Hesperidin is a flavonoid compound found in citrus fruits, particularly oranges and lemons. It has been shown to have some health benefits, such as anti-inflammatory, antioxidant, and immune-modulatory activities. Some studies have reported on hesperidin’s health benefits on rheumatoid arthritis.

 

    Rheumatoid arthritis is a chronic inflammatory disease characterized by the destruction of articular cartilage and bone in a chronic phase. Pathology of rheumatoid arthritis suggests autoimmunity linked to inflammation.

 

    The preventive and therapeutic effects of the Citrus flavonoid hesperidin on the development of collagen-induced arthritis were investigated in a mouse model of rheumatoid arthritis. Mice were given orally hesperidin three times a week starting from either the onset (day 21) of arthritis or on day 31 when the collagen-induced arthritis development had reached a plateau. In both cases, treatment with hesperidin resulted in significant suppression of clinical scores and improvement of histological features (1).

 

    Hesperidin was given 3 times a week (150 mg/kg) from the onset (day 21) and thereafter, which showed a significant preventative effect with the improvement of clinical scores on days 42, 45, and 47. The clinical scores were 10.6±1.0, 9.9±0.9, and 10.0±0.9 for the arthritic control group on these days, respectively, while the clinical scores were significantly reduced to 6.3±0.6, 5.8±0.6 and 5.3±0.7 for the hesperidin treatment group, respectively (p<0.05).

 

    Hesperidin was given starting on day 31 as therapy showed significantly improved clinical scores at late stages, but the activity of hesperidin was weaker than that of prednisolone, a steroid drug that is often used to treat chronic illnesses such as arthritis. Histological evaluation of knee joints on day 49 showed that treatment with hesperidin reduced the damage of interchondral joints and significantly suppressed the increase of synovial cells, infiltration of inflammatory cells, and pannus formation (p<0.05) (1).

 

    The production of tumor necrosis factor-alpha (TNF-α) and Interleukin-1 beta (IL-1β) is considered to be the hallmark of the pathogenesis of rheumatoid arthritis, an autoimmune disease with chronic inflammation of the joint, followed by erosion of cartilage and bone. TNF-α is a cytokine that has been identified as a major regulator of inflammatory responses and is known to be involved in the pathogenesis of some inflammatory and autoimmune diseases. IL-1β is also a cytokine, which increases inflammation. Treatment with hesperidin caused downregulation of TNF- α mRNA expression in lesions. These results suggested that oral administration of hesperidin could be effective in preventing and treating human rheumatoid arthritis (1).

 

    In another collagen-induced arthritic rat study, hesperidin was given at a dose of 160 mg/kg body weight was given since induction daily until the 20th day. The effect of treatment in the rats was monitored by clinical scoring, biochemical parameters, and histological evaluations in joints. A steady increase in oxidative damage and a significant decrease in antioxidant defense enzymes were observed in the joints of arthritic rats as compared to the control. The results showed that hesperidin had significant antioxidant potential. Its anti-arthritic efficacy was evident from the reduction in joint swelling and severity of the arthritis condition. The treatment with hesperidin was effective in bringing about significant changes in all the parameters studied in collagen-induced arthritis rats (2).

 

    These data confirmed that erosive destruction of the joint cartilage in collagen-induced arthritis was due to free radicals released by activated neutrophils and produced by other biochemical pathways. The disease process could be ameliorated by hesperidin treatment. Hesperidin could be effective in treating human rheumatoid arthritis patients (2).

 

    In another induced-arthritis rat study, hesperidin was administered at 40, 80, and 160 mg/kg from day 12 to 21 from the induction time. The Chinese herbal remedy Tripterygium wilfordii Hook. f. has been known for hundreds of years as a therapeutic agent for rheumatoid arthritis. Tripterygium glycosides extracted from the root of Tripterygium wilfordii Hook. f., was used at 40 mg/kg dose as a positive control in this study (3).

 

    Compared to those of control arthritis rats, hesperidin at doses of 80 and 160 mg/kg significantly inhibited secondary paw swelling and restored the index of immune organs (thymus and spleen) of arthritis rats. Synoviocyte proliferation in arthritis rats was suppressed after hesperidin treatment, which was accompanied by decreased transcription as well as the production of TNF-α and IL-1β from synoviocytes. Hesperidin also markedly increased IL-10 at both protein and transcription levels in arthritis rats. There was a dose-response of hesperidin on the various parameters, and the effects of the highest dose 160 mg/kg were equivalent to those of the positive control Tripterygium glycosides at 40 mg/kg (3).

 

    This study results further illustrated that hesperidin could have a therapeutic effect on arthritis, and the mechanisms were partly related to inhibiting synoviocyte activity and modulating inflammatory cytokine production of synoviocytes which play a crucial role in the pathogenesis of arthritis (3).

 

    In another rat arthritis study, induction of arthritis was confirmed on the 14th day before oral administration of 40 and 80 mg/kg of hesperidin or dexamethasone for 45 days. Dexamethasone is a drug, which is prescribed to relieve inflammation (swelling, heat, redness, and pain) and to treat arthritis (4).

 

    Compared to the control arthritic rat group, treatments with both doses of hesperidin and dexamethasone significantly diminished paw swelling/edema and arthritis score as well as enhanced latency in the thermal hyperalgesia test (p < 0.05). Hesperidin treatment in arthritis rats showed significant improvement in red blood cells and platelet counts as well as hemoglobin and hematocrit compared to the arthritis control rat group (p < 0.01). In addition, hesperidin treatment significantly reduced serum inflammatory biomarker levels and decreased the liver reactive oxygen species levels of rats induced with arthritis (p<0.05). The reduced activities of liver antioxidant enzymes in arthritic rats were significantly increased with hesperidin treatment in arthritic rats (p<0.05). This study suggests that hesperidin demonstrated an anti-arthritic effect via modulation of inflammation as well as protection against oxidative damage. Hesperidin again was demonstrated for its efficacy as a potential immune-modulatory, anti-inflammatory and anti-oxidant agent (4).

 

    Presently, there are several drug therapies to treat rheumatoid arthritis, but they have some serious side effects. To avoid these side effects, many patients opt for other substitutes like natural anti-inflammatory products with little or no side effects to alleviate their arthritis symptoms.

 

    Hesperidin is a natural flavanone glycoside found in abundance in citrus fruits. Normal intake of hesperidin or related compounds has been observed to show no signs of toxicity. Hesperidin has been reported to have a wide range of pharmacological properties, such as antioxidant, anti-inflammatory, hypolipidemic, anti-carcinogenic, and anti-rheumatic effects as demonstrated by the arthritis studies mentioned in this blog. These study results may be useful to those of you who have concerns about arthritis symptoms such as joint swelling and pain. You may help with joint health by boosting hesperidin intake like eating more citrus fruits.

 

References:

1. Kawaguchi, K., Maruyama, H., Kometani, T., & Kumazawa, Y. (2006). Suppression of Collagen-Induced Arthritis by Oral Administration of the Citrus Flavonoid Hesperidin. Planta Medica, 72(5), 477–479. doi:10.1055/s-2005-916254

2. Umar, S., Kumar, A., Sajad, M., Zargan, J., Ansari, M. M., Ahmad, S., … Khan, H. A. (2012). Hesperidin inhibits collagen-induced arthritis possibly through suppression of free radical load and reduction in neutrophil activation and infiltration. Rheumatology International, 33(3), 657–663. doi:10.1007/s00296-012-2430-4

3. Li, R., Cai, L., Xie, X., Yang, F., & Li, J. (2009). Hesperidin suppresses adjuvant arthritis in rats by inhibiting synoviocyte activity. Phytotherapy Research, 24(S1), S71–S76. doi:10.1002/ptr.2906 

4. Adefegha, S. A., Bottari, N. B., Leal, D. B., Andrade, C. M. de, & Rosa Schetinger, M. (2020). Interferon gamma/Interleukin-4 Modulation, Anti-inflammatory and Antioxidant Effects of Hesperidin in Complete Freund’s Adjuvant (CFA)-Induced Arthritis Model of Rats. Immunopharmacology and Immunotoxicology, 1–34. doi:10.1080/08923973.2020.181480