Protective Effect and Mechanism of Boswellic Acid and Myrrha Sesquiterpenes with Different Proportions of Compatibility on Neuroinflammation by LPS-Induced BV2 Cells Combined with Network Pharmacology

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 21; p. 3946
• Main Authors: Miao, Xiao-Dong, Zheng, Li-Jie, Zhao, Zi-Zhang, Su, Shu-Lan, Zhu, Yue, Guo, Jian-Ming, Shang, Er-Xin, Qian, Da-Wei, Duan, Jin-Ao
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 31.10.2019; MDPI
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Alzheimer's disease; Animals; Anti-inflammatory agents; Biocompatibility; boswellic acid; bv2 cells; Cardiovascular system; Cell Line; Cell Shape - drug effects; Cell Survival - drug effects; Chinese medicine; Commiphora - chemistry; Correlation analysis; Cytotoxicity; different proportions compatibility; frankincense; Gene expression; Gene Expression Regulation - drug effects; Gene Ontology; IL-1β; Immune system; Inflammation; Inflammation - drug therapy; Inflammation - pathology; Interleukin 6; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; Interleukin-6 - genetics; Interleukin-6 - metabolism; Kinases; Lipopolysaccharides; Mice; Microglia - drug effects; Microglia - pathology; myrrha; myrrha sesquiterpenes; Nervous system; network pharmacology; neuroinflammation; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; NF-kappa B - metabolism; Nitric oxide; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; Nitric-oxide synthase; Pharmacology; Phosphors; Phosphorylation - drug effects; Protein expression; Proteins; Proto-Oncogene Proteins c-akt - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sesquiterpenes - pharmacology; Sesquiterpenes - therapeutic use; Signal transduction; TLR4 protein; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Triterpenes - pharmacology; Triterpenes - therapeutic use; Tumor necrosis factor-TNF; BV2 cells; network pharmacology; neuroinflammation; boswellic acid; frankincense; myrrha sesquiterpenes; different proportions compatibility; myrrha
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24213946

Frankincense and myrrha (FM), commonly used as a classical herbal pair, have a wide range of clinical applications and definite anti-inflammatory activity. However, anti-neuroinflammation effects and mechanisms are not clear. In this study, we adopted a lipopolysaccharide (LPS)-induced microglial (BV2) cell model and a network pharmacology method to reveal the anti-neuroinflammatory effects and mechanisms of boswellic acid (BA) and myrrha sesquiterpenes (MS) with different proportions of compatibility. The data showed that the different ratios of BA and MS had different degrees of inhibition of interleukin-1β (IL-1β), IL-6, and inducible nitric oxide synthase (iNOS) mRNA expression, down-regulated the phosphor-nuclear factor kappa B/nuclear factor kappa B (p-NF-ҡB)/(NF-ҡB), phosphorylated protein kinase b/protein kinase b (p-AKT/AKT), and Toll-like receptor 4 (TLR4) protein expression levels, and increased phospho-PI3 kinase (p-PI3K) protein expression levels. When the ratios of BA and MS were 10:1, 5:1, and 20:1, better effective efficacy was exhibited. According to the correlation analysis between the effect index and bioactive substances, it was suggested that 2-methoxy-5-acetoxy -fruranogermacr-1(10)-en-6-one (Compound 1), 3 -acetyloxylanosta-8,24-dien-21-oic acid (Compound 2), 11-keto-boswellic acid (Compound 3), and 3-acetyl-11-keto- -boswellic acid (Compound 4) made important contributions to the treatment of neuroinflammation. Furthermore, based on the network pharmacological analysis, it was found that these four active compounds acted on 31 targets related to neuroinflammation and were involved in 32 signaling pathways which mainly related to the immune system, cardiovascular system, and nervous system, suggesting that BA and MS could be used to treat neuroinflammation.