Temporal metabolic trajectory analyzed by LC-MS/MS based targeted metabolomics in acute pancreatitis pathogenesis and Chaiqin Chengqi decoction therapy

Huang, Yan; Wen, Yongfu; Wang, Rui; Hu, Liqiang; Yang, Jian; Pu, Qianlun; Han, Chenxia; Cai, Wenhao; Peng, Yang; Wang, Yiqin; Jiang, Hongli; Hong, Jiwon; Phillips, Anthony R.J.; Fu, Xianghui; Huang, Wei; Xia, Qing; Du, Dan

doi:10.1016/j.phymed.2022.153996

Cited by 9 publications

(23 citation statements)

References 49 publications

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“…Regarding the dose of CQCQD, it has been demonstrated in our recently published study that the single clinically-equivalent dose of CQCQD (5.5 g/kg) 3 times is more effective than other doses ( Liang et al, 2021 ; Huang et al, 2022 ). Therefore, in the treatment group, obese mice were given oral gavage of CQCQD (5.5 g/kg) 3 times every 2 h, starting 2 h after the first EtOH injection.…”

Section: Methodsmentioning

confidence: 93%

Transcriptomics and Network Pharmacology Reveal the Protective Effect of Chaiqin Chengqi Decoction on Obesity-Related Alcohol-Induced Acute Pancreatitis via Oxidative Stress and PI3K/Akt Signaling Pathway

et al. 2022

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Obesity-related acute pancreatitis (AP) is characterized by increasing prevalence worldwide and worse clinical outcomes compared to AP of other etiologies. Chaiqin chengqi decoction (CQCQD), a Chinese herbal formula, has long been used for the clinical management of AP but its therapeutic actions and the underlying mechanisms have not been fully elucidated. This study has investigated the pharmacological mechanisms of CQCQD in a novel mouse model of obesity-related alcohol-induced AP (OA-AP). The mouse OA-AP model was induced by a high-fat diet for 12 weeks and subsequently two intraperitoneal injections of ethanol, CQCQD was administered 2 h after the first injection of ethanol. The severity of OA-AP was assessed and correlated with changes in transcriptomic profiles and network pharmacology in the pancreatic and adipose tissues, and further docking analysis modeled the interactions between compounds of CQCQD and their key targets. The results showed that CQCQD significantly reduced pancreatic necrosis, alleviated systemic inflammation, and decreased the parameters associated with multi-organ dysfunction. Transcriptomics and network pharmacology analysis, as well as further experimental validation, have shown that CQCQD induced Nrf2/HO-1 antioxidant protein response and decreased Akt phosphorylation in the pancreatic and adipose tissues. In vitro, CQCQD protected freshly isolated pancreatic acinar cells from H2O2-elicited oxidative stress and necrotic cell death. The docking results of AKT1 and the active compounds related to AKT1 in CQCQD showed high binding affinity. In conclusion, CQCQD ameliorates the severity of OA-AP by activating of the antioxidant protein response and down-regulating of the PI3K/Akt signaling pathway in the pancreas and visceral adipose tissue.

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Section: Methodsmentioning

confidence: 93%

Transcriptomics and Network Pharmacology Reveal the Protective Effect of Chaiqin Chengqi Decoction on Obesity-Related Alcohol-Induced Acute Pancreatitis via Oxidative Stress and PI3K/Akt Signaling Pathway

et al. 2022

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“…Over the past 30 years, the Chinese herbal formula CQCQD has been widely used as an adjunctive therapy of conventional comprehensive treatment for AP in our hospital. A plethora of basic research studies from our group have revealed that CQCQD reduced pro-inflammatory indices and improved pancreatic and multiple organ injuries in experimental AP models [23,[49][50][51][52][53]. However, high-quality evidence from clinical studies to demonstrate its efficacy in AP patients is still lacking.…”

Section: Discussionmentioning

confidence: 99%

AGI grade-guided chaiqin chengqi decoction treatment for predicted moderately severe and severe acute pancreatitis (CAP trial): study protocol of a randomised, double-blind, placebo-controlled, parallel-group, pragmatic clinical trial

Chen

Yang

Guo

et al. 2022

Trials

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Background Acute pancreatitis (AP) is a common digestive disease with increased incidence globally but without internationally licenced pharmacological therapy. Moderately severe and severe acute pancreatitis (MSAP/SAP) contributes predominately for its morbidities and mortality and has been managed in West China Hospital for decades using the traditional Chinese medicinal formula chaiqin chengqi decoction (CQCQD). The current study tests whether the early administration of CQCQD will result in improved clinical outcomes in predicted MSAP/SAP patients. Methods This is a single-centre, randomised, controlled, double-blind pragmatic clinical trial. AP patients aged 18–75 admitted within 72 h of onset will be assessed at admission for enrolment. We excluded the predicted mild acute pancreatitis (Harmless Acute Pancreatitis Score > 2 at admission) and severe organ failure (Sequential Organ Failure Assessment [SOFA] score of respiratory, cardiovascular, or renal systems > 3) at admission. Eligible patients will be randomly allocated on a 1:1 basis to CQCQD or placebo control administration based on conventional therapy. The administration of CQCQD and placebo is guided by the Acute Gastrointestinal Injury grade-based algorithm. The primary outcome measure will be the duration of respiratory failure (SOFA score of respiratory system ≥ 2) within 28 days after onset. Secondary outcome measures include occurrence of new-onset any organ failure (SOFA score of respiratory, cardiovascular, or renal system ≥ 2) and new-onset persistent organ failure (organ failure lasts > 48 h), dynamic surrogate biochemical markers and clinical severity scores, gut-centred treatment modalities, local complications status, intensive care need and duration, surgical interventions, mortality, and length of hospital stay. Follow-up will be scheduled on 6, 12, and 26 weeks after enrolment to assess AP recurrence, local complications, the requirement for surgical interventions, all-cause mortality, and patient-reported outcomes. Discussion The results of this study will provide high-quality evidence to appraise the efficacy of CQCQD for the early management of AP patients. Trial registration Chictr.org.cn Registry (ChiCTR2000034325). Registered on 2 July, 2020.

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“…Pancreatic tissue was fixed in 10% formalin, embedded in paraffin, sectioned into 2 μm, and used for hematoxylin and eosin (HE) staining. The pancreas histological damage scoring, serum amylase, and lipase were measured according to our previous study . HE and biochemical index were analyzed from seven mice per group.…”

Section: Methodsmentioning

confidence: 99%

“…HE and biochemical index were analyzed from seven mice per group. Statistical power was deemed to be sufficient based on our previous observations in the CER-AP mice model . All the statistical analyses were performed using GraphPad Prism 8.3.0.…”

Section: Methodsmentioning

confidence: 99%

Temporal Proteomic and Lipidomic Profiles of Cerulein-Induced Acute Pancreatitis Reveal Novel Insights for Metabolic Alterations in the Disease Pathogenesis

Wang

Tao

et al. 2023

ACS Omega

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The pathophysiological mechanisms of acute pancreatitis (AP) are complex and have remained a mystery to date, but metabolism is gradually recognized as an important driver of AP onset and development. We used a cerulein-induced AP mouse model to conduct liquid chromatography–mass spectrometry (LC–MS/MS)-based time-course proteomics and lipidomics in order to better understand the underlying metabolic alterations linked with AP. Results showed that a series of significant changes in proteins over time with a boost in expression were enriched in lipase activity, lipoprotein, and lipids absorption and transport regulation. Furthermore, 16 proteins associated with lipid metabolism and signaling pathways together with the whole lipid species changing profile led to the vital identification of changing law in glycerides, phosphoglycerides, and free fatty acids. In addition to lipid metabolism and regulation-associated proteins, several digestive enzymes and adaptive anti-trypsin, stress response, and energy metabolism-related proteins showed an increment in abundance. Notably, central carbon and branched chain amino acid metabolism were enhanced during 0–24 h from the first cerulein stimulation. Taken together, this integrated proteomics and lipidomics revealed a novel metabolic insight into metabolites transforming rules that might be relevant to their function and drug targets investigation. (Created with .)

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Temporal metabolic trajectory analyzed by LC-MS/MS based targeted metabolomics in acute pancreatitis pathogenesis and Chaiqin Chengqi decoction therapy

Cited by 9 publications

References 49 publications

Transcriptomics and Network Pharmacology Reveal the Protective Effect of Chaiqin Chengqi Decoction on Obesity-Related Alcohol-Induced Acute Pancreatitis via Oxidative Stress and PI3K/Akt Signaling Pathway

Transcriptomics and Network Pharmacology Reveal the Protective Effect of Chaiqin Chengqi Decoction on Obesity-Related Alcohol-Induced Acute Pancreatitis via Oxidative Stress and PI3K/Akt Signaling Pathway

AGI grade-guided chaiqin chengqi decoction treatment for predicted moderately severe and severe acute pancreatitis (CAP trial): study protocol of a randomised, double-blind, placebo-controlled, parallel-group, pragmatic clinical trial

Temporal Proteomic and Lipidomic Profiles of Cerulein-Induced Acute Pancreatitis Reveal Novel Insights for Metabolic Alterations in the Disease Pathogenesis

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