Metabolomics and Network Pharmacology-Based Investigation into the Mechanisms Underlying the Therapeutic Effect of a New Chinese Traditional Medicine (Cui Nai Ling) on Bromocriptine-Induced Hypogalactia

Xianglong Meng; Chenzi Lyu; Junnan Ma; Xiaoyan Zhang; Cong Hu; Xiaojuan Su; Chenxu Ning; Wenbin Xie; Shuosheng Zhang

doi:10.1155/2021/8857449

Metabolomics and Network Pharmacology-Based Investigation into the Mechanisms Underlying the Therapeutic Effect of a New Chinese Traditional Medicine (Cui Nai Ling) on Bromocriptine-Induced Hypogalactia

Evid Based Complement Alternat Med. 2021 Jun 16:2021:8857449. doi: 10.1155/2021/8857449. eCollection 2021.

Authors

Xianglong Meng¹, Chenzi Lyu¹, Junnan Ma², Xiaoyan Zhang¹, Cong Hu³, Xiaojuan Su¹, Chenxu Ning¹, Wenbin Xie¹, Shuosheng Zhang¹

Affiliations

¹ Experimental Teaching Center, College of Chinese Materia Medica and Food Engineering, Shanxi University of Chinese Medicine, Jinzhong 030619, China.
² Department of Formulaology, Institute of Integrative Medicine, Dalian Medical University, Dalian 116044, China.
³ School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang 330013, China.

Abstract

As a traditional veterinary medicine to promote lactation, Cui Nai Ling (CNL) can not only increase milk supply and promote health but also improve the overall physiological function and immunity of the animals. In order to further improve CNL's effect on lactation, we have previously made a new CNL (NCNL) by adding Tetrapanacis Medulla and replacing Vaccariae Semen with fried Vaccariae Semen in CNL. We have demonstrated that the lactation-promoting effect of NCNL is better than that of CNL. However, the underlying mechanisms by which NCNL promotes lactation are unclear. In this study, we performed metabolomics, network pharmacology, and pharmacodynamic studies to explore the underlying mechanisms by which NCNL promotes lactation in rats with bromocriptine-induced hypogalactia. The results showed that NCNL significantly improved the loss of appetite in female adult rats and the weight loss of pups caused by the disorder of lactation. Biochemical analysis showed that NCNL could regulate the levels of PRL, T4, E2, Ca, UREA, GLU, ALT, AST, TCHO, and TG in serum. The pathological results showed that NCNL could promote lactation and increase the mammary gland index by improving breast acinar tissue morphology in rats with hypogalactia. Network pharmacology studies showed that NCNL promotes lactation through P13K-Akt, insulin resistance, and prolactin signaling pathways, among which the most frequently affected pathway was the P13K-Akt signaling pathway. Metabolomics studies showed that NCNL can significantly upregulate phenylalanine, tyrosine, and tryptophan biosynthesis and tyrosine metabolism pathways and downregulate cysteine and methionine metabolism pathways. NCNL can significantly increase the serum prolactin concentration, improve the glucose and lipid metabolism disorders, and regulate PI3K-Akt, insulin resistance, and prolactin pathways to affect the amino acids' metabolism in the mammary gland and ultimately exert its therapeutic effect on bromocriptine-induced postpartum hypogalactia. These findings revealed the effect and application value of NCNL on animals with postpartum hypogalactia.