Deciphering the mechanisms of Yinlan Tiaozhi capsule in treating hyperlipidemia by combining network pharmacology, molecular docking and experimental verification

Abstract

Yinlan Tiaozhi capsule (YLTZC) has been widely used to treat hyperlipidemia (HLP). However, its material basis and underlying pharmacological effects remain unclean. The current study aimed to explore the mechanisms involved in the treatment of YLTZC on HLP based on network pharmacology, molecular docking, and experimental verification. Firstly, UPLC-Q-TOF–MS/MS was used to comprehensively analyze and identify the chemical constituents in YLTZC. A total of 66 compounds, mainly including flavonoids, saponins, coumarins, lactones, organic acids, and limonin were characterized and classified. Simultaneously, the mass fragmentation pattern of different types of representative compounds was further explored. By network pharmacology analysis, naringenin and ferulic acid may be the core constituents. The 52 potential targets of YLTZC, including ALB, IL-6, TNF, and VEGFA, were considered potential therapeutic targets. Molecular docking results showed that the core active constituents of YLTZC (naringenin and ferulic acid) have a strong affinity with the core targets of HLP. Lastly, animal experiments confirmed that naringenin and ferulic acid significantly upregulated the mRNA expression of ALB and downregulated the mRNA expression of IL-6, TNF, and VEGFA. In sum, the constituents of YLTZC, such as naringenin and ferulic acid, might treat HLP by regulating the mechanism of angiogenesis and inhibiting inflammatory responses. Furthermore, our data fills the gap in the material basis of YLTZC.

Metabolomics analysis delineates the therapeutic effects of Yinlan Tiaozhi capsule on triton WR-1339 -induced hyperlipidemia in mice

“…Hyperlipidemia is characterized by abnormal lipid levels in the blood and constitutes a potentially harmful disease leading to CVDs with high mortality ( Ge et al, 2022 ). Previous studies found that YL may treat hyperlipidemia by modulating angiogenesis and suppressing inflammatory responses ( Chen et al, 2019 ; Xiao et al, 2023a ). Therefore, we investigated the hypolipidemic effects of YL in hyperlipidemia mice to understand whether the YL could reverse triton WR-1339-induced dyslipidemia and metabolic abnormalities and exert anti-inflammatory and angiogenic effects, as well as to observe the changes of metabolites in mice to illuminate the underlying mechanism of hyperlipidemia alleviation.…”

“…Combined with the group’s previous research and clinical trials ( Chen et al, 2019 ; Li et al, 2019 ; Li et al, 2020 ; Xiao et al, 2023a ), the animal experimental process is shown in Figure 1 , and the experimental program is specified as follows: The 24 male KM mice were raised in a barrier system under standard room temperature 24°C ± 2°C with the humidity of 70% ± 5%. The mice were subjected to 12 h light/dark cycle conditions and fed with normal food and water.…”

“…Yinlan Tiaozhi capsule (YL) is a formulated traditional Chinese medicine (TCM) comprising Citri Grandis Exocarpium, Ginkgo Folium, Gynostemma pentaphyllum, and propolis. It has been clinically used for the treatment of hyperlipidemia and is presently in the phase II clinical stage (2012L01011) ( Chen et al, 2019 ; Xiao et al, 2023a ; Xiao et al, 2023b ). Previously, the chemical constituents of YL were investigated using UPLC-Q-TOF-MS/MS, and an overall of 66 compounds were identified, which mainly included flavonoids, saponins, lactones, and organic acids.…”

“…Previously, the chemical constituents of YL were investigated using UPLC-Q-TOF-MS/MS, and an overall of 66 compounds were identified, which mainly included flavonoids, saponins, lactones, and organic acids. The primary components of YL, such as naringenin and ferulic acid, may treat hyperlipidemia by modulating angiogenic mechanisms and suppressing the inflammatory response, according to network pharmacology integrated with molecular docking and experimental verification ( Xiao et al, 2023a ). Meanwhile, preliminary data showed that the anti-hyperlipidemia actions of YL may be associated with the inhibition of PXR expression, promotion of bile acid excretion, TG hydrolysis, and RCT processes( Xiao et al, 2023a ).…”

“…The primary components of YL, such as naringenin and ferulic acid, may treat hyperlipidemia by modulating angiogenic mechanisms and suppressing the inflammatory response, according to network pharmacology integrated with molecular docking and experimental verification ( Xiao et al, 2023a ). Meanwhile, preliminary data showed that the anti-hyperlipidemia actions of YL may be associated with the inhibition of PXR expression, promotion of bile acid excretion, TG hydrolysis, and RCT processes( Xiao et al, 2023a ). YL contains multiple active ingredients and achieves its pharmacological effects through multiple pathways and targets.…”