The Impact of Saussurea lappa Ethanolic Extract on Interleukin-6 Levels and Tertiary Follicles in Female Wistar Rats (Rattus norvegicus strain Wistar) Exposed to Lead

Introduction: One of the causes of infertility is ovulation disorders. The ovulation process is related to tissue remodeling, and one of the triggers is the inflammatory process, which is mediated by pro-inflammatory cytokines such as IL-6, the only cytokine capable of modulating the secretion of other cytokines. Therefore, it can strengthen the inflammatory process. The correlation between IL-6 and reduced reproductive fertility indicates that high levels of circulating IL-6 inhibit fertility. Saussurea lappa contains a variety of bioactivities, including anti-inflammatory substances that can lower IL-6 activity. Reducing the production of IL-6 thereby increasing the number of tertiary follicles.Materials and Methods: This study aims to determine how Saussarea lappa root extract affects the level of IL-6 and the number of tertiary follicles in the ovaries of female rats (Rattus norvegicus strain Wistar) exposed to lead. This study has a true experimental design with a post-test control group. 24 female white rats were induced to lead at a dose of 1.5 mg/kg and separated into four groups: one control group and three treatment groups, which were subsequently given Saussurea lappa root extract at doses of 200 mg/kg, 400 mg/kg, and 600 mg/kg for 21 days. An immunohistochemistry method was developed using the ImageJ application. We observed IL-6 expression in 5 light microscope fields of view at 400 times magnification and obtained a brown color image with percentage results. Hematoxylin eosin staining was made, and the number of ovarian tertiary follicles was counted in all groups at 400 times magnification. All data were evaluated with Kruskal-Wallis, Post Hoc, and Mann-Whitney tests.Results: The Kruskal-Wallis test revealed a significant effect of Saussurea lappa root extract on ovarian IL-6 expression in the treatment group (p = 0,003). The Post Hoc indicated that a dose of 600mg/kg had affected IL-6 expression (p = 0,027). The Kruskal-Wallis test showed a result of 0.020, which means there is a significant effect of Saussurea lappa root extract on the number of tertiary follicles. The Mann-Whitney test showed that a dose of 600mg/kg had the most effect on increasing the number of tertiary follicles (p=0.014). At a dose of 600 mg/kg, significant reductions in IL-6 expression and increases in the number of tertiary follicles were observed.Conclusion: Saussarea lappa root extract has the effect of reducing IL-6 expression and increasing the number of tertiary follicles in the ovaries of female rats (Rattus norvegicus Wistar strain) induced by lead at a dose of 600 mg/kg.