Utilizing network pharmacology and experimental validation to investigate the underlying mechanism of phellodendrine on inflammation

Abstract

Background Phellodendrine, one of the characteristic and important active components of Cortex phellodendri, has been proven to show anti-inflammatory effects. However, the underlying mechanism of phellodendrine on inflammation remains largely unclear. Aim of the study In this study, network pharmacology and experimental validation were used to explore the underlying mechanism of phellodendrine on inflammation. Materials and Methods PubChem and SwissADME database were used to evaluate the drug-likeness and other characteristics of phellodendrine. The targets of phellodendrine for the treatment of inflammation were analyzed with multiple databases. Other extensive analyses including protein–protein interaction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were accomplished with the STRING database, Cytoscape software, and DAVID database. Moreover, the effect of phellodendrine on anti-inflammation was proven in RAW264.7. Results The network pharmacology results indicated that phellodendrine had drug potential. Phellodendrine acted directly on 12 targets, including PTGS1, PTGS2, HTR1A, and PIK3CA, and then regulated cAMP, estrogen, TNF, serotonergic synapse, and other signaling pathways to exert anti-inflammatory effects. The experimental results showed that phellodendrine reduced the levels of IL-6 compared with the LPS group in 24 h and changed the mRNA expression of PTGS1, PTGS2, HSP90ab1, AKT1, HTR1A, PI3CA, and F10. Conclusion Our research preliminarily uncovered the therapeutic mechanisms of phellodendrine on inflammation with multiple targets and pathways. Phellodendrine may be a potential treatment for inflammation-related diseases related to the cAMP and TNF signaling pathways.

Screening and Mechanism Study of Three Antagonistic Drugs, Oxysophoridine, Rutin, and Phellodendrine, against Zearalenone-Induced Reproductive Toxicity in Ovine Oocytes

“…Rutin promoted SOD2 , LC3 and BAX , and inhibited ULK2 , CAS3 and CAS9 , which is consistent with reports stating that it enhances the expression of antioxidant enzymes (e.g., SOD , CAT , GPX ) and inhibits the expression of apoptotic genes such as CAS3 , CAS7 , CAS9 , and P53 [ 26 , 30 ]. Phellodendrine promoted SOD1 , SOD2 , ATG3 and LC3 , and inhibited CAS3 and CAS9 , which is consistent with reports of it regulating the AMPK/mTOR pathway, reducing PTGS1 , PTGS2 , AKT phosphorylation, and NF-kB3, and having autophagy, anti-inflammatory, and antioxidant effects [ 31 , 32 , 33 ]. All three compounds promoted the expression of oxidative stress-related genes, reduced the accumulation of intracellular ROS, inhibited the expression of apoptotic genes, reduced mitochondrial damage, promoted polar body emissions, and inhibited cell apoptosis.…”

Proteomic Analysis of <i>Staphylococcus aureus</i> Treated with ShangKeHuangShui

“…Our previous studies have shown that SKHS contains various potential natural compounds, such as phellodendrine and obacunone, 17) that exhibit antibacterial or anti-inflammatory effects. 41,42) Molecular docking studies have elucidated that both phellodendrine and obacunone, components found in SKHS, exhibit robust binding affinity with ptpA. However, their binding affinity with arlR_1 appears to be relatively weak.…”

Systematic Screening of the Chemical Constituents of Lanqin Oral Liquid by Ultra-High-Performance Liquid Chromatography Combined with Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

“…Flavonoids, for example, baicalein, baicalin, wogonin, wogonoside, oroxylin A, and scutellarin, show anti-inflammatory activity [29,30], and baicalin also shows an antipyretic effect [31]. Alkaloids, for example, phellodendrine and berberine, show anti-inflammatory activity [32,33], and indigo and indirubin show antioxidant activity [34]. Terpenoids, for example, geniposidic acid, protects LPS-induced ALI through the TLR4/MyD88 signaling pathway [35], and geniposide, genipin, and crocin-I show anti-inflammatory activity [36][37][38].…”