# Bioactive Compounds from Herbal Medicine Targeting Multiple Myeloma
## 3 Flavonoids in Multiple Myeloma
### Baialein  
Baialein is one of the main biologically active compounds present in the root of _Scutellariae radix_[123]. The molecular formula of baialeine is C15H10O5, as can be seen in Figure 2. The particular structure is the di-orthohydroxyl functional group, located on ring A of its molecular structure [124].  
Baialein has a wide range of biological activities, such as antioxidant activity [125], anti-inflammatory [126], antiviral [127], antitumor activity and lower toxicity [123].  
Baialein has inhibited many types of cancer, for example, gastric cancer, hepatocellular carcinoma, lung cancer, pancreatic cancer, bladder cancer, colorectal cancer, prostate  
Figure 1: The chemical structure of apigenin.  
Figure 2: The chemical structure of baialein.  
cancer, ovarian and cervical cancer, breast cancer, multiple myeloma, melanoma and osteosarcoma [123].  
The antitumor activity of baialein is due to cell cycle regulation by inhibition of several cyclins/cyclin-dependent kinases [128], attenuating MAPK, Akt and mTOR activities or neutralizing free radicals [129], inducing apoptosis by activating caspase -9, -3 [130] and tumor invasion and metastases inhibition by decreasing MMP-2, -9 expression [131].  
Baialein inhibited the U266 cells proliferation and stimulated their apoptosis. Baialein also increased cereblon (CRBN) mRNA level and downregulated IKZF1 and IKZF3 transcription factors by proteasomal degradation. MM patients had a lower expression of IKZF3 and IKZF1, providing a better survival rate than those with a higher expression of IKZF1 and IKZF3 [132].  
[PERSON] et al. [133] reported inhibitory effects of baialein inhibited in RPMI 8226 cells and significantly reduced ATP-binding cassette protein expression, G subfamily, ABC -transporter proteins family [133], which is thought to be involved in drug resistance in cancer [134]. Previously, [PERSON] et al. [135] showed that baialein significantly reduced the RPMI8226 cells by decreasing ABCG2 expression.  
Baialein treatment inhibited the proliferation and migration of MM cells by downregulating the expression of \(\beta\)-catenin, cyclin D1, c-myc, and 87 integrin [136].  
[PERSON] et al. [137] demonstrated that baialein inhibited STAT1 phosphorylation, as well as IL-6-mediated phosphorylation of Jak, MAPK, STAT3, and Akt. Baialein increased the U266 cell sensitivity to dexamethasone and inhibited IL-6-induced bcl-xl gene expression. Baialein also showed a strong inhibitory effect on Erk1/2 phosphorylation. Thus, baialein could be considered an active inhibitor of IL-6-induced protein phosphorylation, and a potential agent in the treatment of MM.  
Co-administration of baialein with dexamethasone inhibited MPC-1-immature myeloma cells by activation of peroxisome proliferator-activated (PPARs) and glucocorticoid receptors, having a synergistic inhibitory effect on NF-kB [138].  
Previously, [PERSON] et al. [139] showed in vitro baialein inhibition of the MM cells, especially MPC-1-immature MM cells. Baialein inhibited IkB-\(\alpha\) phosphorylation, followed by reduced IL-6 and XIAP gene expression and activation of caspase-9 and -3.