Use evaluation of medical-grade honey on the integrity of rat articular cartilage

Abstract

Introduction

Dysregulation of articular tissue homeostasis induces degenerative changes and musculoskeletal diseases such as osteoarthritis, for which current pharmacological treatments neither slow progression nor prevent the functional loss of the joint. Medical-grade honey contains a high concentration of active compounds, such as polyphenols and flavonoids, with the potential to modulate the catabolic/anabolic balance of the chondrocyte, which is relevant to osteoarthritis progression.

Objective

To evaluate the effect of intra-articular administration of medical-grade honey on the integrity of hyaline cartilage.

Methods

Twenty-four male Wistar rats (mean weight 130 g) were randomly divided into two groups: medical-grade honey (MGH) and saline solution (SS). Three intra-articular injections (10 μL/dose/week) were administered into the right knee; the contralateral knee served as the control. After sacrifice, macroscopic analysis of the femoral condyles and histology (hematoxylin-eosin, safranin O-fast green, and alcian blue) were performed. The expression of type II collagen (Col-II), type I collagen (Col-I), matrix metalloproteinase 3 (MMP-3), and Ki67 was assessed by immunofluorescence. Total phenolic compounds, AST, ALT, albumin, and total protein were quantified in serum. Data were expressed as the mean ± standard deviation; after verifying normality (Shapiro-Wilk), differences were assessed by one-way ANOVA with Bonferroni-corrected pairwise comparisons (p < 0.05).

Results

Intra-articular administration of MGH preserved the native characteristics of the tissue. Macroscopic analysis showed undamaged, smooth femoral cartilage similar to the control, and histology revealed a high density of chondrocytes with abundant matrix in both groups. By immunofluorescence, one-way ANOVA revealed significant intergroup differences for Col-II, Col-I, and MMP-3. The MGH group preserved Col-II (898.9 ± 173.6 AU) relative to the control (1053.5 ± 30.8 AU; ns) and significantly reduced Col-I (1094.2 ± 98.4 vs 1633.5 ± 297.8 AU; p < 0.001), a marker of dedifferentiation. MMP-3 was significantly higher in the MGH group (1292.3 ± 157.1 AU) than in the control (834.1 ± 158.2 AU; p < 0.001) and SS (660.9 ± 44.9 AU); however, this increase coexisted with preserved Col-II and reduced Col-I, a pattern consistent with matrix remodeling rather than net catabolism. Serum phenolic concentrations were similar between the control (13.1 ± 0.59 mg GAE/100 μL) and treated rats (13.2 ± 0.73 mg GAE/100 μL; p = 0.536), and AST, ALT, albumin, and total protein did not differ from the control.

Conclusion

Intra-articular administration of MGH was innocuous to healthy articular cartilage in Wistar rats. It preserved the macroscopic and histological architecture, maintained the chondrocytic phenotype (Col-II preserved, Col-I significantly reduced), and induced no hepatic or protein-related serum alterations. The significant increase in MMP-3, concurrent with the preservation of anabolic markers, is consistent with physiological matrix remodeling rather than catabolism. These findings support the safety of MGH for intra-articular injection and lay the groundwork for evaluating its chondroprotective efficacy in osteoarthritis models, with a view to preserving joint function and preventing musculoskeletal disability.