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Effect of Fucoidan on Osteoarthritis in Obese Rats

June 10, 2024

In this blog, I’m going to discuss and share the findings of a study titled “Effect of Fucoidan on Anterior Cruciate Ligament Transection and Medial Meniscectomy Induced Osteoarthritis in High-Fat Diet-Induced Obese Rats” conducted by Sabri Sudirman et al. The study aims to examine the impact of Fucoidan on rats with diet-induced obesity who undergo surgery-induced osteoarthritis.

Among older adults population, osteoarthritis (OA) has emerged as one of the most prevalent disorders. Obesity and OA-related mechanical damage can be connected to joint loading, cartilage breakdown, bone loss, and inflammation. Among its various biological activities, Fucoidan demonstrates antitumor, antiviral, anticoagulant, antiobesity, and immunomodulatory properties.

Initially, male SD rats were categorized into two primary groups: a sham group and an obese group. The obese group was given a high-fat diet for 4 weeks to develop obesity (approximate body weight >20% of ideal). The body weight of HFD-induced obese rats was significantly increased compared to the sham group (p < 0.05). After 40 days of treatment with Fucoidan, body weight decreased by 9%. The presence of the metabolic/obesity phenotype suggests that weight-bearing joints experience a greater amount of stress, making it crucial to consider the role of adipokines in the progression of osteoarthritis. In obese animals, white fat (adipose tissue) deposition increases significantly due to adipocyte hyperplasia and hypertrophy. Oral administration of Fucoidan reduced body weight in HFD-induced obese rats. In the study, it was observed that the presence of Fucoidan from Cladosiphon okamuranus led to a decrease in adipose tissue weight, including perirenal and epididymal adipose tissue.

Higher levels of malondialdehyde (MDA) are found in obese subjects compared to normal-weight subjects. According to the study’s findings, it was observed that the administration of Fucoidan from Cladosiphon okamuranus led to an increase in her superoxide dismutase (SOD) activity, as well as a decrease in malondialdehyde (MDA) levels, as depicted in Figure 1.

At the end of the experiment, rat joint sections were stained with hematoxylin and eosin staining to observe morphological changes due to surgery-induced OA. The findings presented in Figure 2 demonstrate a notable decrease in cartilage thickness among participants with obesity osteoarthritis (OBOA), whereas a positive improvement was observed in the group that underwent Fucoidan treatment. Other joint sections were stained with Safranin-O and Fast Green to observe proteoglycan loss due to OA. In the OBOA group, histological examination of the joints showed a significant loss of proteoglycans within the cartilage matrix. Fucoidan treatment prevented further proteoglycan loss, as shown in Figure 3. As shown in Figures 4 and 5, there was no OA in the articular cartilage of the sham group (grade 0). The utilization of high-concentration Fucoidan as a therapeutic approach demonstrated its effectiveness in mitigating articular cartilage damage and maintaining the quality of the articular cartilage at grade 1.

Fucoidan administered orally has been shown to be beneficial in alleviating pain associated with OA. This is demonstrated by the decrease in hindlimb force differences and joint swelling following OA surgery. Measurement of the knee width revealed that the operated joint showed swelling after surgery, but it recovered within 2 weeks. The joint where ACLT (anterior cruciate ligament transection) + MMx (medial meniscectomy) was performed remained swollen for a long time due to inflammation caused by OA. By effectively utilizing Fucoidan for treatment purposes, the swelling was reduced, as indicated by the decreasing difference in knee width between the hind limbs over a period of time.

The anti-inflammatory effects of Fucoidan, which is extracted from Cladosiphon okamuronus, have been demonstrated in countering inflammation induced by a high-fat diet. This hypolipidemic property acted against fat accumulation and protected joints and cartilage in HFD-induced male rats with ACLT (anterior cruciate ligament transection) + MMx (medial meniscectomy) surgery-induced OA. In addition to that, the supplementation of Fucoidan was found to lead to a decrease in levels of leptin and IL-1β. Leptin regulates chondrocyte proliferation and differentiation. Excess leptin exposure can stimulate chondrocyte differentiation and osteophyte formation. Thus, the regulation of pro-inflammatory markers such as IL-1β, IL-6, IP-10, and leptin in obese conditions may be involved in the progression of OA in serum and synovial fluid. According to the results, it was suggested that the administration of Fucoidan orally could potentially be beneficial in improving osteoarthritis associated with obesity and injuries to the meniscus or ligament.

Figure -1) The effect of Fucoidan treatment on the antioxidant activities in HFD-induced obese male rats with ACLT + MMx surgery-induced OA.
Figure -2) The histopathological difference between the knee joints in the HFD-induced obese male rats with ACLT + MMx
Figure -3) The histopathological difference between the knee joints in HFD-induced obese male rats with ACLT + MMx

Source: Nutrients. 2018 Jun; 10(6): 686. doi: 10.3390/nu10060686