Acute pancreatitis (AP) is a life-threatening gastrointestinal disorder for which no effective pharmacological treatments are currently available. One of the pharmacological targets that merits further research is the neurokinin 1 receptor (NK1R), which is found on pancreatic acinar cells and responds to the neuropeptide substance P (SP) that participates in AP. Although a few studies have stated the involvement of SP/NK1R in neurogenic inflammation in AP development, the regulatory mechanism remains unclear. In this study, we found that following activation of NK1R by SP, β-arrestin1, a scaffold protein of NK1R, down-regulated transcription of Adss, Adsl, and Ampd in the purine nucleotide cycle, thereby inhibiting mitochondrial function through fumarate depletion. Interestingly, we identified magnolol as a new and natural NK1R inhibitor with a non-nitrogenous biphenyl core structure. It exhibited a beneficial effect on AP by restoring purine nucleotide cycle metabolic enzymes and fumarate levels. Our study not only provides new therapeutic strategies, leading compounds, and drug translation possibilities for AP, but also provides important clues for the study of downstream mechanisms driven by SP in other diseases.

OBJECTIVE: Microcirculatory disturbance is pathologically critical to acute pancreatitis (AP), which can be effectively alleviated by traditional Chinese medicine (TCM) formulas that activate blood flow. However, there has been no evidence-based research to date. Therefore, a well-designed systematic review and meta-analysis is necessary to elucidate the therapeutic transformative benefit of improving microcirculation during AP. This study aims to confirm the therapeutic efficacy of TCM formulas and explore the potential mechanisms underlying their effects on AP treatment. METHODS: Studies from eight databases including Pubmed, Embase, Web of Science, Cochrane Library, CNKI, CBM, Wanfang, and Chinese VIP, were screened for the eligible randomized controlled trials (RCTs). The APACHE II score and effectiveness rate were set as primary outcomes, while mortality rate, complications, total hospital stays, serum amylase recovery time, the time until the disappearance of abdominal pain, microcirculation indicators, and inflammation indicators were chosen as secondary outcomes. A systematic review and meta-analysis were subsequently conducted. Network pharmacology analysis was performed to analyze potential bioactive components with relevant targets of the core herbs included in the TCM formulas for activating blood flow. RESULTS: A total of 51 RCTs (n = 3 721) were included. Compared with conventional western medical treatments alone, TCM groups were associated with lower APACHE II score (SMD =  - 1.36, 95% CI: -2.01 to - 0.71, P = 0.000) and higher effectiveness rate (RR: 1.22, 95% CI: 1.18 to 1.26, P = 0.000). Furthermore, the formulas for activating blood flow demonstrated significant efficacy in improving both microcirculation and inflammation indicators. Additionally, six core Chinese herbal medicines including Rhei Radix et Rhizoma with the highest frequency, Aurantii Fructus Immaturus, Paeoniae Radix Rubra, Bupleuri Radix, Salviae Miltiorrhizae Radix et Rhizoma, and Corydalis Rhizoma were filtered out from the adopted TCM formulas. Finally, 166 shared targets between the six herbs and AP were identified. KEGG analysis indicated that lipid and atherosclerosis pathway is highly related to microcirculation. CONCLUSION TCM formulas for activating blood flow significantly improve microcirculation and alleviate AP. Further high-quality, well-designed RCTs and deep mechanism exploration are required.

Objective:To explore the material basis and molecular mechanism of Liu-He-Dan (LHD) in treating acute pancreatitis (AP).Methods:Active chemical components of LHD, their corresponding targets and related AP pathogenic genes were searched and selected in the Encyclopedia of Traditional Chinese Medicine (ETCM) and disease information related databases (OMIM, DisGeNET, HPO, and NCBI), respectively. The protein-protein interaction (PPI) was analyzed through the STRING database. Enrichment analysis on those targets was performed by using CPBD and STRING databases to examine the function and pathway involved in the treatment of AP by active chemical components of LHD. Finally, " Chinese medicinal materials-active chemical components-targets-pathways" network was constructed by Cytoscape 3.6.0.Results:Network analysis showed that a total of 111 active chemical components of LHD were correlated with 39 targets of AP. The gene ontology functional enrichment analysis of 39 targets by CPBD and STRING databases obtained 575 enrichment results of biological process, 49 results of molecular function and 26 results of cellular components; Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis obtained 46 enrichment results involved in pancreatic secretion, bile secretion, RRAR signaling pathway, arachidonic acid metabolism and calcium signaling.Conclusions:The molecular mechanism of LHD in the treatment of AP by multiple components, multiple targets and multi-signaling pathways was preliminarily determined, which provides a basis for further analysis on active chemical components of LHD and molecular function.

Objective To investigate the correlation between the types of constitution in TCM and the sleep status in the PLA Navy divers. Methods Eighty-nine PLA Navy divers who performed 10m diving professional training were selected. Constitution in TCM was classified and determined by the standardized standard Constitution in Chinese Medicine Questionnaire, sleep status was evaluated by the Pittsburgh Sleep Quality Index. Results 62.9% of Navy divers were the mild constitution in TCM. The eight kinds of the biased constitution in TCM are ranked with yang deficiency, phlegm-dampness, dampness-heat, qi deficiency, yin deficiency, blood stasis, qi stagnation and special intrinsic quality. Among 78 Navy divers with good sleep quality, there were 49 divers (72.1%) with the mild constitution in TCM and 19 (27.9%) with the biased constitution in TCM. Among 21 Navy divers with poor sleep quality, there were 7 divers (33.3%) with the mild constitution in TCM (accounting for) and 14 (66.7%) with the biased constitution in TCM. For Navy divers with poor sleep quality, the sleep quality scores were positive correlated with the blood stasis constitution in TCM (r=0.481,P<0.05). Conclusion Sleep status is correlated with the types of the constitution in TCM, and regulating constitution in TCM can improve sleep quality in PLA Navy divers.

Objective To explore the correlation between TCM constitution and sleep status in escort troops. Methods Standardized TCM Constitution Questionnaire and Pittsburgh Sleep Quality Index (PSQI) were used to investigate escort troops. Factors of PSQI and constitution types were analyzed. Results The results of PSQI showed the number of escort troops who had bad sleeping (PSQI>7) was 64, which accounted for 46%of the escort troops, among which, 45 people (70.3%) were justified as biased constitution, while 19 were normal constitution (29.7%). The top three biased constitution in bad sleeping were:qi deficiency, phlegm-dampness and dampness-heat. PSQI factors such as sleep disorder, daytime dysfunction and total score had positive correlation with qi deficiency, yang deficiency, yin deficiency, dampness-heat and blood stasis, and negative correlation with normal constitution. Conclusion Sleep condition of escort troops has correlation with TCM constitution, which indicates that sleep status could be improved by regulating TCM constitution.