Integrated Serum Pharmacochemistry, Metabolomics, and Network Pharmacology to Reveal the Material Basis and Mechanism of Danggui Shaoyao San in the Treatment of Primary Dysmenorrhea

Abstract

Danggui Shaoyao San (DSS), a well-known formula, has been successfully applied in treating primary dysmenorrhea (PD) in China. However, its material basis and mechanism are still unrevealed. This current research aims to reveal the material basis and mechanism of DSS in treating PD by an integrative approach of serum pharmacochemistry, metabolomics, and network pharmacology. The results showed that DSS markedly relieved the physiological and pathological symptoms of PD as confirmed by the improvement of writhing behavior, inhibition of uterine edema, callback of clinical biochemical indexes, and metabolic profiles. Furthermore, a metabolomic analysis demonstrated that the therapeutic effect of DSS was attributed to the modulation of arachidonic acid metabolism, pentose and glucuronate interconversions, and phenylalanine metabolism. Meanwhile, 23 blood ingredients were identified after the oral administration of DSS. By analyzing the correlation coefficient of the identified biomarkers and blood components, active compounds closely associated with core metabolic pathways were extracted. Taking these active compounds as a basis, network pharmacology prediction was executed. It was found that active components of DSS including alisol B,23-acetate, chlorogenic acid, levistilide A, cianidanol, senkyunolide A, atractylenolide II, and sedanolide, were germane to steroid hormone biosynthesis, arachidonic acid metabolism, sphingolipid signaling pathway, etc. Interestingly, PTGS2 and PTGS1 related to the arachidonic acid metabolism may be pivotal targets of DSS. The current study proved that the integration of serum pharmacochemistry, metabolomics, and network pharmacology, was a powerful approach to investigate the material basis and the molecular mechanisms of DSS, and provided a solid basis for DSS application.

Quality control for a traditional Chinese medicine, Millettia speciosa Champ, using ultra-high-performance liquid chromatography fingerprint, serum pharmacochemistry and network pharmacology

“…24 Several theories and strategies, including metabolomic, ngerprint, serum pharmacology/ pharmacochemical and network pharmacology, have also been developed, facilitating screening for potential active components and studying the cooperative functions of multiple TCM components. 17,25 Additionally, UPLC-MS can be used to assess small particles and high-pressure systems, allowing improved chromatographic resolution and more sensitive analysis in less time and at higher analytical speeds. Thus it has oen been applied for separating traces and complex compounds, becoming among the most efficient pharmaceutical analysis methods.…”

“…16 TCM serum pharmacochemistry can be used to screen for effective TCM substances from the compounds absorbed into blood after oral administration; this process can reveal drug absorption and metabolism, as well as drug interactions. 17 Network pharmacology is a prediction platform for constructing TCM component–disease–target networks based on big data, allowing investigators to comprehensively evaluate TCM effectiveness and mechanisms. 18…”

Combining Semi-targeted Metabolomics and Machine Learning to Identify Metabolic Alterations in Serum and Urine of Hospitalized Patients with COVID-19

“…However, recent studies have linked an increase in the pentose glucuronate interconversion with alterations in the microbiome of patients with mouth infections [31,32]. Further, pharmacological studies have reported that the effects of some anti-inflammatory agents are mediated through the modulation of this metabolic pathway in humans and experimental animals [33,34].…”

Lianweng Granules Alleviate Intestinal Barrier Damage via the IL-6/STAT3/PI3K/AKT Signaling Pathway with Dampness-Heat Syndrome Diarrhea

“…Currently, TCM has been widely used to treat gastrointestinal diseases [ 6 ], but the unknown material basis and pathways of action have seriously hindered its internationalization [ 7 ]. Serum pharmacochemistry aims to screen the efficacious substance matrix of TCM from the components absorbed into the blood after oral administration, reflecting the multi-component synergy for overall biological effects and has gained wide acceptance and application [ 8 ], but it does not involve the study of functional mechanisms, while network pharmacology can make up for the lack of serum pharmacochemistry by constructing complex biological networks in the organism and predicting the functional mechanisms during drug therapy [ 9 ].…”