Table 4.
Traditional Herbal Medicine Targeting NETs
| Target | Active Ingredients | Source | Route of Application | Model | Dose | Mechanism | Disease | Ref. |
|---|---|---|---|---|---|---|---|---|
| Protein | Andrographolide | Andrographis paniculata | i.p. | C57BL/6 mice | 25, 50 mg/kg | Inhibited PMA-induced upregulation of PAD4 expression, reversed histone-3 citrullination, and inhibited autophagy of neutrophils and NETs production. | Rheumatoid arthritis | [180] |
| HMEI-A (self-naming) | Hirudinaria manillensis | Co-incubation | PMNs | 10 µg/mL | Inhibit NETs formation. | Inflammation | [181] | |
| Chikusetsusaponin V | Panax japonicus | p.o. | C57BL/6 mice | 50, 100, 200 mg/kg | Inhibit NETs formation by reducing HMGB1 expression. | Acetaminophen-damaged liver | [182] | |
| Polysaccharide (KSWP) | Kochia scoparia | i.g. | ICR mice | 300 µL (5 g/kg) | Selective inhibition of human neutrophil elastase and significant inhibition of NETs formation in a dose-dependent manner. | Acute lung injury | [183] | |
| - | SiWuTang | p.o. | C57BL/6 J mice | 2.6, 5.2, 10.4 g/kg | Inhibits NETs production by reducing cathepsin, elastase, and MPO levels. | Bile duct ligation-induced liver fibrosis | [184] | |
| ROS | Polydatin | Polygonum cuspidatum | i.p. | DBA/1 mice | 45 mg/kg | Inhibit NETs production by blunting ROS production. | Rheumatoid arthritis; collagen-induced arthritis | [185] |
| Sal B and DHT I | Danshen | i.p. | BALB/c athymic nude mice | 780 mg/kg | Block the activity of MPO and NADPH to disrupt NETs formation. | Tumor | [186] | |
| Gingerol | Ginger | Co-incubation | PMNs | 1–10 µM | Inhibits NETosis by blunting ROS production. | Lupus and antiphospholipid syndrome-related NETs | [187] | |
| TTC | Celastrus orbiculatus | Co-incubation | PMNs | 5–80 µg/mL | Inhibits ROS and blocks NETs generation in a NOX-dependent pathway. | Inflammation | [188] | |
| Epicatechin, catechin hydrate, rutin trihydrate | – | Co-incubation | PMNs | 4–100 µM; 4–100 µM; 0.1–150 µM | Inhibit the formation of ROS-dependent NETs. | NETs- related diseases | [189] | |
| Quercetin | – | i.p. | C57BL/6 mice | 30 mg/kg | Inhibits neutrophil infiltration and ROS production through autophagy-dependent pathways. | Rheumatoid arthritis | [190] | |
| Signaling pathway | – | ReDuNing injection (approval number Z20050217) | i.p. | C57BL/6 Mice | 5, 10 mL/kg | Inhibits NETs generation by blunting the MAPK pathway. | Acute lung injury | [191] |
| SYA, HSYA, AHSYB | Xuebijing injection (approval number Z20040033) |
i.p. | C57BL/6J mice | 5 × 10−5 mol/kg | Inhibits the production of inflammatory factors, infiltration of inflammatory cells, and NETs production by inhibiting activation of TLR signaling. | Acute lung injury | [192] | |
| – | Ephedra–almond herbal pair | Co-incubation | PMNs | 0.5–8 mM | Inhibits NETs formation by blunting expression of the HMGB1/TLR4 pathway. | Asthma | [193] |
Abbreviations: AHSYB, anhydrosafflor yellow B; DHT I, 5,16-dihydrotanshinone; HSYA, hydroxysafflor yellow A; HMGB1, high-mobility group protein B1; i.g., intragastric; i.p., intraperitoneal injection; KSWP, polysaccharide of Kochia scoparia; MPO, myeloperoxidase; MAPK, mitogen-activated protein kinase; NADPH, nicotinamide adenine dinucleotide phosphate; NETs, neutrophil extracellular traps; NOX, NADPH oxidase; PAD, peptidyl arginine deiminase; PMA, phorbol Myristate Acetate; PMNs, polymorphonuclear cells; p.o., peros; ROS, reactive oxygen species; Sal B, salvianolic acid B; SYA, safflor yellow A; TLR, toll-like receptor; TTC, total terpenoids of Celastrus orbiculatus.