# In Silico Modeling Study of Curcumin Diffusion and Cellular Growth
## 3 Results and Discussion
### Integration of Fibroblast Proliferation and Curcumin Diffusion Models
Therefore, as described in Table 3, the same dose-dependent tendency is observed, independently of the curcumin diffusion model. The dose-dependent effect of curcumin on confluence is summarized in Figure 10. Considering a 42.82% confluence as the control, the lowest concentration of curcumin demonstrated the most beneficial effect and represented the highest confluence. As curcumin concentration increases, this beneficial effect reduces, resulting in a lower confluence percentage. This trend is similar to that obtained in [14], in which the authors analyzed the effect of curcumin on the extent of wound healing in early-passage human dermal fibroblasts. In their experimental results, a 0.25 \(\upmu\)M dose had an extent of wound closure of approximately 1.5 (control being 1). Both release models achieved a confluence of 1.4 times the controls for the same dose in our results. The rest of our results showed similar effects to those described in [14] for both release models. Likewise, the authors of [46] conducted a proliferation assay on olfactory ensheathing cells and tested curcumin's effect at doses of 0.1, 0.5, 1, 10, and 20 \(\upmu\)M. Low concentrations were more effective in stimulating cell proliferation, although a concentration of 0.5 was the optimal, not necessarily the lowest. It was found that curcumin's stimulatory effect decreases for concentrations greater than 10 \(\upmu\)M, as shown in the present study. Figure 10: Dose-dependent effect of curcumin on fibroblast confluence. (**a**) Korsmeyer–Peppas model for curcumin diffusion. (**b**) [PERSON]’s hyperbolic model for curcumin diffusion. Behavior is very similar for both models. The authors of [50] observed the same dose-dependent effect on mouse 3T3-L1 preadipocytes. The cell culture was treated with various curcumin concentrations for 24 h. Low concentrations had a positive effect, increasing cell proliferation, while high concentrations had an inhibitory effect. Interestingly, a concentration of 0.02 uM of curcumin had the most stimulating effect on cell proliferation and migration. Moreover, only doses equal to or greater than 50 uM decreased cell proliferation. Contrary to our results, a dose of 20 uM stimulated cell proliferation after 24 h, although to a lesser extent than lower concentrations. Similarly, curcumin stimulates the proliferation of neural progenitor cells [69], 0.5 uM being the most effective concentration, whereas doses greater than 1 uM have an inhibitory effect. Curcumin's dose-dependent effect may differ between cell lines, thus resulting in a different therapeutic window. At doses above 10 uM, there is an inhibition in migration and proliferation of fibroblasts, and apoptotic cell death occurs [14; 46; 47; 48; 49]. The cytotoxic effect of high doses, especially 10, 15, and 20 uM, has been studied in various types of cancer cells [49] to demonstrate curcumin's possible antitumor properties. These results were successfully replicated, as shown in Figure 10. For doses greater than 10 uM, the inhibitory effect increases as the concentration increases, resulting in worse results than the controls. The reduced cell migration can be seen in Figure 9 for both models, as only a limited number of internal cells have reached the scratch line. However, apoptotic cell death was not integrated into the present model to simplify the simulation's output. Thus, this process could be added to develop a more realistic model.