Agarwood Extract Mitigates Intestinal Injury in Fluorouracil-Induced Mice

Abstract

Agarwood is used to treat gastrointestinal diseases. Although our previous studies demonstrated that agarwood ethanol extract produced by the whole-tree agarwood-inducing technique (WTAAE) improves intestinal peristalsis, the intestinal protective effect of WTAAE remains unclear. This study aimed to evaluate the protective effect of WTAAE on the intestinal injury induced by fluorouracil (5-FU) and explore its potential mechanism. Institute of Cancer Research (ICR) mice were given agarwood ethanol extracts (AAEs) (details in materials part), including WTAAE (0.71, 1.42 and 2.84 g/kg), wild agarwood ethanol extract (WAAE) and burning-chisel-drilling agarwood ethanol extract (FBAAE) (2.84 g/kg). A colon injury model was induced by 5-FU. After 14 d of treatment, the histopathology and biochemical and molecular parameters were measured. Our results indicated that WTAAE enhanced the intestinal advancing rate and alleviated the severity of colon injury similar the WAAE and better than FBAAE. Simultaneously, WTAAE reduced the nitric oxide (NO) concentration and increased the glutathione (GSH) and superoxide dismutase (SOD) levels. WTAAE also reduced the levels of interleukin-17 (IL-17) and IL-33 and elevated the level of IL-10. Furthermore, WTAAE upregulated the mRNA expression of the nuclear factor-E2-related factor 2-antioxidant response element (Nrf2-ARE) pathway and downregulated the mRNA levels of the nuclear factor-kappaB (NF-κB) pathway. WTAAE had a mitigating effect on intestinal damage, suggesting that it could be used as an intestinal protective and adjuvant therapy drug for intestinal injury induced by chemical drugs.

Agarwood Alcohol Extract Protects against Gastric Ulcer by Inhibiting Oxidation and Inflammation

“…NO plays a crucial role in various physiological processes, such as dilating blood vessels and stimulating gastric angiogenesis of ulcers. Some studies have demonstrated that the endogenous NO provides protection for the gastric mucosa [ 36 , 37 ]. However, the excessive NO could also stimulate cell proliferation of the gastric mucosa and granulation tissue formation [ 38 ].…”

“…GSH and SOD are important antioxidants, which protect the gastric mucosa from oxidative damage [ 39 ], as they could scavenge free radicals. Therefore, the lower levels of GSH and SOD also indicate the severity of oxidative stress damage [ 37 , 40 ]. With the gastric mucosa damaged by ethanol, GSH, SOD, and GSH-Px decreased significantly, while NO and MDA increased [ 41 ].…”

“…Previous research showed that gastric ulcers caused by ethanol may activate the innate immune system and upregulate the levels of proinflammatory cytokines, such as TNF- α , IL-1 β , and IL-6 [ 43 ]. Furthermore, IL-10 played an important role in downregulating the inflammatory pathway and preventing autoimmune pathologies [ 37 , 44 , 45 ]. Our results suggested that AAEs has potential anti-inflammatory effects on the ethanol-induced gastric damage.…”

“…It is well known that NF- κ B is a vital transcription factor in the acute-phase inflammatory processes, which could induce upregulation of the proinflammatory cytokines TNF- α , IL-6, and IL-1 β [ 43 ]. When gastric mucosa cells stimulated by exogenous stimuli containing ethanol, NF- κ B was activated and combined with specific gene-starting factors, which triggered the target inflammatory cytokines and aggravated gastric mucosal damage [ 37 , 46 ]. The results of this study suggested that pretreatment with AAEs inhibited NF- κ B activation and decreased the expression of NF- κ B, which could possibly contribute to alleviating the inflammatory injury of gastric ulcer.…”

Pharmacokinetic studies of six major 2‐(2‐phenylethyl) chromones in rat plasma using ultra high performance liquid chromatography with tandem mass spectrometry after oral administration of agarwood ethanol extract

“…Agarwood has been used as a digestive, sedative, anti-emetic, and antipyretic drug in China for centuries [3,4]. Previous investigations have found that the ethanol extract of agarwood has a wide range of pharmacological properties, such as antioxidant [5,6], anti-diabetes [7], anti-asthma [8], gastrointestinal regulation [9,10], anti-inflammatory [5,11], and sedativehypnotic activity [12]. The 2-(2-phenylethyl) chromones derivatives, sesquiterpenes, and low molecular weight aromatic compounds are the primary chemical constituents of agarwood [13][14][15], and 2-(2-phenylethyl) chromones have been identified as potential markers of agarwood [16].…”