Anti-inflammatory and Apoptotic Effects of Levisticum Officinale Koch Extracts on HT 29 and Caco-2 Human Colorectal Carcinoma Cell Lines.

BACKGROUND: Colorectal cancer is among the deadliest cancers in the world. Due to the occurrence of side effects related to current standard therapy, researchers are seeking better alternative treatments. For many years, herbs have been a promising source for discovering therapeutic compounds. Therefore, the primary objective of this research was to examine the distinctive apoptotic and anti-inflammatory properties exhibited by Levisticum officinale Koch (lovage) on HT-29 and Caco-2 cell lines. MATERIALS AND METHODS: The maceration method was used to prepare different extracts (ethanol, dichloromethane, petroleum, and residues) from the plant. These extracts were then tested on two colon cancer cell lines - HT-29 and Caco-2 - using the MTT assay to determine the half-maximal inhibitory concentration (IC50) values. In addition, we evaluated the expression levels of several inflammatory genes (IKKb, IKKa, and REIB) using real-time PCR. We also assessed Cox-2 protein expression using western blot analysis. The western blot was also used to analyze apoptosis-related proteins, including Caspase-3, BAX, and Bcl-2. RESULTS: The dichloromethane extract of Levisticum officin (DELO) exhibited a high cytotoxic effect on Caco-2 and HT-29 cell lines, with IC50 values of 106.0±2 µg/mL in HT-29 cells and 175.3±4 µg/mL in Caco-2 cells after 72 hours. None of the lovage extracts showed a significant cytotoxic effect on non-cancerous cells (3T3 cell line). Furthermore, the group treated with DELO showed a lower expression level of inflammatory genes and COX-2 protein compared to the control group. Notably, treatment with DELO resulted in an increase in Caspase-3 protein and BAX/Bcl-2 ratio in both HT-29 and Caco-2 cells. CONCLUSION: According to this study, DELO has the potential to act as an anti-inflammatory and anti-cancer agent. Further research on the compounds present in DELO and their effect on various signaling pathways could help in the development of new drugs for diseases where inflammation or cells escape from apoptosis play a crucial role.

Hydroalcoholic Extract of Levisticum officinale Increases cGMP Signaling Pathway by Down-Regulating PDE5 Expression and Induction of Apoptosis in MCF-7 and MDA-MB-468 Breast Cancer Cell Lines

Background: This study aimed to investigate Levisticum officinale hydroalcoholic extract (LOHE) effect on both cGMP signaling pathway and phosphodiesterase 5 (PDE5) gene expression pattern and to examine the role of LOHE in apoptosis induction of MCF-7 and MDA-MB-468 cell lines. Methods: The half maximal inhibitory concentration (IC50) of LOHE was examined in both cell lines using the MTT assay. Using IC50 values of LOHE on both cells, the type of cell death was detected by flowcytometric analysis. The values of PDE5 and cGMP were evaluated by real-time PCR and ELISA methods, respectively. Results: The IC50 values were measured as 150 µg/ml for MDA-MB-468 and 200 µg/ml for MCF-7. At 12 hour of treatment, a significant decrease in the PDE5 expression and maximum increase in the amount of intracellular cGMP were observed (p < 0.05). However, these effects were more noticeable in MDA-MB-468 triple-negative cells. Conclusion: Our data suggest that LOHE extract could be a potential source for new strategies towards targeting both PDE5 and cGMP signaling pathways.

Catechol-O-Methyltransferase (COMT) Gene (Val158Met) and Brain-Derived Neurotropic Factor (BDNF) (Val66Met) Genes Polymorphism in Schizophrenia: A Case-Control Study.

Objective: Several studies have shown that some polymorphisms of genes encoding catechol-O-methyltransferase (COMT), the key enzyme in degrading dopamine, and norepinephrine and the human brain-derived neurotropic factor (BDNF), a nerve growth factor, are strong candidates for risk of schizophrenia (SCZ). In the present study, we aimed at examining the effects of COMT Val158Met (G>A) and BDNF Val66Met (G>A) polymorphisms on SCZ risk in a sample of Iranian population. Method: This case- control study included 92 SCZ patients and 92 healthy controls (HCs). Genotyping of both variants (COMT Val158Met (G>A) and BDNF Val66Met (G>A)) were conducted using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR). Results: The findings revealed that the COMT Val158Met (G>A) polymorphism was not associated with the risk/protective of SCZ in all models (OR=0.630, 95%CI=0.299-1.326, P=0.224, GA vs. GG, OR=1.416, 95%CI=0.719-2.793, P=0.314, AA vs. GG, OR=1.00, 95%CI=0.56-1.79, P=1.00 GA+AA vs. GG, OR=1.667, 95%CI=0.885-3.125, P=0.11, AA vs. GG+GA, OR=1.247, 95%CI=0.825-1.885, P=0.343, A vs. G,). However, BDNF Val66Met (G>A) variant increased the risk of SCZ (OR = 2.008 95%CI = 1.008-4.00, P = 0.047, GA vs. GG, OR = 3.876 95%CI = 1.001-14.925, P = 0.049. AA vs. GG, OR = 2.272. 95%CI = 1.204-4.347, P = 0.011, GA+AA vs. GG, OR = 2.22 95%CI = 1.29-3.82. P = 0.005, A vs. G). Conclusion: The results did not support an association between COMT Val158Met (G>A) variant and risk/protective of SCZ. Moreover, it was found that BDNF Val66Met (G>A) polymorphism may increase the risk of SCZ development. Further studies and different ethnicities are recommended to confirm the findings.