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Introduction
Sepsis is the generalized inflammatory response elicited by an infectious process [1]. More than 75,000 patients die of septic shock every year in the USA, making this syndrome the leading cause of death in noncoronary intensive care units [2,3]. The respiratory system is the most frequently affected organ system, and lung dysfunction such as acute lung injury (ALI) or adult respiratory distress syndrome (ARDS) is the first step in the development of multiple organ failure [4–6]. Despite the many advances elucidating the pathogenesis and treatment of sepsis, no satisfactory therapy has been developed for ALI/ARDS to date [7].
In Gram-negative bacteria, LPS play a dominant role in the process of sepsis, and macrophages play an essential role in inflammation in response to LPS [8]. Macrophages mediate inflammatory responses by overproducing proinflammatory cytokines including interleukin 1β (IL-1β), IL-6, tumor necrosis factor α (TNFα), and nitric oxide (NO) synthesized by inducible NO synthase (iNOS) [8]. It has been demonstrated that the induction of heme-oxygenase-1 (HO-1) expression in RAW264.7 macrophages inhibits LPS-activated sepsis [9]. Thus, HO-1, as a regulator of inflammation, is considered to be a therapeutic target.
Toona sinensis Roem (TS) or Cedrela sinensis, commonly known as Chinese mahogany or Chinese Toona, is a perennial deciduous arbor that belongs to the Meliaceae family [10,11]. TS is widely distributed over eastern Asia, and TS leaves have long been used as a vegetable in Taiwan, China, and Malaysia [12]. Previous pharmacological and bioactivity studies on the aqueous extract of TS leaves (TSL) have revealed anticancer [13], antioxidant [14–16], antidiabetes [17,18], and antivirus [19] activity, improvements in learning and memory in senescence-accelerated mice [20], and the reduction of steroidogenesis in mouse Leydig cells [21]. In addition, no studies have reported significant toxicity from TSL thus far [12,22]. TSL is also used as Chinese traditional medicine for the treatment of enteritis, dysentery, and eye infections [23]. Therefore, TSL might have beneficial effects on anti-inflammation. This study investigated the anti-inflammatory activity of TSL against lung injury in a cecal ligation and puncture (CLP)-induced septic model, and the macrophage release of NO/iNOS by the induction of LPS.
Materials and methods
Preparation of TSL
The TSL, an advanced bioactive fraction, used in this study was purchased from Taiwan...