Combinatorial chemistry & high throughput screening · 2026
The Integration of Pharmacokinetics, Cardiac Tissue Distribution, Network Pharmacology, and Experimental Verification to Reveal the Bioactive Components and Pharmacological Mechanisms of Guanxinning Tablet Against Coronary Heart Disease.
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Li Jun, Wang Yingchao, Li Miaofu, Wang Mulan, Shen Peiqiang, Tao Yi, Wang Yule
Аннотация
INTRODUCTION: Coronary heart disease (CHD) is a leading cause of morbidity and mortality worldwide, yet therapeutic options remain limited. Guanxinning tablet (GXNT), a component-based Chinese medicine containing Danshen and Chuanxiong, has demonstrated clinical efficacy and safety for CHD patients with heart-blood stagnation syndrome. However, its bioactive constituents and underlying pharmacological mechanisms remain undefined. This study aimed to identify the bioactive components of GXNT and elucidate its anti-CHD mechanisms.
METHODS: The pharmacokinetics and cardiac distribution of five GXNT constituents were investigated using a validated ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Network pharmacology revealed pivotal targets and pathways against CHD, which were verified by molecular docking and in vitro experiments.
RESULTS: A validated UPLC-MS/MS method was developed to quantify danshensu, salvianolic acid B, protocatechuic acid, ferulic acid, and senkyunolide I in biological samples. These compounds showed promising in vivo bioactivity, marked by rapid absorption, high systemic exposure, and efficient cardiac distribution. The detailed network analyses linked GXNT's efficacy to inflammation-related pathways, identifying TLR4, NFKB1, TNF, IL6, IL1B, and AKT1 as hub targets. The docking results confirmed strong binding affinities between five compounds and these targets. Cell experiments demonstrated that GXNT and its bioactive components exerted cardioprotection by normalizing the overexpression of key inflammatory factors.
DISCUSSION: Firstly, the pharmacokinetic properties of GXNT's bioactive components require further investigation using a rodent disease model of CHD. Secondly, in vivo follow-up animal experiments are needed to validate the present findings further. Thirdly, beyond inflammation-related signaling pathways, the relationship between GXNT's anti-CHD action and other enriched pathways (e.g., the AGE-RAGE signaling pathway in diabetic complications, the HIF-1 signaling pathway, and the PI3K-Akt signaling pathway) warrants further exploration.
CONCLUSION: The favorable pharmacokinetics and cardiac distribution of five GXNT constituents underscored their bioactive potential. GXNT and its bioactive compounds exerted cardioprotective effects against CHD, partly by regulating TLR4/NF-κB-mediated inflammation-related pathways. These findings provide insights into the bioactive components and mechanisms of GXNT against CHD, supporting its further development and quality control.
METHODS: The pharmacokinetics and cardiac distribution of five GXNT constituents were investigated using a validated ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Network pharmacology revealed pivotal targets and pathways against CHD, which were verified by molecular docking and in vitro experiments.
RESULTS: A validated UPLC-MS/MS method was developed to quantify danshensu, salvianolic acid B, protocatechuic acid, ferulic acid, and senkyunolide I in biological samples. These compounds showed promising in vivo bioactivity, marked by rapid absorption, high systemic exposure, and efficient cardiac distribution. The detailed network analyses linked GXNT's efficacy to inflammation-related pathways, identifying TLR4, NFKB1, TNF, IL6, IL1B, and AKT1 as hub targets. The docking results confirmed strong binding affinities between five compounds and these targets. Cell experiments demonstrated that GXNT and its bioactive components exerted cardioprotection by normalizing the overexpression of key inflammatory factors.
DISCUSSION: Firstly, the pharmacokinetic properties of GXNT's bioactive components require further investigation using a rodent disease model of CHD. Secondly, in vivo follow-up animal experiments are needed to validate the present findings further. Thirdly, beyond inflammation-related signaling pathways, the relationship between GXNT's anti-CHD action and other enriched pathways (e.g., the AGE-RAGE signaling pathway in diabetic complications, the HIF-1 signaling pathway, and the PI3K-Akt signaling pathway) warrants further exploration.
CONCLUSION: The favorable pharmacokinetics and cardiac distribution of five GXNT constituents underscored their bioactive potential. GXNT and its bioactive compounds exerted cardioprotective effects against CHD, partly by regulating TLR4/NF-κB-mediated inflammation-related pathways. These findings provide insights into the bioactive components and mechanisms of GXNT against CHD, supporting its further development and quality control.