TABLE 4.
Natural products inhibited ferroptosis.
| Classification | Compounds | Functional targets | Diseases | Test models | Mechanisms/Effects | Refs |
|---|---|---|---|---|---|---|
| Terpenoids | Cryptotanshinone | STAT3 | Pancreatic cancer | PANC-1, CFPAC1 cells | Inhibiting STAT3; Blocking erastin-induced ferroptosis | Gao et al. (2018) |
| Glycyrrhizin (GLY) | HMGB1 | Acute liver failure (ALF) | L02 hepatocytes; ALF mice | Reducing levels of Fe2+, MDA, ROS and lactic dehydrogenase (LDH); Increasing NRF2, HO-1 GPX4 and GSH levels; Hepatoprotective effect | Wang Y. et al. (2019) | |
| Bakuchiol and 3-hydroxybakuchiol, isolated from Cullen corylifolium | Unknow | Ferroptosis-related diseases | HT22 cells | Inhibiting erastin-induced ferroptosis | Yaseen et al. (2021) | |
| Flavonoids | Baicalein | ALOX12; ALOX15; PTGS2; GPX4 | Post-traumatic epilepsy (PTE); Ferroptosis-induced diseases | HT22, PANC-1, BxPc3, Molt-4, Jurkat cells; FeCl3-induced PTE mice | Decreasing ROS, 4-HNE, PTGS2 and ALOX12/15; Inhibiting GSH depletion and increasing GPX4 expression | (Xie et al., 2016b; Probst et al., 2017; Li Q. et al., 2019) |
| Quercetin; quercetin Diels-Alder anti-dimer (QDAD) | Antioxidant pathway | T2DM; Degenerative diseases | Bone marrow-derived mesenchymal stem cells (BMSCs); T2DM mice | Lowering iron level; Upregulating GSH, GPX4 and antioxidant pathway | (Li D. et al., 2020; Li X. et al., 2020) | |
| Puerarin | NOX4; GPX4; FTH1 | Heart failure | H9c2 cells; Heart failure model rats | Inhibiting NOX4 expression; Increasing GPX4 and FTH1 expression | Liu et al. (2018) | |
| Morachalcone D, Morachalcone E | GPX4; NRF2; SLC7A11 | Neuro-degenerative diseases | HT22 cells | Preventing ROS production, GSH depletion and iron accumulation; Increasing SLC7A11, GPX4, NRF2 and HO-1 levels; Neuroprotective effect | Wen et al. (2020) | |
| Butein; (s) -Butin | Antioxidant pathway | Degenerative diseases | BMSCs | Making cells resistant to ferroptosis | Liu J. et al. (2020) | |
| Sterubin | Unknown | Neuro-degenerative diseases | HT22, BV2, MC65 cells | Activating NRF2/ATF4 Signaling; Protecting against oxytosis/ferroptosis by maintaining GSH levels | Fischer et al. (2019), Maher et al. (2020) | |
| 7-O-Esters of taxifolin: 7-O-cinnamoyl-taxifolin; 7-O-feruloyl-taxifolin | GSH; NRF2 | Alzheime’s disease (AD) | BV-2, HT22 cells; AD model mice | Scavenging free radical; Maintaining GSH under stress conditions; Increasing NRF2 level; Neuroprotective effect | Gunesch et al. (2020) | |
| 6 flavonoids isolated from Cullen corylifolium | Unknow | Ferroptosis-related diseases | HT22 cells | Inhibiting erastin-induced ferroptosis | Yaseen et al. (2021) | |
| Kaempferol, Kaempferide | ARE; ROS | Neuro-degenerative diseases | HT22 cells | Inducing ARE activity; Suppressing intracellular ROS and mitochondrial superoxide anion production | Takashima et al. (2019) | |
| Polyphenols | Proanthocyanidin (PACs) | Unknown | Spinal cord injury (SCI) | SCI mice | Reducing iron, ACSL4 and ALOXs levels and oxidative stress; Increasing GSH, GPX4, NRF2 and HO-1 levels | Zhou et al. (2020) |
| Curcumin | Iron; GPX4 | Acute kidney injury; Pancreatic damage | HK-2, MIN6 cells; Proximal murine tubular epithelial cells (MCTs) Rhabdomyolysis mice | Activating HO-1; Reducing inflammation and oxidative stress; Inhibiting TLR4/NF-κB axis; Decreasing iron level, GPX4 inactivation, GSH depletion, and lipid peroxidation | Guerrero-Hue et al. (2019), Kose et al. (2019) | |
| Epigallocatechin gallate (EGCG) | Iron; GPX4 | Pancreatic damage | Mouse MIN6 pancreatic β cells | Decreasing iron level, GPX4 inactivation, GSH depletion, and lipid peroxidation | Kose et al. (2019) | |
| Iso-thiocyanates | Sulforaphane | NRF2 | Oligospermia | Oligospermia mice | NRF2 agonist; Up-regulating GPX4 and FPN protein expression | Zhao et al. (2020) |
| Phenyl-propanoids | Psoralidin | ALOX5; Keap1-NRF2 pathway | Ferroptosis-related diseases | HT22 cells | Inhibiting ALOX5 and Keap1-NRF2 protein-protein interactions; Neuroprotective effect | Yaseen et al. (2021) |
| Artepillin C | ROS | Neuro-degenerative diseases | HT22 cells | Reducing intracellular ROS and mitochondrial superoxide anion production | Takashima et al. (2019) | |
| Lignins | Nordi-hydroguaiaretic acid (NDGA) | ALOX5 | Iron overload related diseases | BT474, HT-1080, Molt-4, Jurkat, AML12 cells | Reversing ferroptosis caused by GPX4 inhibition; Protecting cells from iron overload, lipid peroxidation, ROS generation | Hangauer et al. (2017), Probst et al. (2017), Fang et al. (2018) |
| Multiple | Brown Rice extract | GPX4 | Vascular endothelial disorders | HUVECs | Compensating GPX4 loss and preventing LDH release; Decreasing lipid peroxides | Sakai et al. (2017) |
| Naotaifang Extract | SLC11A2 (DMT1); Iron; GPX4 | Acute brain injury | MCAO rats | Decreasing TFRC and SLC11A2 expressions; Reducing ROS, MDA and iron accumulations; Increasing SLC7A11, GPX4 expressions and GSH level; Neuroprotective effect | Lan et al. (2020) | |
| Moxibustion | GPX4; FTH1 | Parkinson’s disease (PD) | PD model rats | Upregulating GPX4 and FTH1 levels; Neuroprotective effect | Lu et al. (2019) |