A putative Chondroprotective role for IL-1β and MPO in herbal treatment of experimental osteoarthritis

Abstract

Background: Herbal treatment may have a chondroprotective and therapeutic effect on Osteoarthritis (OA). We investigated the mechanism of action of ginger and curcumin rhizomes cultivated in Egypt in treatment of OA in rat model.

Methods: Thirty-five albino rats were intra-articularly injected with Monosodium Iodoacetate in the knee joint. Ginger and curcumin was orally administered at doses of 200 and 400 mg/kg (F200 and F400). Serum levels of cartilage oligomeric matrix protein (COMP), hyaluronic acid (HA), malondialdehyde (MDA), myeloperoxidase (MPO), Interleukin-1 beta (IL-1β) and superoxide dismutase activity (SOD) were measured using ELISA. The composition of the herbal formula hydro-ethanolic extract was characterized using UPLC-ESI-MS. Histopathological changes in injected joints was examined using routine histopathology. Statistical analysis was performed using one-way ANOVA.

Results: Serum levels of COMP, HA, MPO, MDA, and IL-1β were significantly decreased in F 200, F 400 and V groups when compared to OA group (P value <0.0001). On the other hand SOD levels were significantly elevated in treated groups compared to OA groups (P value <0.0001).

Conclusions: The ginger/curcumin at 1:1 had chondroprotective effect via anti-inflammatory and antioxidant effect in rat OA model. Further pharmacological and clinical studies are needed to evaluate this effect.

Keywords: COMP; Curcumin; Ginger; HA; IL-1β; MDA; MPO; Osteoarthritis.

Fig. 1

a Serum level of COMP (ng/ml) in the experimental groups. Herbal formula treatment decreased serum level of COMP in the osteoarthritic rats at the end of 1 month treatment; C = control; OA = osteoarthritis; F 200 = herbal formula 200 mg/kg; F 400 = herbal formula 400 mg/kg; V = Voltaren. Results were expressed as mean ± SEM and analyzed using one-way ANOVA followed by Bonferroni’s post hoc test a = Significant from control at P < 0.0001, b = Significant from OA at P < 0.0001, c = Significant from F 400 at P < 0.0001. b Serum level of HA (Pg/ml) in the experimental groups. Herbal formula treatment decreased serum level of HA in the osteoarthritic rats at the end of 1 month treatment; C = control; OA = osteoarthritis; F 200 = herbal formula 200 mg/kg; F 400 = herbal formula 400 mg/kg; V = Voltaren. Results were expressed as mean ± SEM and analyzed using one-way ANOVA followed by Bonferroni’s post hoc test a = Significant from control at P < 0.0001, b = Significant from OA at P < 0.0001, c = Significant from F 400 at P < 0.0001, c’ = Significant from F 400 at P < 0.005

Fig. 2

Serum level of MPO (U/ml) in the experimental groups. Herbal formula treatment decreased serum level of MPO in the osteoarthritic rats at the end of 1 month treatment; C = control; OA = osteoarthritis; F 200 = herbal formula 200 mg/kg; F 400 = herbal formula 400 mg/kg; V = Voltaren. Results were expressed as mean ± SEM and analyzed using one-way ANOVA followed by Bonferroni’s post hoc test a = Significant from control at P < 0.0001, b = Significant from OA at P < 0.0001, c = Significant from F 400 at P < 0.0001, c’ = Significant from F 400 at P < 0.01

Fig. 3

Serum level of IL-1 Beta (Pg/ml) in the experimental groups. Herbal formula treatment decreased serum level of IL-1 Beta in the osteoarthritic rats at the end of 1 month treatment; C = control; OA = osteoarthritis; F 200 = herbal formula 200 mg/kg; F 400 = herbal formula 400 mg/kg; V = Voltaren. Results were expressed as mean ± SEM and analyzed using one-way ANOVA followed by Bonferroni’s post hoc test, a = Significant from control at P < 0.0001, b = Significant from OA at P < 0.0001, c = Significant from F 400 at P < 0.0001, c’ = Significant from F 400 at P < 0.002

Fig. 4

Serum level of MDA (nmole/ml) in the experimental groups. Herbal formula treatment decreased serum level of MDA in the osteoarthritic rats at the end of 1 month treatment; C = control; OA = osteoarthritis; F 200 = herbal formula 200 mg/kg; F 400 = herbal formula 400 mg/kg; V = Voltaren. Results were expressed as mean ± SEM and analyzed using one-way ANOVA followed by Bonferroni’s post hoc test, a = Significant from control at P < 0.0001, b = Significant from OA at P < 0.0001, c = Significant from F 400 at P < 0.0001

Fig. 5

Serum level of SOD (U/ml) in the experimental groups. Herbal formula treatment increased serum level of SOD in the osteoarthritic rats at the end of 1 month treatment; C = control; OA = osteoarthritis; F 200 = herbal formula 200 mg/kg; F 400 = herbal formula 400 mg/kg; V = Voltaren. Results were expressed as mean ± SEM and analyzed using one-way ANOVA followed by Bonferroni’s post hoc test, a = Significant from control at P < 0.0001, b = Significant from OA at P < 0.0001, c = Significant from F 400 at P < 0.0001

Fig. 6

Photomicrograph of a control group showing normal chondrocytes shape and orientation. b From osteoarthritis group showing denudation, erosion, clefting (arrow) and degeneration of chondrocytes. c F400 group showing superficial fibrillation (arrow head) with more or less normal orientation and some edema (arrow). d From F200 group superficial fibrillation (arrow), proliferation and clustering of chondrocytes, (arrow head) cracking and simple fissures. e From Voltarin treated group showing Loss of superficial layer, chondrocytes necrosis and simple fissures (arrow) H&Ex400

Fig. 7

A schematic representation of possible mechanisms by which ginger and curcuma extracts can regulate inflammation level in osteoarthritis. Adapted from Leong et al., 2013 [41]