基于TLR2信号通路探究裂褶菌β-葡聚糖对口腔上皮细胞炎症的调控作用

doi:10.3969/j.issn.2097-2806.2026.10.009

Abstract

Abstract:

Schizophyllum commune β-glucan （Gioactive SPG-PF） is a natural microbial polysaccharide characterized by a β- （1→3） -glucan backbone with β- （1→6） -glucose side chains, known for its antioxidant and anti-inflammatory activities. However, its mechanism of action within the oral microenvironment remains unclear. This study aimed to investigate whether Gioactive SPG-PF can regulate inflammatory responses in oral epithelial cells via the TLR2 pathway, thereby providing a theoretical basis for its development as a novel oral soothing ingredient. An inflammatory model was established using TR146 cells stimulated with inactivated Fusobacterium nucleatum, and the anti-inflammatory effects of Gioactive SPG-PF was evaluated. The results show that Gioactive SPG-PF exhibits significant dose-dependent inhibition of IL-6 and IL-8 protein secretion, and downregulates the transcriptional expression of TLR2, IL6, and IL8 genes. Further molecular docking analysis indicates that the monosaccharide （n=1） and disaccharide （n=2） repeating units of Gioactive SPG-PF can bind with high affinity to the active site of the TLR2 protein, exhibiting a binding mode similar to that of the classical TLR2 inhibitor CU-CPT22. In conclusion, Gioactive SPG-PF effectively suppresses inflammatory responses in oral epithelial cells, potentially through the modulation of the TLR2 signaling pathway, providing experimental and theoretical support for its development as a new oral soothing ingredient.

Key words: Gioactive SPG-PF, Fusobacterium nucleatum, TLR2, inflammation, molecular docking

CLC Number:

TQ658

Yucheng Lin, Fei Zhou, Qing Liu, Yina Lu. A β-glucan from Schizophyllum commune attenuates Fusobacterium nucleatum-induced inflammatory responses in oral epithelial cells via TLR2 signaling[J].China Surfactant Detergent & Cosmetics, 2026, 56(10): 1362-1370.

Figures/Tables 6

Fig.1

Tab.1

Tab.2

Fig.2

Fig.3

Fig.4

References 36

[1]	Sedghi L, DiMassa V, Harrington A, et al. The oral microbiome: role of key organisms and complex networks in oral health and disease[J]. Periodontology 2000, 2021, 87 (1) : 107-131. doi: 10.1111/prd.v87.1
[2]	Mukherjee S, Chopra A, Karmakar S, et al. Periodontitis increases the risk of gastrointestinal dysfunction: an update on the plausible pathogenic molecular mechanisms[J]. Critical Reviews in Microbiology, 2025, 51 (1) : 187-217. doi: 10.1080/1040841X.2024.2339260
[3]	Pignatelli P, Nuccio F, Piattelli A, et al. The role of Fusobacterium nucleatum in oral and colorectal carcinogenesis[J]. Microorganisms, 2023, 11 (9) : 2358.
[4]	Kaisho T, Akira S. Toll-like receptors and their signaling mechanism in innate immunity[J]. Acta Odontologica Scandinavica, 2001, 59 (3) : 124-130. pmid: 11501880
[5]	McClure R, Massari P. TLR-dependent human mucosal epithelial cell responses to microbial pathogens[J]. Frontiers in Immunology, 2014, 5: 386. doi: 10.3389/fimmu.2014.00386 pmid: 25161655
[6]	Jin M, Fang J, Wang J, et al. Regulation of toll-like receptor (TLR) signaling pathways in atherosclerosis: from mechanisms to targeted therapeutics[J]. Acta Pharmacologica Sinica, 2023, 44 (12) : 2358-2375. doi: 10.1038/s41401-023-01123-5
[7]	Jia B, Zhang B, Li J, et al. Emerging polymeric materials for treatment of oral diseases: design strategy towards a unique oral environment[J]. Chemical Society Reviews, 2024, 53 (7) : 3273-3301. doi: 10.1039/D3CS01039B
[8]	Carrouel F, Viennot S, Ottolenghi L, et al. Nanoparticles as anti-microbial, anti-inflammatory, and remineralizing agents in oral care cosmetics: a review of the current situation[J]. Nanomaterials, 2020, 10 (1) : 140.
[9]	Eren O T, Armağan R, Talmaç M A. Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids[M]// KorkusuzF. Musculoskeletalresearch and basic science. Cham: Springer International Publishing, 2016: 683-693.
[10]	Ellison S J. The role of phenoxymethylpenicillin, amoxicillin, metronidazole and clindamycin in the management of acute dentoalveolar abscesses—a review[J]. British Dental Journal, 2009, 206 (7) : 357-362. doi: 10.1038/sj.bdj.2009.257 pmid: 19357666
[11]	Lanas Á, Scarpignato C. Microbial flora in NSAID-induced intestinal damage: a role for antibiotics?[J]. Digestion, 2006, 73 (S1) : 136-150. doi: 10.1159/000089789
[12]	Queen J, Zhang J, Sears C L. Oral antibiotic use and chronic disease: long-term health impact beyond antimicrobial resistance and Clostridioides difficile[J]. Gut Microbes, 2020, 11 (4) : 1092-1103. doi: 10.1080/19490976.2019.1706425
[13]	Cecerska-Heryć E, Wiśniewska Z, Serwin N, et al. Can compounds of natural origin be important in chemoprevention? Anticancer properties of quercetin, resveratrol, and curcumin—A comprehensive review[J]. International Journal of Molecular Sciences, 2024, 25 (8) : 4505.
[14]	Zhao Y, Wu J, Liu X, et al. Decoding nature: multi-target anti-inflammatory mechanisms of natural products in the TLR4/NF-κB pathway[J]. Frontiers in Pharmacology, 2025, 15: 1467193. doi: 10.3389/fphar.2024.1467193
[15]	Lu C, Qing L, Yina L. Phyllanthus emblica fruit extract alleviates halitosis and reduces the inflammatory response to oral bacteria[J]. Journal of Applied Oral Science, 2024, 32: e20240047.
[16]	Spahr A, Divnic-Resnik T. Impact of health and lifestyle food supplements on periodontal tissues and health[J]. Periodontology 2000, 2022, 90 (1) : 146-175. doi: 10.1111/prd.12455 pmid: 35916868
[17]	Kwon T H, Salem D M, Levin L. Nonsurgical periodontal therapy based on the principles of cause-related therapy: rationale and case series[J]. Quintessence International, 2019, 50 (5) : 370-376. doi: 10.3290/j.qi.a42292 pmid: 30915426
[18]	Sharma N, Yeasmen N, Dube L, et al. Rise of plant-based beverages: A consumer-driven perspective[J]. Food Reviews International, 2024, 40 (10) : 3315-3341. doi: 10.1080/87559129.2024.2351920
[19]	杨志豪, 杨震寰, 刘青, 等. 响应面法优化裂褶菌液体培养条件[J]. 生物技术, 2025, 35 (5) : 584-588.
[20]	Abd Razak D L, Abd Ghani A, Lazim M I M, et al. Schizophyllum commune (Fries) mushroom: a review on its nutritional components, antioxidative, and anti-inflammatory properties[J]. Current Opinion in Food Science, 2024, 56: 101129. doi: 10.1016/j.cofs.2024.101129
[21]	Gou Z, Peng Z, Wang S, et al. Efficient production and skincare activity evaluation of schizophyllan, a β-glucan derived from Schizophyllum commune NTU-1[J]. International Journal of Biological Macromolecules, 2023, 241: 124504. doi: 10.1016/j.ijbiomac.2023.124504
[22]	Lagha A B, Grenier D. Tea polyphenols inhibit the activation of NF-κB and the secretion of cytokines and matrix metalloproteinases by macrophages stimulated with Fusobacterium nucleatum[J]. Scientific Reports, 2016, 6 (1) : 1-11. doi: 10.1038/s41598-016-0001-8
[23]	Polito A J, Proud D. Epithelial cells as regulators of airway inflammation[J]. Journal of Allergy and Clinical Immunology, 1998, 102 (5) : 714-718. pmid: 9867498
[24]	Lee B C, Kim M S, Choi S H, et al. Involvement of capsular polysaccharide via a TLR2/NF-κB pathway in Vibrio vulnificus-induced IL-8 secretion of human intestinal epithelial cells[J]. International Journal of Molecular Medicine, 2010, 25 (4) : 581-591.
[25]	Su L, Wang Y, Wang J, et al. Structural basis of TLR2/TLR1 activation by the synthetic agonist diprovocim[J]. Journal of Medicinal Chemistry, 2019, 62 (6) : 2938-2949. doi: 10.1021/acs.jmedchem.8b01583 pmid: 30829478
[26]	Liu R, Perez-Aguilar J M, Liang D, et al. Binding site and affinity prediction of general anesthetics to protein targets using docking[J]. Anesthesia & Analgesia, 2012, 114 (5) : 947-955.
[27]	Durai P, Shin H J, Achek A, et al. Toll-like receptor 2 antagonists identified through virtual screening and experimental validation[J]. The FEBS Journal, 2017, 284 (14) : 2264-2283. doi: 10.1111/febs.2017.284.issue-14
[28]	Zhao T, Yang M, Ma L, et al. Structural modification and biological activity of polysaccharides[J]. Molecules, 2023, 28 (14) : 5416.
[29]	Brown G D, Gordon S. Immune recognition of fungal β-glucans[J]. Cellular Microbiology, 2005, 7 (4) : 471-479. doi: 10.1111/j.1462-5822.2005.00505.x pmid: 15760447
[30]	Goodridge H S, Reyes C N, Becker C A, et al. Activation of the innate immune receptor dectin-1 upon formation of a ‘phagocytic synapse’[J]. Nature, 2011, 472 (7344) : 471-475. doi: 10.1038/nature10071
[31]	Ferwerda B, Ferwerda G, Plantinga T S, et al. Human dectin-1 deficiency and mucocutaneous fungal infections[J]. New England Journal of Medicine, 2009, 361 (18) : 1760-1767. doi: 10.1056/NEJMoa0901053
[32]	Bryce R A, Hillier I H, Naismith J H. Carbohydrate-protein recognition: molecular dynamics simulations and free energy analysis of oligosaccharide binding to concanavalin A[J]. Biophysical Journal, 2001, 81 (3) : 1373-1388. pmid: 11509352
[33]	McGreal E P. Structural basis of pattern recognition by innate immune molecules[M]// Kishore U. Target pattern recognition in innate immunity. New York: Springer, 2009: 139-161.
[34]	Behzadi P, García-Perdomo H A, Karpiński T M. Toll‐like receptors: general molecular and structural biology[J]. Journal of Immunology Research, 2021 (1) : 9914854.
[35]	Kitchen D B, Decornez H, Furr J R, et al. Docking and scoring in virtual screening for drug discovery: methods and applications[J]. Nature Reviews Drug Discovery, 2004, 3 (11) : 935-949. doi: 10.1038/nrd1549 pmid: 15520816
[36]	Pérez S. Computational modeling of protein-carbohydrate interactions: current trends and future challenges[M]// Baker D C. Advances in carbohydrate chemistry and biochemistry:Vol. 83. Cambridge, MA: Academic Press, 2023: 133-149.

Primer sequence （5'→3'）	Primer
F: ATCCTCCAATCAGGCTTCTCT R: GGACAGGTCAAGGCTTTTTACA	TLR2
F: TGGCTGCAGGACATGACAAC R: TGAGGTGCCCATGCTACATTT	IL-6
F: TCAGAGACAGCAGAGCACACAA R: GGCCAGCTTGGAAGTCATGT	IL-8
F: TGACAACTTTGGTATCGTGGAAGG R: AGGCAGGGATGATGTTCTGGAGAG	GAPDH

	Vehicle control	Model control	Positive control	Gioactive SPG-PF
	Vehicle control	Model control	Positive control	0.16%	0.31%	0.63%	1.25%	2.50%	5.00%
OD_{450 nm}	1.406 6	1.333 4	1.489 2	1.341 1	1.220 9	1.197 2	1.119 3	1.017 4	0.891 5
	1.290 6	1.222 1	1.297 6	1.340 5	1.254 2	1.226 4	1.118 3	0.935 2	0.828 2
	1.301 6	1.235 9	1.214 2	1.278 9	1.257 0	1.195 7	1.096 1	0.936 3	0.835 5
Cell viability	105.53%	100.04%	111.72%	100.61%	91.59%	89.82%	83.97%	76.33%	66.88%
	96.82%	91.69%	97.35%	100.57%	94.09%	92.01%	83.90%	70.16%	62.13%
	97.65%	92.72%	91.09%	95.95%	94.30%	89.70%	82.23%	70.24%	62.68%
Mean	100.00%	94.81%	100.06%	99.04%	93.33%	90.51%	83.37%	72.24%	63.90%
SD	4.80%	4.55%	10.58%	2.68%	1.51%	1.30%	0.98%	3.54%	2.60%
P value	> 0.05		> 0.05	> 0.05	> 0.05	> 0.05	< 0.05	< 0.001	< 0.001
Significance	ns		ns	ns	ns	ns	*	***	***

A β-glucan from Schizophyllum commune attenuates Fusobacterium nucleatum-induced inflammatory responses in oral epithelial cells via TLR2 signaling

RichHTML

PDF (PC)

Like

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 6

References 36

Related Articles 15

Metrics

Comments

Recommended 10

[1]	Xiaona Pei, Yanfang Zhou, Linyuan Tian, Limin Fan. Evaluation of the multifunctional efficacy and matrix stability of the probiotic metabolite indole-3-lactic acid as a functional ingredient in oral care products [J]. China Surfactant Detergent & Cosmetics, 2026, 56(9): 1222-1232.
[2]	Zhiming He, Jiawen Huang, Yi Zhan, Desong Wu, Yufeng Zha. Comparative study on the soothing efficacy of different extracts of Panax notoginseng [J]. China Surfactant Detergent & Cosmetics, 2026, 56(8): 1053-1061.
[3]	Yanju Feng, Hongyan Dong, Yuan Meng, Yuqi Zhang, Minjia Yuan, Congyan Li. Study on the efficacy and mechanism of Platycladus orientalis extracted by supercritical CO₂ in prevention and treatment of androgenetic alopecia [J]. China Surfactant Detergent & Cosmetics, 2026, 56(5): 595-602.
[4]	Jun Liang, Xiaoming Shi. Whitening effect of glabridin and its mechanism [J]. China Surfactant Detergent & Cosmetics, 2026, 56(5): 635-643.
[5]	Guoping Wu, Bin Li, Shan Huang. Study on the inhibitory effect and mechanism of Terminalia chebula Retz extract on tyrosinase activity [J]. China Surfactant Detergent & Cosmetics, 2026, 56(10): 1354-1361.
[6]	Wenyuan Chen, Xiaolan Chen, Jing Wan, Qin Deng, Yong Gao. Exploring the material basis and mechanisms of the action of Hibiscus mutabilis L. for its anti-inflammatory effects based on network pharmacology and cell experiments [J]. China Surfactant Detergent & Cosmetics, 2026, 56(1): 55-64.
[7]	Zhengang Peng, Zhengwan Huang, Zhe Liu, Xiaoxiao Lin. Studies on the anti-hair loss mechanism of Aquilaria sinensis leaf extract by integrated metabolomics and network pharmacology [J]. China Surfactant Detergent & Cosmetics, 2025, 55(6): 767-778.
[8]	Shiya Xie, Mingwei Liu, Lei Xiao, Shaolin Hu. Study on the antibacterial activity and anti-inflammatory activity of dandelion polyphenols [J]. China Surfactant Detergent & Cosmetics, 2025, 55(5): 633-639.
[9]	Xianxian Cao,Yonglei Yuan,Feifei Wang. Study on the antioxidant and anti-inflammatory activities of extracts from Salvia plebeia R. Br. [J]. China Surfactant Detergent & Cosmetics, 2025, 55(10): 1291-1298.
[10]	Ling Zhang, Jing Liu, Bingtian Zhao, Cheng Yang. Study on relieving skin inflammation and mechanisms of Modified Jiedu Xiaozheng Yin [J]. China Surfactant Detergent & Cosmetics, 2025, 55(1): 41-48.
[11]	Youliang Zhou, Wanshan Lu, Zhiwei Cheng, Kun Dong. LC-MS/MS combined with network pharmacology and molecular docking to explore the targets and mechanisms of antioxidant effects of strawberry leaves [J]. China Surfactant Detergent & Cosmetics, 2025, 55(1): 63-74.
[12]	Wenjie Zhang, Feng Shi, Ruiqing Xian, Yuxiang Dong, Kai Guo, Shengli Ji. Study on the synthesis and biological activity of P7 lipopeptide [J]. China Surfactant Detergent & Cosmetics, 2024, 54(9): 1050-1058.
[13]	Guanru Shao, Kunyang Zhang. Rhein attenuates UVB-induced skin photoaging injury by inhibiting p38 MAPK phosphorylation [J]. China Surfactant Detergent & Cosmetics, 2024, 54(7): 836-843.
[14]	Hui Liu, Sijia Yang, Hankun Ren, Zhaohui Qu, Libo Zheng, Shujing Li. Research progress of extraction and isolation of natural plant polysaccharides and their applications in skin care [J]. China Surfactant Detergent & Cosmetics, 2024, 54(6): 708-717.
[15]	Juanli Liu, Huiping Xu, Yanfang Liu, Zhenhua Dong, Meiyan Wang. Analysis of the effectiveness of Lotus leaf extract in inhibiting oral bacteria and improving gingival inflammation [J]. China Surfactant Detergent & Cosmetics, 2024, 54(10): 1235-1242.