Table 2. Additional examples of pharmacological mechanisms of action for plant-derived 1,4-NQs.
| Plant-derived 1,4-NQ(s) | Pharmacological mechanism of action | Reference(s) |
|---|---|---|
| Shikonin | Protection of brain against ischemic stroke damage by attenuated TLR4, p-p38MAPK, NF-κB, TNF-α and MMP-9 expression, and upregulated claudin-5 expression | 255 |
| Suppression of epithelial–mesenchymal transition and downregulation of expression of Slug and MMP-2, -9 and -14 in thyroid cancer cells | 223 | |
| Management of inflammatory bowel disease by inhibiting activation of NF-κB and STAT3 | 256 | |
| Promotion of intestinal wound healing via induction of TGF-β release | 257 | |
| Inhibition of expression of the pro-inflammatory cytokine TNF-α through selective blockade of pre-mRNA splicing | 258 | |
| Inhibition of IFN-γ induced K17 overexpression by interfering with STAT3 signaling in psoriasis pathogenesis | 259 | |
| Inhibition of lipopolysaccharide-induced release of HMGB1 via IFN-β and NF-κB signaling pathways in inflammation | 260 | |
| Inhibition of STAT3-, FAK- and Src-mediated signaling in breast cancer | 261 | |
| Suppression of IL-17-induced VEGF expression via blockage of the JAK2/STAT3 pathway in psoriasis pathogenesis | 262 | |
| Inhibition of c-MYC expression with involvement of ERK/JNK/MAPK and AKT pathways in leukemia cells | 263 | |
| Suppression of orphan nuclear receptor Nr4a family gene expression for treating allergic diseases | 264 | |
| Shikonin derivatives | Inhibition of the transcriptional activation of the human TNF-α promoter in treating inflammatory diseases | 265 |
| Inhibition of tumor angiogenesis via inhibition of VEGFRs | 266 | |
| Shikonin and alkannin | Inhibition of cancer cell glycolysis via inhibition of tumor-specific PKM2 | 267 |
| Plumbagin | Decreased expression of TNF-α, IFN-γ and IL-17 in murine ulcerative colitis | 268 |
| Amelioration of autoimmune encephalomyelitis via downregulation of JAK–STAT and NF-κB signaling pathways | 269 | |
| Antiproliferative activity against lung epithelium carcinoma cells by disruption of the microtubule network through tubulin binding | 270 | |
| Inhibition of cytochrome P450s | 271,272 | |
| Inhibition of telomerase and induction of cell death in human brain tumor cells | 273 | |
| Induction of cell cycle arrest and autophagy; suppression of epithelial to mesenchymal transition involving the PI3K/Akt/mTOR-mediated pathway in human pancreatic cancer cells | 274 | |
| Induction of G2/M arrest, apoptosis, and autophagy via p38 MAPK- and PI3K/Akt/mTOR-mediated pathways in human tongue carcinoma cells | 275 | |
| Binding to and inhibition of five cancer signaling proteins (PI3Kc, AKT1/PKBa, Bcl-2, NF-κB and Stat3) | 276 | |
| Interference with the binding of ER-alpha to ERE and antagonism at the death receptor complex in BRCA1 breast cancer cells | 277 | |
| 5-O-Acyl plumbagins | Inhibition of mammalian DNA polymerase and suppression of inflammatory response | 278 |
| 7-Methyljuglone | Suppression of PI3K/Akt signaling in breast cancer cells | 279 |
| Juglone | Inactivation of cysteine-rich proteins required for progression through mitosis | 251 |
| Prevention of metabolic endotoxemia-induced hepatitis and neuroinflammation via suppression of the TLR4/NF-κB signaling pathway | 280 | |
| Juglone and plumbagin | Inhibition of protein tyrosine phosphatases, leading to increased phosphorylation and activation of epidermal growth factor receptor in HaCaT keratinocytes | 219 |
| Acetylshikonin, shikonin, juglone, lawsone, plumbagin and lapachol | Inhibition of monoamine oxidases regulating neurotransmitter levels and cell signaling, growth and differentiation | 281–283 |
Abbreviations: ERE, estrogen responsive elements; IFN, interferon; IL-17, interleukin-17; MMP, matrix metallopeptidase; NF-κB, nuclear factor κB; 1,4-NQ, 1,4-naphthoquinone; PKM2, pyruvate kinase-M2; TGF-β, transforming growth factor-β; TLR4, Toll-like receptor 4; TNF-α, tumor-necrosis factor-α; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor.