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image of Yangweishu Granules Prevent Stress Gastric Ulcer by Inhibition of TLR4/MyD88/IKB-α Signaling Pathway

Abstract

Introduction

This study aimed to investigate the therapeutic effect and mechanism of Yangweishu granules (YWS) for stress gastric ulcer (SGU).

Methods

The rat SGU model was established using the water immersion restraint stress method (WIRS). The therapeutic effect of YWS was evaluated by observing the histological changes of the stomach tissue, the levels of inflammatory factors, and oxidative stress. Meanwhile, the potential core targets and signaling pathways of YWS in anti-SGU action were analyzed using network pharmacology methods, and the related pathways were experimentally verified.

Results

YWS decreased the expressions of TNF-α, IL-1β, IL-6, and MDA in serum, and increased the levels of IL-4, IL-10, SOD, and GSH-PX. Network pharmacology analysis suggested that YWS may act on the targets of TLR4, AKT1, IL-10, TNF-α, IL-1β, and TP53 through the toll-like receptor pathway to treat SGU. RT-PCR, immunohistochemical, and Western blot results showed that YWS significantly inhibited the TLR4/MyD88/IKB-α pathway. Molecular docking results showed that the main active component of YWS could bind tightly to the TLR4 protein.

Discussion

This study established an animal model of SGU and preliminarily investigated the therapeutic effects and mechanism of YWS. To more comprehensively evaluate its application value in the treatment of peptic ulcers, subsequent studies should construct various types of ulcer models, further systematically assess the efficacy of YWS, and deeply explore its potential mechanism.

Conclusion

YWS could alleviate WIRS-induced SGU in rats, and its potential mechanism was found to involve the inhibition of the TLR4/MyD88/ IKB-α signaling pathway.

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2026-01-09
2026-01-29
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References

  1. Işık M. Özbayer C. Dönmez D.B. Erol K. Çolak E. Üstüner M.C. Değirmenci İ. Dose‐dependent protective effects of Lactobacillus rhamnosus GG against stress‐induced ulcer. J. Sci. Food Agric. 2024 104 13 8109 8119 10.1002/jsfa.13641 38856115
    [Google Scholar]
  2. Alamri Z.Z. Apigenin attenuates indomethacin-induced gastric ulcer in rats: Emphasis on antioxidant, anti-inflammatory, anti-apoptotic, and TGF-β1 enhancing activities. Naunyn Schmiedebergs Arch. Pharmacol. 2024 397 11 8803 8814 10.1007/s00210‑024‑03200‑w 38842560
    [Google Scholar]
  3. Guo Y. Wu Y. Huang T. Huang D. Zeng Q. Wang Z. Hu Y. Liang P. Chen H. Zheng Z. Liang T. Zhai D. Jiang C. Liu L. Zhu H. Liu Q. Licorice flavonoid ameliorates ethanol-induced gastric ulcer in rats by suppressing apoptosis via PI3K/AKT signaling pathway. J. Ethnopharmacol. 2024 325 117739 10.1016/j.jep.2024.117739 38301986
    [Google Scholar]
  4. Meng X. Liu J. Kang J. Wang M. Guan Z. Tian D. Chen X. Lamivudine protects mice from gastric ulcer by activating PGK1 to suppress ferroptosis. Biochem. Pharmacol. 2024 227 116440 10.1016/j.bcp.2024.116440 39029631
    [Google Scholar]
  5. Li L. Zang H. Jiang Y. Zhang Y. Mu S. Cao, J Acupuncture at Back Shu and Front Mu acupoints prevents gastric ulcer by regulating the TLR4/MyD88/NF κB signaling pathway. Evid. Based Complement. Alternat. Med. 2021 2021 8214052 10.1155/2021/8214052
    [Google Scholar]
  6. Li W.S. Lin S.C. Chu C.H. Chang Y.K. Zhang X. Lin C.C. Tung Y.T. The gastroprotective effect of naringenin against ethanol-induced gastric ulcers in mice through inhibiting oxidative and inflammatory responses. Int. J. Mol. Sci. 2021 22 21 11985 10.3390/ijms222111985 34769415
    [Google Scholar]
  7. Gong H. Zhao N. Zhu C. Luo L. Liu S. Treatment of gastric ulcer, traditional Chinese medicine may be a better choice. J. Ethnopharmacol. 2024 324 117793 10.1016/j.jep.2024.117793 38278376
    [Google Scholar]
  8. Ma C. Zhang L. Huang Q. Deng Q. Huang F. Xu J. Canolol alleviates ethanol-induced gastric ulcer by inhibiting p38 MAPK/NF-κB/NLRP3 pathway. J. Agric. Food Chem. 2025 73 15 9103 9111 10.1021/acs.jafc.5c00621 40179001
    [Google Scholar]
  9. Mukherjee S. Karmakar S. Babu S.P.S. TLR2 and TLR4 mediated host immune responses in major infectious diseases: A review. Braz. J. Infect. Dis. 2016 20 2 193 204 10.1016/j.bjid.2015.10.011 26775799
    [Google Scholar]
  10. Mukherjee S. Bayry J. The Yin and Yang of TLR4 in COVID-19. Cytokine Growth Factor Rev. 2025 82 70 85 10.1016/j.cytogfr.2024.10.001 39490235
    [Google Scholar]
  11. Al Asmari A. Al Shahrani H. Al Masri N. Al Faraidi A. Elfaki I. Arshaduddin M. Vanillin abrogates ethanol induced gastric injury in rats via modulation of gastric secretion, oxidative stress and inflammation. Toxicol. Rep. 2016 3 105 113 10.1016/j.toxrep.2015.11.001 28959528
    [Google Scholar]
  12. Krag M. Perner A. Wetterslev J. Wise M.P. Borthwick M. Bendel S. McArthur C. Cook D. Nielsen N. Pelosi P. Keus F. Guttormsen A.B. Moller A.D. Møller M.H. Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patients. Intensive Care Med. 2015 41 5 833 845 10.1007/s00134‑015‑3725‑1 25860444
    [Google Scholar]
  13. Chen L. He T. Wang R. Liu H. Wang X. Li H. Jing M. Zhou X. Wei S. Zou W. Zhao Y. Integrated approaches revealed the therapeutic mechanisms of zuojin pill against gastric mucosa injury in a rat model with chronic atrophic gastritis. Drug Des. Devel. Ther. 2024 18 1651 1672 10.2147/DDDT.S454758 38774485
    [Google Scholar]
  14. Chinzon D. Domingues G. Tosetto N. Perrotti M. Safety of long-term proton pump inhibitors: Facts and myths. Arq. Gastroenterol. 2022 59 2 219 225 10.1590/s0004‑2803.202202000‑40 35830032
    [Google Scholar]
  15. He M. Lim X.Y. Li J. Li L. Zhang T. Mechanisms of acupuncture at Zusanli (ST36) and its combinational acupoints for stress gastric ulcer based on the correlation between Zang-fu and acupoints. J. Integr. Med. 2025 23 1 1 11 10.1016/j.joim.2024.12.003 39736482
    [Google Scholar]
  16. Sun L. Luo F. Chen S. Zheng Q. Wang L. Hou Y. Wang K. Yao J. Yan X. Shi Y. Li Y. Acupuncture as an adjunctive therapy for gastric ulcer: A modified Delphi consensus study. Complement. Ther. Med. 2023 79 102997 10.1016/j.ctim.2023.102997 37865304
    [Google Scholar]
  17. Xia Q. Hu J. Jiao Z. Wang G. Sun J. Pang X. Ma Y. Huang Y. Liang X. Guo J. Peng C. Jin C. Jia X. Gui S. Exploring the mechanisms of Yang Wei Shu granule for the treatment of chronic atrophic gastritis using UPLC-QTOF-MS/MS, network pharmacology, and cell experimentation. J. Ethnopharmacol. 2025 341 119326 10.1016/j.jep.2025.119326 39798675
    [Google Scholar]
  18. Liu C.Y. Li Z. Cheng F.E. Nan Y. Li W.Q. Radix codonopsis: A review of anticancer pharmacological activities. Front. Pharmacol. 2025 15 1498707 10.3389/fphar.2024.1498707 39840099
    [Google Scholar]
  19. Li J. Wang T. Zhu Z. Yang F. Cao L. Gao J. Structure features and anti-gastric ulcer effects of inulin-type fructan cp-a from the roots of codonopsis pilosula (Franch.) nannf. Molecules 2017 22 12 2258 10.3390/molecules22122258 29258255
    [Google Scholar]
  20. Gunes-Bayir A. Guler E.M. Bilgin M.G. Ergun I.S. Kocyigit A. Dadak A. Anti-inflammatory and antioxidant effects of carvacrol on N-Methyl-N′-Nitro-N-nitrosoguanidine (MNNG) induced gastric carcinogenesis in wistar rats. Nutrients 2022 14 14 2848 10.3390/nu14142848 35889805
    [Google Scholar]
  21. He R.P. Jin Z. Ma R.Y. Hu F.D. Dai J.Y. Network pharmacology unveils spleen-fortifying effect of Codonopsis Radix on different gastric diseases based on theory of “same treatment for different diseases” in traditional Chinese medicine. Chin. Herb. Med. 2020 13 2 189 201 36117498
    [Google Scholar]
  22. Boezio B. Audouze K. Ducrot P. Taboureau O. Network‐based approaches in pharmacology. Mol. Inform. 2017 36 10 1700048 10.1002/minf.201700048 28692140
    [Google Scholar]
  23. Jiao X. Jin X. Ma Y. Yang Y. Li J. Liang L. Liu R. Li Z. A comprehensive application: Molecular docking and network pharmacology for the prediction of bioactive constituents and elucidation of mechanisms of action in component-based Chinese medicine. Comput. Biol. Chem. 2021 90 107402 10.1016/j.compbiolchem.2020.107402 33338839
    [Google Scholar]
  24. Zhao L. Zhang H. Li N. Chen J. Xu H. Wang Y. Liang Q. Network pharmacology, a promising approach to reveal the pharmacology mechanism of Chinese medicine formula. J. Ethnopharmacol. 2023 309 116306 10.1016/j.jep.2023.116306 36858276
    [Google Scholar]
  25. Zhao D.Q. Xue H. Sun H.J. Nervous mechanisms of restraint water-immersion stress-induced gastric mucosal lesion. World J. Gastroenterol. 2020 26 20 2533 2549 10.3748/wjg.v26.i20.2533 32523309
    [Google Scholar]
  26. Guth P.H. Aures D. Paulsen G. Topical aspirin plus HCl gastric lesions in the rat. Cytoprotective effect of prostaglandin, cimetidine, and probanthine. Gastroenterology 1979 76 1 88 93 10.1016/S0016‑5085(79)80133‑X 361495
    [Google Scholar]
  27. Chen G. Xie X. Peng F. Wang T. Chen J. Li G. Liu J. Peng C. Protective effect of the combination of essential oil from patchouli and tangerine peel against gastric ulcer in rats. J. Ethnopharmacol. 2022 282 114645 10.1016/j.jep.2021.114645 34530094
    [Google Scholar]
  28. Selim H.M. Negm W.A. Hawwal M.F. Hussein I.A. Elekhnawy E. Ulber R. Zayed A. Fucoidan mitigates gastric ulcer injury through managing inflammation, oxidative stress, and NLRP3-mediated pyroptosis. Int. Immunopharmacol. 2023 120 110335 10.1016/j.intimp.2023.110335 37201406
    [Google Scholar]
  29. Ding L. Sontz E.A. Saqui-Salces M. Merchant J.L. Interleukin-1β suppresses gastrin via Primary cilia and induces antral hyperplasia. Cell. Mol. Gastroenterol. Hepatol. 2021 11 5 1251 1266 10.1016/j.jcmgh.2020.12.008 33347972
    [Google Scholar]
  30. Zhang L. Zhou X. Zhang Q. Liu Y. Wang Y. Yan, C Wenweishu Capsule alleviates gastric mucosal lesion in rats with chronic gastritis by inhibiting NF κB pathway. Chin J. Cell. Mol. Immunol. 2020 36 4 297 303
    [Google Scholar]
  31. Huang Y.E. Chen S.Y. Li T.J. Tsai Y.S. Chen C.C. Yen G.C. Gastroprotective effects of Pediococcus acidilactici GKA4 and Lactobacillus brevis GKL93 against ethanol-induced gastric ulcers via regulation of the immune response and gut microbiota in mice. Food Funct. 2024 15 23 11491 11507 10.1039/D4FO04106B 39480654
    [Google Scholar]
  32. García-Rayado G. Navarro M. Lanas A. NSAID induced gastrointestinal damage and designing GI-sparing NSAIDs. Expert Rev. Clin. Pharmacol. 2018 11 10 1031 1043 10.1080/17512433.2018.1516143 30139288
    [Google Scholar]
  33. Nur Azlina M.F. Qodriyah H.M.S. Chua K.H. Kamisah Y. Comparison between tocotrienol and omeprazole on gastric growth factors in stress-exposed rats. World J. Gastroenterol. 2017 23 32 5887 5894 10.3748/wjg.v23.i32.5887 28932080
    [Google Scholar]
  34. Huang Y. Wang M.M. Yang Z.Z. Ren Y. Zhang W. Sun Z.R. Nie S.N. Pretreatment with intestinal trefoil factor alleviates stress-induced gastric mucosal damage via Akt signaling. World J. Gastroenterol. 2020 26 48 7619 7632 10.3748/wjg.v26.i48.7619 33505140
    [Google Scholar]
  35. Lu S. Wu D. Sun G. Geng F. Shen Y. Tan J. Sun X. Luo Y. Gastroprotective effects of Kangfuxin against water-immersion and restraint stress-induced gastric ulcer in rats: Roles of antioxidation, anti-inflammation, and pro-survival. Pharm. Biol. 2019 57 1 770 777 10.1080/13880209.2019.1682620 31696757
    [Google Scholar]
  36. Fu Y. Wu H. Cui H. Li Y. Li C. Gastroprotective and anti‐ulcer effects of oxymatrine against several gastric ulcer models in rats: Possible roles of antioxidant, antiinflammatory, and prosurvival mechanisms. Phytother. Res. 2018 32 10 2047 2058 10.1002/ptr.6148 30024074
    [Google Scholar]
  37. Liu X. Zhang J. Ge L. Progress in the prevention and treatment of stress ulcer with traditional Chinese medicine. Inner. Mong. J. Trad. Chin. Med. 2023 42 155 157
    [Google Scholar]
  38. Zheng J. Jiao Z. Yang X. Ruan Q. Huang Y. Jin C. Gui S. Xuan Z. Jia X. Wenweishu granule plays a protective role against stress-induced gastric ulcers by inhibiting the PI3K/AKT signaling pathway. Biol. Pharm. Bull. 2025 48 6 849 859 10.1248/bpb.b24‑00882 40533167
    [Google Scholar]
  39. Zhao Z. Liu T. Experimental study on traditional chinese medicine in the prevention and treatment of gastric injury after stress. Zhongguo Zhongyiyao Xiandai Yuancheng Jiaoyu 2022 20 201 202
    [Google Scholar]
  40. Kim M.H. Lee S.H. Hwang D.Y. Park Y.B. Ham S.H. Yang W.M. Protective effects of Banhasasim-tang, a herbal medicine, against cold restraint stress-induced gastric ulcers. Pak. J. Pharm. Sci. 2022 35 1 9 13 35221266
    [Google Scholar]
  41. Pan S. Yu X. Liu M. Liu J. Wang C. Zhang Y. Ge F. Fan A. Zhang D. Chen M. Banxia Xiexin decoction promotes gastric lymphatic pumping by regulating lymphatic smooth muscle cell contraction and energy metabolism in a stress-induced gastric ulceration rat model. J. Ethnopharmacol. 2024 328 118015 10.1016/j.jep.2024.118015 38499261
    [Google Scholar]
  42. Han L. Li T. Wang Y. Lai W. Zhou H. Niu Z. Weierning, a Chinese patent medicine, improves chronic atrophic gastritis with intestinal metaplasia. J. Ethnopharmacol. 2023 309 116345 10.1016/j.jep.2023.116345
    [Google Scholar]
  43. Zheng J. Jiao Z. Yang X. Ruan Q. Huang Y. Jin C. Gui S. Xuan Z. Jia X. Network pharmacology-based exploration of the mechanism of Wenweishu granule in treating chronic atrophic gastritis with spleen-stomach cold deficiency syndrome. J. Ethnopharmacol. 2025 345 119591 10.1016/j.jep.2025.119591 40054637
    [Google Scholar]
  44. North S.H. Shriver-Lake L.C. Taitt C.R. Ligler F.S. Rapid analytical methods for on-site triage for traumatic brain injury. Annu. Rev. Anal. Chem. 2012 5 1 35 56 10.1146/annurev‑anchem‑062011‑143105 22462400
    [Google Scholar]
  45. Tsikas D. Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples: Analytical and biological challenges. Anal. Biochem. 2017 524 13 30 10.1016/j.ab.2016.10.021 27789233
    [Google Scholar]
  46. Dey A. Cederbaum A.I. Alcohol and oxidative liver injury. Hepatology 2006 43 2 Suppl. 1 S63 S74 10.1002/hep.20957
    [Google Scholar]
  47. Reid M.B. Reactive oxygen species as agents of fatigue. Med. Sci. Sports Exerc. 2016 48 11 2239 2246 10.1249/MSS.0000000000001006 27285492
    [Google Scholar]
  48. Bhattacharyya A. Chattopadhyay R. Mitra S. Crowe S.E. Oxidative stress: An essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol. Rev. 2014 94 2 329 354 10.1152/physrev.00040.2012 24692350
    [Google Scholar]
  49. Brzozowski T. Kwiecień S. Konturek P.C. Konturek S.J. Mitis-Musiol M. Duda A. Bielański W. Hahn E.G. Comparison of nitric oxide-releasing NSAID and vitamin C with classic NSAID in healing of chronic gastric ulcers; involvement of reactive oxygen species. Med. Sci. Monit. 2001 7 4 592 599 11433182
    [Google Scholar]
  50. Balogun S.O. Damazo A.S. de Oliveira Martins D.T. Helicteres sacarolha A. St.- Hil. A. St.- Hil. Gastroprotective and possible mechanism of actions in experimental animals. J. Ethnopharmacol. 2015 166 176 184 10.1016/j.jep.2015.03.021 25792014
    [Google Scholar]
  51. Tong Y. Liu L. Wang R. Yang T. Wen J. Wei S. Jing M. Zou W. Zhao Y. Berberine attenuates chronic atrophic gastritis induced by MNNG and its potential mechanism. Front. Pharmacol. 2021 12 644638 10.3389/fphar.2021.644638 33841162
    [Google Scholar]
  52. Wang B. Zhou W. Zhang H. Wang W. Zhang B. Li S. Exploring the effect of Weifuchun capsule on the toll-like receptor pathway mediated HES6 and immune regulation against chronic atrophic gastritis. J. Ethnopharmacol. 2023 303 115930 10.1016/j.jep.2022.115930 36403744
    [Google Scholar]
  53. Salem N.A. Wahba M.A. Eisa W.H. El-Shamarka M. Khalil W. Silver oxide nanoparticles alleviate indomethacin-induced gastric injury: A novel antiulcer agent. Inflammopharmacology 2018 26 4 1025 1035 10.1007/s10787‑017‑0424‑2 29204780
    [Google Scholar]
  54. Minematsu T. Nakagami G. Yamamoto Y. Kanazawa T. Huang L. Koyanagi H. Sasaki S. Uchida G. Fujita H. Haga N. Yoshimura K. Nagase T. Sanada H. Wound blotting: A convenient biochemical assessment tool for protein components in exudate of chronic wounds. Wound Repair Regen. 2013 21 2 329 334 10.1111/wrr.12017 23438022
    [Google Scholar]
  55. Ermis A. Aritici Colak G. Acikel-Elmas M. Arbak S. Kolgazi M. Ferulic acid treats gastric ulcer via suppressing oxidative stress and inflammation. Life 2023 13 2 388 10.3390/life13020388 36836745
    [Google Scholar]
  56. Niu W. Pang Q. Lin T. Wang Z. Zhang J. Tai M. Zhang L. Zhang L. Gu M. Liu C. Qu K. A causal role of genetically elevated circulating interleukin-10 in the development of digestive cancers. Medicine 2016 95 7 2799 10.1097/MD.0000000000002799 26886630
    [Google Scholar]
  57. Ouyang W. O’Garra A. IL-10 family cytokines IL-10 and IL-22: From basic science to clinical translation. Immunity 2019 50 4 871 891 10.1016/j.immuni.2019.03.020 30995504
    [Google Scholar]
  58. Wu Y. Li Y. Jin X.M. Dai G.H. Chen X. Tong Y.L. Ren Z.M. Chen Y. Xue X.M. Wu R.Z. Effects of granule dendrobii on chronic atrophic gastritis induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats. World J. Gastroenterol. 2022 28 32 4668 4680 10.3748/wjg.v28.i32.4668 36157922
    [Google Scholar]
  59. Jiao W. Mi S. Sang Y. Jin Q. Chitrakar B. Wang X. Wang S. Integrated network pharmacology and cellular assay for the investigation of an anti-obesity effect of 6-shogaol. Food Chem. 2022 374 131755 10.1016/j.foodchem.2021.131755 34883426
    [Google Scholar]
  60. Xia Q.D. Xun Y. Lu J.L. Lu Y.C. Yang Y.Y. Zhou P. Hu J. Li C. Wang S.G. Network pharmacology and molecular docking analyses on Lianhua Qingwen capsule indicate Akt1 is a potential target to treat and prevent COVID‐19. Cell Prolif. 2020 53 12 12949 10.1111/cpr.12949 33140889
    [Google Scholar]
  61. Liu T. Wang J. Tong Y. Wu L. Xie Y. He P. Lin S. Hu X. Integrating network pharmacology and animal experimental validation to investigate the action mechanism of oleanolic acid in obesity. J. Transl. Med. 2024 22 1 86 10.1186/s12967‑023‑04840‑x 38246999
    [Google Scholar]
  62. Singh A. Vanga S.K. Orsat V. Raghavan V. Application of molecular dynamic simulation to study food proteins: A review. Crit. Rev. Food Sci. Nutr. 2018 58 16 2779 2789 10.1080/10408398.2017.1341864 28723250
    [Google Scholar]
  63. Płóciennikowska A. Hromada-Judycka A. Borzęcka K. Kwiatkowska K. Co-operation of TLR4 and raft proteins in LPS-induced pro-inflammatory signaling. Cell. Mol. Life Sci. 2015 72 3 557 581 10.1007/s00018‑014‑1762‑5 25332099
    [Google Scholar]
  64. Wang Y. Sadike D. Huang B. Li P. Wu Q. Jiang N. Fang Y. Song G. Xu L. Wang W. Xie M. Regulatory T cells alleviate myelin loss and cognitive dysfunction by regulating neuroinflammation and microglial pyroptosis via TLR4/MyD88/NF-κB pathway in LPC-induced demyelination. J. Neuroinflammation 2023 20 1 41 10.1186/s12974‑023‑02721‑0 36803990
    [Google Scholar]
  65. Chen C.Y. Kao C.L. Liu C.M. The cancer prevention, anti-inflammatory and anti-oxidation of bioactive phytochemicals targeting the TLR4 signaling pathway. Int. J. Mol. Sci. 2018 19 9 2729 10.3390/ijms19092729 30213077
    [Google Scholar]
  66. Gao Y. Fang X. Tong Y. Liu Y. Zhang B. TLR4-mediated MyD88-dependent signaling pathway is activated by cerebral ischemia-reperfusion in cortex in mice. Biomed. Pharmacother. 2009 63 6 442 450 10.1016/j.biopha.2008.06.028
    [Google Scholar]
  67. Bollenbach M. Salvat E. Daubeuf F. Wagner P. Yalcin I. Humo M. Letellier B. Becker L.J. Bihel F. Bourguignon J.J. Villa P. Obrecht A. Frossard N. Barrot M. Schmitt M. Phenylpyridine-2-ylguanidines and rigid mimetics as novel inhibitors of TNFα overproduction: Beneficial action in models of neuropathic pain and of acute lung inflammation. Eur. J. Med. Chem. 2018 147 163 182 10.1016/j.ejmech.2018.01.049 29432948
    [Google Scholar]
  68. Zhou L. Liu Z. Wang Z. Yu S. Long T. Zhou X. Bao Y. Astragalus polysaccharides exerts immunomodulatory effects via TLR4-mediated MyD88-dependent signaling pathway in vitro and in vivo. Sci. Rep. 2017 7 1 44822 10.1038/srep44822 28303957
    [Google Scholar]
  69. Liu M. Xie J. Sun Y. TLR4/MyD88/NF-κB-mediated inflammation contributes to cardiac dysfunction in rats of PTSD. Cell. Mol. Neurobiol. 2020 40 6 1029 1035 10.1007/s10571‑020‑00791‑9 31939007
    [Google Scholar]
  70. Zhang D. Xiang M. Jiang Y. Wu F. Chen H. Sun M. Zhang L. Du X. Chen L. The protective effect of polysaccharide SAFP from Sarcodon aspratus on water immersion and restraint stress-induced gastric ulcer and modulatory effects on gut microbiota dysbiosis. Foods 2022 11 11 1567 10.3390/foods11111567 35681318
    [Google Scholar]
  71. Wang Y. Liang K. Kong W. Intestinal trefoil factor 3 alleviates the intestinal barrier function through reducing the expression of tlr4 in rats with nonalcoholic steatohepatitis. Arch. Med. Res. 2019 50 1 2 9 10.1016/j.arcmed.2019.03.004 31101239
    [Google Scholar]
  72. Meng Y. Xu Y. Chang C. Qiu Z. Hu J. Wu Y. Zhang B. Zheng G. Extraction, characterization and anti-inflammatory activities of an inulin-type fructan from Codonopsis pilosula. Int. J. Biol. Macromol. 2020 163 1677 1686 10.1016/j.ijbiomac.2020.09.117 32979437
    [Google Scholar]
  73. Guan Y. Ruan J. Tan P. Qian S. Zhou S. Zhang A. Fu Y. Zhao S. Ran Y. Feng X. Wang Y. Wu X. Zhang B. Ji W. Wu L. Guo X. Hesperidin alleviates endothelial cell inflammation and apoptosis of Kawasaki disease through inhibiting the TLR4/IĸBα/NF-ĸB pathway. Chem. Biol. Interact. 2025 411 111445 10.1016/j.cbi.2025.111445 39987982
    [Google Scholar]
  74. Muhammad T. Ikram M. Ullah R. Rehman S. Kim M. Hesperetin, a citrus flavonoid, attenuates LPS-induced neuroinflammation, apoptosis and memory impairments by modulating TLR4/NF-κB signaling. Nutrients 2019 11 3 648 10.3390/nu11030648 30884890
    [Google Scholar]
  75. Tang S. Liu W. Zhao Q. Li K. Zhu J. Yao W. Gao X. Combination of polysaccharides from Astragalus membranaceus and Codonopsis pilosula ameliorated mice colitis and underlying mechanisms. J. Ethnopharmacol. 2021 264 113280 10.1016/j.jep.2020.113280 32822821
    [Google Scholar]
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