Sheng Wang1, Yang Zhao2, Junqing Zhang3, Xiaoxing Huang4, Yifei Wang5, Xiaotao Xu6, Bin Zheng7, Xue Zhou8, Huajie Tian9, Li Liu10, Qibing Mei11. 1. China State Institute of Pharmaceutical Industry, Shanghai 200040, China; State Key Laboratory of New Drug & Pharmaceutial Process, Shanghai Institute of Pharmaceutial Industry, Shanghai 200437, China. Electronic address: wang1986sheng@163.com. 2. Vascular Biology Program, Centenary Institute, The University of Sydney, Shanghai 2042, NSW, Australia. Electronic address: 183034355@qq.com. 3. Hainan Provincial Key Laboratory of Research and Development of Tropical Medicinal Plants, Hainan Medical University, Haikou 571199, China. Electronic address: a1986bc@126.com. 4. China State Institute of Pharmaceutical Industry, Shanghai 200040, China; State Key Laboratory of New Drug & Pharmaceutial Process, Shanghai Institute of Pharmaceutial Industry, Shanghai 200437, China. Electronic address: 30695140@qq.com. 5. China State Institute of Pharmaceutical Industry, Shanghai 200040, China; State Key Laboratory of New Drug & Pharmaceutial Process, Shanghai Institute of Pharmaceutial Industry, Shanghai 200437, China. Electronic address: 279695361@qq.com. 6. China State Institute of Pharmaceutical Industry, Shanghai 200040, China; State Key Laboratory of New Drug & Pharmaceutial Process, Shanghai Institute of Pharmaceutial Industry, Shanghai 200437, China. Electronic address: 594045591@qq.com. 7. China State Institute of Pharmaceutical Industry, Shanghai 200040, China; State Key Laboratory of New Drug & Pharmaceutial Process, Shanghai Institute of Pharmaceutial Industry, Shanghai 200437, China. Electronic address: 443749358@qq.com. 8. China State Institute of Pharmaceutical Industry, Shanghai 200040, China; State Key Laboratory of New Drug & Pharmaceutial Process, Shanghai Institute of Pharmaceutial Industry, Shanghai 200437, China. Electronic address: 547979179@qq.com. 9. China State Institute of Pharmaceutical Industry, Shanghai 200040, China; State Key Laboratory of New Drug & Pharmaceutial Process, Shanghai Institute of Pharmaceutial Industry, Shanghai 200437, China. Electronic address: 892782662@qq.com. 10. China State Institute of Pharmaceutical Industry, Shanghai 200040, China; State Key Laboratory of New Drug & Pharmaceutial Process, Shanghai Institute of Pharmaceutial Industry, Shanghai 200437, China. Electronic address: liuli1129@hotmail.com. 11. China State Institute of Pharmaceutical Industry, Shanghai 200040, China; State Key Laboratory of New Drug & Pharmaceutial Process, Shanghai Institute of Pharmaceutial Industry, Shanghai 200437, China. Electronic address: qibingmei@126.com.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: The fructus Alpinia oxyphylla Miq. (AOM) has been used for treating diarrhea with spleen deficiency and gastralgia for thousands of years. A number of traditional Chinese medicine formulae provide AOM as an alternative herbal treatment for diarrhea, but the scientific basis for this usage has not been well defined. AIM OF THE STUDY: In this study, we tried to investigate the antidiarrheal activity and possible mechanisms of Fructus AOM, aiming to enrich our understanding to the scientific meanings and theoretical significance of Fructus AOM in clinical practice. MATERIALS AND METHODS: The fructus of AOM collected from Hainan province in China were macerated in the 95% ethanol to obtain the crude 95% ethanol extract, followed by subjected to chromatographic separation over a Diaion HP20 column to obtain 90% and 50% ethanol eluted fractions. The activities of the crude extract and fractions on castor oil induced acute diarrhea, rhubarb induced chronic diarrhea, gastrointestinal transit (GIT) in mice, and contractions of isolated guinea-pig ileum were evaluated. Additionally, nitric oxide (NO), gastrointestinal peptides gastrin (GAS), motilin (MTL) and somatostatin (SS) levels that related to gastrointestinal motilities were detected to demonstrate the potential mechanisms. Ultimately, LC-MS/MS method was utilized to ensure the chemical consistency. RESULTS: The 95% ethanol extract and 90% ethanol eluted fraction significantly delayed the onset time and decreased the wet faeces proportion compared with control group in the castor oil induced acute diarrhea mice. In terms of further evaluation of antidiarrheal activity, the 95% ethanol extract and 90% ethanol elution displayed significant inhibition of the intestinal propulsion at the two highest oral doses of 20 g crude drug/kg and 1g/kg. Moreover the 95% ethanol extract (10 and 20 g crude drug/kg) and 90% ethanol elution (0.5 and 1g/kg) could significantly inhibit the GIT, which was partially attributed to the increase in NO and SS levels, and the decreased MTL. In vitro spontaneous contractions of the isolated guinea pig ileum induced by carbachol, neostigmine and histamine were attenuated by both the extract and elution. Phytochemical analysis of 95% ethanol extract and its fractions identified the presence of diphenylheptanes, sesquiterpenes, and flavones as the major components. CONCLUSIONS: Our in vivo and in vitro data could partly support and justify the traditional usage of Fructus AOM on the treatment of diarrhea in traditional medicine.
ETHNOPHARMACOLOGICAL RELEVANCE: The fructus Alpinia oxyphylla Miq. (AOM) has been used for treating diarrhea with spleen deficiency and gastralgia for thousands of years. A number of traditional Chinese medicine formulae provide AOM as an alternative herbal treatment for diarrhea, but the scientific basis for this usage has not been well defined. AIM OF THE STUDY: In this study, we tried to investigate the antidiarrheal activity and possible mechanisms of Fructus AOM, aiming to enrich our understanding to the scientific meanings and theoretical significance of Fructus AOM in clinical practice. MATERIALS AND METHODS: The fructus of AOM collected from Hainan province in China were macerated in the 95% ethanol to obtain the crude 95% ethanol extract, followed by subjected to chromatographic separation over a Diaion HP20 column to obtain 90% and 50% ethanol eluted fractions. The activities of the crude extract and fractions on castor oil induced acute diarrhea, rhubarb induced chronic diarrhea, gastrointestinal transit (GIT) in mice, and contractions of isolated guinea-pig ileum were evaluated. Additionally, nitric oxide (NO), gastrointestinal peptides gastrin (GAS), motilin (MTL) and somatostatin (SS) levels that related to gastrointestinal motilities were detected to demonstrate the potential mechanisms. Ultimately, LC-MS/MS method was utilized to ensure the chemical consistency. RESULTS: The 95% ethanol extract and 90% ethanol eluted fraction significantly delayed the onset time and decreased the wet faeces proportion compared with control group in the castor oil induced acute diarrheamice. In terms of further evaluation of antidiarrheal activity, the 95% ethanol extract and 90% ethanol elution displayed significant inhibition of the intestinal propulsion at the two highest oral doses of 20 g crude drug/kg and 1g/kg. Moreover the 95% ethanol extract (10 and 20 g crude drug/kg) and 90% ethanol elution (0.5 and 1g/kg) could significantly inhibit the GIT, which was partially attributed to the increase in NO and SS levels, and the decreased MTL. In vitro spontaneous contractions of the isolated guinea pig ileum induced by carbachol, neostigmine and histamine were attenuated by both the extract and elution. Phytochemical analysis of 95% ethanol extract and its fractions identified the presence of diphenylheptanes, sesquiterpenes, and flavones as the major components. CONCLUSIONS: Our in vivo and in vitro data could partly support and justify the traditional usage of Fructus AOM on the treatment of diarrhea in traditional medicine.
Authors: Jiao-Xia Wu; An Jia; Yin-Feng Tan; Han Xu; Jian-Ping Tian; Yan Wang; Hai Long Li; Bing-Miao Gao; Yong-Hui Li Journal: BMC Complement Med Ther Date: 2020-07-13