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The present study investigated the effects of valerian methanolic extract and valerenic acid on the expression of LL-37 gene and protein in A549 and MRC5 line cells. After preparing Valerian seeds, sowing them in March 2020, and harvesting the rhizome in October 2020, the extract was prepared from the valerian rhizome by maceration method. Valerian acid content was determined using high performance liquid chromatography (HPLC). Two cell lines (A549 and MRC-5) were used to study the effects of valerian extract, and the MTT test was used to evaluate cell viability. The expression of LL-37 mRNA and protein was assessed by Real-Time PCR and western blot, respectively. In vivo safety assessments and histopathological analysis were also conducted. Data was analyzed by Graphpad Prism 8 software. Valerian methanolic extract and valerenic acid upregulated the LL-37 mRNA and protein expression in both treated cell lines. Valerenic acid showed a greater effect on upregulating LL-37 expression than valerian methanolic extract. A549 cells were more sensitive to valerian methanolic extract compared to MRC5 cells, and its cell viability was reduced. Furthermore, liver and kidney-related safety assessments showed that valerian methanolic extract had no toxic effects. In general, it was concluded that the methanolic extract of valerian as well as the resulting valerenic acid as the most important component of the extract has the ability to upregulate LL-37expression. Therefore, methanolic extract of valerian and valerenic acid can be considered for improving the immune system.

Introduction: Concerns have been raised about the toxic effects of medicinal plants due to their increased consumption. Therefore, the aim of the present study was to investigate the hepatotoxic effects of aqueous extract of valerian in laboratory mice. Methods: After preparation of plant materials and aqueous extract of valerian, concentrations of 10 and 20 mg/kg body weight were administered to laboratory mice for 14 days. On the day 14th, blood samples were taken from the hearts of mice after anesthesia and the serum levels of the enzymes alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) were studied. Furthermore, the animals' weight was recorded at 0, 7 and 14 days and weight changes were also studied. Results: The results of the present study showed the concentration-dependent effects of aqueous extract of valerian on increasing serum levels of liver enzymes such as ALT, AST, ALP and GGT and the highest serum levels of these enzymes were observed at a concentration of 20 mg/kg. Moreover, the concentration of 20 mg/kg aqueous extract of valerian caused severe weight loss in mice over a period of 14 days. Conclusion: In general, it was concluded that a concentration of 20 mg/kg causes liver damage. However, low concentrations of 10 mg/kg valerian extract showed no toxic effects on the liver. Therefore, in the formulations prepared from valerian, attention to the concentration of the extract is very important and the use of lower concentrations to prevent hepatotoxicity is very important.

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