Table 2.
Summary of Chinese herbal medicines or herbal natural compounds in improving diabetes and its complications via the ferroptosis pathway.
| Chinese herbal medicines or herbal natural compounds | Source | Experimentalmodels | Possible mechanisms | Type of disease | Outcomes |
|---|---|---|---|---|---|
| GBE-5 [77] | Ginseng berry | HepG2 cells (the KEGG metabolic pathway enrichment analysis) | ferroptosis | T2DM | Hypoglycemic effect. |
| Cryptochlorogenic acid [78] | Mulberry leaf | INS-1 cells; SD rats |
Inhibit ferroptosis via the activation of XC−/GPX4/Nrf2 and inhibition of NCOA4. | T2DM | Improve the blood glucose level and islet injury. |
| Quercetin [79] | Flavonoids | C57BL/6J mice | Inhibit ferroptosis by increasing GSH activity, SOD activity, and GPX4 expression, and decreasing xCT, MDA expression and iron concentrations. | T2DM | Alleviate ferroptosis of pancreatic β Cells. |
| Puerarin [80] | Radix puerariae | HBZY-1 cells SD rat |
Decrease cellular LDH and Lipid ROS Downregulate the expression of ferroptosis inducer ACSL4. Elevate the level of GPX4 level. |
DN | Attenuate excessive extracellular matrix accumulation. |
| Platycodin D [81] | Dry root of Platycodon grandiflorm | HK-2 cells | Inhibit HG-induced ferroptosis. Downregulate ACSL4 and TFR1 expression Up-regulate GPX4, FTH-1 and SLC7A11 expression. |
DN | Reverse the effects of HG condition on cell death. |
| Glabridin [82] | The main active component in licorice. | NRK-52E cells SD rats |
Represse ferroptosis by increasing SOD and GSH activity, and GPX4, SLC7A11, and SLC3A2 expression, and decreasing MDA and iron concentrations, and TFR1 expression. | DN | Ameliorate the renal pathologicalchanges and the renal function Reduce FBG, HOMA-β, and HOMA-insulin index. |
| Umbelliferone [27] | widely exists in Umbelliferae plants | db/db mice | Attenuate HG-induced ferroptosis by activating the Nrf2/HO-1 pathway. | DN | Improve the renal pathological damage and ROS accumulation of db/db mice. |
| Calycosin [83] | Astragali Radix | HK-2 db/db mice | Inhibit HG-induced decrease in glutathione and GPX4 expression. Inhibit the increase of LDH, MDA, lipid ROS and NCOA4. |
DN | Protective effect on DN may be through inhibition of ferroptosis pathway. |
| Sennoside A [84] | Rhei Rhizoma | C57BL/6J mice | Reduce oxidative stress. Downregulate the expression of Nrf2, HMOX-1, and PTGS2. Increase the expression of GPX4. Inhibit the Nrf2/HMOX-1 signaling pathway. |
DN | Inhibit the level of ferroptosis in the treatment of DN. |
| Germacrone [38] | Rhizoma Curcuma | db/db mice | Regulate ferroptosis by targeting mmu_mmu_circRNA_0000309/miR-188–3p/GPX4 signaling pathway. | DN | Ameliorate kidney damage. |
| Berberine [85] | Rhizoma Coptidis | MPC5 | Activate Nrf2/HO-1/GPX4 pathway. | DN | Alleviate podocyte plasma membrane blistering and mitochondrial shrinkage under high glucose conditions. |
| Naringin [86] | Citrus plants | SD rats | Regulate ferroptosis by targeting the Nrf2/GPX4 pathway. | DCAN | Relieve DCAN mediated by the P2Y14 receptor of satellite glial cells in the superior cervical ganglia. |
| Resveratrol [87] | Mainly from grapes, polygonum, peanuts and other plants. | H9c2 cells | Inhibit ferroptosis by up-regulating the expression of HSF1. | DCM | Improve HG-induced cardiomyocyte injury. |
| Gegen Qinlian Decoction (GQD) [88] |
Including Pueraria, Scutellaria, Coptidis, Licorice. | C57BL/KsJ-db/db mice | Regulate the expression of ferroptosis-related genes, reduce the level of lipid peroxidation in myocardial tissue, and up-regulate the expression of GPX4. | DCM | Improve cardiac remodeling and diastolic function in db/db mice with damp-heat syndrome. |
| Sulforaphane [52] | Cruciferous vegetables like cauliflower. | ECTs AMPKa2-KOmale mice |
Activate NRF2 and inhibite cardiac cell ferroptosis by upregulating ferritin and SLC7A11 levels. | DCM | Prevent diabetic cardiomyopathy via AMPK/Nrf2 pathways. |
| Baicalein [89] | Scutellaria | BMSCs SD rats |
Inhibition of ferroptosis by up-regulating the SLC7A11/GPX4 axis. | DOP | Prevent the occurrence of DOP. |
| Artemisinin [90] | Compositae Artemisia annua | C57BL/6J | Reduce the ROS and MDA contents, increase Nrf2, HO-1, GSH and GPX4. | DCI | Improve cognitive impairment by inhibiting hippocampal ferroptosis via activating Nrf2. |
| Astragaloside-IV [39] | Astragalus membranaceus | ARPE-19 RPE | Increase mir-138–5p expression in RPE cells and promote expression of Sirt1 and Nrf2 in the nucleus. | DR | Alleviate high- glucose-induced ferroptosis by disrupting the expression of miR-138–5p/Sirt1/Nrf2. |
| Tu-Xian Mixture [68] | It is composed of dodder, fairy spirit spleen, privet root, pueraria and rhodiola. | SD rat | It may be related to the ferroptosis pathway. | DCI | Improve the cognitive function of diabetic cognitive dysfunction rats. |
Partial abbreviation: SD rats: Sprague-Dawley rats; xCT-: the substrate-specific subunit of system Xc-; FBG: fasting blood glucose; ECTs: engineered cardiac tissues; BMSCs: bone marrow mesenchymal stem cells.