# Korean Panax Ginseng Reduces Orthodontic Tooth Movement in Rats
## 4 Discussion  
Orthodontic tooth movement takes advantage of the inflammatory mechanisms that start once a tooth is moved towards its surrounding alveolar bone [1; 2]. Inflammatory mechanisms culminate in the formation and activation of the bone-resorbing osteoclasts, making space for the tooth to move [1; 2]. This is what happens on the pressure side. On the tension side, bone-forming osteoblasts are initiated to allow the bony support to be regained and to hold the tooth in its new position. Thus, if force-induced inflammation is of major importance for OTM [3; 4], then the causes of changes in inflammation may also affect OTM. This view is perhaps simplified but works as a working hypothesis. On a molecular level, we learned that OTM is diminished by Nrf2-HO1 signaling [13] and that ginseng extracts can increase Nrf2-HO1 signaling [11; 12]. Thus, the suggestion that ginseng extracts possibly attenuate OTM is well-supported. In support of this assumption, our data show that, at higher concentrations of the ginseng extract, namely 150 and 300 mg of G115 per kg of body weight, OTM was significantly reduced compared with the untreated normal group. In this view, we have to consider anti-inflammatory compounds to decrease OTM. Some examples are that, through the inhibition of prostaglandin production, OTM is reduced in rats [5; 6; 7]. Consistently, ginseng extract and its ginseng decrease prostaglandin production in macrophages [38]. Still, (I) how the ginseng and maybe other compounds released by ginseng reaches periodontal space, (II) if the effects of ginseng extracts are indirect via suppression of the inflammatory signals required for osteoclastogenesis and bone resorption, and (III) if ginseng compounds may even directly decrease the resorptive capacity of the mature osteoclasts remain unclear. We propose that a reduction in OTM is caused by the systemic anti-inflammatory activity of the bioactive compounds of ginseng extracts. The weight loss in rats treated with 150 and 300 mg of G115 per kg body weight was originally not considered an endpoint but was significant. Our findings are less surprising if we appreciate that ginseng extracts reduced obesity-related lipid metabolism in mice fed a long-term high-fat diet [39]. Additionally, in high-fat-diet rats, weight reduction, especially fat mass reduction, was observed in the ginseng extract-treated group [40]. Weight loss  
Figure 3: Body weight changes by Panax ginseng extracts. can be linked to changes in lipid metabolism by lowering the levels of cholesterol, low-density lipoprotein-cholesterol, and serum triglycerides [39], which may even affect the formation of bioactive lipid mediators that control the resolution of inflammation such as resolvins [41]. Hence, our observation, however independent of OTM measurements, supports observations of the effect of ginseng extracts on reducing body weight. Care should be taken when interpreting the preclinical findings as an adult person has to reach a daily intake of around 10-30 g of the G115 ginseng extract to lose weight, which is comparatively much. We have to admit that a rodent model does not necessarily represent a clinical situation and that dosing cannot be directly translated into patients. One other limitation of our descriptive study is that the underlying mechanisms by which G115 ginseng extracts reduce OTM and lower body weight remain unclear. It would be interesting to confirm the activation of the Nrf-HO1 axis by ginseng in our model [19; 20] and to show that this axis is responsible for the suppression of osteoclastogenesis [22; 23], based on the observation that Nrf-HO1 signaling attenuated OTM in mice [21]. Future studies should therefore use Nrf2 or HO1 knockout mice where, at least in theory, G115 ginseng extracts should not reduce OTM. Another limitation is that we did not include a control group where an agonist of Nrf-HO1 signaling pushes OTM.