Utilizing network pharmacology and other tools to examine active components and mechanism of action of Magnolia officinalis rheum rhabarbarum decoction in treating Streptococcus pyogenes skin infections

Abstract

Infections caused by Streptococcus pyogenes and the growing threat of antibiotic resistance pose significant global health challenges. This study investigates the antibacterial properties of Magnolia officinalis Rheum rhabarbarum Decoction against Streptococcus pyogenes skin infections. By combining UHPLC-MS/MS, network pharmacology, and molecular docking techniques, we identified eight bioactive compounds in the formulation and explored their potential interactions with Streptococcus pyogenes-related targets. Our analysis revealed that compounds such as Sinensetin, Nobiletin, and (+)-Magnoflorine regulate immune pathways (IL-17, TNF), inhibit the production of inflammatory factors, and disrupt bacterial membranes and metabolic processes, achieving dual antibacterial and anti-inflammatory effects. In vitro experiments showed that the decoction exhibited a minimum inhibitory concentration (MIC) of 20 mg/mL against Streptococcus pyogenes, significantly reducing the secretion of pro-inflammatory factors such as IL-1α, IL-6, IL-36, and TNF-α. These results suggest that Magnolia officinalis Rheum rhabarbarum Decoction offers a promising multi-target strategy for treating drug-resistant Streptococcus pyogenes infections and may serve as a potential alternative to traditional antibiotics.

Keywords

Network pharmacology / Drug discovery / Molecular docking / Streptococcus pyogenes

References

[1] Alves-BarrocoC, Paquete-FerreiraJ, Santos-SilvaT, et al.. Singularities of pyogenic Streptococcal biofilms–from formation to health implication. Front Microbiol, 2020, 11584947.

[2] ArconJP, DefelipeLA, ModenuttiCP, et al.. Molecular dynamics in mixed solvents reveals protein–ligand interactions, improves docking, and allows accurate binding free energy predictions. J Chem Inf Model, 2017, 57: 846-863.

[3] BaeS, GuH, GwonMG, et al.. Therapeutic effect of bee venom and Melittin on skin infection caused by Streptococcus pyogenes. Toxins, 2022, 14663.

[4] BakerSJ, PayneDJ, RappuoliR, et al.. Technologies to address antimicrobial resistance. PNAS, 2018, 115: 12887-12895.

[5] BakerP, HuangC, RadiR, et al.. Skin barrier function: the interplay of physical, chemical, and Immunologic properties. Cells, 2023, 122745.

[6] CaesarLK, CechNB. Synergy and antagonism in natural product extracts: when 1 + 1 does not equal 2. Nat Prod Rep, 2019, 36: 869-888.

[7] CaiYS, ZuoXM, ZuoYY, et al.. Transcriptomic analysis reveals shared gene signatures and molecular mechanisms between obesity and periodontitis. Front Immunol, 2023, 141101854.

[8] Collaborators AR (2022) Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis.lancet. 399:629–655. https://doi.org/10.1016/S0140-6736(21)02724-0

[9] FerreiraJA, QueirozSCN. Multiresidue method for determination of pesticides in coconut (Cocos nucifera Linn.) endosperm by using GC–MS/MS and UHPLC–MS/MS analysis J. Food Compos Anal, 2021, 97103764.

[10] GaoZP, JiangSF, ZhongWM, et al.. Linalool controls the viability of Escherichia coli by regulating the synthesis and modification of lipopolysaccharide, the assembly of ribosome, and the expression of substrate transporting proteins. Food Res Int, 2023, 164112337.

[11] GeB, HuCJ, QianYM, et al.. Sinensetin interferes with Staphylococcus aureus infections by targeting staphylocoagulase and improves infection survival rates in mouse model of pneumonia. J Appl Microbiol, 2024, 135lxae235.

[12] GuoY, HouEH, WenTY, et al.. Development of membrane-active honokiol/magnolol amphiphiles as potent antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA). J Med Chem, 2021, 64: 12903-12916.

[13] GuoB, ZhuangTT, LiCC, et al.. MiRNA-132/212 encapsulated by adipose tissue-derived exosomes worsen atherosclerosis progression cardiovasc. Diabetol, 2024, 23331.

[14] HowdenBP, GiulieriSG, Wong Fok LungT, et al.. Staphylococcus aureus host interactions and adaptation. Nat Rev Microbiol, 2023, 21: 380-395.

[15] HuT, ZouTH, LeSY, et al.. Tanshinone IIA confers protection against myocardial ischemia/reperfusion injury by inhibiting ferroptosis and apoptosis via VDAC1. Int J Mol Med, 2023, 52109.

[16] HurstJR, ShannonBA, CraigHC, et al.. The Streptococcus pyogenes hyaluronic acid capsule promotes experimental nasal and skin infection by preventing neutrophil-mediated clearance. PLoS Pathog, 2022, 18e1011013.

[17] LiNS, ShanNY, LuLG, et al.. tRFtarget: a database for transfer RNA-derived fragment targets. Nucleic Acids Res, 2021, 49: D254-D260.

[18] LiPY, WenFZ, YanHJ, et al.. Antimicrobial activity of Emodin in combination with visible light against Escherichia coli and Staphylococcus aureus: applications for food safety technology. LWT, 2023, 181114750.

[19] LiuY, YangXC, GanJH, et al.. CB-Dock2: improved protein–ligand blind Docking by integrating cavity detection, Docking and homologous template fitting. Nucleic Acids Res, 2022, 50: W159-W164.

[20] MoosS, RegenT, WanK, et al.. IL-17 signaling in keratinocytes orchestrates the defense against Staphylococcus aureus skin infection. J Investig Dermatol Symp Proc, 2023, 143: 1257-1267. e10

[21] Müller-HeuptLK, VierengelN, GroßJ, et al.. Antimicrobial activity of Eucalyptus globulus, Azadirachta indica, glycyrrhiza glabra, rheum palmatum extracts and Rhein against Porphyromonas gingivalis. Antibiotics, 2022, 11186.

[22] NwaborOF, ChukamnerdA, TerbtothakunP, et al.. Synergistic effects of polymyxin and Vancomycin combinations on carbapenem-and polymyxin-resistant Klebsiella pneumoniae and their molecular characteristics. Microbiol Spectr, 2023, 11: e01199-e01123.

[23] PadilhaCS, Von Ah MoranoAE, KrügerK, et al.. The growing field of immunometabolism and exercise: key findings in the last 5 years. J Cell Physiol, 2022, 237: 4001-4020.

[24] ParkKH, MakkiHMM, KimSH, et al.. Narirutin ameliorates alcohol-induced liver injury by targeting MAPK14 in zebrafish larvae. Biomed Pharmacother, 2023, 166115350.

[25] PasparakisM, HaaseI, NestleFO. Mechanisms regulating skin immunity and inflammation. Nat Rev Immunol, 2014, 14: 289-301.

[26] PliszkoA. Typification of two natural hybrids in Rumex (Polygonaceae). Kew Bull, 2019, 7417.

[27] ReissZ, RobF, KolarM, et al.. Skin microbiota signature distinguishes IBD patients and reflects skin adverse events during anti-TNF therapy. Front Cell Infect Microbiol, 2023, 121064537.

[28] SigginsMK, LynskeyNN, LambLE, et al.. Extracellular bacterial lymphatic metastasis drives Streptococcus pyogenes systemic infection. Nat Commun, 2020, 114697.

[29] SongYL, ZhangXL, CaiMH, et al.. Active and passive immunizations with htsa, a Streptococcal Heme transporter protein, protect mice from subcutaneous group A Streptococcus infection. J Microbiol Immunol Infect, 2020, 53: 87-93.

[30] SpolnikG, WachP, RudzinskiKJ, et al.. Improved UHPLC-MS/MS methods for analysis of isoprene-derived organosulfates anal. Chem, 2018, 90: 3416-3423.

[31] SunJW, XieY, ChenZY, et al.. Antimicrobial activity and mechanism of Magnolia officinalis root extract against methicillin-resistant Staphylococcus aureus based on mannose transporter. Ied Crop Prod, 2023, 201116953.

[32] Toja-Camba FJ, Hermelo-Vidal G, Feitosa-Medeiros C et al (2024) Head-to-Head comparison of UHPLC-MS/MS and alinity C for plasma analysis of Risperidone and Paliperidone pharmaceuticals. 17:1446. https://doi.org/10.3390/ph17111446

[33] UrgesaG, LuLS, GaoJW, et al.. Natural sunlight-mediated Emodin photoinactivation of Aeromonas hydrophila. Int J Mol Sci, 2024, 255444.

[34] WangJC, MaCQ, LiM, et al.. Streptococcus pyogenes: pathogenesis and the current status of vaccines. Vaccines, 2023, 111510.

[35] WuJS, ZhangFQ, LiZZ, et al.. Integration strategy of network Pharmacology in traditional Chinese medicine: a narrative review. J Tradit Chin Med, 2022, 42479.

[36] YangF, XueYJ, WangFL, et al.. Sustained release of magnesium and zinc ions synergistically accelerates wound. Healing Bioact Mater, 2023, 2688.

[37] Zhang H, Xiao X, Wang LP et al (2024) Human adipose and umbilical cord mesenchymal stem cell-derived extracellular vesicles mitigate Photoaging via TIMP1/Notch1 signal transduct target ther. 9:294. https://doi.org/10.1038/s41392-024-01993-z

[38] ZhengQ, LiS, LiXJY, et al.. Advances in the study of emodin: an update on Pharmacological properties and mechanistic basis. Chin Med, 2021, 16: 1-24.

[39] ZhengSQ, DengRR, HuangGJ, et al.. Effects of Honokiol combined with Resveratrol on bacteria responsible for oral Malodor and their biofilm. J Oral Microbiol, 2024, 162361402.

[40] ZhouW, HuZN, WuXW, et al.. Elucidation of the underlying mechanism of Hua-ban Decoction in alleviating acute lung injury by an integrative approach of network Pharmacology and experimental verification. Mol Immunol, 2023, 156: 85-97.

[41] ZhuZP, LingXY, WangGJ, et al.. G-CSFR-induced leukocyte transendothelial migration during the inflammatory response is regulated by the ICAM1-PKCa axis: based on multiomics integration analysis. Cell Biol Toxicol, 2024, 40: 1-22.

[42] ZouZS, SinghP, PinknerJS, et al.. Dihydrothiazolo ring-fused 2-pyridone antimicrobial compounds treat Streptococcus pyogenes skin and soft tissue infection. Sci Adv, 2024, 10eadn7979.

Funding

National Natural Science Foundation of China(82302535)

Natural Science Foundation of Heilongjiang Province(LH2023H008)

RIGHTS & PERMISSIONS

The Author(s)