Exploring the Anti-inflammatory Effects of Protopine Total Alkaloids of Macleaya Cordata (Willd.) R. Br

Abstract

Macleaya cordata (Willd). R. Br. is a Chinese medicinal plant commonly used externally to treat inflammatory-related diseases such as arthritis, sores, and carbuncles. This study aimed to evaluate the anti-inflammatory activity of protopine total alkaloids (MPTAs) in Macleaya cordata (Willd.) R. Br. in vivo tests in rats with acute inflammation showed that MPTA (2.54 and 5.08 mg/kg) showed significant anti-inflammatory activity 6 h after carrageenan injection. Similarly, MPTA (3.67 and 7.33 mg/kg) showed significant anti-inflammatory activity in the mouse ear swelling test. In addition, the potential mechanisms of the anti-inflammatory effects of MPTA were explored based on network pharmacology and molecular docking. The two main active components of MPTA, protopine and allocryptopine, were identified, and the potential targets and signaling pathways of MPTA's anti-inflammatory effects were initially revealed using tools and databases (such as SwissTargetPrediction, GeneCards, and STRING) combined with molecular docking results. This study provides the basis for the application of MPTA as an anti-inflammatory agent.

Keywords: Macleaya cordata (Willd.) R. Br.; acute inflammation; anti-inflammatory; molecular docking; network pharmacology; protopine total alkaloids.

Figure 1

Chemical structure formulas of the main components. (A) Protopine (PRO); (B) allocryptopine (ALL).

Figure 2

Characteristic chromatograms of different batches of MPTA. The horizontal coordinate is the retention time. The vertical coordinate is the signal value.

Figure 3

Control characteristics spectrum of MPTA. Peak 1: protopine; Peak 2: allocryptopine; Peak 3: sanguinarine; and Peak 4: chelerythrine.

Figure 4

VENN diagram for MPTA and AI. Number of potential targets of MPTA against acute inflammation (AI). ALL, number of potential targets predicted for allocryptopine; PRO, number of potential targets predicted for protopine; AI, number of target genes for acute inflammation screened from the disease database.

Figure 5

(A) The “drug-component-disease-target” network diagram of MPTA's anti-inflammatory effects. Blue triangular nodes represent MPTA; pink circular nodes represent active compounds; dark yellow diamond nodes represent acute inflammation (AI); and bright green square nodes represent targets of MPTA for inflammation. (B) PPI diagram of MPTA's anti-inflammatory targets. The circular nodes represent the potential target proteins of MPTA's anti-inflammatory action; the larger the radius of the nodes, the greater their degree; the lines between the nodes represent the interaction between the targets; the darker the color of the lines, the stronger the interaction between the nodes. The five darkest nodes in the center are the core targets calculated by the Hubba algorithm.

Figure 6

(A) The “drug-signaling pathway-target” network of MPTA's anti-inflammatory effects. Yellow circular nodes represent active compounds; green diamond nodes represent core targets screened; and lavender triangular nodes represent signal transduction pathways. (B) GO enrichment analysis of MPTA. The three colors represent biological processes, cellular components, and molecular functions in that order. The horizontal coordinate represents the biological function to which the core target is enriched; the vertical coordinate represents the number of genes. (C) KEGG analysis of MPTA. The horizontal coordinate represents the number of genes involved in the enrichment; the vertical coordinate represents the KEGG pathway that was enriched.

Figure 7

Molecular docking results for MPTA. (A) Docking mode for ALL-MAPK3; (B) docking mode for PRO-MAPK3; (C) docking mode for ALL-SRC; (D) docking mode for PRO-SRC; (E) docking mode for ALL-MTOR; (F) docking mode for PRO-MTOR; (G) docking mode for ALL-PIK3CA; (H) docking mode for PRO-PIK3CA; (I) docking mode for ALL-PTGS2; and (J) docking mode for PRO-PTGS2.