Cellular and molecular immunomodulatory potential of red wine polyphenols in apical periodontitis

Ricci, R.; Pereira, B.M.; Alvarado, J.D.A.; Sales-Junior, R.O.; Machado, N.E.S.; Santos, D.C. dos; Pederro, F.H.M.; Ferraz, M.C.; Frasnelli, S.C.T.; Rodrigues, J.S.M.; Oliveira, S.H.P.; Cintra, L.T.A.; Kishen, A.; Gomes-Filho, J.E.

doi:10.1590/1414-431X2025e15099

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Research Article • Braz. J. Med. Biol. Res. 59 • 2026 • https://doi.org/10.1590/1414-431X2025e15099 linkcopy

Cellular and molecular immunomodulatory potential of red wine polyphenols in apical periodontitis

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

This in vitro and in vivo study assessed dealcoholized red wine (DRW) effects on cytokine profile in macrophage (MQ)-periodontal ligament fibroblast (PDLFs) co-cultures and its impact on blood parameters, inflammatory/bone markers, cytokine expression, and periapical bone loss in rat apical periodontitis (AP). A MQ-PDLFs co-culture and Wistar rats with induced AP were exposed to DRW or red wine (W), with DMEM or water as controls (C). Cell cultures were analyzed for cytokine profile using a multiplex immunoassay. Rats underwent blood profiling, radiography, qRT-PCR, and histometric analysis of AP. Statistical significance was set at 5%. Multiplex analysis of the co-culture revealed that DRW induced lower interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels compared to C and W, higher IL-10 level than C, and lower IL-1β level only compared to W (P<0.05). Radiographic images confirmed AP development in rats. DRW showed a reduced monocyte count compared to C (P<0.05), but the inflammatory/bone markers in plasma were similar (P>0.05). Additionally, DRW showed lower IL-1β expression than C, and higher IL-10 expression only compared to W in AP (P<0.05). Periapical bone loss was similar among groups (P>0.05). In conclusion, DRW promoted an anti-inflammatory profile in co-cultures and in vivo. However, these effects did not translate into differences in lesion size or bone loss within the experimental model evaluated.

Key words:
Apical periodontitis; Bone remodeling; Dealcoholized red wine; Inflammation; Red wine

Blood parameters	Groups
	C	DRW	W
Leukocytes (×10³/µL)	9.131±1.871^a	8.925±1.480^a	8.593±1.132^a
Neutrophils (cells/µL)	1.868±0.748^a	1.884±0.683^a	1.814±0.432^a
Lymphocytes (cells/µL)	6.711±1.278^a	6.770±0.988^a	6.307±0.951^a
Monocytes (cells/µL)	404.4±160.5^b	209.8±157.6^a	356.3±135.2^a,b
Eosinophils (cells/µL)	109.9±75.69^a	146.3±54.77^a	103.2±119.7^a

Group	Histometric analysis (mm²)
C	2283.976±310.672
DRW	2099.349±671.320
W	2094.260±563.611

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[TFN01t01] Data are reported as means±SD. Different superscript lower-case letters in rows indicate a significant difference among the groups (P<0.05, one-way ANOVA followed by Tukey's test for multiple comparisons). C: control; DRW: dealcoholized red wine; W: red wine.