RESUMO
The rhizome of Atractylodes macrocephala Koidz (AM) is a constituent of various Qi booster compound prescriptions. We evaluated inflammatory responses in macrophages and T cells isolated from mice following oral administration of AM water extract (AME). Peritoneal exudate cells were isolated from thioglycollate-injected mice and alterations in scavenger receptors were examined. Peritoneal macrophages were stimulated with lipopolysaccharide (LPS). Serum cytokine responses to intraperitoneal LPS injection were also evaluated. Splenocytes were isolated and their composition and functional responses were measured. The content of atractylenolide I and atractylenolide III, known anti-inflammatory ingredients, in AME was 0.0338 mg/g extract and 0.565 mg/g extract, respectively. AME increased the number of SRA(+)CD11b(+) cells in response to thioglycollate. Peritoneal macrophages isolated from the AME group showed no changes in inflammatory markers such as tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, inducible nitric oxide synthase, and cyclooxygenase-2 but exhibited a decrease in CD86 expression. Interestingly, AME decreased the serum levels of TNF-α and IL-6 upon intraperitoneal injection of LPS. Regarding the adaptive immune system, AME increased the CD4(+) T cell population and major histocompatibility complex class II molecule expression in the spleen, and cultured splenocytes from the AME group showed increased production of IL-4 concurrent with decreased interferon-γ production during T cell activation. AME promoted the replenishment of peritoneal macrophages during the inflammatory response but its anti-inflammatory activity did not appear to be mediated by the modulation of macrophage activity. AME also altered the immune status of CD4 T cells, promoting the Th2 response.
RESUMO
Chronic, low-grade inflammatory responses occur in obese adipose tissue and play a crucial role in the development of insulin resistance. Macrophages exposed to high glucose upregulate the expression of SRA, a macrophage-specific scavenger receptor. The present study investigated whether Prunus yedoensis (PY) bark extract affects the inflammatory response and scavenger receptor gene expression observed in a diet-induced obesity model in vivo. Oral administration of PY extract significantly reduced fasting blood glucose levels without a change in body weight in mice fed a high fat diet for 17 weeks. PY extract significantly suppressed expression of inflammatory and macrophage genes such as tumor necrosis factor-α, interleukin-6, and F4/80 in epididymal adipose tissue. Among scavenger receptor genes, SRA expression was significantly reduced. The inhibitory responses of PY extract and its fractions were determined through evaluation of scavenger receptor expression in THP-1 cells. PY extract and its ethyl acetate fraction decreased the levels of SRA mRNA and phospho-ERK1/2 during monocyte differentiation. Our data indicate that the anti-inflammatory effects of PY extract and its downregulation of SRA seem to account for its hypoglycemic effects.
RESUMO
BACKGROUND: Osteopontin (OPN) is one of important molecular targets in cancer progression, metastasis as a calcium-binding, extracellular-matrix-associated protein of the small integrin-binding ligand and, N-linked glycoprotein. In the present study, anti-metastatic mechanism of ethanol extracts of Ocimum sanctum (EEOS) was elucidated on OPN enhanced metastasis in NCI-H460 non- small cell lung cancer cells. METHODS: Cell viability was measured by MTT assay. Adhesion and invasion assays were carried out to see that EEOS inhibited cell adhesion and invasion in OPN treated and non-treated NCI-H 460 cells. RT-PCR was used to determine the mRNA levels of uPA, uPAR, and EGFR. RESULTS: EEOS significantly inhibited cell adhesion and invasion in OPN treated and non treated NCI-H460 cells, though EEOS did not show any toxicity up to 200 µg/ml. EEOS effectively attenuated the expression of OPN and CD44 and also OPN activated the expression of CD44 in NCI-H460 cells. In addition, EEOS effectively suppressed the expression of phosphatidylinositide 3-kinases (PI3K) and cyclooxygenase 2 (COX-2) and the phosphorylation of Akt at protein level in OPN treated NCI-H460 cells. Also, EEOS significantly attenuated the expression of urokinase plasminogen activator (uPA), its receptor (uPAR) and epidermal growth factor receptor (EGFR) at mRNA level and reduced vascular endothelial growth factor (VEGF) production and MMP-9 activity in OPN treated NCI-H460 cells. Furthermore, PI3K/Akt inhibitor LY294002 enhanced anti-metastatic potential of EEOS to attenuate the expression of uPA and MMP-9 in OPN treated NCI-H 460 cells. CONCLUSION: Overall, our findings suggest that anti-metastatic mechanism of EEOS is mediated by inhibition of PI3K/Akt in OPN treated NCI-H460 non-small cell lung cancer cells.
