The crude polysaccharides of Citrus aurantium L. var. amara Engl (CAVAPs) were extracted and their bioactivities including DPPH radical scavenging activity, cytotoxicity to human breast cancer cells, MCF-7, as well as lung cancer cells, HCC827, and their immune-enhancement activity were evaluated. Results showed that CAVAPs exhibited better immunoenhancement activity compared to the DPPH radical scavenging and anticancer activities. Subsequently, the immune enhancement activity of CAVAPs on RAW264.7 cells was further observed and the results displayed that CAVAPs could significantly stimulate the production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in RAW264.7 cells, and promote the mRNA expression levels of inducible nitric oxide synthase (iNOS), TNF-α, interleukin-1 beta (IL-1β), and IL-6. Furthermore, western blot analysis demonstrated that the phosphorylated extracellular signal-regulated kinase (ERK), phosphorylated c-Jun N-terminal kinase (JNK), phosphorylated p38 and phosphorylated p65 were all remarkably increased in CAVAP-treated RAW264.7 cells. All these results indicated that CAVAPs might activate macrophages through the mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathway. Additionally, a three-level-three-factor Box-Behnken design (BBD) was performed to optimize the extraction process of CAVAPs for the purpose of application and further research. The maximum extraction yield reached 4.49 ± 0.25%.
Citrus aurantium L. var. amara Engl. (CAVA) was traditionally used as a digestant or expectorant in China. Crude polyphenols (CAVAP-W) extracted from blossoms of CAVA were mainly composed of eriocitrin/neoeriocitrin, eriocitrin/neoeriocitrin, rhoifolin, hesperidin, naringin, rutin, veronicastroside, neohesperidin, and hesperetin by LC-MS analysis. CAVAP-W showed significant anticomplement and anti-inflammatory effects. Due to the close relationship between anticomplement and anti-inflammatory activity, the anti-inflammatory effect was further investigated and the results showed that CAVAP-W significantly suppressed production of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and mRNA expression of inducible nitric oxide synthase (iNOS), IL-6, TNF-α, IL-1β, and cyclooxygenase-2 (COX-2) in lipopolysaccharides-stimulated RAW264.7 cells. Furthermore, CAVAP-W inhibited mitogen-activated protein kinase (MAPK) phosphorylation and NF-κB activation through suppressing nuclear translocation of nuclear factor-kappa B (NF-κB) P65, degradation and phosphorylation of IκBα, phosphorylation of IκKα/ß, c-Jun N-terminal kinase (JNK), and P38, and activation of COX-2, thereby exerting the anti-inflammatory effects.
Salvianolic acid B (Sal B) has a significant protective effect on myocardial ischaemia-reperfusion (I/R) injury. Therefore, the aims of this study were to determine the effects of Sal B on myocardial ischaemic-reperfusion (I/R) injury in rats and to explore whether its underlying mechanism of cardioprotection occurs through activating the expression of the phosphoinositide 3-kinase/ protein, kinase B (PI3K/Akt) and inhibiting the expression of high mobility group protein 1 (HMGB1). Ninety Sprague-Dawley rats were randomized into five groups: group 1 (sham-operated), group 2 (myocardial I/R), group 3 (low dose of Sal B+I/R), group 4 (high dose of Sal B+I/R), and group 5 (high dose of Sal B+I/R+LY294002, which is a specific PI3k inhibitor). All I/R rats received 30 min myocardial ischaemia followed by 24-h reperfusion. Cardiac function, infarct size, myocardial injury marker levels, inflammatory response and cardiomyocyte apoptosis as well as Bcl-2, Bax, P-Akt, HMGB1 and TLR4 expression were measured. In the current study, Sal B significantly ameliorated myocardial I/R injury in a dose-dependent manner, ameliorated cardiac function, reduced myocardial infarction size, decreased myocardial injury marker expression, decreased inflammatory responses, reduced apoptosis, activated PI3K/Akt expression and inhibited HMGB1 expression. However, all effects of Sal B were significantly reversed by LY294002. Overall, the present study indicated that Sal B attenuated myocardial I/R injury by activating PI3K/Akt and inhibiting the release of HMGB1 in rats.
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