Study on the mechanism of action of Tianma Chuanxiong medicine in the treatment of hypertension based on network pharmacology and molecular docking technology
In recent years, hypertension has become one of the diseases with a high global prevalence. If left uncontrolled for a long time, this disease can cause damage to many target organs, leading to a series of complications such as cardiovascular and renal diseases. The adult prevalence rate in our country has reached 46.4%. At present, relevant studies have shown that Tianma combined with Chuanxiong is commonly used for the treatment of hypertension and central nervous system diseases. Tianma is an essential medicine for treating dizziness and headaches caused by liver yang hyperactivity, as it can relieve wind, spasm, and calm liver yang. Modern pharmacological research has found that Tianma has pharmacological effects such as lowering blood pressure, anti myocardial ischemia, and improving blood supply to the brain. Chuanxiong promotes blood circulation, removes blood stasis, and eliminates external wind. Modern pharmacological research has found that Chuanxiong has pharmacological effects such as lowering blood pressure, improving endothelial function, and increasing coronary blood flow. The combination of two drugs not only soothes liver yang and promotes blood circulation to remove blood stasis, but also improves vascular endothelium, lowers blood pressure, and protects target organs from damage.

Due to the complex composition and wide-ranging effects of traditional Chinese medicine, as well as the complexity of its interactions with the body, it is difficult to explain the mechanism of action of Tianma Chuanxiong medicine in treating hypertension at the molecular level. However, network pharmacology based on drug disease target interactions can reveal the process of multi molecule drug synergy, which is similar to the principle of traditional Chinese medicine in diagnosing and treating diseases. This study uses network pharmacology and molecular docking methods to explore the targets and mechanisms of Tianma Chuanxiong medicine in the treatment of hypertension, providing more scientific basis for the subsequent treatment of hypertension and drug screening (clinical application).

At present, hypertension is one of the diseases with high incidence rate in China, and chronic long-term hypertension will cause a series of complications. In traditional Chinese medicine, it is classified as “dizziness” and “headache”. According to literature, the combination of Tianma and Chuanxiong is one of the top ten traditional Chinese medicines for treating hypertension. Tianma can relieve wind and spasms, while Chuanxiong can promote blood circulation, remove blood stasis, dispel wind and relieve pain. The combination of the two complements each other and is a classic drug pair for treating the central nervous system. It also frequently appears as an important drug pair in the treatment of hypertension.

This study identified 83 potential targets of Tianma Chuanxiong medicine for the treatment of hypertension, involving 71 active ingredients. Among them, Tianma extract, sitosterol, meta hydroxybenzoic acid, para hydroxybenzoic acid, and other active ingredients are the effective ingredients of Tianma in treating hypertension; Active ingredients such as ferulic acid, ligustilide, ligustilide, and sitosterol are effective components of Chuanxiong in treating hypertension. Analysis of medication patterns has also revealed that Tianma Chuanxiong is the main drug involved in treating hypertension; Studies have shown that Tianma Chuanxiong medicine can enhance the absorption of active ingredients such as ferulic acid in Chuanxiong and prolong their action time in terms of pharmacodynamics. Chuanxiong Chuanxiong lactone can increase the amount of Tianma active ingredients entering the brain, prolong their half-life, and thus improve their bioavailability.

The top targets in PPI analysis include tumor necrosis factor (TNF), prostaglandin G/H synthase 2 (PTGS2), human endothelin-1 (EDN1), recombinant human interleukin (IL1B), human leptin (LEP), insulin-like growth factor (IGF1), estrogen receptor gene (ESR1), dopamine receptor (DRD2), glucocorticoid receptor gene (NR3C1), peroxisome proliferator receptor gene (PPARG), apolipoprotein (APOE), etc. Among them, PTGS2 mainly causes inflammatory reactions; EDN1 is an endogenous important factor in regulating vascular constriction, playing a crucial role in maintaining vascular tone and cardiovascular homeostasis. In addition, androgen receptor (AR) and estrogen receptor (ER) α and β are expressed in important vascular tissues such as endothelial cells and vascular smooth muscle cells. AR acts as a mediator of androgens by binding to them. The estrogen receptor gene (ESR1) encodes ER α, which plays a more important cardioprotective role than ER β in vasodilation, promoting neovascularization, and cardiomyocyte apoptosis. PPARG is mainly expressed in adipose tissue and is closely related to insulin resistance, adipocyte differentiation, and body immunity. Therefore, it is speculated that Tianma Chuanxiong can play a role in regulating blood pressure levels through inflammation, insulin resistance, and blood lipid regulation.

In GO and KEGG analysis, 20 signaling pathways related to hypertension were screened from Tianma Chuanxiong, and the calcium signaling pathway may be closely related to it. Previous studies have shown that endothelial injury leads to the release of inflammatory mediators involved in the pathological process of hypertension, promoting and exacerbating the development of hypertension. Studies have shown that the inflammatory response mediated by the TLR4/NF – κ B pathway and immune system abnormalities are one of the pathological mechanisms that cause hypertension. TNF – α, also known as tumor necrosis factor, can bind to receptors and activate the TNF pathway to produce pro-inflammatory complexes. It can be seen that TNF – α can promote smooth muscle cell proliferation through multiple signaling pathways, leading to an increase in intracellular calcium concentration, vascular constriction, and blood pressure elevation. The calcium signaling pathway regulates the homeostasis of calcium ions through the calcium ion sensor STIM1, thereby regulating the stability of vascular cells. It also exerts various effects such as lipid regulation, anti-inflammatory, and improvement of endothelial function, thereby regulating the multifactorial and multi segmental processes involved in the occurrence and development of hypertension, and delaying pathological progression. This is consistent with the literature reports that Tianma Chuanxiong medicine inhibits the NF – κ B pathway by reducing the levels of inflammatory factors such as TNF, regulates endothelial cells, regulates intracellular calcium and sodium homeostasis, inhibits inflammatory reactions, and achieves blood pressure reduction. Modern pharmacological studies have shown that liver calming and yang lowering drugs can reduce blood pressure by improving endothelial function, regulating the RAAS system, and modulating the central sympathetic nervous system. Furthermore, from the perspective of molecular docking, the binding activity between proteins and ligands was explained. Based on literature, the top three key targets TNF, PTGS2, and END1 were selected, and three positive drugs related to proteins were combined. The ligand was selected to correspond to the corresponding compound. The results showed that in the intervention effect of Tianma Chuanxiong medicine on hypertension, the binding activity of its protein ligand was better than that of the positive drug; The gastrodin and m-hydroxybenzoic acid in Tianma have strong interaction with the target, while the ferulic acid and ligustilide in Chuanxiong have strong interaction with the target, indicating their synergistic effect, consistent with the literature. The corresponding targets are also significantly enriched in multiple signaling pathways such as calcium signaling pathway and TNF signaling pathway, fully demonstrating the synergistic effect of the drug on multiple pathways.

In summary, this study preliminarily explored the mechanism of action of Tianma Chuanxiong medicine in treating hypertension through the use of network pharmacology and molecular docking methods, revealing that Tianma Chuanxiong medicine may act on multiple targets such as TNF, PTGS2, END1 through potential active ingredients such as sitosterol, meta hydroxybenzoic acid, para hydroxybenzoic acid, gastrodin, ferulic acid, Chuanxiong indole, and ligustilide quinone; Through the calcium signaling pathway, cancer pathway, and TNF signaling pathway, the drug participates in intracellular calcium and sodium ion transport, vascular endothelial function, inflammatory response, glucose and lipid metabolism, and oxidative stress to exert antihypertensive effects. This proves that the drug has a synergistic effect on the treatment of hypertension through multi-component, multi pathway, and multi-target interactions, laying a theoretical foundation for further molecular biology verification of Tianma Chuanxiong medicine in the treatment of hypertension.