Search results for: COX-2

Authors: Lamees A. Ben Saad, Kah Hwi Kim, Chin Chew Quah, Mustafa Shahimi

Abstract:

Background: Punica granatum (pomegranate) was used as a traditional medicine in different parts of the world. It has been used in the treatment of pain and inflammatory conditions such as peptic ulcer. The numerous risks associated with nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of pain and inflammation give rise to using medicinal herbs as alternative therapies. This study aimed to evaluate the anti-inflammatory effect of the ethyl acetate pomegranate fraction (EtOAc) by determination of its inhibitory effects on lipopolysaccharide (LPS), stimulated nitric oxide (NO), prostaglandin E2 (PGE-2), interleukin-6 (IL-6) and cyclooxxgenase-2 (COX2) release from RAW264.7cells. Methods: The inhibitory effect of EtOAc was evaluated on (LPS) induced NO production, PGE2, and IL-6 quantified by immunoassay kit and prostaglandin E2 competitive ELISA kit. COX2 production is an in vitro indication of possible anti-inflammatory activity and was estimated by Western blotting. Results: EtOAc potentially inhibited LPS-induced nitric oxide, prostaglandin, and IL-6 production. With these findings, it was evident that the EtOAc could reduce the LPS-induced cyclooxygenase-2 (COX-2) at the protein level in a dose-dependent manner as determined by Western blotting. Conclusion: The results emphasize potential therapeutic applications of Punica granatum in the treatment of inflammation.

Keywords: inflammation, Punica granatum, cytotoxicity, cytokines

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Authors: Azza H. El-Medany, Hanan H. Hagar, Omnia A. Nayel, Jamila H. El-Medany

Abstract:

In search for drugs that can target cancer cell micro-environment in as much as being able to halt malignant cellular transformation, the natural dietary phytochemical curcumin was currently assessed in DMH-induced colorectal cancer rat model. The study enrolled 50 animals divided into a control group (n=10) and DMH-induced colorectal cancer control group (n=20) (20mg/kg-body weight for 28 weeks) versus curcumin-treated group (n=20) (160 mg/kg suspension daily oral for further 8 weeks). Treatment by curcumin succeeded to significantly decrease the percent of ACF and tended to normalize back the histological changes retrieved in adenomatous and stromal cells induced by DMH. The drug also significantly elevated GSH and significantly reduced most of the accompanying biochemical elevations (namely MDA, TNF-α, TGF-β and COX2) observed in colonic carcinomatous tissue, induced by DMH, thus succeeding to revert that of MDA, COX2 and TGF-β back to near normal as justified by being non-significantly altered as compared to normal controls. The only exception was PAF that was insignificantly altered by the drug. When taken together, it could be concluded that curcumin possess the potentiality to halt some of the orchestrated cross-talk between cancerous transformation and its micro-environmental niche that contributes to cancer initiation, progression and metastasis in this experimental cancer colon model. Envisioning these merits to a drug with already known safety preferentiality, awaits final results of current ongoing clinical trials, before curcumin can be added to the new therapeutic armamentarium of anticancer therapy.

Keywords: curcumin, dimethyl hydralazine, aberrant crypt foci, malondialdehyde, reduced glutathione, cyclooxygenase-2, tumour necrosis factor-alpha, transforming growth factor-beta, platelet activating factor

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Authors: Prashantkumar Waghe, N. Prakash, N. D. Prasada, L. V. Lokesh, M. Vijay Kumar, Vinay Tikare

Abstract:

Arsenic is a naturally occurring metalloid with potent toxic effects. It is ubiquitous in the environment and released from both natural and anthropogenic sources. It has the potential to cause various health hazards in exposed populations. Arsenic exposure through drinking water is considered as one of the most serious global environmental threats including Southeast Asia. The aim of present study was to evaluate the modulatory role of subacute exposure to sodium (meta) arsenite on the antinociceptive, anti-inflammatory and antipyretic responses mediated by meloxicam in rats. Rats were exposed to arsenic as sodium arsenite through drinking water for 28 days. A single dose of meloxicam (2 mg/kg b. wt.) was administered by oral gavage on the 29th day. The exact time of meloxicam administration depended on the type of test. Rats were divided randomly into 5 groups (n=6). Group I served as normal control and received arsenic free drinking water, while rats in group II were maintained similar to Group I but received meloxicam on 29th day. Groups III, IV and V were pre-exposed to arsenic through drinking water at 0.5, 5.0 and 50 ppm, respectively, for 28 days and was administered meloxicam next day and; pain and inflammation carried out by using formalin-induced nociception and carrageenan-induced inflammatory model(s), respectively by using standard protocol. For assessment of antipyretic effects, one more additional group (Group VI) was taken and given LPS @ 1.8 mg/kg b. wt. for induction of pyrexia (LPS control). Higher dose of arsenic inhibited the meloxicam mediated antinociceptive, anti-inflammatory and antipyretic responses. Further, meloxicam inhibited the arsenic induced level of tumor necrosis factor-α, inetrleukin-1β, interleukin -6 and COX2 mediated prostaglandin E2 in hind paw muscle. These results suggest a functional antagonism of meloxicam by arsenic. This may relate to arsenic mediated local release of tumor necrosis factor-α, inetrleukin-1β, interleukin -6 releases COX2 mediated prostaglandin E2. Based on the experimental study, it is concluded that sub-acute exposure to arsenic through drinking water aggravate pyrexia, inflammation and pain at environment relevant concentration and decrease the therapeutic efficacy of meloxicam at higher level of arsenite exposure. Thus, the observation made has clinical relevance in situations where animals are exposed to arsenite epidemic geographical locations.

Keywords: arsenic, analgesic activity, meloxicam, Wistar rats

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Authors: Pattanapon Kayansamruaj, Ha Thanh Dong, Nopadon Pirarat, Channarong Rodkhum

Abstract:

Streptococcus iniae (SI) is a devastating pathogenic bacteria causing heavy mortality in farmed fish. The application of commercialized bacterin vaccine has been reported failures as the outbreaks of the new serotype of SI were emerged in farms after vaccination and subsequently caused severe losses. In the present study, we attempted to develop effective DNA vaccines against SI infection using Nile tilapia (Oreochromis niloticus) as an animal model. Two monovalent DNA vaccines were constructed by the insertion of coding sequences of cell wall-associated virulence factors-encoding genes, comprised of eno (α-enolase) and mtsB (hydrophobic membrane protein), into cytomegalovirus expression vector (pCI-neo). In the animal trial, 30-g Nile tilapia were injected intramuscularly with 15 µg of each vaccine (mock vaccine group was injected by naked pCI-neo) and maintained for 35 days prior challenging with pathogenic SI at the dosage of 107 CFU/fish. At 13 days post-challenge, the relative percent survival of pEno, pMtsB and mock vaccine were 57%, 45% and 27%, respectively. The expression levels of immune responses-associated genes, namely, IL1β, TNF-α, TGF-β, COX2, IL-6, IL-12 and IL-13, were investigated from the spleen of experimental animal at 7 days post-vaccination (PV) and 7 days post-challenge (PC) using quantitative RT-PCR technique. Generally, at 7 days PV, the pEno vaccinated group exhibited highest level of up-regulation (1.7 to 2.9 folds) of every gene, but TGF-β, comparing to pMtsB and mock vaccine groups. However, at 7 days PC, pEno group showed significant up-regulation (1.4 to 8.5 folds) of immune-related genes as similar as mock vaccine group, while pMtsB group had lowest level of up-regulation (0.7 to 3.3 folds). Summarily, this study indicated that the pEno and pMtsB vaccines could elicit the immune responses of the fish and the magnitude of gene expression at 7 days PV was also consistent with the protection level conferred by the vaccine.

Keywords: gene expression, DNA vaccine, Nile tilapia, Streptococcus iniae

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Authors: Farrah Putri Salmanida, Mei-Li Wu, Rika Wahyuningtyas, Wen-Bin Chung, Hso-Chi Chaung, Ko-Tung Chang

Abstract:

Within the field of immunotherapy, oncolytic virotherapy (OVT) employs dual approaches that directly eliminate tumor cells while preserving healthy ones and indirectly reprogram the tumor microenvironment (TME) to elicit antitumor responses. Within the TME, tumor associated macrophages (TAMs) manifest characteristics akin to those of anti-inflammatory M2 macrophages, thus earning the designation of M2-like TAMs. In prior research, two antigens denoted as A1 (g6Ld10T) and A3 (ORF6L5), derived from a complete sequence of ORF5 with partial sequence of ORF6 in Porcine Reproductive and Respiratory Syndrome Virus Genotype 2 (PRRSV-2), demonstrated the capacity to repolarize M2-type porcine alveolar macrophages (PAMs) into M1 phenotypes. In this study, we sought for utilizing OVT strategies by introducing A1 or A3 on TAMs to endow them with the anti-tumor traits of M1 macrophages while retaining their capacity to target cancer cells. Upon exposing human THP-1-derived M2 macrophages to a cross-species test with 2 µg/ml of either A1 or A3 for 24 hours, real time PCR revealed that A3, but not A1, treated cells exhibited upregulated gene expressions of M1 markers (CCR7, IL-1ß, CCL2, Cox2, CD80). These cells reacted to virus-derived antigen, as evidenced by increased expression of pattern-recognition receptors TLR3, TLR7, and TLR9, subsequently providing feedback in the form of type I interferon responses like IFNAR1, IFN-ß, IRF3, IRF7, OAS1, Mx1, and ISG15. Through an MTT assay, only after 15 µg/ml of A3 treatment could the cell viability decrease, with a predicted IC50 of 16.96 µg/ml. Interestingly, A3 caused dose-dependent toxicity to a rat C6 glial cancer cell line even at doses as low as 2.5 µg/ml and reached its IC50 at 9.419 µg/ml. Using Annexin V/7AAD staining and PCR test, we deduced that a significant proportion of C6 cells were undergoing the early apoptosis phase predominantly through the intrinsic apoptosis cascade involving Bcl-2 family proteins. Following this stage, we conducted a test on A3’s repolarization ability, which revealed a significant rise in M1 gene expression markers, such as TNF, CD80, and IL-1ß, in M2-like TAMs generated in vitro from murine RAW264.7 macrophages grown with conditioned medium of 4T1 breast cancer cells. This was corroborated by the results of transcriptome analysis, which revealed that the primary subset among the top 10 to top 30 significantly upregulated differentially expressed genes (DEGs) dominantly consisted of M1 macrophages profiles, including Ccl3, Ccl4, Csf3, TNF, Bcl6b, Stc1, and Dusp2. Our findings unveiled the remarkable potential of the PRRSV-derived antigen A3 to repolarize macrophages while also being capable of selectively inducing apoptosis in cancerous cells. While further in vivo study is needed for A3, it holds promise as an adjuvant by its dual effects in cancer therapy modalities.

Keywords: cancer cell apoptosis, interferon responses, macrophage repolarization, recombinant protein

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