1. Department of Acupuncture and Moxibution, Dongeui University College of Korean Medicine, Busan 47227, Republic of Korea
2. Department of Parasitology and Genetics, Kosin University College of Medicine, Busan 49267, Republic of Korea
3. Anti-Aging Research Center and Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 47227, Republic of Korea
4. Department of Marine Life Sciences, Jeju National University, Jeju 63243, Republic of Korea
5. Department of Anatomy and Cell Biology, Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan 49201, Republic of Korea
6. Department of Food and Nutrition, College of Nursing, Healthcare Sciences & Human Ecology, Dongeui University, Busan 47340, Republic of Korea
7. Department of Physiology, Peripheral Neuropathy Research Center, College of Medicine, Dong-A University, Busan 49201, Republic of Korea
#These authors contributed equally to this work.
Baicalein, a flavonoid extracted from the roots of Scutellaria baicalensis Georgi., has various pharmacological effects due to its high antioxidant activity. However, no study has yet been conducted on the protective efficacy of baicalein against oxidative stress in Schwann cells. In this study, we evaluated the protective effect of baicalein on DNA damage and apoptosis induced by hydrogen peroxide (H2O2) in HEI193 Schwann cells. For this purpose, HEI193 cells exposed to H2O2 in the presence or absence of baicalein were applied to cell viability assay, immunoblotting, Nrf2-specific small interfering RNA (siRNA) transfection, comet assay, and flow cytometry analyses. Our results showed that baicalein effectively inhibited H2O2-induced cytotoxicity and DNA damage associated with the inhibition of reactive oxygen species (ROS) accumulation. Baicalein also weakened H2O2-induced mitochondrial dysfunction, increased the Bax/Bcl-2 ratio, activated caspase-9 and -3, and degraded poly(ADP-ribose) polymerase. In addition, baicalein increased not only the expression but also the phosphorylation of nuclear factor-erythroid 2 related factor 2 (Nrf2) and promoted the expression of heme oxygenase-1 (HO-1), a critical target enzyme of Nrf2, although the expression of kelch-like ECH-associated protein-1 was decreased. However, the inhibition of Nrf2 expression by transfection with Nrf2-siRNA transfection abolished the expression of HO-1 and antioxidant potential of baicalein. These results demonstrate that baicalein attenuated H2O2-induced apoptosis through the conservation of mitochondrial function while eliminating ROS in HEI193 Schwann cells, and the antioxidant efficacy of baicalein implies at least a Nrf2/HO-1 signaling pathway-dependent mechanism. Therefore, it is suggested that baicalein may have a beneficial effect on the prevention and treatment of peripheral neuropathy induced by oxidative stress.
Keywords: Baicalein, Schwann cells, oxidative stress, DNA damage, apoptosis, Nrf2/HO-1