A New Therapeutic Trend: Natural Medicine for Ameliorating Ischemic Stroke via PI3K/Akt Signaling Pathway
Abstract
:1. Introduction
2. Correlation between PI3K/Akt Signaling Pathway and Ischemic Stroke
2.1. Structural Characteristics and Activation of PI3K and Akt
2.2. Ischemic Stroke Activates PI3k/Akt Signaling Pathway, Link to the Relevant Cascade Reaction
2.2.1. The Pathological Mechanism of Ischemic Stroke
2.2.2. Neuroinflammation Caused by Ischemic Stroke with PI3K/Akt Signaling Pathway
2.2.3. Apoptosis Caused by Ischemic Stroke with PI3K/Akt Signaling Pathway
2.2.4. Oxidative Stress Caused by Ischemic Stroke with PI3K/Akt Signaling Pathway
2.2.5. Autophagy Caused by Ischemic Stroke with PI3K/Akt Signaling Pathway
3. Natural Medicine for the Treatment of Ischemic Stroke through PI3K/Akt Signaling Pathway
3.1. Herbal Medicine
3.1.1. Chuanxiong
3.1.2. Salvia miltiorrhiza
3.1.3. Radix Angelicae sinensis
3.1.4. Astragalus membranaceus
3.1.5. Safflower
3.1.6. Ginkgo biloba leaf
3.1.7. Erigeron breviscapus
3.1.8. Ginseng
3.1.9. Radix Paeoniae Rubra
3.1.10. Panax notoginseng
3.2. Herbal Prescriptions
3.2.1. Buyang Huanwu Decoction
3.2.2. Taohong Siwu Decoction
3.2.3. Xiaoyao San
3.2.4. Danhong Injection
3.2.5. Sanhua Decoction
3.2.6. Xingnaojing Injection
3.3. Animal Medicine
3.3.1. Earthworm
3.3.2. Leech
3.3.3. Scorpion
3.4. Commonly Used Prescriptions of Traditional Chinese Medicine Containing Insects
3.4.1. Tongxinluo Capsule
3.4.2. Naoxintong Capsule
3.4.3. Shuxuetong Injection
3.5. Dosage of Natural Medicine in Animals and Humans
4. Future Prospects
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Natural Medicine | Plant Atlas | Active Ingredients | Model | Regulation of PI3K/Akt Signaling Pathway | Main Purposed Effects | Ref(s) |
---|---|---|---|---|---|---|
Herbal medicine | ||||||
Chuanxiong | Ligustrazine | PC12 Cells SD rats Human amniotic epithelial cells | ↑p-PI3K and p-Akt | Anti-neuronal apoptosis Anti-inflammation Activating autophagy | [61,62,63,64,65,66,67] | |
Salvia miltiorrhiza | Tanshinone; Danshensu; Salvianolic Acid. | SD rats Neural stem/precursor cells | ↑p-PI3K and p-Akt | Inhibit apoptosis Anti-inflammation Anti-oxidative stress | [68,69,70,71,72,73,74,75] | |
Radix Angelicae sinensis | Angelica Polysaccharides; Ferulic Acid; Ligustilide. | PC12 Cells SD rats CIRI rats | ↑p-PI3K and p-Akt | Anti-oxidative stress Anti-neuronal apoptosis | [76,77,78,79,80] | |
Astragalus membranaceus | Astragalus Polysaccharides; Astragalus Saponins; Flavonoids. | SD rats OGD/R HT22 cells | ↑p-PI3K and p-Akt | Anti-neuronal apoptosis Anti-inflammation | [81,82,83,84,85,86] | |
Safflower | Safflower Yellow | SD rats | ↑p-PI3K, p-Akt, GSK3β | Anti-oxidative stress Anti-neuronal apoptosis Anti-inflammation | [87,88,89,90,91,92,93] | |
Ginkgo biloba leaf | Ginkgo Flavonoids; Ginkgolides. | SD rats brain endothelial cell | ↑p-Akt, p-GSK3β, VEGF | Anti-inflammation Anti-oxidative stress | [94,95,96,97,98,99] | |
Erigeron breviscapus | Flavonoids Scutellarin (Breviscapine) | SD rats A375 cells | ↑p-Akt, eNOS | Anti-oxidative stress Anti-neuronal apoptosis | [100,101,102,103] | |
Ginseng | Ginsenoside | Mice SD rats | ↑p-Akt, p-mTOR, p-ERK | Anti-oxidative stress Anti-neuronal apoptosis Anti-inflammation | [104,105,106,107,108,109,110,111] | |
Radix Paeoniae Rubra | Paeoniflorin | Mice SD rats | ↑p-PI3K and p-Akt | Anti-inflammation Anti-neuronal apoptosis | [112,113,114,115] | |
Panax notoginseng | Panax Notoginseng; Saponins. | Mice SD rats bEnd 3 cells H9c2 cells | ↑p-Akt/Akt, p-mTOR, Nrf2 | Anti-neuronal apoptosis Anti-inflammation | [116,117,118,119,120,121] | |
Herbal prescriptions | ||||||
Buyang Huanwu Decoction | Propyl Gallate; Formononetin; Hydroxysafflor Yellow A; Formononetin; Astragaloside IV; Inosine, Paeoniflorin; Paeonol; Ligustrazine; Ferulic Acid. | HT22 cells mice | ↑p-PI3K, p-Akt, p-Bad | Anti-neuronal apoptosis Anti-inflammation | [122,123,124,125,126] | |
Taohong Siwu decoction | Hydroxysafflor Yellow A; Paeoniflorin; Paeonol; Ligustrazine; Ferulic Acid. | SD rats | ↑p-Akt | Anti-inflammation Anti-neuronal apoptosis | [127,128,129,130] | |
Xiaoyao San | Saikoside; Ferulic Acid; Ligustilide; Atractylenolide; Paeoniflorin; Albiflorin; Liquiritin; Glycyrrhizic Acid; Pachymic Acid. | PC12 cells | ↑p-PI3K and p-Akt | Anti-neuronal apoptosis | [131,132] | |
Danhong injection | Ferulic Acid; Cryptotanshinone; Quercetin; Anhydrosafflor Yellow B. | SD rats | ↑p-PI3K, p-Akt, GSK3β | Anti-inflammation Anti-neuronal apoptosis | [133,134,135,136,137,138] | |
Sanhua decoction | Flavonoids; Anthraquinones; Coumarins; Phenylpropanoid Glycosides; Alkaloids; Lignans. | SD rats | ↑p-PI3K and p-Akt | Anti-inflammation Anti-neuronal apoptosis | [139,140,141] | |
Xingnaojing injection | Turmeric; Moschus; Borneolum Syntheticum; Fructus Gardeniae. | SD rats | ↑p-Akt, eNOS | Anti-oxidative stress Anti-neuronal apoptosis | [142,143,144,145] |
Natural Medicine | Insect Atlas | Active Ingredients | Model | Regulation of PI3K/Akt Signaling Pathway | Main Purposed Effects | Ref(s) |
---|---|---|---|---|---|---|
Insect medicine | ||||||
Earthworm | Lumbrokinase | SD rats mice | ↑: p-PI3K and p-Akt | Anti-neuronal apoptosis Anti-inflammation | [147,148,149,150,151] | |
Leech | Hirudin; Fibrinolysin. | IPF rats SD rats mice | ↑: p-Akt | Anti-neuronal apoptosis Anti-inflammation | [152,153,154,155,156] | |
Scorpion | Adenosine; Dipeptides. | SD rats K562 cell | ↑: p-Akt | Anti-neuronal apoptosis | [157,158,159,160] | |
Insect prescriptions | ||||||
Tongxinluo capsule | Ginsenoside; Hirudin; Denosine; Paeoniflorin. | SD rats mice | ↑: p-Akt | Anti-neuronal apoptosis | [161,162,163,164,165] | |
Naoxintong capsule | Adenosine; Hirudin; Tanshinone; Danshensu; Salvianolic Acid. | SD rats | ↑: p-Akt | Anti-neuronal apoptosis | [166,167,168,169] | |
Shuxuetong injection | Hirudin; Lumbrokinase. | SD rats | ↑: p-Akt, VEGF | Anti-oxidative stress Anti-neuronal apoptosis | [170,171,172,173] |
Medicine | Dose in Animals | Dose in Human | Ref(s) |
---|---|---|---|
Active ingredients | |||
Ligustrazine | 20 mg/kg/d in rat (i.p.) | 80–240 mg/d (i.v.) | [67,174] |
Tanshinone IIA | 30 mg/kg/d in rat (i.v.) 10 mg/kg/d in mice (i.p.) | 60 mg/d (i.v.) | [75,175,176,177] |
Ligustilide | 20–40 mg/kg/day in rat (p.o.) 5–20 mg/kg/d in mice (i.p.) | / | [178,179] |
Hydroxysafflor Yellow A | 10–40 mg/kg/d in rat (i.v.) 2 mg/kg/d in mice (i.v.) | 25–70 mg/d (i.v.) | [93,180,181] |
Ginsenoside Rd | 25 mg/kg/d in rat (i.p.) 10–50 mg/kg/d in mice (i.p.) | 10–20 mg/d (i.v.) | [182,183,184] |
Ginsenoside-Rb1 | 25–100 mg/kg/d in rat (i.p.) | / | [185] |
Ginsenoside-Rg1 | 20 mg/kg/d in rat (i.p.) 10–40 mg/kg/d in mice (i.p.) | / | [107,186] |
Paeoniflorin | 40 mg/kg/d in rat (i.p.) | 3–9 g/d (i.v.) | [112,187] |
Panax notoginseng Saponins | 25–100 mg/kg/d in rat (i.p.) 45 mg/kg/d in mice (i.p.) | 500 mg/d (i.v.) | [117,188,189] |
Salvianolic Acid B | 10–20 mg/kg/d in rat (i.p.) | / | [70] |
Breviscapus | 3–6 mL/kg in rat (i.v.) | / | [190] |
Astragaloside IV | 2g/kg/d in rat (i.v.) 20 mg/kg in rat (i.p.) 200 mg/kg in mice (i.p.) | / | [82,83,191] |
Lumbrokinase | / | 1,800,000 units/d (p.o.) | [151] |
Hirudin | 10–40 mg/kg in mice (p.o.) | 2.25 g/d (p.o.) | [153,156] |
Prescriptions | Formula/dose | ||
Buyang Huanwu Decoction | 10–40 g/kg in rat (p.o.) 1.0 g/kg in mice (p.o), twice daily | raw Astragalus 30 g, angelica 15 g, longan meat 15 g, antler gum 10 g, Salvia miltiorrhiza 10 g, frankincense 10 g, myrrh 10 g, and dried pine 5 g | [192,193,194,195] |
Taohong Siwu decoction | 4.5–18 g/kg/d in rat (p.o.) | / | [196] |
Danhong injection | 0.75–3 mL/kg in rat (i.v.), twice daily 3 mL/kg/d in mice (i.m.) | 20–40 mL/d (i.v.) | [134,138,197,198] |
Sanhua decoction | 10 g/kg/d in rat (p.o.) | / | [140] |
Xingnaojing injection | 0.75–3 mL/kg/d in rat (i.m.) 6 mg/kg/d in mice (i.m.) | 20 mL/12 h (i.v.) | [143,199] |
Tongxinluo capsule | 100 mg/kg/d in rat (p.o.) 0.75–3.0 g/kg/d in mice (p.o.) | 1.56–3.12 g/d (p.o.) | [161,162,163] |
Naoxintong capsule | 0.5 g/kg/d in rat (p.o.) | 2.4 g/d (p.o.) | [200,201,202] |
Shuxuetong injection | 6 mL/kg/d in rat (i.v.) 0.27–1.08 mg/kg/d in rat (i.p.) | 6–10 mL/d (i.v.) | [171,172,203] |
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Liu, X.; Xiao, X.; Han, X.; Yao, L.; Lan, W. A New Therapeutic Trend: Natural Medicine for Ameliorating Ischemic Stroke via PI3K/Akt Signaling Pathway. Molecules 2022, 27, 7963. https://doi.org/10.3390/molecules27227963
Liu X, Xiao X, Han X, Yao L, Lan W. A New Therapeutic Trend: Natural Medicine for Ameliorating Ischemic Stroke via PI3K/Akt Signaling Pathway. Molecules. 2022; 27(22):7963. https://doi.org/10.3390/molecules27227963
Chicago/Turabian StyleLiu, Xian, Xinyu Xiao, Xue Han, Lan Yao, and Wei Lan. 2022. "A New Therapeutic Trend: Natural Medicine for Ameliorating Ischemic Stroke via PI3K/Akt Signaling Pathway" Molecules 27, no. 22: 7963. https://doi.org/10.3390/molecules27227963