Content area
Full text
Received Oct 16, 2017; Revised Dec 6, 2017; Accepted Dec 13, 2017
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
1. Introduction
Chronic and uncontrolled inflammation plays a critical role in various pathological conditions, including autoimmune disorders, cardiovascular diseases, and cancers [1]. LPS, a component from the outer membranes in Gram-negative bacteria, can induce macrophages with a serial of inflammatory cascades characterized by the nitric oxide (NO) accumulation and release of inflammatory mediators through the activation of the MAPK signaling pathway. NO, a gaseous free radical, is produced by nitric oxide synthase (NOS) which has three subfamilies including eNOS, nNOS, and inducible nitric oxide synthase (iNOS). iNOS responses are responsible for high level production of NO during pathological inflammation [2].
Chronic inflammation may be regulated by diverse mechanisms and molecules. For example, heme oxygenase- (HO-1), an inducible enzyme for heme degradation, can decrease the expressions of proinflammatory mediators in stimulated macrophages and overexpression of HO-1 is often associated with iNOS suppression [3]. Under the condition of inflammation, MAPKs including JNK, p38, and ERK have also been found to regulate the production of proinflammatory cytokines such as iNOS and IL-1β [4]. Moreover, recent study showed that level of miRNA-155 increases upon LPS stimulation in macrophages and was considered as a potential regulator of inflammation [5].
Hedyotis diffusa Willd (HD) belongs to the Rubiaceae family and is widely distributed in southern China and other Asian countries. Accumulating pieces of evidence suggest that HD possesses potent anti-inflammation and cancer activities [6–9]. Scutellaria barbata D. Don (SB) contains flavonoids and scutebarbatines as its mainly active components and has been evaluated for its bioactivity in immune diseases and cancer [10–12]. In fact, Hedyotis diffusa and Scutellaria barbata (HDSB) were often used as common herb pairs (couplet medicines) for the treatment of inflammation and kinds of cancer in China [13, 14]. However, the effect of HDSB on inflammation is unclear.
The objective of this study is to clarify anti-inflammatory mechanisms of active fraction from HDSB. Our results indicate that EA11, the ethyl acetate fraction extracted at equal ratio of HD and SB, showed the strongest inhibition of NO...