Han, Chenxia, Du, Dan, Wen, Yongjian, Li, Jiawang, Wang, Rui, Jin, Tao, Yang, Jingyu, Shi, Na, Jiang, Kun, Deng, Lihui et al (show 9 more authors)
(2021)
Chaiqin chengqi decoction ameliorates acute pancreatitis in mice via inhibition of neuron activation-mediated acinar cell SP/NK1R signaling pathways.
JOURNAL OF ETHNOPHARMACOLOGY, 274.
114029-.
Abstract
<h4>Ethnopharmacological relevance</h4>Chaiqin chengqi decoction (CQCQD) and its derivatives have been widely used in China for the early management of patients with acute pancreatitis (AP). Numerous studies demonstrate the anti-inflammatory and anti-oxidative effects of CQCQD and derivatives, but whether these effects can be attributed to suppressing neurogenic inflammation, has never been studied.<h4>Aim of the study</h4>To investigate the effects of CQCQD on substance P (SP)-neurokinin 1 receptor (NK1R) based neurogenic inflammation in an experimental AP model.<h4>Material and methods</h4>For AP patients on admission, pain score was accessed by visual analog scale (VAS); the levels of serum SP and expressions of pancreatic SP and NK1R were also determined. For in vivo study, mice received 7 intraperitoneal injections of cerulein (50 μg/kg) at hourly intervals to induce AP, whilst controls received normal saline injections. In the treatment groups, CQCQD (10 g/kg, 200 μl) was intragastrically given at the third, fifth, and seventh of the cerulein injection or the NK1R antagonist CP96345 (5 mg/kg) was intraperitoneally injected 30 min before the first cerulein administration. The von Frey test was performed to evaluate pain behavior. Animals were sacrificed at 12 h from the first cerulein/saline injection for severity assessment. Pharmacology network analysis was used to identify active ingredients of CQCQD for AP and pain. In vitro, freshly isolated pancreatic acinar cells were pre-treated with CQCQD (5 mg/ml), CP96345 (1 μM), or selected active compounds of CQCQD (12.5, 25, and 50 μM) for 30 min, followed by SP incubation for another 30 min.<h4>Results</h4>The VAS score as well as the levels of serum SP and expressions of pancreatic SP-NK1R were up-regulated in moderately severe and severe patients compared with those with mild disease. CQCQD, but not CP96345, consistently and significantly ameliorated pain, pancreatic necrosis, and systemic inflammation in cerulein-induced AP as well as inhibited NK1R internalization of pancreatic acinar cells. These effects of CQCQD were associated with reduction of pancreatic SP-NK1R and neuron activity in pancreas, dorsal root ganglia, and spinal cord. Baicalin, emodin, and magnolol, the top 3 active components of CQCQD identified via pharmacology network analysis, suppressed NK1R internalization and NF-κB signal pathway activation in isolated pancreatic acinar cells.<h4>Conclusions</h4>CQCQD ameliorated cerulein-induced AP and its associated pain via inhibiting neuron activation-mediated pancreatic acinar cell SP-NK1R signaling pathways and its active compounds baicalin, emodin, and magnolol contributed to this effect.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Acute pancreatitis, Chaiqin chengqi decoction, Pain, Substance P, Neurokinin receptor 1, Inflammation |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Clinical Directorate Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 19 Jan 2022 10:27 |
| Last Modified: | 18 Jan 2023 21:15 |
| DOI: | 10.1016/j.jep.2021.114029 |
| Open Access URL: | https://doi.org/10.1016/j.jep.2021.114029 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3147179 |
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