Inhibition of aberrant crypt growth by non-steroidal anti-inflammatory agents and differentiation agents in the rat colon

The present study was carried out to study coumestan derivative wedelolactone in Indomethacin-induced enterocolitis in rats. Wistar rats were randomly divided into three groups containing six animals per group. Group I served as normal control. Group II, Group III & Group IV receive 7.5 mg/kg, s.c, indomethacin on two consecutive days. Group III and Group IV have received a wedelolactone dose of 50 mg/kg, and 100 mg/kg per oral, respectively, for 14 days after the induction with indomethacin. The protective effect was measured based on intestinal parameters of the disease activity index, colitis score, myeloperoxidase (MPO) activity in the colon. The inflammation biomarkers were quantified by ELISA in the rat colon. Further, activity was ascertained by histopathology. Pro-inflammatory functions IL-1a, IL-1b, IL-2, TNF, INFγ, STAT3, and CCL-5 play an important role in the variation of the intestinal immune system. Wedelolactone showed significantly decreased Disease activity index, Colitis score, Myeoloperoxidase activity. Expression of pro-inflammatory was increased in indomethacin-induced groups and was significantly suppressed in animals administered with wedelolactone at 50 mg/kg & 100 mg/kg dose (p<0.01 & p<0.001). Histological reports also revealed that treated groups have comparatively less damage than that of the induced groups. We concluded that wedelolactone showed an anti-inflammatory effect by downregulation of the IL-6/STAT3 inflammatory signaling pathway and the equilibrium production of pro-inflammatory cytokines.

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Manool, a diterpene from Salvia officinalis, exerts preventive effects on chromosomal damage and pre-neoplastic lesions

Mutagenesis ◽

10.1093/mutage/geab001 ◽

2021 ◽

Author(s):

Heloiza Diniz Nicolella ◽

Gabriela Fernandes ◽

Saulo Duarte Ozelin ◽

Francisco Rinaldi-Neto ◽

Arthur Barcelos Ribeiro ◽

...

Keyword(s):

Negative Control ◽

Rat Colon ◽

No Production ◽

Chromosomal Damage ◽

Chemically Induced ◽

Neoplastic Lesions ◽

Serum Biochemical ◽

Anti Inflammatory ◽

Chemopreventive Activity ◽

Higher Doses

Abstract The present study aimed to evaluate the effect of the manool diterpene on genomic integrity. For this purpose, we evaluated the influence of manool on genotoxicity induced by mutagens with different mechanisms of action, as well as on colon carcinogenesis. The results showed that manool (0.5 and 1.0 µg/mL) significantly reduced the frequency of micronuclei induced by doxorubicin (DXR) and hydrogen peroxide in V79 cells but did not influence genotoxicity induced by etoposide. Mice receiving manool (1.25 mg/kg) exhibited a significant reduction (79.5%) in DXR-induced chromosomal damage. The higher doses of manool (5.0 and 20 mg/kg) did not influence the genotoxicity induced by DXR. The anticarcinogenic effect of manool (0.3125, 1.25 and 5.0 mg/kg) was also observed against pre-neoplastic lesions chemically induced in rat colon. A gradual increase in manool doses did not cause a proportional reduction of pre-neoplastic lesions, thus demonstrating the absence of a dose-response relationship. The analysis of serum biochemical indicators revealed the absence of hepatotoxicity and nephrotoxicity of treatments. To explore the chemopreventive mechanisms of manool via anti-inflammatory pathways, we evaluated its effect on nitric oxide (NO) production and on the expression of the NF-kB gene. At the highest concentration tested (4 μg/mL), manool significantly increased NO production when compared to the negative control. On the other hand, in the prophylactic treatment model, manool (0.5 and 1.0 μg/mL) was able to significantly reduce NO levels produced by macrophages stimulated with lipopolysaccharide. Analysis of NF-kB in hepatic and renal tissues of mice treated with manool and DXR revealed that the mutagen was unable to stimulate expression of the gene. In conclusion, manool possesses antigenotoxic and anticarcinogenic effects and its anti-inflammatory potential might be related, at least in part, to its chemopreventive activity.

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Anti-Inflammatory Effects of Protein Kinase Inhibitor Pyrrol Derivate

The Scientific World JOURNAL ◽

10.1155/2016/2145753 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 8

Author(s):

Halyna M. Kuznietsova ◽

Maryna S. Yena ◽

Iryna P. Kotlyar ◽

Olexandr V. Ogloblya ◽

Volodymyr K. Rybalchenko

Keyword(s):

Kinase Inhibitor ◽

Malonic Dialdehyde ◽

Redox Balance ◽

Redox Status ◽

Protein Carbonyl ◽

Rat Colon ◽

Sod Activity ◽

Reference Drug ◽

Grade Scale ◽

Anti Inflammatory

In our previous studies we showed antitumor and anti-inflammatory activities of protein kinases inhibitor pyrrol derivate 1-(4-Cl-benzyl)-3-Cl-4-(CF3-fenylamino)-1H-pyrrol-2,5-dione (MI-1) on rat colon cancer model. Therefore anti-inflammatory effect of MI-1 on rat acetic acid induced ulcerative colitis (UC) model was aimed to be discovered. The anti-inflammatory effects of MI-1 (2.7 mg/kg daily) compared to reference drug Prednisolone (0.7 mg/kg daily) after 14-day usage were evaluated on macro- and light microscopy levels and expressed in 21-grade scale. Redox status of bowel mucosa was also estimated. It was shown that in UC group the grade of total injury (GTI) was equal to 9.6 (GTIcontrol=0). Increase of malonic dialdehyde (MDA) by 89% and protein carbonyl groups (PCG) by 60% and decrease of superoxide dismutase (SOD) by 40% were also observed. Prednisolone decreased GTI to 3 and leveled SOD activity, but MDA and PCG remained higher than control ones by 52% and 42%, respectively. MI-1 restored colon mucosa integrity and decreased mucosa inflammation down to GTI = 0.5 and leveled PCG and SOD. Thus, MI-1 possessed anti-inflammatory properties, which were more expressed that Prednisolone ones, as well as normalized mucosa redox balance, and so has a prospect for correction of inflammatory processes.

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