Clinacanthus nutans Protects Cortical Neurons Against Hypoxia-Induced Toxicity by Downregulating HDAC1/6

Abstract

Many population-based epidemiological studies have unveiled an inverse correlation between intake of herbal plants and incidence of stroke. C. nutans is a traditional herbal medicine widely used for snake bite, viral infection and cancer in Asian countries. However, its role in protecting stroke damage remains to be studied. Despite of growing evidence to support epigenetic regulation in the pathogenesis and recovery of stroke, a clear understanding of the underlying molecular mechanisms is still lacking. In the present study, primary cortical neurons were subjected to in vitro oxygen-glucose deprivation (OGD)-reoxygenation and hypoxic neuronal death was used to investigate the interaction between C. nutans and histone deacetylases (HDACs). Using pharmacological agents (HDAC inhibitor/activator), loss-of-function (HDAC siRNA) and gain-of-function (HDAC plasmid) approaches, we demonstrated an early induction of HDAC1/2/3/8 and HDAC6 in neurons after OGD insult. C. nutans extract selectively inhibited HDAC1 and HDAC6 expression and attenuated neuronal death. Results of reporter analysis further revealed that C. nutans suppressed HDAC1 and HDAC6 transcription. Besides ameliorating neuronal death, C. nutans also protected astrocytes and endothelial cells from hypoxic-induced cell death. In summary, results support ability for C. nutans to suppress post-hypoxic HDACs activation and mitigate against OGD-induced neuronal death. This study further opens a new avenue for the use of herbal medicines to regulate epigenetic control of brain injury.

Expression of DHA-Metabolizing Enzyme Alox15 is Regulated by Selective Histone Acetylation in Neuroblastoma Cells

“…Western blot analysis of proteins was performed as previously described [ 30 ], with mouse monoclonal antibody to Alox15 (1:500, Abcam, New Territories, HK) and antibodies to MAP-2, NeuN or α-tubulin (1:500, Santa Cruz, CA, USA). Protein bands were visualized by an enhanced chemiluminescence system (Merck Millipore, MA, USA).…”

A Comprehensive Review on Phytochemistry and Pharmacological Activities of Clinacanthus nutans (Burm.f.) Lindau

“…In vitro studies suggested that the neuroprotective effect of C. nutans was promising. From the studies by Tan et al [ 74 ] and Tsai et al [ 75 ], the 80% ethanol extract with a dose concentration less than 10 μ g/mL was able to suppress post-hypoxic histone deacetylase (HDAC) activation and hypoxic neuronal death in an oxygen-glucose deprivation- (OGD-) reoxygenation assay. It also decreased the levels of cytosolic phospholipase 2 (cPLA2) mRNA expression in mouse primary cortical neurons subjected to 0.5 h of OGD injury.…”

Alterations in Herbage Yield, Antioxidant Activities, Phytochemical Contents, and Bioactive Compounds of Sabah Snake Grass (Clinacanthus Nutans L.) with Regards to Harvesting Age and Harvesting Frequency

“…For the past few decades, the research for C. nutans has been progressively done in a rapid trend. Broad-spectrum of pharmacological activities, which includes antioxidant [ 4 ], antiviral (herpes simplex virus (HSV), varicella-zoster virus, papillomavirus, and dengue virus) [ 5 ], anti-inflammatory [ 6 ], antibacterial [ 7 , 8 , 9 ], analgesic [ 10 , 11 , 12 ], antivenom [ 13 , 14 , 15 ], immunomodulating [ 16 , 17 ], neuroprotective [ 18 , 19 , 20 ], antidiabetic [ 21 , 22 , 23 ], α-glucosidase inhibitory [ 24 ], lipid-elevated inhibition [ 25 ], plasmid DNA protective [ 26 ], anti-angiogenic [ 27 ], anticancer [ 28 ], anti-proliferative [ 28 ], and antitumor as the latest biological action identified [ 29 ], has been very well reported in previous studies. Owing to significant economic benefits towards human health, the demand for this herb has been increased in recent years.…”