Investigation of centella asiatica's effect on fetal brain damage caused by steroid-induced prenatal stress on pregnant mice

Stress factors that the offspring are exposed to during pregnancy are defined as prenatal stress and appear as the cause of psychosocial problems in childhood and adulthood. There is a great deal of research that explains the relationship between prenatal stress and cognitive behavioral, physical and emotional problems and autism. In vivo studies in various animal species have shown that maternal administration of synthetic glucocorticoid therapy such as of dexamethasone or betamethasone inhibits neurogenesis and reduces fetal neuronal cell proliferation in the neocortex and hippocampus dentate gyrus of the offspring. Centella Asiatica, which has been used in traditional Asian medicine for centuries to treat many diseases, is a herbaceous and perennial plant from the Apiaceae family. It has been used in modern medicine for a long time, particularly in skin diseases. There are studies suggesting that it is effective in the treatment of scars and burns; and skin diseases such as psoriasis, eczema, keloid, and hypertrophic scars. Recent studies suggest that Centella Asiatica has important effects apart from the skin, notedly in the central nervous system. It has been suggested that Centella Asiatica has neuroprotective, anxiolytic, anticonvulsant, neurogenic, synapse-enhancing effects and that it may be useful in the treatment of conditions such as Alzheimer's, Parkinson's, Huntington's disease and stroke. In our study, the effects of oral Centella Asiatica administration on fetal brain damage caused by prenatal stress environment imitated by intraperitoneal administration of cortisone on pregnant mice were investigated. In our study, 18 female and 9 male Balb/c mice were used and pregnancy was achieved. Mice were divided into three groups as control (n=6), test (n=6) and treatment group (n=6). Between the 9th and 15th days of pregnancy, for a total of 5 days, 1mg/kg/day normal saline (N/S) administrated to the control group intraperitoneally; 1mg/kg/day dexamethasone administrated to the test group intraperitoneally; the treatment group received 1mg/kg/day dexamethasone by intraperitoneal route and 1mL/kg per day Centella Asiatica by oral gavage. Pregnancies were terminated on the 18,5th day, embryo brains were dissected and fixed in formaldehyde. Fetal lengths (cm) and width (cm), height (cm) and weights of the fetal brains were measured and recorded. For analysis, hematoxylin-eosin staining, cresyl violet staining and immunohistochemical staining (Cas3 and Lc3ß) were performed. In our study, it was observed that dexamethasone administration to the pregnant mice caused a significant decrease in fetal brain width, height and weight values. However, in the treatment group in which we administrated dexamethasone and Centella Asiatica, fetal brain measurements were similar to the control group. There is evidence that Centella Asiatica inhibits the progression to apoptosis. In our study, it was observed that Centella Asiatica administration prevented the progression to apoptosis and reduced the formation of damage in the examined period (short term) with the analyses performed using Cas3 immunohistochemical staining. It has also been suggested that Centella Asiatica has suppressive effects on autophagy. In our study, with Lc3ß immunohistochemical staining method, autophagy was observed to be less in the treatment group treated with Centella Asiatica compared to the test group.