Comparative study on the pharmacodynamic difference of oral administration of Xiaojin Pills accompanied with Chinese Baijiu and water

Abstract

Ethnopharmacological relevanceXiaojin Pills is a classic prescription for the treatment of mammary glands hyperplasia with a history of nearly 300 years, and is also the first choice of Chinese patent medicine for the clinical treatment of mammary glands hyperplasia in contemporary traditional Chinese medicine clinic. Clinical and animal studies have shown that Xiaojin Pills has the effects of anti-mammary glands hyperplasia, promoting blood circulation, anti-inflammation and analgesia. However, its initial administration method was “taking orally after soaked with Chinese Baijiu”, the modern method was changed to “taking orally with water” in recent 20 years. Whether there is any difference in the efficacy of the two administration methods is still unknown. Aim of the studyTo reveal the difference in efficacy and metabolic mechanism of anti-mammary gland hyperplasia between the oral administration of Xiaojin Pills accompanied with Chinese Baijiu (XJP&B) and water (XJP&W). Materials and methodsCOX-2 inhibition rate test and anti-platelet aggregation activity test were used to investigate the efficacy difference between the 40 vol% Chinese Baijiu and water extracts of Xiaojin Pills on anti-inflammatory and blood-activating in vitro. Kunming male mice (20 ± 5 g) and SD female rats (200–220 g) were orally treated with XJP&B and XJP&W, respectively. Then the difference in anti-inflammatory and analgesic effects between XJP&B and XJP&W were evaluated via xylene-induced ear swelling test, formaldehyde-induced pain test, and acetic acid-induced writhing test in mice. Determination of nipple diameter, pathological examination of mammary gland tissue, determination of serum E2, P and FSH content and hemorheological parameters of rats with mammary gland hyperplasia were performed to explore the efficacy difference in anti-mammary gland hyperplasia between XJP&B and XJP&W. Metabolomics was used to study the difference of anti-mammary gland hyperplasia mechanism between XJP&B and XJP&W. ResultsThe results showed that the effect of XJP&B was superior to that of XJP&W in anti-platelet aggregation, inhibition of inflammation and pain, and anti-mammary gland hyperplasia. Interestingly, the advantages were more significant under low-dose condition. In addition, the mechanism of the two combinations against mammary gland hyperplasia was indeed different. Their common metabolic pathways include tryptophan metabolism and alanine, aspartic acid and glutamic acid metabolism. However, Chinese Baijiu and XJP&B also have additional regulatory effects on linoleic acid metabolic pathway. ConclusionIn brief, this research demonstrated that the efficacy of XJP&B was better than that of XJP&W in activating the blood, anti-inflammation, analgesia and anti-mammary gland hyperplasia, which means that XJP&B has synergistic and superior effects. The special dose-effect relationship under the condition of XJP&B was also found, laying the foundation for clinical treatment to reduce the dosage and shorten the medication cycle, which is beneficial to reduce the economic burden of patients.