Deciphering the combination mechanisms of Gualou–Xiebai herb pair against atherosclerosis by network pharmacology and HPLC-Q-TOF-MS technology

Abstract

Introduction: Gualou (Trichosanthes kirilowii Maxim)–Xiebai (Allium macrostemon Bunge) (GLXB) is a well-known herb pair against atherosclerosis (AS). However, the combination mechanisms of GLXB herb pair against AS remain unclear.Objective: To compare the difference in efficacy between GLXB herb pair and the single herbs and to explore the combination mechanisms of GLXB against AS in terms of compounds, targets, and signaling pathways.Methods: The combined effects of GLXB were evaluated in AS mice. The main compounds of GLXB were identified via quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS) and UNIFI informatics platforms. The united mechanisms of GLXB in terms of nodes, key interactions, and functional clusters were realized by network pharmacology. At last, the anti-atherosclerotic mechanisms of GLXB were validated using enzyme-linked immunosorbent assay (ELISA) and Western blot in AS mice.Results: The anti-atherosclerotic effects of the GLXB herb pair (6 g/kg) were more significant than those of Gualou (4 g/kg) and Xiebai (2 g/kg) alone. From the GLXB herb pair, 48 main components were identified. In addition, the GLXB herb pair handled more anti-atherosclerotic targets and more signaling pathways than Gualou or Xiebai alone, whereas 10 key targets of GLXB were found using topological analysis. Furthermore, the GLXB herb pair (6 g/kg) could suppress the inflammatory target levels of IL-6, IL-1β, TNF-α, ALOX5, PTGS2, and p-p38 in AS mice. GLXB herb pair (6 g/kg) could also ameliorate endothelial growth and function by regulating the levels of VEGFA, eNOS, p-AKT, VCAM-1, and ICAM-1 and reducing macrophage adhesion to vascular wall in AS mice. GLXB herb pair (6 g/kg) could improve the blood lipid levels in AS mice. In addition, the regulating effects of GLXB herb pair (6 g/kg) on levels of IL-1β, TNF-α, ALOX5, VEGFA, eNOS, VCAM-1, ICAM-1, and blood lipids were more significant than those of Gualou (4 g/kg) or Xiebai alone (2 g/kg).Conclusion: The combination mechanisms of the GLXB herb pair were elucidated in terms of components, targets, and signaling pathways, which may be related to suppressing inflammation, regulating vascular endothelial growth/function, and improving blood lipid levels.

Potential Effects of Traditional Chinese Medicine in Anti-Aging and Aging-Related Diseases: Current Evidence and Perspectives

“… 42 In atherosclerotic mice, TCM can suppress the inflammatory response, ameliorate endothelial growth/function and improve blood lipid levels, leading the effect of anti-atherosclerosis. 43 Similarly, berberine (BBR) in Coptis chinensis and other Berberis plants has been shown to attenuate trimethylamine/trimethylamine-N-oxide production and mitigate atherosclerotic lesion areas in mice via manipulation of the gut microbiome. 44 Dehydrocorydaline, an alkaloidal compound isolated from Corydalis yanhusuo , inhibits macrophage inflammation by targeting macrophage p65- and ERK1/2-mediated pathways to ameliorate atherosclerosis in mice.…”

Deciphering the toxicity-effect relationship and action patterns of traditional Chinese medicines from a smart data perspective: a comprehensive review

“…This technique analyzes the multi-level and multi-faceted biological network relationships between “drug-target-disease” to predict the possible mechanism of action of drugs and provide important references for the discovery of pharmacological effect and mechanisms. Network analysis is widely used in botanical drug for target prediction and drug discovery in various diseases, including COVID-19 ( Sun et al, 2023a ; Jiang et al, 2023 ), cardiovascular diseases ( Liu et al, 2022 ), diabetes ( Sun et al, 2023b ), and cancers ( Chen and Han, 2022 ; Iksen et al, 2023 ). Although network analysis has redefined the application of Chinese medicine in the diagnosis and treatment of diseases, it has several limitations.…”

Leaf Extract of Perilla frutescens (L.) Britt Promotes Adipocyte Browning via the p38 MAPK Pathway and PI3K-AKT Pathway

“…As a result, it poses a challenge to systemically investigate the reaction ingredients of the PF extract on vital molecules to promote browning. Since the traditional approaches are limited, a novel systemic approach, network pharmacology, which was established based on the theory of Shao Li published in 2013, was employed in the present study [ 14 ]. Network pharmacology, as a in silico technique, focuses on the synergy of multicomponent and multitarget systems, which is very suitable for plant extract study.…”