Table 3 Natural products targeting ferroptosis in other pulmonary disease

COPD

Curcumin

Phenols

Turmeric

BEAS-2B cells; Sprague–Dawley male rats

In vitro: 5, 10, 20 μM;

In vivo: 100 mg/kg

Up-regulating SLC7A11/GPX4 axis and FTH1; down-regulating TFR1

Up-regulating the protein levels of SLC7A11, GPX4, and FTH1; down-regulating the protein levels of TFR1; decreasing lipid peroxidation, GSH depletion, and iron overload; anti-oxidative stress: decreasing the contents of MDA and ROS

[165]

COPD

Dihydroquercetin

Flavonoids

Onion, French maritime pine bark, milk thistle, and Douglas fir bark

HBE cells;

In vitro: 40, 80 μM;

In vivo: 50 mg/kg (low-dose), 100 mg/kg (high-dose)

Activating Nrf2-mediated pathway

Decreasing production of MDA and ROS, increasing SOD activity; up-regulating the protein levels of SLC7A11 and GPX4; decreasing lipid peroxidation; attenuating mitochondria damage

[17]

COPD

Tongxinluo

Formulas

Chinese herbal medicine

HPMECs; male C57BL/6 and ApoE-/- mice

In vitro: 200, 400, 800 μg/ml;

In vivo: 0.75 g/kg

Up-regulating the protein expression of GPX4 and FSP1

Increasing protein levels of GPX4, FSP1; decreasing protein levels of ACSL4; ameliorating pathological lung injury and pulmonary function: FRC, RI, Cdyn, MV; ameliorating dyslipidaemia and atherosclerotic lesions; protecting pulmonary microvascular endothelial barrier; enhancing the antioxidant capacity: GSH, SOD, MDA, NO; increasing HPMECs viability

[31]

COPD

Scutellarein

Flavonoids

Scutellaria altissima L; S.baicalensis Georgi; S Barbara D. Don

BEAS-2B cells; C57BL/6 mice

In vitro: 5 μM;

In vivo: 5, 10, 20 mg/kg

Chelating Fe2 + and interacting with ALOX15

Chelates Fe2 + and interacts with ALOX15 to reduce lipid peroxidation, reverse GPX4 downregulation, and block Nrf2/HO-1 and JNK/p38 pathway overactivation

[169]

Asthma

FAGS and CK

Other

Ginseng sprouts and its ginsenoside

Female C57BL/6 mice

In vivo: 300 mg/kg (FAGS: low-dose), 600 mg/kg (FAGS: high-dose); 50 μM (CK);

Up-regulating SLC7A11/GPX4 axis

Inducing airway hyperresponsiveness and IgE production; decreasing airway Inflammation: declining contents of inflammatory cells and Th2 cytokines; attenuating oxidative stress: decreasing contents of ROS and MDA; increasing the SLC7A11 and GPX4 expression levels, decreasing the 4-HNE expression level and iron accumulation

[173]

Asthma

Quercetin

Flavonoids

Variety of plants

RAW 264.7 cells; male C57BL/6 mice

In vitro: 10 μM;

In vivo: 25 mg/kg

Inhibiting M1 macrophage polarization

Up-regulating expression of SLC7A11 and GPX4; decreasing total levels of inflammatory cytokines: TNF-α, IL-6, IL-1β, and IL-17A; alleviating lipid peroxidation: MDA, 4-HNE; decreasing the mRNA levels of M1'makers: CD86, iNOS, MF1

[174]

PF

Dihydroquercetin

Flavonoids

Yew, larch and cedrus brevifolia bark

HBE cells, MRC-5 cells; C57BL/6 mice

In vitro: 40 μM;

In vivo: 10 mg/kg (low-dose), 50 mg/kg (high-dose)

Inhibiting ferritinophagy

Reducing the levels of profibrotic markers: α-SMA, collagen1 and fibronectin; decreasing the levels of ferropotosis relative factors: Fe2 + , ROS, MDA,

4-HNE content, lipid peroxidation; increasing levels of GPX4, GSH; up-regulating the ferritinophagy markers FTH1 and NCOA4, down-regulating autophagy makers LC3

[177]

PF

Tuberostemonine

Alkaloids

Stemona

HLF cells; C57BL/6 mice

In vitro: 350, 550, 750 μM;

In vivo: 50 mg/kg (low-dose), 100 mg/kg (high-dose)

Up-regulating SLC7A11/GPX4 axis

Reducing inflammation and collagen deposition;

up-regulating SLC7A11, GPX4 and GSH;

down-regulating the accumulation of iron and ROS

[178]

LIRI

Tanshinone IIA

Quinones

Salvia miltiorrhiza

C57BL/6 mice

In vivo: 30 μg/kg

Activating the PI3K/Akt/mTOR pathway

Decreasing lung injury score, W/D ratio, MPO and MDA contents; inhibiting inflammatory response: decreasing the expression of IL-1β, IL-6 and TNF-a, increasing the expression of IL-10; inhibiting ferroptosis: increasing levels of GPX4, SLC7A11 and GSH, and decreasing levels of Ptgs2 and MDA; decreasing apoptosis: increasing in the Bcl-2, and decreasing in the Bax, Bim, Bad and caspase3

[187]

LIRI

Salidroside

Glycosides

Rhodiola rosea

MLE-12 cells and RAW 264.7 cells; Male C57BL/6 and Nrf2 − / − mice

In vitro: 40 µM;

In vivo: 50 mg/kg

Activating the Nrf2/SLC7A11 signaling axis

Reducing lipid peroxides and iron overload,

up-regulating the expression of ferroptosis tightly related proteins Nrf2, SLC7A11, and GPX4

[188]