Traditional Chinese medicine formulas alleviated acute pancreatitis via improvement of microcirculation: A systematic review and meta-analysis

Abstract

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.

Keywords: Rhei Radix et Rhizoma; activating blood flow; acute pancreatitis; meta-analysis; microcirculatory disturbance; network pharmacology.

Fig. 1

PRISMA flow diagram of study selection and identification.

Fig. 2

Risk of bias summary (A) and bias graph (B).

Fig. 3

Forest plot following meta-analysis of the APACHE II score in Acute pancreatitis (AP) patients after treating with TCM formulas for activating blood flow.

Fig. 4

Meta-analysis of the effectiveness rate in AP patients after treating with TCM formulas for activating blood flow. Forest plot following meta-analysis of the effectiveness after using the formulas for activating blood flow (A). Sensitive analysis results of the formulas for activating blood flow in effectiveness (B). Funnel plot for publication bias (C). Begg’s funnel plot analysis for potential publication bias (D). Egger’s funnel plot analysis for revealing potential publication bias (E).

Fig. 5

Forest plot following meta-analysis of the changes for AP patients in microcirculation indicators including D-D, D-dimer (A), PAF, platelet-activating factor (B), FIB, fibrinogen (C), ET, endothelin (D), TXA2, thromboxane A2, NO (E), nitric oxide (F), and PGI2, prostaglandin I2 (G) after treating with TCM formulas for activating blood flow.

Fig. 6

Meta-analysis of IL-6 in AP patients with TCM formulas for activating blood flow. Forest plot following meta-analysis of IL-6 after using TCM formulas for activating blood flow (A). Sensitive analysis results of TCM formulas for activating blood flow in IL-6 (B). Funnel plot for publication bias (C). Begg’s funnel plot analysis for testing potential publication bias (D). Egger’s funnel plot analysis for revealing potential publication bias (E).

Fig. 7

Results of the medication rule analysis for the included 51 studies. (A) Bar chart showing the frequency and percentage of the 70 Chinese herbal medicines belonging to the included studies. (B) The association rule diagram about drug combinations for the 26 high-frequency Chinese herbal medicines. (C) Network contribution map showing potential six core Chinese herbal medicines in TCM formulas for activating blood flow of the 51 studies.

Fig. 8

Network pharmacology prediction of the six core Chinese herbal medicines for AP. The “herb-component-target” network showing targets of bioactive ingredients which belong to the six Chinese herbal medicines (A). Proportional Venn diagram showing the intersection of targets for AP and the six core Chinese herbal medicines (B). The result of PPI analysis for potential targets of the six herbs and AP (C). Highly relevant results of GO analysis for treating AP items (D).Results of the KEGG enrichment analysis revealing five signaling pathways highly relevant to the microcirculation of the six Chinese herbal medicines (E).