New Insights for Cellular and Molecular Mechanisms of Aging and Aging-Related Diseases: Herbal Medicine as Potential Therapeutic Approach

Table 2

Preclinical studies of herbal medicine for aging-related diseases.

Active ingredients	Dosage	Administration	Model	Possible mechanism	Reference
In vitro studies
EGb	10, 25, and 50 mg/L	Pretreatment for 24 h	EPCs cultured on fibronectin-coatedculture dishes	Activation of telomerase through the PI3k/Akt signaling pathway	[169]
Ginsenoside Rg1	10 μmol/L	Cultured for 6 h	Aging Sca-1+ hematopoietic cells	Regulating the p16-Rb signaling pathway, repairing worn telomeres, and maintaining telomerase activity	[174]
PNS	5, 25, and 50 μg/mL	Pretreatment for 4 h	D-Galactose induced aging H9c2 cells	Increase antioxidant capacity and reduce apoptosis	[180]
Astragalus membranaceus	100, 200, 400, and 600 μg/mL	Pretreatment for 24 h	Cardiomyocyte model of oxidative stress	Attenuating the oxidative injury and arresting the influx of Ca^2+ to block cell death	[182]
Lycium barbarum	15, 30, and 60 μg/mL	Pretreatment for 24 h	Primary hippocampal neurons	Activating the PI3K/Akt/mTOR signaling pathway	[188]
Angelica sinensis	—	—	Aging hematopoietic stem cells	Increase in the length of telomere and the activity of telomerase, downregulation of the expression of P53 protein	[194]
Ligustrazine	50, 100, and 200 μM	Pretreated for 24 h	Hypoxia-induced injury of HUVECs	Upregulation of miR-135b and subsequent activation of JNK/SAPK and PI3K/AKT/mTOR pathways	[201]
Gynostemma pentaphyllum extract	0.5-5.0 mg/mL	—	Mouse dermal fibroblasts induced oxidative stress	Reduce oxidative stress	[208]
Resveratrol	5, 10, and 50 μM	Cultured for 24 h	H2O2 induced aging of HUVECs	Upregulation of autophagy	[212]
Curcumin	1, 5, 10, and 20 μM	Treatment for 48 h	Rat adipose tissue-derived stem cells	Promoting TERT gene expression	[221]
In vivo studies
EGb-761	20,40, 80, and 100 mg/kg	i.g. every 3 days, for 12 months	Aged mice (24 months) of middle cerebral artery occlusion	Upregulation of phosphatase PP2A and diminished extracellular signal-regulated kinase (ERK) activation	[170]
EGb	200, 400 mg/kg/day	i.g. 12 weeks	Streptozotocin-induced diabetic ApoE^-/- mice	Inhibiting endoplasmic reticulum stress via restoration of autophagy through the mTOR signaling pathway	[171]
Ginsenoside Rg1	20 mg/kg/day	i.p. 28 days	D-Galactose-induced aging mice	Antioxidation and downregulation of the p19/p53/p21 signaling pathway	[173]
Panax notoginseng saponins	10, 30, and 60 mg/kg/day	i.g. 6 months	Natural aging rats	Attenuating oxidative damage	[179]
Astragalus membranaceus	100, 200, 400, and 600 mg/kg	i.g. twice per day for 7 times	Rat model of persistent myocardial ischemia	Reducing oxidative damage and free radical generation	[182]
Astragalosides	8, 16, and 32 mg/kg	i.g. 14 days	Rats with learning and memory impairment	Downregulate the mRNA levels of APP and β-secretase, decrease expression of APP and Aβ1–40 in hippocampus	[183]
Astragalus polysaccharides	100, 200, and 300 mg/kg/d	i.g. 7 weeks	D-Galactose induced aging mice	Scavenging ROS, inhibiting mitochondrial PT, and increasing the activities of antioxidases	[184]
Lycium barbarum	0.5 or 2.0 g/kg	i.g. 4 weeks	A mouse model of AD induced by the combination of AlCl3 and D-galactose	Modulation of the mitochondrial pathway of apoptosis and the cholinergic system	[186]
Goji berry	150, 300 mg/kg	i.g. 6 weeks	Natural aging rats	Antioxidative stress	[187]
Rhodiola rosea	60, 120 mg/kg	i.g. 9 weeks	Abdominal aorta of atherosclerosis rats	Hypolipemic, antioxidant, and anti-inflammatory activities	[190]
Angelica polysaccharide	140 mg/kg	i.p. 27 days	Aging nestin-GFP mice induced by D-galactose	Enhancing the antioxidant and anti-inflammatory capacity, upregulation of p53/p21 signaling pathway	[196]
Tetramethylpyrazine	1, 3, and 10 mg/kg	i.p. 7 or 14 days	6-OHDA-induced Parkinson’s disease mice	Activation of PI3K/Akt/GSK3β signaling pathway	[200]
Resveratrol	30, 100 mg/kg/d	i.g. 2 weeks	Mice with chemotherapy-induced ovarian aging	Attenuating oxidative stress injury by activating Nrf2	[210]
Curcumin	100, 200, and 400 mg/kg/d	i.g. 6 months	Natural aging rats	Suppressing age-related changes in inflammatory indices	[220]
Baicalein	10, 30 mg/kg/day	i.p. 7 days	MPP^+-induced Parkinson’s disease mice	Inhibit inflammatory activities and MPP^+-induced apoptosis and autophagy	[231]

Abbreviations: EGb: Ginkgo biloba extract; EPCs: endothelial progenitor cells; HUVECs: human umbilical endothelial vein cells; i.g.: intragastric gavage; i.p.: intraperitoneally injected.