Research Advances and Prospects on Mechanism of Sinomenin on Histamine Release and the Binding to Histamine Receptors

• Published in: International journal of molecular sciences Vol. 20; no. 1; p. 70
• Main Authors: Zhang, Yu-Shi, Han, Jia-Yin, Iqbal, Omer, Liang, Ai-Hua
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24.12.2018; MDPI
• Subjects: Activation; adverse reaction mechanism; Analgesics; Animal models; Apoptosis; Binding; Biological activity; Breast cancer; Cardiac function; Cell proliferation; Cervical cancer; Chinese medicine; clinical application; Codeine; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; Cytokines; Dendritic cells; Dextran; Dextran sulfate; Gelatinase A; Hedgehog protein; Hematologic Diseases - etiology; Histamine receptors; Histamine Release; histamine/histamine receptor; Humans; Immune system; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - metabolism; Immunosuppressive Agents - therapeutic use; Inflammation; Inflammatory bowel diseases; Intestine; Kinases; Lung cancer; Lymphocytes; Lymphocytes B; Lymphocytes T; Macrophages; MAP kinase; Metabolites; Metastases; Metastasis; Molecular Docking Simulation; Molecular structure; Monocytes; Morphinans - chemistry; Morphinans - metabolism; Morphinans - therapeutic use; Morphine; Narcotics; Organic chemistry; pharmacological mechanism; Phenanthrene; Protein Binding; Receptors, Histamine - chemistry; Receptors, Histamine - metabolism; Review; Rheumatic Diseases - drug therapy; Signal transduction; sinomenine; Smooth muscle; Sodium salts; virtual molecular docking; China; virtual molecular docking; histamine/histamine receptor; clinical application; pharmacological mechanism; sinomenine; adverse reaction mechanism
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20010070

Sinomenine (SIN) is widely used in China to treat a variety of rheumatic diseases (RA), and has various pharmacological effects such as anti-inflammatory, analgesic, and anti-tumor effects. However, due to the histamine release characteristics of SIN, its adverse reactions such as allergic reactions, gastrointestinal reactions, and circulatory systemic reactions have been drawing increasing attention. We present here a systematic review of the chemical structure, pharmacological effects, clinical application, and adverse reactions of SIN, a detailed discussion on the relationship between histamine/histamine receptor and mechanism of action of SIN. In addition, we simulated the binding of SIN to four histamine receptors by using a virtual molecular docking method and found that the bonding intensity between SIN and receptors varied in the order shown as follows: H1R > H2R ~ H3R > H4R. The docking results suggested that SIN might exhibit dual regulatory effects in many processes such as cyclooxygenase-2 (COX-2) expression, NF-κB pathway activation, and degranulation of mast cells to release histamine, thereby exhibiting pro-inflammatory (adverse reactions)/anti-inflammatory effects. This study provides a theoretical basis for the clinical treatment of inflammations seen such as in RA using SIN, and also suggests that SIN has great potential in the field of cancer treatment and will have very important social and economic significance.