Immunostimulatory and anti­obesity activities of Adenocaulon himalaicum leaves in RAW264.7 and 3T3­L1 cells.

The present study investigated the immunostimulatory activity and anti-obesity activity of Adenocaulon himalaicum leaf extracts (AHL) in RAW264.7 cells and 3T3-L1 cells. AHL increased the production of immunostimulatory factors, such as NO, inducible nitric oxide synthase (iNOS), IL-1ß, IL-6 and TNF-α and activated the phagocytotic activity in RAW264.7 cells. Inhibition of Toll-like receptor 4 (TLR4) attenuated the AHL-mediated production of immunostimulatory factors and activation of phagocytic activity in RAW264.7 cells. Inhibition of p38 and JNK blocked the AHL-mediated production of immunostimulatory factors, whereas inhibition of TLR4 suppressed the AHL-mediated phosphorylation of p38 and JNK. Additionally, AHL blocked the lipid accumulation in 3T3-L1 cells. AHL downregulated proliferator-activated receptor γ, CCAAT enhancer binding protein α and perilipin-1 levels, while upregulating adipose triglyceride lipase, phosphorylated (p-)hormone-sensitive lipase, p-adenosine monophosphate activated protein kinase, uncoupling protein 1, peroxisome-proliferator-activated receptor-γ coactivator-1 α and PR domain containing 16 levels in 3T3-L1 cells. These findings suggested that AHL may exert immunostimulatory activity through macrophages via TLR4-mediated activation of p38 and JNK and anti-obesity activity by blocking lipid accumulation via the inhibition of adipogenesis and induction of lipolysis and browning of white adipocytes.