Shitao Peng1, Zhiqian Song1, Chun Wang1, Dongrui Liang1, Xiaoying Wan1, Zhenli Liu2, Aiping Lu3, Zhangchi Ning4. 1. China Academy of Chinese Medical Sciences, Institute of Basic Theory for Chinese Medicine, Beijing 100700, China. 2. China Academy of Chinese Medical Sciences, Institute of Basic Theory for Chinese Medicine, Beijing 100700, China. Electronic address: zhenli_liu@sina.com. 3. School of Chinese Medicine, Hong Kong Baptist University, Hong Kong 00825, China. Electronic address: lap64067611@126.com. 4. China Academy of Chinese Medical Sciences, Institute of Basic Theory for Chinese Medicine, Beijing 100700, China. Electronic address: yizhangyichi1573@sina.com.
Abstract
BACKGROUND: Boswellic acids in Olibanum (known as frankincense) are potent anti-inflammatory properties in treating ulcerative colitis (UC), but its low bioavailability limited drug development. Evidence accumulated that vinegar processing of frankincense exerts positive effects on improving absorption of compositions. The underlying mechanism is unknown. In recent decades, spectacular growth and multidisciplinary integration of metabolic application were witnessed. The relationship between drug absorption and curative effect has been more or less established. However, it remains a knowledge gap in the field between drug absorption and endocrine metabolism. PURPOSE: To investigate the enhancement mechanism of vinegar processing in the absorption of boswellic acids via the aspect of bile acid metabolism. METHODS: The effects of raw frankincense (RF) and processed frankincense (PF) were compared by the UC model of rats. The plasma concentration of boswellic acids and the hepatic and colonic bile acids contents were quantified by UPLC-TQ-MS. The levels of mRNA and protein associated with bile acid metabolism were also compared. RESULTS: The results showed that PF exhibited re-markable mitigating effects on UC with the elevated plasma level of boswellic acid and upregulated expression of the absorption-related protein multidrug resistance-associated protein 2 (MRP2) and organic anion transporting polypeptide 1B3 (OATP1B3) in the liver and colon. It improved colonic lithocholic acid (LCA), which promoted the expression of bile acid nuclear receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR), resulting in the upregulation of MRP2 and OATP1B3. CONCLUSION: This paper revealed the mechanisms behind the absorption promotion effects of processing. Bile acids metabolism exhibits potential status in pharmaceutical development. The results shed light on the interdisciplinary collaboration between the metabolism and drug absorption fields.
BACKGROUND: Boswellic acids in Olibanum (known as frankincense) are potent anti-inflammatory properties in treating ulcerative colitis (UC), but its low bioavailability limited drug development. Evidence accumulated that vinegar processing of frankincense exerts positive effects on improving absorption of compositions. The underlying mechanism is unknown. In recent decades, spectacular growth and multidisciplinary integration of metabolic application were witnessed. The relationship between drug absorption and curative effect has been more or less established. However, it remains a knowledge gap in the field between drug absorption and endocrine metabolism. PURPOSE: To investigate the enhancement mechanism of vinegar processing in the absorption of boswellic acids via the aspect of bile acid metabolism. METHODS: The effects of raw frankincense (RF) and processed frankincense (PF) were compared by the UC model of rats. The plasma concentration of boswellic acids and the hepatic and colonic bile acids contents were quantified by UPLC-TQ-MS. The levels of mRNA and protein associated with bile acid metabolism were also compared. RESULTS: The results showed that PF exhibited re-markable mitigating effects on UC with the elevated plasma level of boswellic acid and upregulated expression of the absorption-related protein multidrug resistance-associated protein 2 (MRP2) and organic anion transporting polypeptide 1B3 (OATP1B3) in the liver and colon. It improved colonic lithocholic acid (LCA), which promoted the expression of bile acid nuclear receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR), resulting in the upregulation of MRP2 and OATP1B3. CONCLUSION: This paper revealed the mechanisms behind the absorption promotion effects of processing. Bile acids metabolism exhibits potential status in pharmaceutical development. The results shed light on the interdisciplinary collaboration between the metabolism and drug absorption fields.