# Alpha-Mangostin Suppresses LPS-Induced Inflammation in Human Dental Pulp Cells
## 4 Discussion  
\(\alpha\)-MG is known to possess diverse biological properties. Many studies have revealed the inhibitory effects of \(\alpha\)-MG on inflammation using human cell lines, such as adipocytes [13], macrophage-like U397 cells [14; 15], and macrophage-like THP-1 cells [16]. To the best of our knowledge, there are no studies investigating the inhibitory effects of \(\alpha\)-MG on LPS-treated hDPCs. Therefore, we hypothesized that \(\alpha\)-MG could have similar anti-inflammatory effects on hDPCs.  
We also examined the cytotoxic effects of LPS and \(\alpha\)-MG on hDPCs. The results showed that non-cytotoxic concentrations of LPS increased mRNA and protein expressions of IL-1\(\beta\) and IL-6. However, pretreating cells with non-cytotoxic concentrations of \(\alpha\)-MG (especially with 3 \(\mu\)g/mL) caused a decrease in the upregulation of mRNA and protein expression in hDPCs stimulated with LPS.  
Consistent with our results, a previous study showed that \(\alpha\)-MG suppressed LPS-induced IL-6 gene expression in macrophage-like cells [13] and adipocytes [17]. Likewise, \(\alpha\)-MG also blocked the activation of LPS-induced RAW 264.7 cells and inhibited the secretions of inflammatory mediators, such as NO, COX-2, IL-1\(\beta\) andmIL-6 [18].  
Meanwhile, cell adhesion molecules involved in cell-cell or cell-extracellular matrix binding have been associated with immune cell activation [19], leukocyte migration [20], and cellular mechanisms of growth or apoptosis. Of the CAMs, ICAM-1 and VCAM-1 attract mononuclear cells and neutrophils [21] to inflamed sites to induce inflammatory responses. This study also examined whether \(\alpha\)-MG suppressed the expressions of ICAM-1 and VCAM-1 in hDPCs after LPS treatment. The results of the present study show that LPS stimulation led to an increase in the mRNA and protein expression of ICAM-1 and VCAM-1. Furthermore, pretreatment with \(\alpha\)-MG (especially with 3 \(\mu\)g/mL \(\alpha\)-MG) prevented this upregulation in ICAM-1 and VCAM-1 expression. These results indicate that \(\alpha\)-MG could attenuate the gene expression and secretion of inflammatory mediators, such as IL-1\(\beta\), IL-6, ICAM-1, and VCAM-1 in hDPCs, and the most effective and non-cytotoxic concentration was 3 \(\mu\)g/mL.  
Previous studies reported that \(\alpha\)-MG inhibited LPS-induced inflammatory responses via several intracellular signaling pathways, such as the MAPK [13; 14; 15] and NF-kB [22; 23] pathways. This study found that treating LPS-stimulated hDPCs with 3 \(\mu\)g/mL \(\alpha\)-MG inhibited the phosphorylation of MAPK-related proteins, such as ERK, JNK, and p38, implying that \(\alpha\)-MG could exert its anti-inflammatory effects by suppressing the MAPK pathway. Moreover, there was a decrease in the phosphorylated p65 levels after \(\alpha\)-MG treatment, indicating that \(\alpha\)-MG could also partially influence the NF-kB pathway. Further studies are needed to clarify underlying molecular mechanisms.  
The results from the present study also highlight the positive effects of \(\alpha\)-MG on ALP activity. Increased ALP levels are relevant to the odontoblastic differentiation of hDPCs [24]. Consequently, \(\alpha\)-MG may affect the differentiating hDPCs and possibly promote mineralization. Follow-up experiments and in vivo studies are needed to support the use of \(\alpha\)-MG for treating inflammatory conditions in the human dental pulp.