ABSTRACT
Hovenia dulcis, one of the traditional medicinal plants, is currently being used as a functional ingredient for the development of health functional foods that protects the liver from alcohol damage in Korea. A variety of pharmacological effects of Hovenia dulcis have been reported so far, but studies on immune-enhancing activity are insufficient. Thus, in this study, we report that Hovenia dulcis branches (HDB) induce the activation of macrophages. HDB increased the production of immunostimulatory factors and phagocytosis in RAW264.7 cells. TLR4 inhibition blocked HDB-mediated production of immunostimulatory factors. In addition, the JNK inhibition reduced the HDB-mediated production of immunostimulatory factors, and the HDB-mediated JNK activation was blocked by the TLR4 inhibition. HDB increased the level of LC3-II and p62/SQSTM1. TLR4 inhibition blocked HDB-mediated increase in the level of LC3-II and p62/SQSTM1. These findings indicate that HDB may induce TLR4/JNK-dependent macrophage activation and TLR4-dependent macrophage autophagy.
ABSTRACT
It has been reported that H. mollendorffii roots (HMR) have various pharmacological activities such as anti-inflammatory activity and immunostimulatory activity. However, the anti-obesity activity of HMR has not been studied. Thus, we evaluated in vitro anti-obesity of HMR in mouse preadipocytes, 3T3-L1 cells. HMR reduced the lipid accumulation and triglyceride (TG) contents in 3T3-L1 cells. HMR inhibited the protein expressions such as CCAAT/enhancer-binding protein alpha (CEBPα), peroxisome proliferator-activated receptor gamma (PPARγ), perilipin-1, adiponectin, fatty acid-binding protein 4 (FABP4), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) related to the lipid accumulation of the mature adipocytes. In addition, HMR induced the proteasomal degradation of CEBPα related to the differentiation of the preadipocytes into the mature adipocytes by activating c-Jun N-terminal kinases (JNK) and glycogen synthase kinase 3 beta (GSK3ß). Based on the results of this study, HMR inhibited the differentiation of preadipocytes into mature adipocytes through the CEBPα degradation via JNK and GSK3ß activation and subsequently blocked lipid accumulation of mature adipocytes through inhibiting lipid accumulation-related proteins such as CEBPα, PPARγ, perilipin-1, adiponectin, FABP4, FAS, and ACC.
ABSTRACT
Honeyberry (Lonicera caerulea) has long been used as a traditional medicine in China, Japan and northern Russia. Functional studies of honeyberry have mainly focused on the fruits, which have been reported to exert various pharmacological activities, including antiinflammatory activity, with limited or no studies on the other parts of the plant, such as the leaves and branches. In the present study, the antiinflammatory effects of extracts of the leaves (HBL), branches (HBB) and fruit (HBF) of honeyberry plant were evaluated in lipopolysaccharide (LPS)stimulated RAW264.7 cells. HBL and HBB significantly inhibited the production of pro-inflammatory mediators in LPSstimulated RAW264.7 cells, and the inhibitory effects of HBL and HBB were stronger than those of HBF. HBL and HBB blocked the nuclear accumulation of p65 independently of IκBα. HBL did not inhibit the phosphorylation of ERK1/2 or p38; however, HBB effectively inhibited the phosphorylation of p38 but not ERK1/2. HBL and HBB increased the expression of heme oxygenase1 (HO1) protein by inducing the nuclear accumulation of nuclear factor erythroid 2related factor 2 (Nrf2) through the activation of the reactive oxygen species (ROS)/p38 pathway; the reduction in inducible nitric oxide synthase (iNOS) and interleukin1ß (IL1ß) expression by HBL and HBB was inhibited by HO1 knockdown. In addition, HBL and HBB increased the expression of activating transcription factor3 (ATF3), and the reduction in iNOS and IL1ß expression by HBL and HBB was inhibited by ATF3 knockdown. Collectively, HBL and HBB inhibited LPSinduced nuclear factorκB activation by blocking the nuclear accumulation of p65, increasing HO1 expression through activation of the ROS/p38/Nrf2 pathway, and increasing ATF3 expression. Furthermore, HBB inhibited LPSinduced p38 phosphorylation. These findings suggest that HBL and HBB may have great potential as natural products for the development of antiinflammatory drugs.
