Asian Pacific Journal of Tropical Biomedicine

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Objective: To assess the nuclear factor-erythroid 2-related factor-2 (Nrf2) modulatory effect of caffeic acid and protocatechuic acid and determine the anti-tumor activity of these phenolic compounds against Ehrlich ascites carcinoma growth in mice. Methods: Antioxidant activity of protocatechuic acid and caffeic acid was assessed using ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH). Nrf2 activation potential of phenolic compounds was tested by quantitative realtime polymerase chain reaction, and luciferase complementation reporter assays. In vivo efficacy was tested using the Ehrlich ascites carcinoma model. Results: FRAP and DPPH radical scavenging assays showed that caffeic acid and protocatechuic acid were more potent compared with cinnamic acid and benzoic acid. Luciferase complementation reporter assays identified caffeic acid and protocatechuic acid as the activators of Nrf2. Both caffeic acid and protocatechuic acid upregulated the expression of Nrf2 target genes heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and glutamate-cysteine ligase modifier subunit (GCLM) and the activity of NAD(P)H:quinone oxidoreductase 1 (NQO1) when tested on HCT-116 cells using a cell-based assay system at 9 h. In addition, intraperitoneal administration of caffeic acid and protocatechuic acid to Ehrlich ascites carcinoma bearing mice suppressed tumor growth and angiogenesis. Conclusions: Caffeic acid and protocatechuic acid can modulate Nrf2 and inhibit Ehrlich ascites carcinoma cells.

Objective: To investigate the protective and therapeutic role of ginseng against silicon dioxide nanoparticles (SiO₂NPs)-induced toxicity in the lungs. Methods: Sixty male rats were divided into five groups (n = 12/ group); group 1 was used as a control, group 2 received ginseng, group 3 was treated with SiO₂NPs, and group 4 was pretreated with ginseng one week before SiO₂NPs, while group 5 was given SiO₂NPs one week before supplementation with ginseng. Animals were treated with both ginseng and SiO₂NPs orally for five weeks. Real-time PCR was used to measure gene expression. Besides, DNA damage and cell cycle changes were determined by comet assay and flow cytometry, respectively. Histological study was also done to assess the effect of ginseng on SiO₂NPs-induced toxicity. Results: SiO₂NPs increased lipid peroxidation and decreased the activities of antioxidant enzymes. SiO₂NPs induced apoptosis in lung tissues as revealed by upregulation of Bax and caspase 3 and downregulation of Bcl-2 as well as the induction of DNA damage. SiO₂NPs also caused inflammation as indicated by upregulation of the inflammation-related genes [interleukin 1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), cyclooxygenase 2 (COX2), and transforming growth factor-beta 1 (TGFβ1)] as well as cell cycle arrest in the G₀/G₁ phase of lung cells. Moreover, histopathological examination proved the biochemical and molecular perturbations that occurred due to SiO₂NPs toxicity. However, ginseng alleviated SiO₂NPs-induced toxicity in rat lung. Conclusions: Ginseng has a potent preventive and therapeutic effect and could be used in the treatment of SiO₂NPs-induced pulmonary toxicity.

Polyphenols are the secondary metabolic products of plants and are considered as active constituents to possess therapeutic effects. To date, a vast number of scientific literature addressed the potential of polyphenols as bio-efficient compounds owing to their structural diversity. Due to the presence of several hydroxyl groups, they are metabolized quickly due to conjugation reaction and thus, readily produce toxic metabolites as a defense material against many pathogens, reflecting their safety strategy. This review focuses on the anti-quorum sensing and biofilm inhibition activity of polyphenols, which display their potential to treat bacterial infections by combating the virulence caused by pathogenic agents. Thus, for mitigating quorum sensing-controlled pathogenesis, the use of polyphenol-based phytochemicals holds immense potential to cure infections. The application of polyphenol as sensitizing agent/ adjuvant therapeutics which act in synergism with antibiotics is highly remarkable.

Objective: To investigate the anti-inflammatory effects of the total flavonoids from Saussurea involucrata on lipopolysaccharides (LPS)-stimulated murine RAW264.7 macrophages and explore its underlying mechanism of action. Methods: Total flavonoids from Saussurea involucrata were extracted using chromatographic column method. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The production of nitric oxide was detected by Griess assay and the release of cytokines (IL-10 and TNF-α) and chemokines (MCP-1, MIP-1a, and CCL5/RANTES) was determined by ELISA to evaluate the anti-inflammatory activity of total flavonoids from Saussurea involucrata. Moreover, nuclear translocation of p65, c-Jun, and IRF3 was detected by immunofluorescence microscopy and Western blotting analysis was performed to determine the expression of related proteins. Results: Total flavonoids extracted from Saussurea involucrata were 751.5 mg/g and the content of rutin was 506.5 mg/g. The production of inflammatory mediators including nitric oxide, cytokines, and chemokines was effectively inhibited by total flavonoids from Saussurea involucrata. Meanwhile, total flavonoids also suppressed the nuclear translocation of p65, c-Jun, and IRF3 in LPS-stimulated RAW264.7 cells. The LPS-induced expression of iNOS and COX-2 was remarkably reduced by treatment with total flavonoids from Saussurea involucrata. Moreover, total flavonoids decreased the expression levels of p-IKKa/β, p-TBK1, p-p38, p-ERK, p-JNK, p-p65, p-c-Jun, and p-IRF3 in LPS-exposed RAW264.7 macrophages. Conclusions: Total flavonoids from Saussurea involucrata potentially inhibit the secretion of pro-inflammatory mediators, which may be related to inhibition of p65, c-Jun, and IRF3 signaling pathways in LPS-stimulated RAW264.7 cells.

Objective: To investigate whether ethanol extracts of Chondracanthus tenellus (EECT) could improve immunomodulatory property of murine monocyte/macrophage RAW 264.7 cells. Methods: Cell viability, phagocytic ability, and nitric oxide were measured. The levels of prostaglandin E₂ and cytokines were determined using enzyme-linked immunosorbent assay kits. Expression of immunoregulatory response protein was detected by Western blotting assay. Results: As the concentration of EECT increased, the morphology of the cells changed to a typical active macrophage shape, and the phagocytic activity increased significantly. EECT also effectively enhanced the production and secretion of immunomodulatory mediators, such as nitric oxide and prostaglandin E₂, and cytokines. In addition, compared with the control group, EECT markedly stimulated the expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88, one of the TLR4 adapter molecules. Furthermore, EECT promoted the nucleus translocation of nuclear factor-kappa B (NF-κB) by increasing the phosphorylation and degradation of the inhibitor of NF-κB-α, indicating activation of the NF-κB signaling pathway. Meanwhile, similar trends were found in cells treated with lipopolysaccharide as a positive control. Conclusions: Taken together, the results indicate that EECT has an immunomodulatory effect by increasing the production of immunomodulatory mediators and cytokines through activation of the TLR4/NF-κB signaling pathway. EECT could be used as a potential candidate for medication or dietary supplements to increase immune activity.

Online since 13^th December 2017