, Nrf2/HO-1, Caspase-3, GSH-Px, SOD, CAT, MDA, TNF-a, IL-1β, IL-6, LDH, MMP-9, TIMP-1, shh | (Candelario-Jalil et al., 2007; Simao et al., 2012b; Wei et al., 2015; He et al., 2017; Koronowski et al., 2017; Yang et al., 2018b) | |
| Ellagic acid | 10–100 mg/kg | Bax, bcl 2, cyt C, caspase 3, PI3K/Akt, NOS, MDA, wnt/β-catenin, ZO-1, AQP 4, MMP-9 | (Kaihua and Jiyu 2020; Liu, Z. B. et al., 2017; Nejad et al., 2015; Wang, F. et al., 2019) | |
| Glycoside | Asiaticoside | 20, 40, 60 mg/kg | TNF- α, IL-6, IL-1β, MCP1, ROS, MDA, LDH, SOD, bcl 2, bax, caspase3, NOD2, p38 MAPK, NF-kB p65, JNK, ERK, IκBα | (Chen et al., 2014; Zhang et al., 2020b) |
| Salidroside | 25, 50, 100 mg/kg (in vivo), 1, 10, 100 µM (in vitro) | Caspase-3, Bcl-2, bax, ROS, iNOS, LDH, PARP, FGF2, cAMP/PKA/CREB, TNF-α, IL-1β, IL-6, Arg1, TGFβ, IL-2, IL-8, akt, HIF-1α, HIF- 2α, HIF- 3α, EPO, nrf2/HO-1, NF-κB p50, PI3K/PKB, cyt-c, MMP9, Claudin 5, occludin | (Li et al., 2020; Liu et al., 2018; Wei et al., 2017; Zhang, Y. et al., 2018; Zhang X. et al., 2019; Zhong et al., 2019; Zuo et al., 2018) | |
| Iridoid glycoside | Geniposide | 5, 10, 20 mg/kg | LDH, TNF-α, IL-1β, IL-6, IL-8, IL-18, NLRP3, ASC, caspase-1, raf/mek1/2/erk1/2, MCP-1, ZO-1, occludin, Claudin-5, β-catenin, PI3K/Akt, Bcl-2/Bax, AchE, NOS, MDA, SOD | (Fu et al., 2020; Huang et al., 2017; Li, W. et al., 2016; Liu, Q et al., 2019) |
| Catalpol | 5, 10, 20 mg/kg (in vivo) 0.3 mM, 2.8 mM, 27.6 mM, 275.9 mM (in vitro) | ET-1, SOD, MDA, CGRP, EPO, STAT3, VEGF, JAK2/STAT3, bax, Bcl-2, ROS, NO, iNOS, GSH-Px, GSH | (Dong, X. et al., 2016; Li et al., 2006; Li et al., 2008; Liu, Y. R et al., 2014) | |
| Picroside II | 10, 20 mg/kg | TLR4, TNF-α, NF-κB p65, ERK1/2, ROS, NOX2, Rac-1 ROCK, MLCK, MMP-2, claudin-5, MEK/erk1/2-cox2, ROS, caspase 3, cyt C | (Guo et al., 2010; Li, S. et al., 2018; Wang, C. et al., 2015; Zhai et al., 2017; Zhang et al., 2017) | |
| Saponin | Ginsenoside Rg1 | 10, 20, 40 mg/kg | PAR-1, akt, nrf2/HO-1, pparγ/HO-1, ERK, JNK, caspase-3/rock1/mlc, IL-1β, IL-6, TNF-α, IκB, NF-κB p65, AQP4, p38 MAPK, MPO, SOD, CAT, HMGB1, Nrf2/ARE, AMPK/mTOR, AMP/AMPK-GLUT | (Li, S. et al., 2017; Xie, W. et al., 2018; Zheng et al., 2019; Zhou et al., 2014) |
| Astragaloside IV | 10–50 mg/kg (in vivo), 0.1–10 μM (in vitro) | STAT-3/TNF-α/il-1β, JNK3, MPO/TNF-α/il-1β, NF-κB, akt, LC3II/LC3I, p62, Fas, FasL, Caspase-8, bax, Bcl-2, bid, cyt C, Caspase-3, PI3K/Akt, ICAM-1 | (Li et al., 2012; Li, J et al., 2019; Yin et al., 2020) | |
| Terpenoids | Andrographolide | 5 mg/kg | LDH, caspase-3, ERK1/2, p38 MAPK, JNK1/2, nrf2/HO-1, Lamin B1 | (Chern et al., 2011; Yen et al., 2013; Yen et al., 2016) |
| Ginkgolide B | 1, 2, 4 mg/kg | LDH, IL-1β, TNF-α, TLR4, NF-κB, nrf2/HO-1, NQO1, SOD, akt, BDNF, EGF, NGF | (Liu, Q et al., 2019; Zheng et al., 2018b) | |
| Borneol | 200 mg/kg | Bax, Bcl-2, Claudin-5, VEGF, TNF-α, ROS, NO, iNOS, caspase-3, caspase-9, ICAM-1, NF-κB p65 | (Liu et al., 2011; Dong et al., 2018) | |
| Others | Emodin | 15, 50 mg/kg | ERK-1/2, GLT-1, caspase-3, ERK-1/2, LDH, Bcl-2, bax, akt, CREB, BDNF, TNF-α, IL-1β, IL-6, NF-κB p65, IκBα | (Ahn et al., 2016; Leung et al., 2020) |
| Cordycepin | 5, 10, 20 mg/kg (in vivo), 5, 10, 20, 40, 80 µM (in vitro) | Bcl-2, bax, Caspase-3, p53, MAPK | (Chen, K. et al., 2017; Cheng et al., 2011; Dong et al., 2019; Hwang et al., 2008; Jin, G. et al., 2014) | |
| Panax notoginseng polysaccharide | 100, 300 mg/kg | Bcl-2/Bax, caspase-3, GSH-Px, SOD, IL 10, MDA, TNF-α, IL-1β | (Jia et al., 2014; Sy et al., 2015) | |
| Angelica polysaccharide | 30, 45, 60 mg/kg | SOD, GSH, GSH-PX, MDA, IL-1β, TNF-α, NF-κB | (Dai et al., 2020; Yan and Xie, 2018; Hu et al., 2006; Li, Y. et al., 2019) | |
| Ginkgo biloba polysaccharides | 100, 200, 400 mg/kg | SOD, GSH, GSH-PX, MDA, IL-1β, TNF-α | (Yang et al., 2013) | |
| Black fungus polysaccharide | 50, 100 mg/kg | ROS, MDA, NO; SOD | (Lu et al., 2010; Qian and Min, 2010; Ye et al., 2010) | |
| Fucose | 80, 160 mg/kg | MAPK; SOD; MDA; IL-1β, IL-6, MPO; TNF-α | (Che et al., 2017; Ahn et al., 2019; Kim et al., 2019) | |
| Codonopsis pilosula polysaccharide | 1, 2 g/kg | Nrf2/HO-1; Bcl-2; bax; bax; AChE, SOD; GSH-Px | (Chen, J. et al., 2015; Ma et al., 2019; Li et al., 2018) |