Anti-inflammatory and Cytoprotective Effect ofClinacanthus nutansLeaf But Not Stem Extracts on 7-Ketocholesterol Induced Brain Endothelial Cell Injury

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 thatC. nutanshas the ability to modulate the induction of cytosolic phospholipase A(2)(cPLA(2)) expression in SH-SY5Y cells through the inhibition of histone deacetylases (HDACs). In the current study, we elucidated the effect ofC. nutanson 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 byC. nutansleaf extracts but not stem extracts. 7KC also induced a marked increase in mRNA expression of pro-inflammatory cytokines, IL-1 beta IL-6, IL-8, TNF-alpha and cyclooxygenase-2 (COX-2) in brain endothelial cells, and these increases were significantly inhibited byC. nutansleaf 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 inC. nutansleaves that have anti-inflammatory properties.

Automated summary

Clinacanthus nutans has been traditionally used in herbal medicine in Southeast Asia for various purposes. In this study, it was found that C. nutans leaf extracts could significantly inhibit 7KC-induced damage and inflammation in brain endothelial cells, possibly due to their different chemical profile compared to stem extracts. Further research is needed to identify the specific phytochemicals in C. nutans leaves with anti-inflammatory properties.