Review of the pharmacological effects of astragaloside IV and its autophagic mechanism in association with inflammation

Table 8 The autophagy promotion or inhibition effects of astragaloside IV

Autophagy effects (+, -) and inflammation (R, NR)	Diseases or study model	Effect induced by autophagy	Mechanism (targets or pathways)	Ref.
"+; R"	Lung injury rats induced by PM2.5	(-) GM-CSF, ICAM-1, IFN-γ, TNF-α, IL-6, IL-18 and CRP	The AMPK/mTOR; PI3K/Akt/mTOR pathway	Wang et al[36], Pei et al[37]
"+; R"	Liver injury in T2DM rats	(-) TNFα and IL6	The AMPK/mTOR signalling pathway	Zhu et al[42]
"+; R"	Liver and kidney injury in rats induced by cisplatin	(-) The NLRP3 inflammasome	(+) LC3 II/I and (-) p62	Qu et al[44]
"+; R"	Acute spinal cord injury	(-) neuroinflammation; (-) iNOS, COX-2 and TNF-α	Polarize towards an M2 phenotype in microglial cells	Lin et al[29]
"+; R"	Myocardial hypertrophy by mechanical stress	(-) NLRP3 and IL-1β in cardiomyocytes	(+) LC3 II/I and (-) p62	Zhang et al[20]
"+; R"	H1N1 infection	(-) IL-1β	(+) Autophagosome formation, (+) autolysosomes, (+) the fusion of autophagosome and lysosome	Zhang et al[53]
"+; R"	The rat "McFarlane flap" model	Skin flap survival; (-) TNF-α, IL-1β and IL6 and (-) leukocyte infiltration	(+) Autophagosome formation related protein, Beclin 1 and LC3 II/I	Lin et al[52]
"+; NR"	Lung cancer	Favourable in lung cancer	The p53/AMPK/mTOR signalling pathway	Yang et al[32]
"+; NR"	Lung adenocarcinoma cells	(-) The viability and promote the apoptosis of A549 cells	The AKT and mTOR pathways	Li et al[57]
"+; NR"	Vulvar squamous cell carcinoma	(-) Cell proliferation	The TGF-β/Smad pathway	Zhao et al[50]
"+; NR"	The gastric mucosa	A beneficial effect on gastric mucosa in vivo	(+) Beclin1, p62, ATG5, and ATG12	Cai et al[51]
"+; NR"	Diabetic KK-Ay mice	Improve renal fibrosis and function	The SIRT1–NF-κB pathway; (-) mesangial cell activation through the SIRT1-NF-κB pathway	Wang et al[40,47]
"+; NR"	DPN induced by Schwann cell apoptosis	(-) Myelin sheath injury	(-) The PI3K/Akt/mTOR signalling pathway	Yin et al[41]
"+; NR"	Diabetic rats	(-) Liver injury and insulin resistance	The AMPK/mTOR pathway	Zhu et al[42]
"+; NR"	Nervous system diseases	(-) Parkinson's disease	(-) Astrocyte senescence	Xia et al[31]
"+; NR"	Nervous system diseases	(-) Brain injury caused by ischaemic stroke	Further (+) LC3II/LC3 I	Zhang et al[27]
"+; NR"	Cardiovascular diseases; rat VSMCs induced by Ang II	Favourable effects on mitochondrial dysfunction	Drp1 and parkin are vital to mitochondrial autophagy	Lu et al[58]
"-; R"	Acute respiratory distress syndrome; the pulmonary endothelial ARDS cell model stimulated by LPS	(-) Inflammation and apoptosis	(-) Autophagy proteins	Liu et al[34]
"-; R"	Kidney disease; CGN rats	(-) Kidney injury and (-) inflammation	(-) The PI3K/AKT/AS160 pathway	Lu et al[46]
"-; R"	Graves' orbitopathy	Protect against Graves' orbitopathy; (-) IL-6, IL-8, TNF-α, and MCP-1	(-) Beclin 1, Atg 5 and LC3 II/LC3 I	Li et al[56]
"-; R"	Thermal injury in vitro and in vivo	(-) Inflammatory responses	The PERK-eIF2α pathway	Dong et al[54]
"-; NR"	Heart diseases	(-) The cardiotoxicity of rats; (-) H/R-injured H9C2 cells	PI3K/Akt pathway activation	Huang et al[21]
"-; NR"	Heart diseases	Improve heart dysfunction induced by LPS	(-) Calcium-mediated apoptosis and autophagy by targeting miR-1	Wang et al[19]
"-; NR"	Atherosclerosis; VSMCs in thoracic aorta of mice and in vitro VSMCs model	(-) Mineralization in vitro and in vivo models	(-) DUSP5 and autophagy-related proteins and (+) H19, p-ERK1/2 and p-mTOR	Song et al[59]
"-; NR"	Nerve injury; PC12 cells in response to OGD/R	(-) Excessive autophagy injury	(-) The number of autophagosomes; (-) LC3 II/LC3 I, (+) p62; PI3K I/Akt/mTOR pathway	Huang et al[30]
"-; NR"	Nerve injury; Schwann cells induced by high glucose	(-) Mitophagy and excessive autophagy	(-) Autophagy markers Beclin-1, Atg12, and LC3 II	Wei et al[38]
"-; NR"	Liver injury; L02 hepatocytes induced by iron overload	(-) The damage to L02 hepatocytes	(-) Autophagosome formation; (+) p62, (-) LC3II/LC3 I	Xie et al[43]
"-; NR"	Lung injury caused by PM2.5 in vivo and in vitro	(-) Lung injury	Degraded autophagosomes	Pei et al[37]
"-; NR"	Cancer; NSCLC cells treated with cisplatin	Counteract chemoresistance	(-) Autophagy (Beclin 1) and ER stress (GPR78)	Lai et al[35]
"-; NR"	Cancer	(-) Invasion of cervical cancer	(-) Atg7/Atg12, (-) DCP1A and TMSB4X	Li et al[48]

Autophagy effects (+, -): “+” Indicates autophagy promotion, “-” indicates autophagy inhibition. Inflammation (R, NR): “R” indicates “related”, “NR” indicates “not related”. LC: Lung cancer; GM-CSF: Granulocyte-macrophage colony-stimulating factor; ICAM: Intercellular adhesion molecule; IFN: Inborn errors of interferon; TNF: Tumour necrosis factor; IL: Interleukin; Atg: Autophagy; NLRP3: NLR family, pyrin domain containing 3; H1N1: Influenza A; CRP: C-reactive protein; T2DM: Type 2 diabetes mellitus; iNOS: Inducible nitric oxide synthases; COX-2: Cyclooxygenase-2; KK-Ay: Spontaneous diabetes; DPN: Diabetic peripheral neuropathy; VSMC: Vascular smooth muscle cell; ARDS: Acute respiratory distress syndrome; LPS: Lipopolysaccharide; CGN: Chronic glomerular nephritis; MCP-1: Monocyte chemotactic protein-1; H9C2: A subclone of the original clonal cell line which exhibits many of the properties of skeletal muscle; PC12: A neuron cell line; H/R: Hypoxia/reoxygenation; OGD/R: Oxygen and glucose deprivation/reoxygenation; NSCLC: Non-small cell lung cancer; DCP1A: mRNA-decapping enzyme 1A; TMSB4X: Thymosin beta-4.