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.

Table 2 Glycosides improve hepatic fibrosis by inhibiting oxidative stress

No.	Glycosides	Model	Upregulated molecules	Downregulated molecules	Mechanism	Ref.
1	Wogonoside	Rat	SOD, GSH, IL-10	HA, LN, HYP, MDA, TNF-α, IL-1β, IL-6, TGF-β, MMP-2/9, Smad-3, PI3K/Akt/mTOR, NF-κB p65, PI3K/Akt/mTOR/p70S6K, α-SMA, Col-I	Inhibition of OS can improve hepatic fibrosis	Wang et al[126]
2	Hyperoside	Mice	SOD, GSH-Px, CAT, GSH, Nrf2	GOT, GPT, MDA, TGF-β, Col-I/III	Activating Nrf2 nuclear translocation, inhibiting OS to increase antioxidant and phase II detoxifying enzyme activity can improve hepatic fibrosis	Zou et al[127]
3	Forsythiaside A	Mice	SOD, GSH, CAT, GSH-Px, p450 7a1, FXR, SHP, LRH-1, BSEP, NTCP, OATP-1	HA, LN, PC-III, Col-I/IV, HYP, α-SMA, TNF-α, IL-1β, IL-6, LCA, DCA, HDCA, β-MCA, alloLCA, NorDCA, NorCA, CA, FGF-R4, MRP-2	Inhibiting OS and inflammation, regulating gut microbiota and BA metabolism can improve hepatic fibrosis	Fu et al[128]

α-SMA: Alpha-smooth-muscle actin; OS: Oxidative stress; SOD: Superoxide dismutase; GSH: Glutathione; GSH-Px: Glutathione peroxidase; IL: Interleukin; Nrf2: Nuclear factor erythroid 2-related factor.

Table 3 Single herbal extracts improve hepatic fibrosis by inhibiting oxidative stress

No.	Single herbal extracts	Model	Upregulated molecules	Downregulated molecules	Mechanism	Ref.
1	Salvia miltiorrhiza	Mice	SOD, GSH	Col-1/III, TGF-β, MDA, IL-1α, TNF-α	Reducing MDA content, increasing SOD activity and GSH content, and suppressing OS while also reducing TNF-α and IL-1α can improve hepatic fibrosis	Zhang et al[94]
2	Ginkgo biloba leaf	Rat		MDA, TGF-β1, Col-1	Effectively regulating the OS thioacetamide-induced hepatic fibrosis	Al-Attar et al[100]
3	Clove basil	Rat	CAT	α-SMA, Col-α	Inhibiting OS can significantly suppress HSC activation, as well as the expressions of α-SMA and Col-α, exhibiting its anti-hepatic fibrosis properties	Chiu et al[103]
4	Ceratonia siliqua pod	Mice	GSH, SOD, CAT, GST, GPx, GR	TIMP-2, NO	Inhibiting the production of LPO and NO, increasing the content of GSH, and restoring the activity of antioxidant enzymes can suppress OS, granuloma formation, and hepatic fibrosis	Al-Olayan et al[129]
5	Grape seed	Rat	AOC, GSH	TNF-α, MDA, MPO	Inhibiting neutrophil infiltration and lipid peroxidation, suppressing OS, restoring the oxidative and antioxidant status in tissues can help protect against hepatic fibrosis	Dulundu et al[130]
6	Pomegranate	Rat	SOD, GST, CAT, Nrf2	NF-κB, α-SMA, Cox-2	Reducing OS by regulating Nrf2 and NF-κB can eliminate hepatic fibrosis	Husain et al[131]
7	Taraxacum officinale root	Mice	SOD, mt I/II	α-SMA	Inhibiting OS, inducing HSC inactivation and enhancing liver regeneration capacity are effective in the treatment of hepatic fibrosis	Domitrović et al[132]
8	Myrtus communis	Rat	GSH, SOD	TNF-α, IL-1β, MDA, MPO, TGF-β	Its antioxidant and free radical scavenging activities protect liver tissue from OS damage after bile duct ligation , thereby exerting its anti-fibrotic effects	Sen et al[133]

α-SMA: Alpha-smooth-muscle actin; OS: Oxidative stress; SOD: Superoxide dismutase; GSH: Glutathione; IL: Interleukin; Nrf2: Nuclear factor erythroid 2-related factor; HSC: Hepatic stellate cell.

Table 4 Traditional Chinese medicine formulas improve hepatic fibrosis by inhibiting oxidative stress

No.	Traditional Chinese medicine formulas	Composition	Efficacy	Model	Upregulated molecules	Downregulated molecules	Mechanism	Ref.
1	Yin-Chen-Hao-Tang	Artemisia annua L. 18 g, Gardenia jasminoides Ellis 12 g, Rheum palmatum 6 g	Clearing heat and promoting diuresis to relieve dampness and jaundice	Rat		Col-I, α-SMA, TGF-β, HYP, ROS	Alleviating hepatic fibrosis by enhancing antioxidant capacity, reducing ROS levels, suppressing OS, and inhibiting inflammatory response	Lee et al[106], Mountford et al[108], Chen et al[109]
2	Xiaochaihu Tang (XCHT)	Bupleurum root 12 g, Scutellaria baicalensis 9 g, Ginseng 6g, Pinellia ternata 9 g, Roasted Licorice 5 g, Fresh Ginger 9 g, 4 Red Dates	Soothing liver and relieving depression, regulating stomach and lowering qi counterflow, tonifying qi and strengthening spleen, clearing liver and purging fire	Rat	Nrf2, Nqo1, HO-2, GCLC, GCLM	α-SMA, HA, PCIII, LN	Activating the Nrf2 pathway can attenuate OS and further suppress activated HSCs, thereby improving hepatic fibrosis	Li et al[111], Hu et al[112]
3	Fu Zheng Hua Yu Fang	Salvia miltiorrhiza, Fermented Cordyceps sinensis powder, Peach kernel, Pine pollen, Lycopodium clavatum, Schisandra chinensis (processed)	Activating blood circulation and removing blood stasis, nourishing essence and nurturing liver	Mice		α-SMA, Nqo1, HO-2, GCLC, GCLM, TIMP1, TGF-β1, TGF-RI, PDGF-Rβ, MDA, Col-1aI, TGF-βRI, PDGF-β, MCP-1, MIP-1 mRNA	Effectively suppressing the production of liver ROS, inhibiting OS, and exerting anti-fibrotic effects	Jiang et al[116]
4	CGX	Artemisia annua 5g, Trionyx sinensis shell 5g, Radish seed 5g; White Atractylodes 3g, Pogostemon cablin 3g, Alisma orientale 3g, White Atractylodes 3g, Salvia miltiorrhiza 3g; Poria cocos 2g, Aurantium fruit 2g, Amomum cardamomum 2g, Licorice 1g, Saussurea costus 1g	Clearing liver and activating blood circulation, strengthening spleen and transforming dampness	Rat	GSH-Px, GSH-Rd, GST, SOD, IFN-γ	MDA, PDGF-BB, TGF-β1, CTGF	It inhibits the levels of liver tissue HYP and MDA, while increasing the total GSH content and the activity of GSH-oxidation reduction system enzymes, which suppresses OS and exerts its anti-hepatic fibrosis effects	Kim et al[134]
5	Huangjia Ruangan Granule	Astragalus membranaceus,Trionyx sinensis shell, Pueraria lobata root, Bupleurum root, Ganoderma lucidum,Paeonia lactiflora, Salvia miltiorrhiza, Panax notoginseng, Lycopodium clavatum, Phyllanthus urinaria	Regulating qi and soothing liver, activating blood circulation and relieving hardness	Rat	SOD, GSH	PC-III, Col-IV, LN, HA, α-SMA, MDA, MPO, TNF-α, IL-1β, IL-6, Cox-2, iNOS, TNFR1, p-IκBα, p-P65/P65, p-ERK/ERK, p-JNK/JNK, MAPK p-P38/P38	Antagonizing OS effectively inhibits hepatic fibrosis by regulating TNF/MAPK and NF-κB signaling pathways to suppress liver inflammation	Cai et al[135]

α-SMA: Alpha-smooth-muscle actin; OS: Oxidative stress; SOD: Superoxide dismutase; GSH: Glutathione; IL: Interleukin; IFN: Interferon; Nrf2: Nuclear factor erythroid 2-related factor; HSC: Hepatic stellate cell.