Progress on traditional Chinese medicine in improving hepatic fibrosis through inhibiting oxidative stress

Table 1 Flavonoids improve hepatic fibrosis by inhibiting oxidative stress

No.	Flavonoids	Model	Upregulated molecules	Downregulated molecules	Mechanism	Ref.
1	Mallotus apelta (Lour.) Muell.Arg. leaf	Rat	IkBa, SOD, GSH-Px	HYP, PC-III, Col-I, HA, LN, α-SMA, Col-III, MDA, TNF-α, IL-1β, IL-6, MMP-2/9, TIMP-1, TGF-β1/Smad, IKKβ, NF-κB p65, pNF-κBp65, IκBα, p-IκBα	Improving hepatic fibrosis and reducing ECM accumulation are related to inhibiting OS and regulating the TGF-β1/Smad signaling pathway and NF-κB-dependent inflammatory response	Zhang et al[117]
2	Bidens bipinnata L.	Rat	SOD, GSH-Px	NF-κB, α-SMA, TGF-β1	Inhibiting OS to improve liver injury and protect rats from CCl4-induced hepatic fibrosis	Yuan et al[118]
3	Puerarin	Rat	SOD, CAT	TG, TCHO, LDL, α-SMA, Col-I/III, MDA, IL-1β, IL-6, TNF-α, MCP-1, NF-κB/p65, TGF-β, TGF-β/Smad2/3	Inhibiting OS and inflammation associated with NF-κB signal inactivation, thereby blocking the upregulation of pro-inflammatory cytokines (IL-1β and TNF-α) and chemokines (MCP-1), ultimately improving hepatic fibrosis	Hou et al[119]
4	Hesperidin	Mice		ROS	Regulating liver OS and alleviating mitochondrial dysfunction to reduce fibrosis	Li et al[120]
5	Alpinetin	Mice	IL-10, CAT, GSH-Px, SOD, GSH, Nrf2	HYP, α-SMA, fibronectin, α1(I) procollagen, IL-1β, IL-6, TNF-α, Cox-2, iNOS, MDA, VEGF, VEGFR2, PDGF-βR, HIF-1α	Preventing and treating hepatic fibrosis by inhibiting the anti-inflammatory activity mediated by NLRP3 and the anti-OS activity mediated by Nrf2	Zhu et al[121]
6	Fisetin	Rat	GSH, GSK-3β	MDA, TNF-α, IL-6, TGF-β1, Col-I, TIMP-1, Wnt3a, β-catenin, α-SMA, Cyclin D1	Inhibiting liver OS can suppress Wnt/β-catenin pathway and inhibit HSC activation and proliferation, regulate MMP-9 and TIMP-1, and suppress multiple pro-fibrotic factors, to prevent and treat hepatic fibrosis	El-Fadaly et al[122]
7	Glabridin	Mice	PPAR-γ, GSH, T-AOC	α-SMA, fibronectin, Col-α1(I), MDA	Activation of PPARγ can inhibit inflammation and OS, thereby inhibiting HSC activation and hepatic fibrosis	Zhang et al[123]
8	Morin	Rat	GSH	NO, HYP, TNF-α, iNOS, NF-κB (p65)	Receiving MDA and nitric oxide levels elevation, and restoring GSH to normal levels can inhibit OS and improve hepatic fibrosis	Heeba and Mahmoud[124]
9	Astilbin	Rat	SOD, GSH, GCLC, GCLM, HO-1, NQO1, Nrf2	TGF-β, Col-I/III, HYP, TNF-α, IL-1β, IL-6, MDA	Significant reduction in collagen production, inflammation and OS in vivo can prevent CCL4-induced hepatic fibrosis in rats	Sun et al[125]

α-SMA: Alpha-smooth-muscle actin; ECM: Extracellular matrix; OS: Oxidative stress; TGF-β1: Transforming growth factor-beta 1; NF-κB: Nuclear transcription factor-κB; SOD: Superoxide dismutase; GSH: Glutathione; GSH-Px: Glutathione peroxidase; IL: Interleukin; TNF: Tumor necrosis factor; ROS: Reactive oxygen species; Nrf2: Nuclear factor erythroid 2-related factor; HSC: Hepatic stellate cell.