Over the years, adenocarcinoma (ADC), which has a worse prognosis than squamous cell carcinoma (SCC) of the cervix, has shown an increasing trend. Cyclooxygenase-2 (COX2) expression which has been associated with worse prognosis in several solid cancers was studied for its association with SCC and ADC of the cervix. 35 histologically re-confirmed SCC and 35 ADC were immunohistochemically stained for COX2 using a mouse monoclonal antibody to COX2 (1:100; Dako: Clone CX-294) on a Ventana Benchmark XT. The histoscore was computed as intensity of staining, semi-quantitated on a scale of 0-3 with 0 = negative, 1 = weak, 2 = moderate and 3 = strong staining intensity; multiplied by percentage of immunopositivity on a scale of 0-4 with 0 = <1%, 1 = 1-25%, 2 = 26-50%, 3 = 51-75% and 4 = ≥75% of immunopositive tumour cells. Histoscore 1-3/12 was considered as low and ≥4/12 as high COX2 expression. SCC affected Chinese more than Malays, while Malays had more ADC (p = 0.032). Mean age at presentation of SCC (57.5 years) was about a decade later than ADC at 47.9 years (p = 0.002). 30/35 (85.7%) of SCC and 34/35 (97.1%) of ADC expressed COX2. Histoscores of ADC (median = 4.0, IQR = 3.0-6.0) was significantly higher (p = 0.014) than those of SCC (median = 3.0, IQR = 2.0-3.0). High histoscores (≥4/12) were more frequent in ADC (55.9%) compared with SCC (26.7%) (p = 0.018), implicating COX2, either directly or indirectly, as a possible player in influencing the poorer outcome of ADC compared with SCC.
Macrophage activation is a key event that triggers inflammatory response. The activation is accompanied by metabolic shift such as upregulated glucose metabolism. There are accumulating evidences showing the anti-inflammatory activity of Momordica charantia. However, the effects of M. charantia on inflammatory response and glucose metabolism in activated macrophages have not been fully established. The present study aimed to examine the effect of M. charantia in modulating lipopolysaccharide (LPS)-induced inflammation and perturbed glucose metabolism in RAW264.7 murine macrophages. The results showed that LPS-induced NF-κB (p65) nuclear translocation was inhibited by M. charantia treatment. In addition, M. charantia was found to reduce the expression of inflammatory genes including IL6, TNF-α, IL1β, COX2, iNOS, and IL10 in LPS-treated macrophages. Furthermore, the data showed that M. charantia reduced the expression of GLUT1 and HK2 genes and lactate production (-28%), resulting in suppression of glycolysis. Notably, its effect on GLUT1 gene expression was found to be independent of LPS-induced inflammation. A further experiment also indicated that the bioactivities of M. charantia may be attributed to its key bioactive compound, charantin. Taken together, the study provided supporting evidences showing the potential of M. charantia for the treatment of inflammatory disorders.
Clinacanthus nutans (Lindau) (C. nutans) has diverse uses in traditional herbal medicine for treating skin rashes, insect and snake bites, lesions caused by herpes simplex virus, diabetes mellitus and gout in Singapore, Malaysia, Indonesia, Thailand and China. We previously showed that C. nutans has the ability to modulate the induction of cytosolic phospholipase A2 (cPLA2) expression in SH-SY5Y cells through the inhibition of histone deacetylases (HDACs). In the current study, we elucidated the effect of C. nutans on the hCMEC/D3 human brain endothelial cell line. Endothelial cells are exposed to high levels of the cholesterol oxidation product, 7-ketocholesterol (7KC), in patients with cardiovascular disease and diabetes, and this process is thought to mediate pathological inflammation. 7KC induced a dose-dependent loss of hCMEC/D3 cell viability, and such damage was significantly inhibited by C. nutans leaf extracts but not stem extracts. 7KC also induced a marked increase in mRNA expression of pro-inflammatory cytokines, IL-1β IL-6, IL-8, TNF-α and cyclooxygenase-2 (COX-2) in brain endothelial cells, and these increases were significantly inhibited by C. nutans leaf but not stem extracts. HPLC analyses showed that leaf extracts have a markedly different chemical profile compared to stem extracts, which might explain their different effects in counteracting 7KC-induced inflammation. Further study is necessary to identify the putative phytochemicals in C. nutans leaves that have anti-inflammatory properties.