Table 2.
Summary of representative STs and DSTs with anti-inflammatory and anticancer activity and their mechanisms of action
| Compounds | Source | Anti-inflammatory activity |
Anticancer activity | Molecular mechanisms | References |
|---|---|---|---|---|---|
| Inulanolide A (4) |
I. britannica, I. japonica |
Inhibits the production of NO and TNF-α in LPS-stimulated RAW264.7 cells |
Inhibits cell proliferation, arrests cells in G2-M phase, induces cell apoptosis, suppresses cell migration and invasion in breast cancer cells in vitro, independent of p53 Suppresses breast tumor growth and metastasis in vivo, independent of p53 | Inhibits NF-κB activation Inhibits NFAT1-MDM2 pathway, independent of p53 Modulates the expression of proteins related to cell proliferation, cell cycle progression, apoptosis, and DNA damage |
[64, 74] |
| Japonicone A (5) | I. japonica | Inhibits TNF-α-mediated cytotoxicity in L929 cells Inhibits TNF-α-induced endothelial cell activation Reduces TNF-α-induced hepatic injury in d-GalN sensitized mice |
Inhibits cell proliferation, arrests cells in G2-M phase, and induces cell apoptosis in breast cancer cells in vitro, independent of p53 Suppresses breast tumor growth and metastasis in vivo, independent of p53 |
Binds to TNF-α and selectively inhibits the interaction between TNF-α and TNFR1 Inhibits TNF-α-TAK1-IKK-NF-κB signaling axis and TNF-α-induced NF-κB activation and nuclear translocation and downregulates NF-κB target genes Binds to MDM2 and induces MDM2 degradation Inhibits NFAT1 and NFATl-me-diated MDM2 transcription |
[65, 70–73] |
| Lineariifolianoid A (6) | I. lineariifolia | Has no significant effect on TNF-α-mediated L929 cytotoxicity | Inhibits cell proliferation, arrests cells in G2-M phase, induces cell apoptosis, suppresses cell migration and invasion in breast cancer cells in vitro, independent of p53 | Inhibits NFAT1-MDM2 pathway, independent of p53 Modulates the expression of proteins related to cell proliferation, cell cycle progression, apoptosis, and DNA damage |
[68, 75] |
| Artemisinin (3) | A. annua | Exerts anti-inflammatory activity in TPA-induced skin inflammation in mice | Inhibits cancer cell growth and proliferation, arrests cell cycle at G1 phase, and induces cell apoptosis in vitro
Suppresses xenograft tumor growth and sensitizes cancer cells to chemotherapy in vivo |
Inhibits TNF-α-induced phosphorylation and degradation of IκBα, nuclear translocation of NF-κB p65, and expression of NF-κB target genes Reacts with the ferrous atom and produces free radicals or ROS Inhibits MDM2 expression, independent of p53 Modulates the expression of proteins associated with cell cycle progression and apoptosis, independent of p53 |
[78, 89, 92–94] |
| Artesunate (7) | synthetic derivative | Exerts anti-arthritis activity in K/BxN mouse model of rheumatoid arthritis and rat model of Freund’s complete adjuvant-induced arthritis | Induces cancer cell apoptosis | Inhibits nuclear translocation NF-κB and its transcriptional activity Inhibits PI3K/Akt activation Reacts with the ferrous atom and produces free radicals or ROS | [79–82, 89, 90] |
| Dihydroartemisi-nin (8) | synthetic derivative | Inhibits onset of EAE and ameliorates this disease in EAE-inflicted mice Inhibits OVA-induced chronic airway inflammation in mice Protects rats against bleomycine-induced pulmonary fibrosis and alcoholic liver injury |
Inhibits cancer cell growth and proliferation, arrests cell cycle at G1 phase, and induces cell apoptosis in vitro
Suppresses xenograft tumor growth and sensitizes cancer cells to chemotherapy in vivo |
Inhibits mTOR pathway Inhibits phosphorylation of ERK, p38 MAPK and IκBα, and activation of NF-κB Inhibits mRNA and protein expression of TGF-β1, TNF-α, α-SMA, and NF-κB Activates FXR Reacts with the ferrous atom and produces free radicals or ROS Induces transferrin receptor-1 internalization, decreases iron uptake, and disturbs iron homeostasis Inhibits MDM2 expression, independent of p53 Modulates the expression of proteins associated with cell cycle progression and apoptosis |
[83-86, 89,91, 92, 95, 96] |
| Phosphate ester dimer 14a (9) | synthetic derivative | Not reported | Inhibits cancer cell growth and induces apoptosis | Not reported | [97] |
| Phosphate ester dimer 14b (10) | synthetic derivative | Not reported | Inhibits cancer cell growth and induces apoptosis | Not reported | [97] |
| Phthalate dimer 5 (11) | synthetic derivative | Not reported | Inhibits cervical cancer cell growth without apparent cytotoxicity against normal cervical cells | Not reported | [98] |
| Bis-benzyl alcohol dimer 7 (12) | synthetic derivative | Not reported | Inhibits cervical cancer cell growth without apparent cytotoxicity against normal cervical cells | Not reported | [98] |
| ARS4 (13) | synthetic derivative | Not reported | Inhibits cancer cell growth and proliferation, arrests cells in S phase, induces cell apoptosis, and prevents cell migration in ovarian cancer cells in vitro Suppresses xenograft tumor growth and metastasis in vivo | Inhibits MDM2 expression, independent of p53 Modulates the expression of proteins related to cell cycle progression, apoptosis, and EMT |
[100] |
| Ainsliadimer A (14) | A. macrocephala | Inhibits NO production in LPS-stimulated RAW264.7 cells |
Inhibits cancer cell growth in vitro Represses xenograft tumor growth in vivo | Binds to IKKα/β and allosterically inhibits its activities, resulting in inhibition of NF-κB signaling pathway | [102, 104] |
| Ainsliatrimer A (15) | A. fulvioides | Not reported | Inhibits cancer cell growth and induces apoptosis in vitro | Binds to PPARγ and activates its transcriptional activity | [105–107] |
| Artemilinin A (16) | A. argyi | Not reported | Weak cytotoxicity | Not reported | [108] |
| Isoartemisolide (DSF-52, 17) | A. argyi | Inhibits the production of NO, PGE2 and TNF-α in LPS-stimulated BV-2 microglial cells | Weak cytotoxicity | Inhibits NF-κB, JNK/p38 MAPKs, and Jak2/Stat3 pathways | [108, 109] |
| DSF-27 (18) | A. argyi | Inhibits LPS-induced microglial activation and protects neurons from microglia-mediated neuro-inflammatory injury | Not reported | Inhibits the Syk/NF-κB and Jak2/Stat3 signaling pathways | [110] |
| Diguaiaperfolin (19) | E. perfoliatum | Inhibits NO production and iNOS expression in LPS-stimulated RAW264.7 macrophages | Not reported | Not reported | [111] |
| Shizukaol B (20) | C. japonicas | Inhibits ICAM-1/LFA-1-mediated cell aggregation and monocyte adhesion to HUVEC in human promyelocytic HL-60 cells Inhibits the NO production in LPS-stimulated BV-2 cells |
Not reported | Inhibits the expression of ICAM-1, VCAM-1 and E-selectin | [112, 113] |
| 6-hydroxy-thiobi nupharidine (21) | N. pumilum | Inhibits anti-sheep erythrocyte plaque forming cell formation Possesses potent immunosuppressive activity | Inhibits cancer cell growth, induces apoptosis, and inhibits cell invasion in vitro Suppresses lung metastasis of B16 melanoma cell in mice in vivo |
Inhibits NF-κB pathways and induces cleavage of PARP | [114–119] |
| Microlenin (22) | H. microcephalum | Not reported | Induces Ehrlich ascites carcinoma cell death | Inhibits DNA and protein synthesis | [120–122] |
| Meiogynin A(23) | M. cylindrocarpa | Not reported | Induces cancer cell death and apoptosis | Inhibits Bcl-xL/Bak binding and Mcl-1/Bid binding | [123–127] |
| Parviflorene F (24) | C. parviflora | Not reported | Induces cancer cell death and apoptosis | Increases the expression levels of TRAIL-R2 | [128–130] |
| Cryptoporic acid E (25) | C. volvatus | Not reported | Prevents okadaic acid-stimulated tumor promotion in mouse skin Prevents N-Methyl-N-Nitrosourea-induced colon carcinogenesis in rats Prevents 1,2-dimethylhydrazine-caused colon carcinogenesis in mice |
Inhibits superoxide anion radical release | [131, 132] |