Study on the mechanism of Baihe Dihuang decoction in treating menopausal syndrome based on network pharmacology

Menopausal syndrome (MS) refers to a series of symptoms with autonomic nervous system dysfunction caused by decreased sex hormones before and after menopause. Baihe Dihuang (BHDH) decoction positively affects MS, but its mechanism remains unclear. This study aimed to reveal the underlying mechanism through network pharmacology. The components of the BHDH Decoction were found through HERB, while corresponding targets were obtained from the HERB, Drug Bank, NPASS, Targetnet, and Swisstarget databases. The MS targets were obtained from GeneCards and OMIM. STRING was used to construct the protein-protein interaction networks. OmicShare tools were used for Gene Ontology and Kyoto encyclopedia of genes and genomes analyses. Finally, Autodock Vina 1.1.2 software (https://vina.scripps.edu/downloads/) was used for molecular alignment to verify whether the main active ingredients and key targets had good binding activity. We screened out 27 active ingredients and 251 effective targets of BHDH Decoction, 3405 MS-related targets, and 133 intersection targets between BHDH Decoction and MS. Protein-protein interaction network identified tumor protein P53, Serine/threonine-protein kinase AKT, epidermal growth factor receptor, Estrogen Receptor 1, and jun proto-oncogene as critical targets. Gene ontology analysis showed that these targets were mainly involved in the cellular response to chemical stimulus, response to oxygen-containing compound, cellular response to endogenous stimulus, response to an organic substance, and response to chemical, etc. Kyoto encyclopedia of genes and genomes pathways were mainly enriched in endocrine resistance, pathways in cancer, and the ErbB signaling pathway, etc. Molecular docking results showed that emodin and stigmasterol are strongly associated with Serine/threonine-protein kinase AKT, Estrogen Receptor 1, epidermal growth factor receptor, sarcoma gene, and tumor protein P53. This study preliminarily revealed the multi-component, multi-target, and multi-channel mechanism of BHDH Decoction in treating MS. It provides a reference for in vitro and in vivo research and clinical application of BHDH Decoction in the treatment of MS.

[1]  Jinzheng Zhang,et al.  Analysis of edible characteristics, antioxidant capacities, and phenolic pigment monomers in Lilium bulbs native to China. , 2021, Food research international.

[2]  Niti Sharma,et al.  Phytosterols: Potential Metabolic Modulators in Neurodegenerative Diseases , 2021, International journal of molecular sciences.

[3]  Deyu Tang,et al.  Study on the Mechanism of Liuwei Dihuang Pills in Treating Parkinson's Disease Based on Network Pharmacology , 2021, BioMed research international.

[4]  Angeles C. Tecalco-Cruz,et al.  Estrogenic hormones receptors in Alzheimer’s disease , 2021, Molecular Biology Reports.

[5]  Pan-pan Yang,et al.  Comprehensive Analysis of Secondary Metabolites in the Extracts from Different Lily Bulbs and Their Antioxidant Ability , 2021, Antioxidants.

[6]  R. Terkeltaub,et al.  Consensus statement regarding the efficacy and safety of long-term low-dose colchicine in gout and cardiovascular disease. , 2021, The American journal of medicine.

[7]  Gopal L. Khatik,et al.  p53 regulated senescence mechanism and role of its modulators in age-related disorders. , 2021, Biochemical pharmacology.

[8]  L. Ou,et al.  Effects of Rehmannia glutinosa polysaccharides on bone tissue structure and skeletal muscle atrophy in rats with disuse , 2021, Acta cirurgica brasileira.

[9]  Cuicui Chen,et al.  Lily bulbs polyphenols extract ameliorates oxidative stress and lipid accumulation in vitro and in vivo. , 2021, Journal of the science of food and agriculture.

[10]  Jincheng Guo,et al.  HERB: a high-throughput experiment- and reference-guided database of traditional Chinese medicine , 2020, Nucleic Acids Res..

[11]  J. Lee,et al.  Selective activation of the estrogen receptor-β by the polysaccharide from Cynanchum wilfordii alleviates menopausal syndrome in ovariectomized mice. , 2020, International journal of biological macromolecules.

[12]  M. Evans,et al.  Efficacy of Labisia pumila and Eurycoma longifolia standardised extracts on hot flushes, quality of life, hormone and lipid profile of peri-menopausal and menopausal women: a randomised, placebo-controlled study , 2020, Food & nutrition research.

[13]  T. Jespersen,et al.  Inhibition of Adenosine Pathway Alters Atrial Electrophysiology and Prevents Atrial Fibrillation , 2020, Frontiers in Physiology.

[14]  Juan Li,et al.  The pharmacology, toxicology and therapeutic potential of anthraquinone derivative emodin. , 2020, Chinese journal of natural medicines.

[15]  G. Song,et al.  Stigmasterol Causes Ovarian Cancer Cell Apoptosis by Inducing Endoplasmic Reticulum and Mitochondrial Dysfunction , 2020, Pharmaceutics.

[16]  A. Hevener,et al.  The Impact of Skeletal Muscle ERα on Mitochondrial Function and Metabolic Health. , 2020, Endocrinology.

[17]  Xiaoping Zhou,et al.  Tumor‐associated macrophages secrete CC‐chemokine ligand 2 and induce tamoxifen resistance by activating PI3K/Akt/mTOR in breast cancer , 2019, Cancer science.

[18]  J. Lane,et al.  Evolutionarily conserved regulation of sleep by epidermal growth factor receptor signaling , 2019, Science Advances.

[19]  Matthew S. Tremblay,et al.  Neratinib protects pancreatic beta cells in diabetes , 2019, Nature Communications.

[20]  R. Sharma,et al.  Total Polysaccharides of Lily Bulb Ameliorate Menopause-Like Behavior in Ovariectomized Mice: Multiple Mechanisms Distinct from Estrogen Therapy , 2019, Oxidative medicine and cellular longevity.

[21]  W. D. van Marken Lichtenbelt,et al.  In vitro effects of sitosterol and sitostanol on mitochondrial respiration in human brown adipocytes, myotubes and hepatocytes , 2019, European Journal of Nutrition.

[22]  C. Drake,et al.  Improving Daytime Functioning, Work Performance, and Quality of Life in Postmenopausal Women With Insomnia: Comparing Cognitive Behavioral Therapy for Insomnia, Sleep Restriction Therapy, and Sleep Hygiene Education. , 2019, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[23]  Brian W Davis,et al.  Whole genome sequencing of canids reveals genomic regions under selection and variants influencing morphology , 2019, Nature Communications.

[24]  G. Gao,et al.  Regulation of Circadian Genes by the MAPK Pathway: Implications for Rapid Antidepressant Action , 2019, Neuroscience Bulletin.

[25]  G. Elkins,et al.  Complementary and Alternative Medicine for Menopause , 2019, Journal of evidence-based integrative medicine.

[26]  Chuandi Jin,et al.  Identification of gene biomarkers in patients with postmenopausal osteoporosis , 2018, Molecular medicine reports.

[27]  Guang-xia Xi,et al.  Estrogen receptor 1 gene polymorphisms are associated with metabolic syndrome in postmenopausal women in China , 2018, BMC Endocrine Disorders.

[28]  Li-li Li,et al.  Overexpression of SENP1 reduces the stemness capacity of osteosarcoma stem cells and increases their sensitivity to HSVtk/GCV , 2018, International journal of oncology.

[29]  Huiran Lin,et al.  ESR1 PvuII (rs2234693 T>C) polymorphism and cancer susceptibility: Evidence from 80 studies , 2018, Journal of Cancer.

[30]  Giancarlo Mauri,et al.  MTGO: PPI Network Analysis Via Topological and Functional Module Identification , 2018, Scientific Reports.

[31]  M. Shinohara,et al.  A novel polysaccharide derived from algae extract inhibits cancer progression via JNK, not via the p38 MAPK signaling pathway , 2018, International journal of oncology.

[32]  J. Kaprio,et al.  Menopause and adipose tissue: miR-19a-3p is sensitive to hormonal replacement , 2017, Oncotarget.

[33]  M. Dowsett,et al.  Discovery of naturally occurring ESR1 mutations in breast cancer cell lines modelling endocrine resistance , 2017, Nature Communications.

[34]  S. Sigismund,et al.  Emerging functions of the EGFR in cancer , 2017, Molecular oncology.

[35]  H. van Praag,et al.  JNK1 controls adult hippocampal neurogenesis and imposes cell-autonomous control of anxiety behaviour from the neurogenic niche , 2016, Molecular Psychiatry.

[36]  J. Bolton,et al.  Botanicals and Their Bioactive Phytochemicals for Women’s Health , 2016, Pharmacological Reviews.

[37]  L. Almagro,et al.  Bioactivity of Phytosterols and Their Production in Plant in Vitro Cultures. , 2016, Journal of agricultural and food chemistry.

[38]  P. Jagodziński,et al.  The MAOA, COMT, MTHFR and ESR1 gene polymorphisms are associated with the risk of depression in menopausal women. , 2016, Maturitas.

[39]  W. Mo,et al.  Rehmannia inhibits adipocyte differentiation and adipogenesis. , 2008, Biochemical and biophysical research communications.

[40]  Xueqi Fu,et al.  Black tea and D. candidum extracts play estrogenic activity via estrogen receptor α-dependent signaling pathway. , 2018, American journal of translational research.

[41]  Yuanyuan Wu,et al.  High-fat diet-induced obesity regulates MMP3 to modulate depot- and sex-dependent adipose expansion in C57BL/6J mice. , 2017, American journal of physiology. Endocrinology and metabolism.