Effective suppression of nitric oxide production by HX106N through transcriptional control of heme oxygenase-1

Abstract

Heme oxygenase-1 (HO-1) has been suggested to be a key neuroprotective enzyme because of its widespread distribution in the brain as well as its strong antioxidative effects. HX106N, a water-soluble botanical formulation, has previously been demonstrated to prevent amyloid b-induced memory impairment and oxidative stress in mice by upregulating HO-1 levels. In this study, the underlying molecular mechanisms of HX106N-induced HO-1 expression were investigated using BV-2 cells, a murine microglial cell line, and primary microglia. Treatment with HX106N induced the expression of HO-1 at the transcriptional level through the stress-responsive element-containing enhancer present in the ho-1 promoter. Nuclear factor E2-related factor 2 (Nrf2) was activated in cells treated with HX106N. The results from knockdown assay showed that small interfering RNA of Nrf2 attenuated HX106N-mediated HO-1 expression. Pharmacological inhibitors of p38 and JNK mitogen-activated protein kinases suppressed the HX106N-mediated induction of HO-1. The NF-kB signaling pathway was activated by HX106N and played a role in HX106N-induced HO-1 expression. Furthermore, HO-1 and one of its by-products during the enzymatic degradation of heme, CO, were found to be involved in HX106N-mediated suppression of NO production. Taken together, these data indicate that HX106N exerts potent antioxidative effects by increasing the expression of HO-1 through multiple signaling pathways, leading to the suppression of NO production.

Anti‑inflammatory effects of methanol extract from Peperomia dindygulensis Miq. mediated by HO‑1 in LPS‑induced RAW 264.7 cells

“…Although it has been reported that HO-1 induces NO during cellular senescence, the induction of HO-1 inhibits iNOS to reduce NO by oxidative injury (22). CO and biliverdin, the products of HO-1, are also known to inhibit iNOS (23)(24)(25). Therefore, controlling HO-1 expression is pivotal in modulating anti-inflammatory responses.…”

GC-TOF-MS-Based Metabolomic Analysis and Evaluation of the Effects of HX106, a Nutraceutical, on ADHD-Like Symptoms in Prenatal Alcohol Exposed Mice

“…HX106 is a nutraceutical composed of four different herbal extracts: Arilli of Dimocarpus longan Loureiro (Sapindaceae), tubers of Liriope platyphylla Wang and Tang (Liliaceae), roots of Salvia miltiorrhiza Bunge (Lamiaceae) and rhizomes of Gastrodia elata Blume (Orchidaceae). These compositions were selected and mixed according to the traditional knowledge and information from previous studies [ 24 , 25 ]. HX106 has been reported to improve memory function possibly mediated by the suppression of oxidative stress, neuroinflammation and accumulation of amyloid beta and tau tangle [ 24 , 25 , 26 ].…”

“…These compositions were selected and mixed according to the traditional knowledge and information from previous studies [ 24 , 25 ]. HX106 has been reported to improve memory function possibly mediated by the suppression of oxidative stress, neuroinflammation and accumulation of amyloid beta and tau tangle [ 24 , 25 , 26 ]. Based on these results, HX106 has been applied into clinical study (NCT01956097).…”