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.
