Protective effects of ajwain (Trachyspermum ammi L.) extract against cadmium-induced cytotoxicity and apoptosis in PC12 cells

Abstract

Cadmium (Cd2+) is a heavy metal that can induce cytotoxicity leading to many chronic diseases. Ajwain (Trachyspermum ammi L.) is a popular spice with diverse pharmacological properties. It is used for the remedy of many pathological conditions that could be manifested by Cd2+ exposure e.g. inflammatory, toxic, neurological, genital or respiratory tract disorders. To reduce the Cd2+-induced cytotoxicity and apoptosis, PC12 cells were exposed/co-exposed to Cd2+ (5 or 10 μM) with/without non-toxic dose (240 μg/mL) of ethanolic extract of ajwain (AE) for 24 h. The cytotoxicity and apoptosis were evaluated by cell viability, lactate dehydrogenase (LDH) activity, glutathione levels, genomic DNA fragmentation and expressions of Bax, Bcl-2, Bcl-xL, NF-КB, cytosolic cytochrome c and caspase-3. Cd2+ reduced the cell viability significantly 24 h after exposure; however, the co-exposure of AE with Cd2+ reduced the cell death. The co-exposure also raised up glutathione levels, and decreased LDH activity. AE lessened the DNA fragmentation caused by Cd2+. AE suppressed the Cd2+-induced increased expression of apoptotic protein Bax, and promoted suppressed expressions of anti-apoptotic proteins Bcl-2, Bcl-xL and NF-КB. Moreover, it reduced the cytosolic cytochrome c levels and the caspase-3 expressions increased by Cd2+. Thus, it was suggested that AE reduced cytotoxicity and apoptosis caused by Cd2+ in PC12 cells. It inhibited Cd2+-induced apoptosis through intrinsic pathway possibly boosting up the antioxidant defense. Therefore, AE can be a candidate for a potential agent against heavy metals and/or other toxicants. Additionally, this study validated the ethno-pharmacological therapeutic uses of ajwain in various pathological conditions.