Novel Neohesperidin Dihydrochalcone Analogue Inhibits Adipogenic Differentiation of Human Adipose-Derived Stem Cells through the Nrf2 Pathway.

Obesity, characterized by excess lipid accumulation, has emerged as a leading public health problem. Excessive, adipocyte-induced lipid accumulation raises the risk of metabolic disorders. Adipose-derived stem cells (ASCs) are mesenchymal stem cells (MSCs) that can be obtained from abundant adipose tissue. High fat mass could be caused by an increase in the size (hypertrophy) and number (hyperplasia) of adipocytes. Reactive oxygen species (ROS) are involved in the adipogenic differentiation of human adipose-derived stem cells (hASCs). Lowering the level of ROS is important to blocking or retarding the adipogenic differentiation of hASCs. Nuclear factor erythroid 2-related factor-2 (Nrf2) is a transcription factor that mediates various antioxidant enzymes and regulates cellular ROS levels. Neohesperidin dihydrochalcone (NHDC), widely used as artificial sweetener, has been shown to have significant free radical scavenging activity. In the present study, (E)-3-(4-chlorophenyl)-1-(2,4,6-trimethoxyphenyl)prop-2-en-1-one (CTP), a novel NHDC analogue, was synthesized and examined to determine whether it could inhibit adipogenic differentiation. The inhibition of adipogenic differentiation in hASCs was tested using NHDC and CTP. In the CTP group, reduced Oil Red O staining was observed compared with the differentiation group. CTP treatment also downregulated the expression of PPAR-γ and C/EBP-α, adipogenic differentiation markers in hASCs, compared to the adipogenic differentiation group. The expression of FAS and SREBP-1 decreased in the CTP group, along with the fluorescent intensity (amount) of ROS. Expression of the Nrf2 protein was slightly decreased in the differentiation group. Meanwhile, in both the NHDC and CTP groups, Nrf2 expression was restored to the level of the control group. Moreover, the expression of HO-1 and NQO-1 increased significantly in the CTP group. Taken together, these results suggest that CTP treatment suppresses the adipogenic differentiation of hASCs by decreasing intracellular ROS, possibly through activation of the Nrf2 cytoprotective pathway. Thus, the use of bioactive substances such as CTP, which activates Nrf2 to reduce the cellular level of ROS and inhibit the adipogenic differentiation of hASCs, could be a new strategy for overcoming obesity.

Pueraria montana var. lobata root extract inhibits photoaging on skin through Nrf2 pathway.

Pueraria montana var. lobata is a bioactive substance, in possession of a variety of beneficial health effects, which has long been extensively used as a traditional medication for the treatment of fever, acute dysentery, diabetes, and cardiovascular diseases in North-East Asian countries. The purpose of this study was to evaluate the cytoprotective activity of Pueraria montana var. lobata ethanol extract (PLE) for ultraviolet B (UVB) induced oxidative stress in human dermal fibroblasts (HDF). It was hypothesized that PLE treatment (25-100 µg/mL) would reduce intracellular reactive oxygen species (ROS) levels as well as increase collagen production in UVB-irradiated HDF. The results confirmed this theory, with collagen production increasing in the PLE treatment group in a dose-dependent manner. In addition, regulators of cellular ROS accumulation, including HO-1 and NOQ-1, were activated by Nrf2, which was mediated by PLE. Hence, intracellular levels of ROS were also reduced in the PLE treatment group in a dose-dependent manner. In conclusion, PLE increases collagen production and maintains hyaluronic acid (HA) levels in human dermal fibroblasts exposed to UVB-irradiation, thereby inhibiting photoaging.