Network analysis of pharmacological mechanism of Angelica volatile oil in the treatment of hypertension
Hypertension is a common multiple disease characterized by elevated systemic arterial pressure, which is caused by the interaction of multiple genetic, environmental, and other risk factors. Theory and clinical practice have shown that hypertension can be included in the diagnosis and treatment of diseases such as “headache”, “dizziness”, and “liver wind” in traditional Chinese medicine. Traditional Chinese medicine plays an important role in reducing blood pressure, protecting target organs, and improving the quality of life of patients with hypertension, thanks to its advantages of holistic treatment and consideration of symptoms.

Danggui is a widely used traditional Chinese medicine in clinical practice, with a sweet and mild taste and a warm nature. It is said to have “nine out of ten formulas”. Research has shown that Angelica sinensis contains various chemical components such as volatile oils, polysaccharides, water-soluble substances, fats, and vitamins. The volatile oil in Angelica sinensis is the main active ingredient that has a spasmolytic effect on blood vessels, among which Artemisia annua internal fat is the most active ingredient. However, the pharmacological substances and pathways of action of Angelica sinensis volatile oil with antihypertensive effects are still unclear. At present, the use of network pharmacology to explore the mechanism of drug action is mature and successful. Therefore, network pharmacology methods were adopted to explore the main antihypertensive active substances and target pathways of Danggui volatile oil, providing theoretical basis for clinical use

Hypertension is one of the important factors leading to cardiovascular and cerebrovascular diseases, often causing complications in the heart, brain, and kidneys. The mechanism of inducing blood pressure elevation is relatively complex, and studies have shown that the volatile oil of Angelica sinensis plays a certain role in the prevention and treatment of hypertension. Mainly by inhibiting vascular inflammatory response, regulating the expression of miRNAs related to insulin signaling pathway and vascular endothelial growth factor (VEGF) signaling pathway; Significantly reducing the systolic blood pressure of SHRs and improving the morphology of myocardial tissue have therapeutic effects on hypertension, and the volatile oil of Angelica sinensis also has a certain protective effect on vascular endothelium.

This article uses molecular docking technology to dock the screened core active ingredients of Angelica sinensis volatile oil with key targets, and the docking results show stable docking. Among them, (E) -3-butylidene-4,5-dihydroisobenzofuran-1 (3H) – one has the highest content and can exert a hypotensive effect by reducing oxidative stress damage, anti apoptosis, clearing oxygen free radicals in the body, and alleviating brain cell damage. In addition, this study showed that tetrasiloxane, decamethyl – (decamethyltetrasiloxane), 1,4-benzenediol, 2,3,5-trimethyl – (trimethylhydroquinone), butanoic acid, 4-methoxy -, methyl ester and other components also play a role in lowering blood pressure, suggesting that these components may be new components of Angelica volatile oil for treating hypertension.

PPI network analysis revealed that AKT1, VEGFA, MAPK3, ALB, SRC, and other key targets of Angelica sinensis essential oil for lowering blood pressure. AKT1 is a serine (threonine) kinase that plays an important role in cellular metabolism, survival, cycle regulation, and transcriptional regulation. Miao et al. found in their study on hypertensive myocardial fibrosis that the expression and activation of AKT1 can promote Ange Ⅱ – induced myocardial fibrosis, suggesting that AKT1 plays a role in hypertensive myocardial fibrosis. Vascular endothelial growth factor A (VEGFA) is a potent and specific mitotic agent for endothelial cells, which binds to its receptor to promote endothelial cell division and proliferation, and increase microvascular permeability. Wang et al.’s in vivo experiments showed that vascular VEGF can stimulate the occurrence and growth of blood vessels. It was found that the volatile oil of Angelica sinensis can reduce the level of VEGF in serum, indicating that its antihypertensive effect is related to the level of VEGF in serum. Urinary ALB is closely related to the progression of hypertensive kidney damage. Li’s research has shown that urinary Alb levels can help evaluate early kidney damage in hypertensive patients; There are also studies indicating that changes in UmAlb/Ucr in urine occur earlier than changes in Scr and BUN in serum, thus accurately and sensitively reflecting early hypertensive kidney damage. SRC tyrosine protein kinase is a non receptor oncogene tyrosine kinase. Zeng et al. argue that SRC affects blood pressure through different signaling pathways and has a bidirectional regulatory effect on blood pressure.

In order to analyze the signaling pathways and biological processes involved in the therapeutic targets of Angelica sinensis essential oil for lowering blood pressure, GO functional enrichment and KEGG signaling pathway analysis were conducted on target genes. GO functional enrichment revealed that the biological processes of Angelica sinensis essential oil for treating hypertension include vascular processes in the circulatory system, diameter regulation, vascular size regulation, vascular diameter regulation, blood pressure regulation, negative regulation of vascular diameter, vascular constriction, blood circulation regulation, response to oxygen content, and second messenger mediated signal transduction. It can be found that these biological processes play an important role in the process of lowering blood pressure. KEGG pathway is enriched into many pathways, such as nerve active ligand receptor interaction pathway, cGMP PKG signaling pathway, calcium signaling pathway, AGE-RAGE signaling pathway in diabetes complications, HIF-1 signaling pathway, etc. The neuroactive ligand receptor interaction pathway is the collection of all receptors and ligands related to intracellular and extracellular signaling pathways on the plasma membrane, regulating physiological rhythms, endocrine, emotional, learning, memory, etc. Endocrine disorders are a common cause of hypertension; In addition, negative emotions can directly or indirectly affect hypertension. According to reports, the cGMP PKG signaling pathway can regulate the contraction and relaxation of vascular smooth muscle cells in most tissues, and has anti hypertensive effects. Anti cardiac hypertrophy, anti atherosclerosis, anti vascular injury/restenosis. In addition, the calcium ion signaling pathway controls various processes such as metabolism, secretion, smooth muscle contraction, and proliferation to regulate blood pressure, suggesting that the volatile oil of Angelica sinensis may exert its pharmacological effects by regulating smooth muscle contraction. Renal damage is very likely to occur in hypertensive patients with diabetes. Research shows that AGE can activate the NF – κ B pathway in the kidney through RAGE, and inhibiting NF – κ B can reduce blood pressure and partially reduce myocardial hypertrophy. It is suggested that the essential oil of Angelica sinensis may play a therapeutic role in hypertension with diabetes complications by regulating AGE-RAGE signal pathway. There are studies showing that the HIF-1-mediated signaling pathway may participate in blood pressure regulation by regulating renal medullary function and water salt electrolyte balance.

In summary, this article systematically studied the components and targets of Angelica sinensis essential oil using network pharmacology methods. Using Rstudio software and R programming language, enrichment analysis was conducted at three levels: biological process, cellular component, and molecular function. KEGG enrichment analysis was also performed. Finally, molecular docking and other methods were used to reveal its pharmacological mechanism of synergistic blood pressure reduction through multiple components, targets, and pathways.