Table 6.

Effect of polydatin on respiratory system.

Study Type	Biological Effects	Cell Lines, Animal Types	Doses	References
In vivo, in vitro	┬TGF-β1/Smad3 signaling pathway activity, epithelial–mesenchymal transition, ↓IL-4 and IL-3 levels, ↑Sirt3 expression, Nrf2 and PGC1a levels, INF-γ activity	Mice, human bronchial epithelial cell line (BEAS-2B)	100 mg/kg/day i.p. injection for 31 days	[193]
In vivo	↓MDA level, W/D, ultrastructure injuries, ↑SOD content	Rabbit	-	[198]
In vivo	↓TLR4 and NF-κB expression, ┬inflammatory mediators	Rabbit	-	[197]
In vivo	↓TNF-α, IL-1β, and IL-6 levels, MPO activity, total cells, PMNs in BALF, Bcl-xl expression, ↑Bax and caspase-3 activity	Rat	15, 30, 45 mg/kg via caudal vein once	[199]
In vivo, in vitro	↑mitophagy via Parkin, Bcl-2 expression, ↓mitochondrial-dependent apoptosis, Bax expression, cytochrome c release, caspase-3 activity	Mice, human bronchial epithelial cell line (BEAS 2B cells)	45 mg/kg once, 50 μM for 6 h	[26]
In vivo	┬PLA2	Rat	1 mg/kg i.v. injection once	[203]
In vitro, in vivo	┬TGF-β/Smad/ERK pathway activity, ↓α-smooth muscle actin, collagen I, TNF-α, IL-6, IL-13, MPO, and MDA expression, ↑epithelial cell cadherin expression, SOD activity	Rat	10, 40, and 160 mg/kg/day for 28 days	[196]
In vivo	↓PLA2 activity, hydroxyproline, PGE-2, LTC4, and TGF-β1 levels in BALF	Rat	10, 20, 40 mg/kg intraperitoneal injection once before model establishment	[204]
In vivo, in vitro	┬TGF-β1 activity, ↓ROS activity, ↑Nrf2 signaling pathway activity	Mice, human lung epithelial cell line (BEAS-2B)	100 mg/kg at days 0, 7, 14, 100 μM for up to 48 h	[195]
In vivo	⇅SP-D and UCN expression, ↓serum IgE, IL-4, IL-13, IL-5, MDA, TNF-α, IFN-γ, iNOS, and eosinophil levels, ↑SOD activity, GSH level	Rats	200 mg/kg/day orally for 14 days	[194]
In vitro	↑GSH-Px and SOD content, ↓apoptosis, MDA content, activation-related proteins of the NLRP3 inflammasome, TNF-α, TGF-β, IL-1β, IL-6	Embryonic lung fibroblast MRC-5	12.5, 25, 50, 100, 200, 400 μmol/L for 24 h	[205]
In vitro, in vivo	↑CCSP expression, ┬PLA2 activation	Rats, human bronchial epithelia cells (BEAS-2B cells)	1, 5, 10, 30 mg/kg i.v. injection once, 0.5 m mol/L for 4 h	[54,169,201]
In vivo	↓TUNEL-positive lung cells, TNF-α, IL-1, and IL-6 levels, lung MPO activity, ┬Bax upregulation, caspase-3 activity, Bcl-xl downregulation	Rat	45 mg/kg i.v. injection once	[200]
In vitro, in vivo	┬TLR4/MyD88/NF-κB signaling pathway activity, W/D, MPO, neutrophil number, ↓IL-6, IL-1β, TNF-α, IL-8 levels	Mice, human bronchial epithelial cell line (BEAS-2B cells)	20, 80 mg/kg i.p. injection once, 2 μM, 4 μM, 8 μM for 2 h	[202]
In vivo	┬NF-κB activity, ↓TNF-α and IL-6 levels, lung COX-2 and iNOS expression	Mice	15, 45, 100 mg/kg i.p. injection once	[151]

↓: decrease, ↑: increase, ┬: inhibit, ⇅: regulate, μg: microgram, μM: micromole, BALF: bronchoalveolar lavage fluid, Bax: Bcl-2-associated x, Bcl: B-cell lymphoma 2, CCSP: club cell secretory protein, COX-2: cyclooxygenase-2, ERK: extracellular signal-regulated kinase, GSH: glutathione, GSH-Px: glutathione peroxidase, i.p.: intraperitoneal, i.v.: intravenous, IgE: immunoglobulin E, INF-γ: interferon-γ, iNOS: inducible nitric oxide synthase, IL-3: interleukin-3, IL-4: interleukin-4, IL-13: interleukin-13, kg: kilogram, LTC4: leukotriene C4, MDA: malondialdehyde, mg: milligram, MPO: myeloperoxidase, MyD88: myeloid differentiation factor 88, NF-κB: nuclear factor-κB, NLRP3: nucleotide-binding domain (NOD)-like receptor protein 3, Nrf2: nuclear factor erythroid 2-related factor 2, PGC1a: peroxisome proliferator-activated receptor γ coactivator 1α, PLA2: phospholipase A2, ROS: reactive oxygen species, Sirt3: sirtuin3, Smad3: mothers against decapentaplegic homolog 3, SOD: superoxide dismutase, SP-D: surfactant-d, TGF-β1: transforming growth factor-β1, TLR4: Toll-like receptor 4, TNF-α: tumor necrosis factor-α, TUNEL: terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling, UCN: urocortin, W/D: wet-to-dry.