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Frontiers in Medical Science Research, 2023, 5(4); doi: 10.25236/FMSR.2023.050401.

Exploring the Antibacterial and Antiviral Mechanisms of Baiyaozi Via Network Pharmacology

Author(s)

Xu Jia1, Danting Mao2, Xiaoyang Zhao2, Xingyue Fan1, Yaqin Hou1, Mei He1, Qian Zheng2, Yao Zhao1

Corresponding Author:
Qian Zheng
Affiliation(s)

1Department of Pharmacy, Affiliated Hospital of North Sichuan Medical College, Nanchong, China

2School of Basic Medical Sciences & Forensic Medicine, North Sichuan Medical College, Nanchong, China

Abstract

This paper aims to analyze the antibacterial and antiviral active components of Baiyaozi and predict its molecular mechanisms via network pharmacology. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and literature were used to screen active components of Baiyaozi (Radix Stephania cepharantha), and Pubchem and Swiss Target Prediction were used to collect the targets of the active components. The GeneCards database was used to search and screen the antibacterial and antiviral targets, intersecting with the practical components' targets to obtain the antibacterial and antiviral core targets of Baiyaozi. Then, the active ingredients and target genes were introduced into Cytoscape to construct the active component-target network regulation map of Baiyaozi. The STRING database was used for protein-protein interaction (PPI) network analysis, and the DAVID platform was used to conduct GO functional and KEGG pathway enrichment analyses of common targets. Eight active ingredients of Baiyaozi acted on 67 antibacterial targets and 130 antiviral targets. Cepharanthine, isocorydine, and berberine might be the main antibacterial and antiviral components of Baiyaozi. The GO function and KEGG pathway enrichment analyses of common targets suggested that the antibacterial and antiviral pathways of Baiyao might focus on apoptosis, autophagy, tumor necrosis factor signaling pathway, HIF-1 signaling pathway, and the PI3K-Akt pathway. Also, the comprehensive PPI, GO, and KEGG analysis indicated that HSP90AA1, SRC, and AKT1 might be the main targets. Conclusion: Baiyaozi has multi-component, multi-target, multi-pathway antibacterial and antiviral molecular mechanisms, providing a theoretical reference for further interpretation.

Keywords

Baiyaozi; Traditional Chinese medicine antibiotics; Antiviral; Immune regulation; Network pharmacology

Cite This Paper

Xu Jia, Danting Mao, Xiaoyang Zhao, Xingyue Fan, Yaqin Hou, Mei He, Qian Zheng, Yao Zhao. Exploring the Antibacterial and Antiviral Mechanisms of Baiyaozi Via Network Pharmacology. Frontiers in Medical Science Research (2023) Vol. 5, Issue 4: 1-11. https://doi.org/10.25236/FMSR.2023.050401.

References

[1] Li L (2013) Identifying the use of Baiyaozi, Hongyaozi and Huangyaozi. China Practical medicine 8: 232-233.

[2] Ma J (2014) <National Compendium of Chinese Herbal Medicines>Third Edition Published. Journal of Chinese Medicine Management 22: 594.

[3] Sun XQ, Tian J, Mei JH, Pu J, Gao JJ, et al. (2021) Exploration of the mechanism of Baiyaozi against lung cancer by network pharmacology-molecular docking. Northwest Journal of Pharmacy 36: 224-230.

[4] Fu WJ (2010) A combination of Baiyaozi and antibiotics for the treatment of infectious diseases.CN101716230A[P].

[5] González-Pleiter M, Cirés S, Hurtado-Gallego J, Leganés F, Fernández-Piñas F, et al. (2019) Chapter 20 - Ecotoxicological Assessment of Antibiotics in Freshwater Using Cyanobacteria. Cyanobacteria: 399-417.

[6] Hocquet DAB, Muller AAB, Bertrand XAB (2016) What happens in hospitals does not stay in hospitals: antibiotic-resistant bacteria in hospital wastewater systems (Review). Journal of Hospital Infection: 395-402.

[7] Knight GM, Budd EL, Whitney L, Thornley A, Al-Ghusein H, et al. (2012) Shift in dominant hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) clones over time. Journal of Antimicrobial Chemotherapy (JAC): 2514-2522.

[8] Cross EM, Adams FG, Waters JK, Aragão D, Eijkelkamp BA, Forwood JK (2021) Insights into Acinetobacter baumannii fatty acid synthesis 3-oxoacyl-ACP reductases. Scientific Reports 11: 1-16.

[9] Qiu DS, Song SQ, Deng QH, Fan HY (2020) Traditional Chinese medicine antibiotics — Andrographis paniculata. Life World: 33-35.

[10] Li S, Zhang ZA (2015) Houttuynia cordata:Natural herbal antibiotics. The World of Wellness: 43-44.

[11] Yuan DH (2013) Antibacterial and anti-inflammatory herbal medicine quick check:must know “Natural antibiotics”. Chinese science and technology information: 234.

[12] Ye H, Wei J, Tang K, Feuers R, Hong H (2016) Drug Repositioning Through Network Pharmacology. Curr Top Med Chem 16: 3646-3656.

[13] Liu Y, Tang Q, Rao Z, Fang Y, Jiang X, et al. (2021) Inhibition of herpes simplex virus 1 by cepharanthine via promoting cellular autophagy through up-regulation of STING/TBK1/P62 pathway. Antiviral Res 193: 105143.

[14] Lin LZ, Shieh HL, Angerhofer CK, Pezzuto JM, Cordell GA, et al. (1993) Cytotoxic and antimalarial bisbenzylisoquinoline alkaloids from Cyclea barbata. J Nat Prod 56: 22-29.

[15] Ru JL (2015) Construction and Application of a Systematic Pharmacology Database and Analytical Platform for Chinese Medicines: Northwest Agriculture and Forestry University. 52 p.

[16] Tattersall MH, Sodergren JE, Dengupta SK, Trites DH, Modest EJ, et al. (1975) Pharmacokinetics of actinoymcin D in patients with malignant melanoma. Clin Pharmacol Ther 17: 701-708.

[17] Chen KC, Sun MF, Yang SC, Chang SS, Chen HY, et al. (2011) Investigation into potent inflammation inhibitors from traditional Chinese medicine. Chem Biol Drug Des 78: 679-688.

[18] Ershun Z, Yunhe F, Zhengkai W, Yongguo C, Naisheng Z, et al. (2014) Cepharanthine attenuates lipopolysaccharide-induced mice mastitis by suppressing  the NF-kappaB signaling pathway. Inflammation 37: 331-337.

[19] Sakaguchi S, Furusawa S, Wu J, Nagata K (2007) Preventive effects of a biscoclaurine alkaloid, cepharanthine, on endotoxin or tumor necrosis factor-alpha-induced septic shock symptoms: involvement of from cell death in L929 cells and nitric oxide production in raw 264.7 cells. Int Immunopharmacol 7: 191-197.

[20] Liu Y, Chen L, Liu W, Li D, Zeng J, et al. (2021) Cepharanthine Suppresses Herpes Simplex Virus Type 1 Replication Through the Downregulation of the PI3K/Akt and p38 MAPK Signaling Pathways. Front Microbiol 12: 795756.

[21] Fan H, He ST, Han P, Hong B, Liu K, et al. (2022) Cepharanthine: A Promising Old Drug against SARS-CoV-2. Adv Biol (Weinh): e2200148.

[22] Shamma M, Guinaudeau H (1986) Aporphinoid alkaloids. Nat Prod Rep 3: 345-351.

[23] Song L, Guo Z (2014) In vitro studies on the antioxidant, antibacterial and antiproliferative effects of isocorinoline derivatives. The 12th National Symposium on Chemotherapeutic Pharmacology. Chengdu, Sichuan, China. pp. 6.

[24] Luo J, Wang N, Hua L, Deng F, Liu D, et al. (2022) The Anti-Sepsis Effect of Isocorydine Screened from Guizhou Ethnic Medicine is Closely Related to Upregulation of Vitamin D Receptor Expression and Inhibition of NFkappaB p65 Translocation into the Nucleus. J Inflamm Res 15: 5649-5664.

[25] Chin LW, Cheng YW, Lin SS, et al. (2010) Anti-herpes simplex virus effects of berberine from Coptidis rhizoma, a major component of a Chinese herbal medicine, Ching-Wei-San. Archives of virology 155:1933-1941.

[26] Wu J, Liu T, Rios Z, Mei Q, Lin X, et al. (2017) Heat Shock Proteins and Cancer. Trends Pharmacol Sci 38: 226-256.

[27] Feder ME, Hofmann GE (1999) Heat-shock proteins, molecular chaperones, and the stress response: evolutionary and ecological physiology. Annu Rev Physiol 61: 243-282.

[28] Kreusch A, Han S, Brinker A, Zhou V, Choi HS, et al. (2005) Crystal structures of human HSP90alpha-complexed with dihydroxyphenylpyrazoles. Bioorg Med Chem Lett 15: 1475-1478.

[29] Khandelwal A, Crowley VM, Blagg B (2016) Natural Product Inspired N-Terminal Hsp90 Inhibitors: From Bench to Bedside? Med Res Rev 36: 92-118.

[30] Xu Q, Tu J, Dou C, Zhang J, Yang L, et al. (2017) HSP90 promotes cell glycolysis, proliferation and inhibits apoptosis by regulating PKM2 abundance via Thr-328 phosphorylation in hepatocellular carcinoma. Mol Cancer 16: 178.

[31] Regan PL, Jacobs J, Wang G, Torres J, Edo R, et al. (2011) Hsp90 inhibition increases p53 expression and destabilizes MYCN and MYC in neuroblastoma. Int J Oncol 38: 105-112.

[32] Bohonowych JE, Hance MW, Nolan KD, Defee M, Parsons CH, et al. (2014) Extracellular Hsp90 mediates an NF-kappaB dependent inflammatory stromal program: implications for the prostate tumor microenvironment. Prostate 74: 395-407.

[33] Wang DF, Liu X, Xiao J (2018) The Function and Research Status of Src Protein Kinase in Diseases. Medicine and Philosophy (B) 39: 58-60.

[34] Sha S, Shi Y, Tang Y, Jia L, Han X, et al. (2021) Mycobacterium tuberculosis Rv1987 protein induces M2 polarization of macrophages  through activating the PI3K/Akt1/mTOR signaling pathway. Immunol Cell Biol 99: 570-585.

[35] Li CC, Yuan NN, Bai HF, Wang Y, Wei L, et al. (2021) Prediction of quality markers for Xiaoyan Tuire Granules based on HPLC fingerprint and network pharmacology. Chinese Traditional and Herbal Drugs 52: 3885-3895.

[36] Xu N, Du LH, Liu YH, Chen YC, Wang QM, et al. (2022) Exploration of antibacterial components and molecular mechanism of Lonicera japonica based on network pharmacology. Chemistry of Life 42: 797-807.

[37] Zhou J, Gao YY, Liu JL, Tang XY, Liang D, et al. (2021) Molecular mechanism of Chuanxinlian against bacteria based on network pharmacology. Pharmacy and Clinics of Chinese Materia Medica 12: 22-26.

[38] Li Q, Xie Y, Cui Z, Huang H, Yang C, et al. (2021) Activation of hypoxia-inducible factor 1 (Hif-1) enhanced bactericidal effects of macrophages to Mycobacterium tuberculosis. Tuberculosis (Edinb) 126: 102044.

[39] Kierbel A, Gassama-Diagne A, Mostov K, Engel JN (2005) The phosphoinositol-3-kinase-protein kinase B/Akt pathway is critical for Pseudomonas aeruginosa strain PAK internalization. Mol Biol Cell 16: 2577-2585.

[40] Hou YN, Zhu XY, Cheng GF (2000) The anti-inflammatory mechanism of baicalin. Journal of Pharmacy: 161-164.

[41] Zhang J, Yang ZC (2013) Role of the mTOR signaling pathway in viral infection. International Journal of Virology: 28-31.