Anti-inflammatory and Cytoprotective Effect of Clinacanthus nutans Leaf But Not Stem Extracts on 7-Ketocholesterol Induc
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ORIGINAL PAPER
Anti‑inflammatory and Cytoprotective Effect of Clinacanthus nutans Leaf But Not Stem Extracts on 7‑Ketocholesterol Induced Brain Endothelial Cell Injury Xuan Kuo1 · Deron R. Herr2 · Wei‑Yi Ong1,3 Received: 13 August 2020 / Accepted: 8 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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 A 2 (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. Keywords Sabah snake grass · Oxysterols · Hypercholesterolemia · Diabetes mellitus · Neuroinflammation · Vascular dementia
Introduction Clinacanthus nutans (C. nutans) Lindau is colloquially known as Sabah Snake grass, or belalai gajah in Malay and you dun cao in Mandarin. It belongs to the Acanthaceae family and is native to Southeast Asia. The herb is commonly * Deron R. Herr [email protected] * Wei‑Yi Ong [email protected] 1
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119260, Singapore
2
Department of Biology, San Diego State University, San Diego, CA 92182, USA
3
Neurobiology Programme, Life Sciences Institute, National University of Singapore, Singapore 119260, Singapore
used for treatment of skin rashes, insect and snake bites, and for treating some symptoms caused by the herpes simplex virus, diabetes mellitus and gout. It is also prepared as a tea for treatment of diabetes and cancer (Kamarudin et al. 2017). Different methods of preparation affect the type and amounts of compounds obtained, as well as their range and extent of bioactivities. Analysis of this plant has revealed the identit
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