RNA Sequencing Reveals the Regulation Mechanism of Yunnan Baiyao in Treating Skin Infection Caused by Staphylococcus aureus

Yunnan Baiyao is a well-known traditional Chinese medicine that can be formulated into a powder or capsule form. The mechanism by which it exerts its anti-inflammation effect, which is used in skin care products, needs to be further explored. In this study, we established the Staphylococcus aureus-induced mouse skin inflammatory model to investigate the effects of Yunnan Baiyao by the method of RNA-sequencing technology. The mice were randomly assigned to three groups, and those were control, model, and the Yunnan Baiyao-treated (YNtreated) group. Key genes and pathways were identified using bioinformatics analyses. In the study, we obtained 1,053 differentially expressed genes (DEGs) induced by Yunnan Baiyao. The 233 upregulated genes were enriched in 32 GO terms and 5 KEGG pathways, focused on the items, such as wound healing, cell metabolism, and proliferation, indicating the accelerating effects of Yunnan Baiyao on these aspects. The 820 downregulated genes were enriched mainly in the items, including the regulation of inflammation factor production, immune responses, and regulation of structure dermal components. Besides, Yunnan Baiyao reversed the expressions of 277 (201 decreased and 76 increased DEGs, respectively) induced by S. aureus. Ten key regulatory nodes (MMP2, PLK1, CCNB1, TLR4, CDK1, CCNA2, CDC25C, PDGFRA, MYOC, and KNG1) were identified by the construction of the protein interaction network, half of which were related to cell proliferation. VAV1 was another hub node that was affected by Yunnan Baiyao (Top 20). In the study, VAV1 and TLR4 can be considered key module genes in inflammation regulation. In conclusion, this study found that Yunnan Baiyao can significantly relieve inflammatory symptoms by regulating genes and pathways involved in the regulation of inflammation and immune response and also helped to deepen our understanding of the associated molecular mechanisms.

[1]  Meng Li,et al.  Gene Expression Profile Analyses of the Skin Response of Balb/c-Nu Mice Model Injected by Staphylococcus aureus , 2022, Clinical, cosmetic and investigational dermatology.

[2]  Hye-Jin Park,et al.  Cordyceps militaris as a Bio Functional Food Source: Pharmacological Potential, Anti-Inflammatory Actions and Related Molecular Mechanisms , 2022, Microorganisms.

[3]  Li-hui Gao,et al.  Yunnan Baiyao diminishes lipopolysaccharide-induced inflammation in osteoclasts. , 2020, Journal of food biochemistry.

[4]  Xi-jun Wang,et al.  [Study on absorbed components of Aconitum kusnezoffii under Yunnan Baiyao compatibility in effect of activating blood circulation and removing blood stasis]. , 2019, Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica.

[5]  Huimin Yan,et al.  Yunnan Baiyao reduces hospital-acquired pressure ulcers via suppressing virulence gene expression and biofilm formation of Staphylococcus aureus , 2019, International journal of medical sciences.

[6]  Xu Song,et al.  Tannic Acid Accelerates Cutaneous Wound Healing in Rats Via Activation of the ERK 1/2 Signaling Pathways. , 2019, Advances in wound care.

[7]  Zhou Zhou,et al.  Yunnan Baiyao Conditioned Medium Promotes the Odonto/Osteogenic Capacity of Stem Cells from Apical Papilla via Nuclear Factor Kappa B Signaling Pathway , 2019, BioMed research international.

[8]  L. Murphy,et al.  A prospective evaluation of oral Yunnan Baiyao therapy on thromboelastographic parameters in apparently healthy cats. , 2019, Journal of veterinary emergency and critical care.

[9]  L. Murphy,et al.  A prospective evaluation of oral Yunnan Baiyao therapy on thromboleastographic parameters in apparently healthy dogs , 2018, Journal of veterinary emergency and critical care.

[10]  J. R. Lee,et al.  Oral tolerance modulates the skin transcriptome in mice with induced atopic dermatitis , 2018, Allergy.

[11]  A. Irvine,et al.  Staphylococcus aureus and Atopic Dermatitis: A Complex and Evolving Relationship. , 2017, Trends in microbiology.

[12]  R. Geha,et al.  Staphylococcus aureus Epicutaneous Exposure Drives Skin Inflammation via IL-36-Mediated T Cell Responses. , 2017, Cell host & microbe.

[13]  Ling Li,et al.  The anti-inflammatory effects of Yunnan Baiyao are involved in regulation of the phospholipase A2/arachidonic acid metabolites pathways in acute inflammation rat model , 2017, Molecular medicine reports.

[14]  S. Boysen,et al.  The effects of oral administration of Yunnan Baiyao on blood coagulation in beagle dogs as measured by kaolin-activated thromboelastography and buccal mucosal bleeding times. , 2017, Canadian journal of veterinary research = Revue canadienne de recherche veterinaire.

[15]  Peter W. Mathieson,et al.  RNA sequencing analysis of human podocytes reveals glucocorticoid regulated gene networks targeting non-immune pathways , 2016, Scientific Reports.

[16]  S. Kõks,et al.  Psoriasis-Specific RNA Isoforms Identified by RNA-Seq Analysis of 173,446 Transcripts , 2016, Front. Med..

[17]  M. Nasr-Esfahani,et al.  PPARγ ameliorated LPS induced inflammation of HEK cell line expressing both human Toll-like receptor 4 (TLR4) and MD2 , 2016, Cytotechnology.

[18]  Yi-Fan Hong,et al.  Lipoteichoic acid isolated from Lactobacillus plantarum down-regulates UV-induced MMP-1 expression and up-regulates type I procollagen through the inhibition of reactive oxygen species generation. , 2015, Molecular immunology.

[19]  S. Thomsen,et al.  Incidence rates of atopic dermatitis, asthma, and allergic rhinoconjunctivitis in Danish and Swedish children. , 2015, The Journal of allergy and clinical immunology.

[20]  Mayte Suárez-Fariñas,et al.  RNA sequencing atopic dermatitis transcriptome profiling provides insights into novel disease mechanisms with potential therapeutic implications. , 2015, The Journal of allergy and clinical immunology.

[21]  M. Wakelam,et al.  P-Rex and Vav Rac-GEFs in platelets control leukocyte recruitment to sites of inflammation. , 2015, Blood.

[22]  Kyung-Min Lim,et al.  Suppression of skin inflammation in keratinocytes and acute/chronic disease models by caffeic acid phenethyl ester , 2015, Archives of Dermatological Research.

[23]  B. Jung,et al.  Lactobacillus sakei lipoteichoic acid inhibits MMP-1 induced by UVA in normal dermal fibroblasts of human. , 2013, Journal of microbiology and biotechnology.

[24]  K. Takatsu,et al.  The TLR family protein RP105/MD-1 complex , 2013, Adipocyte.

[25]  Elspeth A. Bruford,et al.  Genenames.org: the HGNC resources in 2013 , 2012, Nucleic Acids Res..

[26]  H. Hua,et al.  Repurposing of Yunnan Baiyao as an Alternative Therapy for Minor Recurrent Aphthous Stomatitis , 2012, Evidence-based complementary and alternative medicine : eCAM.

[27]  G. Cheng,et al.  Neutrophil-derived IL-1β Is Sufficient for Abscess Formation in Immunity against Staphylococcus aureus in Mice , 2012, PLoS pathogens.

[28]  K. Kelly,et al.  Topical Yunnan Baiyao administration as an adjunctive therapy for bleeding complications in adolescents with advanced cancer , 2012, Supportive Care in Cancer.

[29]  A. Di Nardo,et al.  Commensal Bacteria Lipoteichoic Acid Increases Skin Mast Cell Antimicrobial Activity against Vaccinia Viruses , 2012, The Journal of Immunology.

[30]  Hui Dong,et al.  [Effect of Yunnan Baiyao capsules on the socket healing of impacted mandibular third molar extraction]. , 2012, Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology.

[31]  Guowang Xu,et al.  Therapeutic effect of Yunnan Baiyao on rheumatoid arthritis was partially due to regulating arachidonic acid metabolism in osteoblasts. , 2012, Journal of pharmaceutical and biomedical analysis.

[32]  M. Tang,et al.  Filaggrin mutations are associated with recurrent skin infection in Singaporean Chinese patients with atopic dermatitis , 2012, The British journal of dermatology.

[33]  Chen Zu-peng.  Effects of Yunnan Baiyao through inner layer of cerebral dura mater on cerebral perfusion and oxygen metabolism in rabbits with severe traumatic brain injury , 2012 .

[34]  Colin N. Dewey,et al.  RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome , 2011, BMC Bioinformatics.

[35]  C. Tsatsanis,et al.  Distinct Roles of TLR4 and CD14 in LPS-Induced Inflammatory Responses of Neonates , 2009, Pediatric Research.

[36]  S. Blystone,et al.  A Pyk2-Vav1 complex is recruited to beta3-adhesion sites to initiate Rho activation. , 2009, The Biochemical journal.

[37]  C. Liang,et al.  Effects of the preoperative administration of Yunnan Baiyao capsules on intraoperative blood loss in bimaxillary orthognathic surgery: a prospective, randomized, double-blind, placebo-controlled study. , 2009, International journal of oral and maxillofacial surgery.

[38]  Brad T. Sherman,et al.  Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists , 2008, Nucleic acids research.

[39]  Sandhya Rani,et al.  Human Protein Reference Database—2009 update , 2008, Nucleic Acids Res..

[40]  Brad T. Sherman,et al.  Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources , 2008, Nature Protocols.

[41]  Michael J. Lush,et al.  HCOP: a searchable database of human orthology predictions , 2006, Briefings Bioinform..

[42]  C. Caux,et al.  Human Langerhans Cells Express a Specific TLR Profile and Differentially Respond to Viruses and Gram-Positive Bacteria1 , 2006, The Journal of Immunology.

[43]  Sue Povey,et al.  HCOP: The HGNC comparison of orthology predictions search tool , 2005, Mammalian Genome.

[44]  S. Perkins,et al.  Staphylococcal lipoteichoic acid inhibits delayed-type hypersensitivity reactions via the platelet-activating factor receptor. , 2005, The Journal of clinical investigation.

[45]  Rajesh Balkrishnan,et al.  The Burden of Atopic Dermatitis: Impact on the Patient, Family, and Society , 2005, Pediatric dermatology.

[46]  G. J. Gendimenico,et al.  Effects of topical antiinflammatory agents on Freund's adjuvant-induced skin lesions in rats , 2005, Inflammation Research.

[47]  J. Penninger,et al.  The Hemopoietic Rho/Rac Guanine Nucleotide Exchange Factor Vav1 Regulates N-Formyl-Methionyl-Leucyl-Phenylalanine-Activated Neutrophil Functions 1 , 2003, The Journal of Immunology.

[48]  Hanno Steen,et al.  Development of human protein reference database as an initial platform for approaching systems biology in humans. , 2003, Genome research.

[49]  N. Hirokawa,et al.  All kinesin superfamily protein, KIF, genes in mouse and human , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[50]  J. Liu,et al.  [Determination of panaxadiol and panaxatriol in radix notoginseng and Yunnan baiyao by capillary supercritical fluid chromatography]. , 1991, Yao xue xue bao = Acta pharmaceutica Sinica.

[51]  T. Zhu.  [Progress in the pharmacological and clinical study of Yunnan baiyao]. , 1987, Zhong xi yi jie he za zhi = Chinese journal of modern developments in traditional medicine.