Medicinal Herbs and Their Derived Ingredients Protect against Cognitive Decline in In Vivo Models of Alzheimer’s Disease
Abstract
:1. Introduction
2. MHDI-Mediated Suppression of Aβ Accumulation
2.1. Effects of MHDIs on Aβ Accumulation through α-, β-, and γ-Secretase Activity Regulation
2.2. Summary
3. MHDI-Mediated Inhibition of Aβ-Induced Oxidative Stress
3.1. Involvement of Decreased Antioxidant Status and Increased Lipid Peroxidation in Aβ-Induced Oxidative Stress
3.2. Effects of MHDIs on Aβ-Induced Oxidative Stress through Antioxidant Activity and Lipid Oxidation Regulation
3.3. Summary
4. MHDI-Mediated Downregulation of Tau Hyperphosphorylation
4.1. Effects of MHDIs on Aβ-Induced Tau Hyperphosphorylation through PP2A, CDK5, and GSK-3β Expression Regulation
4.2. Summary
5. MHDI-Mediated Reduction of Aβ-Induced Inflammation
5.1. Effects of MHDIs on Aβ-Induced Inflammation through Inflammatory Mediator Regulation
5.2. Effects of MHDIs on Aβ-Induced Inflammation through Receptor for Advanced Glycation End Product- and MAPK-Mediated Signaling Regulation
5.3. Summary
6. MHDI-Mediated Amelioration of Aβ-Induced Synaptic Dysfunction
6.1. Involvement of Synaptic Protein Expression in Aβ-Induced Synaptic Dysfunction
6.2. Effects of MHDIs on Aβ-Induced Synaptic Dysfunction through Synaptic Protein Expression Regulation
6.3. Involvement of Acetylcholine Release in Aβ-Induced Synaptic Dysfunction
6.4. Effects of MHDIs on Aβ-Induced Synaptic Dysfunction through ChAT, ACh, and AChE Level Regulation
6.5. Involvement of Postsynaptic Receptor and Protein Expression in Aβ-Induced Synaptic Dysfunction
6.6. Effects of MHDIs on Aβ-Induced Synaptic Dysfunction through Postsynaptic Receptor and Protein Expression Regulation
6.7. Summary
7. MHDI-Mediated Attenuation of Aβ-Induced Apoptosis
7.1. Involvement of MAPK and PI3K/Akt Signaling in Aβ-Induced Apoptosis
7.2. Effects of MHDIs on Aβ-Induced Apoptosis through MAPK-, PI3K/Akt-, and BDNF/CREB-Mediated Signaling Regulation
7.3. Involvement of Mitochondria-Mediated Apoptotic Cascades in Aβ-Induced Apoptosis
7.4. Effects of MHDIs on Aβ-Induced Apoptosis through Bax-, Cullin 4B-, and β-Catenin-Mediated Signaling Regulation
7.5. Effects of MHDIs on Aβ-Induced Apoptosis through Endoplasmic Reticulum Stress and Autophagy Signaling Regulation
7.6. Summary
8. Conclusions
9. Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Major Ingredients | Isolated from Medicinal Herbs | Anti-Aβ Accumulation Activities | Models | Reference |
---|---|---|---|---|
Notoginseng saponin Rg1 | Panax notoginseng | α-secretase↑, β- secretase↓, γ-secretase↓ | 28 days after Aβ1–42-induced AD | [35] |
Ginsenoside Rg1 | Bcl-2↑, MAP-2↑, NeuN↑, Bax↓, β-secretase↓ | 6 weeks after Aβ25–35-induced AD | [38] | |
Isorphynchophylline | Uncaria tomentosa | BACE-1↓, presenilin 1↓, p-APP (Thr668) ↓ | 129 days in TgCRND8 transgenic mice | [42] |
Major Ingredients | Isolated from Medicinal Herbs | Antioxidative Stress Activities | Models | References |
---|---|---|---|---|
Ginsennoside Rd | Panax ginseng | 4-HNE↓ | 5 days after Aβ1–40-induced AD | [50] |
Lignans | Schisandra chinensis Baill | kynurenic acid↑, Nrf2↑ | 28 days after Aβ25–35-induced AD | [53] |
Bajijiasu | Morinda officinalis | SOD↑, CAT↑, GSH-Px↑, MDA↓ | 25 days after Aβ25–35-induced AD | [23] |
Safflower yellow | Carthamus tinctorius | SOD↑, GSH-Px↑, MDA↓ | 28 days after Aβ1–42-induced AD | [55] |
GJ-4 | Gardenia jasminoides J. Ellis | SOD↑, MDA↓, iNOS↓, COX-2↓, PGE2↓, TNF-α↓ | 10 days after Aβ25–35-induced AD | [56] |
Tenuigenin | Polygala tenuifolia Willd | SOD↑, GSH-Px↑, MDA↓, 4-HNE↓ p-tau (Ser396) ↓, p-tau (Thr181) ↓ | 28 days after STZ-induced AD | [47] |
Ginsenoside Rg3 | P. ginseng C. A. Meyer | SOD↑, CAT↑, GSH-Px↑, MDA↓, | 60 days after D-galactose-induced AD | [57] |
Neferine | Nelumbo nucifera | SOD↑, CAT↑, GSH-Px↑ | 4 days after AlCl3-induced AD | [58] |
Rhodiola crenulata | GSH-Px↓, arachidonic acid↓ | 28 days after Aβ1–42-induced AD | [31] | |
Betalin | Beta vulgaris L. | SOD↑, CAT↑, GSH-Px↑, MDA↓, | 28 days after AlCl3-induced AD | [48] |
Major Ingredients | Isolated from Medicinal Herbs | Anti-p-Tau Activities | Models | References |
---|---|---|---|---|
Dendrobium nobile Lindl. | GSK-3β↓ p-tau (Ser199-202) ↓, p-tau (Ser396) ↓, p-tau (Ser404) ↓, p-tau (Thr231), p-tau (Thr205) | 7 days after LPS-induced AD | [62] | |
Safflower yellow | C. tinctorius | PP2A↑, CDK5↓, GSK-3↓ | 28 days after Aβ1–42-induced AD | [55] |
Emodin | Rheum officinale | PP2A↑, p-CREB↑, SYP↑, SYN-1↑, BACE-1↓, | 14 days after Hcy-induced AD | [61] |
Centella asiatica | PP2A↑, Bcl-2 mRNA↑, GSK-3β↓ | 10 weeks after d-galactose/AlCl3-induced AD | [13] | |
R. crenulata | GSK-3β (Ser9)/GSK-3β↑ | 28 days after Aβ1–42-induced AD | [63] | |
Sulforaphene | Raphani semen | p-Akt (Ser473) ↑, p-GSK-3β (Ser9) ↑, IL-10↑, TNF-α↓, IL-6↓ | 6 weeks after s STZ-induced AD | [64] |
Seed of Litchi chinensis | Akt↑, GSK-3β↓ | 28 days after Aβ25–35-induced AD | [67] |
Major Ingredients | Isolated from Medicinal Herbs | Anti-Inflammation Activities | Models | References |
---|---|---|---|---|
Emodin | R. officinale | microglia activation↓, TNF-α↓, IL-6↓, 5-LO↓, NF-κB↓ | 14 days after Hcy-induced AD | [61] |
Ethyl acetate | Picrasma quassioides Benn | TNF-α↓, IL-1β↓, IL-6↓ | 23 days after Aβ25–35-induced AD | [74] |
Betalin | B. vulgaris L. | TNF-α mRNA↓, IL-1β mRNA↓, IL-6 mRNA↓, iNOS mRNA↓, COX-2 mRNA↓, NF-κB↓ | 28 days after AlCl3-induced AD | [48] |
Neferine | N. nucifera | TNF-α↓, IL-1β↓, IL-6↓, iNOS↓, COX-2↓, NF-κB↓ | 4 days after AlCl3-induced AD | [58] |
Timosaponin BII | Anemarrhena asphodeloides Bunge | TNF-α↓, IL-1β↓, iNOS↓ | 38 days after LPS-induced inflammation and AD | [75] |
Schisandrin | S. chinensis Baill | Sirtuin 1↑, TNF-α↓, IL-1β↓, IL-6↓, NF-κB↓ | 14 days after STZ-induced AD | [72] |
Cuban policosanol | Saccharum officinarum | 4-HNE↓, TNF-α↓, IL-1β↓, IL-6↓ | 4 months in 5xFAD transgenic mice | [18] |
Ginsennoside Rd | Panax ginseng | IL-10↑, HSP70↑, Iba1↓, GFAP↓, TNF-α↓, IL-1β↓, IL-6↓, caspase-3↓ | 5 days after Aβ1–40-induced AD | [50] |
Ginsenoside Rg5 | P. ginseng | BDNF↑, IGF↑, ChAT↑, TNF-α↓, IL-1β↓, iNOS↓, COX-2↓, AChE↓ | 28 days after STZ-induced AD | [81] |
Safflower yellow | C. tinctorius L. | TNF-α↓, IL-1β↓, IL-6↓, iNOS mRNA↓, Arg1↑(marker of M2 microglia), YM-1 mRNA↑ (M2-related cytokine), CD206 mRNA↑ (M2-related cytokine) | 28 days after Aβ1–42-induced AD | [77] |
Tanshinone IIA | salvia miltiorrhiza Bunge | TNF-α↓, IL-1β↓, IL-6↓, RAGE↓, NF-κB↓ | 30 days in APP/PS1 transgenic mice | [68] |
Caffeic acid | Ocimum gratissimum | p-p38 MAPK↓, NF-κB-p65↓, TNF-α↓, IL-6↓, p53↓, AChE↓, CAT↑, GSH-Px↑ | 14 days after Aβ1–40-induced AD | [85] |
Achyranthes bidentata | p-p38 MAPK↓, p-JNK↓ TNF-α↓, IL-1β↓, IL-6↓ | 16 days after Aβ1–40-induced AD | [84] | |
Rosmarinic acid | p-JNK↓, p-c-Jun↓ | 8 months in the triple-transgenic mouse model of AD | [65] | |
Safflower yellow | C. tinctorius L. | Arg1↑, BDNF ↑, TrkB ↑, p-ERK1/2↑ iNOS↓ | 3 months in APP/PS1 transgenic mice | [78] |
Major Ingredients | Isolated from Medicinal Herbs | Restoring Synaptic Dysfunction Activities | Models | References |
---|---|---|---|---|
Berberine | IEG mRNA & protein↑, Arc mRNA & protein↑ | 7 weeks after D-galactose-induced AD | [88] | |
Xanthoceras sorbifolia | PSD-95↑, BDNF↑, p-TrkB/TrkB↑, RhoA↓, ROCK2↓ | 18 days after Aβ25–35-induced AD | [94] | |
Daucosterol palmitate | Alpinia oxyphylla Miq. | SYP↑ | 14 days after Aβ1–42-induced AD | [92] |
Catalpol | Rehmanniae Radix | dynamin 1↑, SYP↑, PSD-95↑, MAP-2↑ | 2 months in aged rats (23–24 months old) | [90] |
Icariin | Epimedium brevicornum Maxim | PSD-95↑, BDNF↑, TrkB↑, Akt↑, CREB↑ | 28 days after Aβ1–42-induced AD | [98] |
Galantamine | Galanthus woronowii | AChE↓ | 7 days after Aβ25–35-induced AD | [106] |
Galantamine | microglial α7 nAChR↑ | 2 weeks after Aβ42-induced AD | [107] | |
Galantamine | AChE↓, GSH-Px↑, caspase-9 activity↓, caspase-3 activity↓ | 57 days in the transgenic Drosophila model of AD | [109] | |
Gastrodia elata Blume | ChAT↑, AChE↓ | 52 days after Aβ25–35-induced AD | [101] | |
Bajijiasu | Morinda officinalis | ACh↑, AChE↓ | 25 days after Aβ25–35-induced AD | [23] |
Lychee seed extract | Litchi chinensis | AChE↓ | 8 weeks in a rat model of T2DM and AD | [112] |
GJ-4 | G. jasminoides J. Ellis | ACh↑, AChE↓ | 10 days after Aβ25–35-induced AD | [56] |
Lignans | S. chinensis Baill | ACh↑ | 1 week in AD rats | [11] |
β-Asarone | Acori graminei Rhizoma | CaMKIIα↑, p-CREB↑, Bcl-2↑ | 4 months in APP/PS1 mice | [117] |
Oleanolic acid | Ligustrum lucidum | NMDAR2B↑, CaMKII↑, PKC↑, BDNF↑, TrkB↑, CREB↑ | 28 days after Aβ25–35-induced AD | [116] |
Major Ingredients | Isolated from Medicinal Herbs | Anti-Apoptotic Activities | Models | References |
---|---|---|---|---|
Icariin | E. brevicornum Maxim | Bcl-2/Bax↑, NF-κB↓,p-ERK1/2/ERK1/2↓, p-p38 MAPK/p38 MAPK↓, p-JNK/JNK↓ | 20 days after IBO-induced AD | [122] |
Butylphthalide | p38 MAPK mRNA & protein↓ | 30 days after Aβ1–42-induced AD | [10] | |
Tinospora sinensis | p-PI3K/PI3K↑, p-Akt/Akt↑ | 21 days after Aβ1–40-induced AD | [125] | |
Icariside II | E. brevicornum Maxim | BDNF↑, TrkB↑, p-CREB/CREB↑ | 5 days after Aβ25–35-induced AD | [29] |
β-asarone | Acorus tatarinowii Schott | ASK 1↓, p-MKK7↓, p-c-Jun↓, Bad mRNA & protein↓, Bax mRNA & protein↓, cleaved caspase-9 mRNA & protein↓ | 28 days of Aβ1–42-induced AD | [119] |
Genistein | Bax↓, cyt c↓, caspase-3↓ | 49 days after Aβ25–35-induced AD | [15]. | |
DMDD | Averrhoa carambola L. | Bcl-2/Bax↑, cleaved caspase-9↓, cleaved caspase-3↓ | 21 days in APP/PS1 transgenic AD mice | [133] |
Scutellarein | Scutellaria baicalensis | Bcl-2↑, Bax↓, caspase-3↓, nucleus NF-κB↓ | 28 days after Aβ-induced AD | [134] |
Ginsenoside Rg3 | P. ginseng C. A. Meyer | Bcl-2↑, Bax↓, caspase-9↓, caspase-3↓, AIF↓ | 60 days after D-galactose-induced AD | [57] |
Tetramethylpyrazine | Ligusticum wallichii | SSTR4↑, CUL4B↓ | 30 days in APP/PS1 transgenic mice | [8] |
Notoginsenoside R2 | P. notoginseng | SOX8↑, β-catenin↑, cleaved caspase-3↓, COX-2↓ | 20 weeks after Aβ25–35-induced AD | [139] |
Crocin | Crocus sativus L. | GRP78↓, CHOP↓, Bax↓, caspase-3↓ | 14 days after Aβ25–35-induced AD | [140] |
Schisandrin | S. chinensis Baill | GRP78↓, CHOP↓, cleaved caspase-12↓ | 14 days after STZ-induced AD | [72] |
Euxanthone | Polygala caudate | Bcl-2/Bax↑, LC3B-II↑ | 16 days after Aβ1–42-induced AD | [145] |
Icariin | E. brevicornum Maxim | p-Akt↑, LC3-II/LC3-I↓, Beclin-1↓, Cathepsin D (neurofibrillary degeneration marker) ↓ | 5 days after Aβ1–42-induced AD | [144] |
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Tsai, Y.-T.; Kao, S.-T.; Cheng, C.-Y. Medicinal Herbs and Their Derived Ingredients Protect against Cognitive Decline in In Vivo Models of Alzheimer’s Disease. Int. J. Mol. Sci. 2022, 23, 11311. https://doi.org/10.3390/ijms231911311
Tsai Y-T, Kao S-T, Cheng C-Y. Medicinal Herbs and Their Derived Ingredients Protect against Cognitive Decline in In Vivo Models of Alzheimer’s Disease. International Journal of Molecular Sciences. 2022; 23(19):11311. https://doi.org/10.3390/ijms231911311
Chicago/Turabian StyleTsai, Yueh-Ting, Shung-Te Kao, and Chin-Yi Cheng. 2022. "Medicinal Herbs and Their Derived Ingredients Protect against Cognitive Decline in In Vivo Models of Alzheimer’s Disease" International Journal of Molecular Sciences 23, no. 19: 11311. https://doi.org/10.3390/ijms231911311