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. 2020 Nov 23;25(22):5467.
doi: 10.3390/molecules25225467.

Herbal Composition LI73014F2 Alleviates Articular Cartilage Damage and Inflammatory Response in Monosodium Iodoacetate-Induced Osteoarthritis in Rats

Hae Lim Kim  1 , Hae Jin Lee  1 , Dong-Ryung Lee  2 , Bong-Keun Choi  2 , Seung Hwan Yang  1
Affiliations

Herbal Composition LI73014F2 Alleviates Articular Cartilage Damage and Inflammatory Response in Monosodium Iodoacetate-Induced Osteoarthritis in Rats

Hae Lim Kim et al. Molecules. .

Abstract

The aim of this study was to determine the anti-osteoarthritic effects of LI73014F2, which consists of Terminalia chebula fruit, Curcuma longa rhizome, and Boswellia serrata gum resin in a 2:1:2 ratio, in the monosodium iodoacetate (MIA)-induced osteoarthritis (OA) rat model. LI73014F2 was orally administered once per day for three weeks. Weight-bearing distribution and arthritis index (AI) were measured once per week to confirm the OA symptoms. Synovial membrane, proteoglycan layer, and cartilage damage were investigated by histological examination, while synovial fluid interleukin-1β level was analyzed using a commercial kit. Levels of pro-inflammatory mediators/cytokines and matrix metalloproteinases (MMPs) in the cartilage tissues were investigated to confirm the anti-osteoarthritic effects of LI73014F2. LI73014F2 significantly inhibited the MIA-induced increase in OA symptoms, synovial fluid cytokine, cartilage damage, and expression levels of pro-inflammatory mediators/cytokines and MMPs in the articular cartilage. These results suggest that LI73014F2 exerts anti-osteoarthritic effects by regulating inflammatory cytokines and MMPs in MIA-induced OA rats.

Keywords: Boswellia serrata extracts; Curcuma longa rhizome extracts; LI73014F2; Terminalia chebula fruit extracts; cartilage degradation; inflammatory response; osteoarthritis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Effects of LI73014F2 on changes in body weight in monosodium iodoacetate (MIA)-induced osteoarthritis in rats. Body weight was evaluated once a week for 3 weeks and data are presented as mean ± SEM (n = 8/group). No significant difference was detected between all the groups.
Figure 2
Figure 2
Effects of LI73014F2 on synovial fluid levels of inflammatory factors in MIA-induced osteoarthritis in rats. The collected synovial fluid was analyzed for the levels of IL-1β using commercial ELISA kits. Data are expressed as mean ± SEM (n = 8/group). ** p < 0.01, compared to the MIA-induced control group; ## p < 0.01, compared to the non-MIA-induced control group.
Figure 3
Figure 3
Effects of LI73014F2 on the expression levels of inflammation-related proteins in articular cartilage. The expression levels of (A) pro-inflammatory cytokines interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α), and (B) inflammatory mediators cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), 5-lipoxygenase (5-LOX), and leukotriene B4 (LTB4) were measured using Western blot analysis; density of the protein bands was quantified and calculated using ImageJ software. Protein expression levels were normalized to those of β-actin and are expressed as mean ± SEM of independent experiments (n = 3/group). ** p < 0.01, compared to the MIA-induced control group; ## p < 0.01, compared to the non-MIA-induced control group.
Figure 3
Figure 3
Effects of LI73014F2 on the expression levels of inflammation-related proteins in articular cartilage. The expression levels of (A) pro-inflammatory cytokines interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α), and (B) inflammatory mediators cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), 5-lipoxygenase (5-LOX), and leukotriene B4 (LTB4) were measured using Western blot analysis; density of the protein bands was quantified and calculated using ImageJ software. Protein expression levels were normalized to those of β-actin and are expressed as mean ± SEM of independent experiments (n = 3/group). ** p < 0.01, compared to the MIA-induced control group; ## p < 0.01, compared to the non-MIA-induced control group.
Figure 4
Figure 4
Effects of LI73014F2 on the histological evaluation of joint activity in MIA-induced osteoarthritis in rats. (A) Cartilage and synovial membrane in knee joints were stained with hematoxylin and eosin (H&E), (B) cartilage cell and proteoglycan layer in knee joints stained with Safranin O, and (C) graded on a 0–13 scale using the Mankin scoring system. (a) Normal Control group, (b) MIA Control group, (c) MIA + LI73014F2 25 mg/kg, (d) MIA + LI73014F2 50 mg/kg, (e) MIA + LI73014F2 100 mg/kg, and (f) MIA + ibuprofen 20 mg/kg. Data are expressed as mean ± SEM (n = 5/group). * p < 0.05, compared to the MIA-induced control group; ## p < 0.01, compared to the non-MIA-induced control group.
Figure 5
Figure 5
Effects of LI73014F2 on the expression levels of matrix metalloproteinases (MMPs) in articular cartilage. The expression levels of MMP-2, MMP-3, and MMP-9 were determined using Western blot analysis; density of the protein bands was quantified and calculated using ImageJ software. Protein expression levels were normalized to those of β-actin and are expressed as mean ± SEM of independent experiments (n = 3/group). * p < 0.05 and ** p < 0.01, compared to the MIA-induced control group; ## p < 0.01, compared to the non-MIA-induced control group.
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