Theobromine mitigates IL-1β-induced oxidative stress, inflammatory response, and degradation of type II collagen in human chondrocytes

Gu, Ronghe; Shi, Yu; Huang, Weiguo; Lao, Chendeng; Zou, Zhuan; Pan, Songmu; Huang, Zonggui

doi:10.1016/j.intimp.2020.106226

Cited by 24 publications

(19 citation statements)

References 33 publications

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“…Theobromine activity in inhibiting phosphodiesterase was suggested as a mechanism of action to reduce obesity and related adipose tissue inflammation in mice [ 58 ]. Anti-inflammatory and antioxidant effects of theobromine through NF-kB downregulation were observed in chondrocytes treated with IL-1β [ 59 ]. The anti-inflammatory effect of theobromine, even in lower concentration than that used in this paper, agrees with recently published data [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Cocoa Bean Shell against Intestinal Damage: An Example of Byproduct Valorization

et al. 2021

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Background: Cocoa bean shell (CBS), a main byproduct of cocoa processing, represents a source of components such as polyphenols and methylxanthines, which have been associated with a reduced risk of several diseases. Therefore, CBS has potential application as a food ingredient. Intestinal mucosa is exposed to immune and inflammatory responses triggered by dietary agents, such as oxysterols, which derive from cholesterol oxidation and are pro-oxidant compounds able to affect intestinal function. We aimed at investigating the capability of the Forastero cultivar CBS, added or not added to ice cream, to protect against the intestinal barrier damage induced by a dietary oxysterol mixture. Methods: Composition and antioxidant capacity of in vitro digested CBS and CBS-enriched ice cream were analyzed by high-performance liquid chromatography and 1,1-diphenyl-2-picryl-hydrazyl radical-scavenging assay, respectively. CaCo-2 cells differentiated into enterocyte-like monolayer were incubated with 60 µM oxysterol mixture in the presence of CBS formulations. Results: The oxysterol mixture induced tight junction impairment, interleukin-8 and monocyte chemoattractant protein-1 cell release, and oxidative stress-related nuclear factor erythroid 2 p45-related factor 2 response Nrf2. Both CBSs protected cells from these adverse effects, probably thanks to their high phenolic content. CBS-enriched ice cream showed the highest antioxidant capacity. Theobromine, which is in high concentrations of CBS, was also tested. Although theobromine exerted no effect on Nrf2 expression, its anti-inflammatory cooperating activity in CBS effect cannot be excluded. Conclusions: Our findings suggest that CBS-enriched ice cream may be effective in the prevention of gut integrity damage associated with oxidative/inflammatory reactions.

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Section: Discussionmentioning

confidence: 99%

Protective Effect of Cocoa Bean Shell against Intestinal Damage: An Example of Byproduct Valorization

et al. 2021

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“…MMP-13 induces the degradation of proteoglycan and type II collagen; thus it is used as an important indicator of cartilage damage. [34][35][36] in A2M injection group we detected higher type II collagen level and lower MMP-13 level, hence the protective effect of supplemental A2M injection could be con rmed. Besides we examined the sGAG concentration in synovial uid from each group.…”

Section: Discussionmentioning

confidence: 59%

Hyaluronic Acid versus Alpha-2-Macroglobulin Intra-Articular Injections for Amelioration of Knee Posttraumatic Osteoarthritis: A Rat Model

Zhu¹,

Guo²,

Yang³

et al. 2020

Preprint

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Background: The study was performed to evaluate whether intra-articular injection of A2M has better effect than current commonly used Hyaluronic Acid (HA) injection therapy to attenuate cartilage degeneration in a rat anterior cruciate ligament transection (ACLT) osteoarthritis (OA) model.Method: In vivo effects of A2M and HA on cartilage degeneration were evaluated in rat surgery induced ACLT OA models. 100 rats were randomly divided into four groups: (a) Sham surgery + saline (Sham + S), (b) ACLT + A2M, (c) ACLT+HA, or (d) ACLT + saline (ACLT+S). The animals were sacrificed at 12 weeks after surgery. Histological staining was performed to assess cartilage damage. The concentration of MMP-13 and sGAG in synovial fluid lavages was measured using ELISA and spectrophotometric quantitative determination. OA-related gene expression was quantified by qPCR.Result: Indian ink staining showed that articular cartilage surface treated by A2M was relatively intact compared with the animals treated by ACLT with saline or HA injection. Histological staining indicated that early supplemental intra-articular injection of A2M attenuated OA pathogenesis in the rat ACLT model compared with the animals treated with saline and HA. However, supplemental intra-articular injection of HA showed no significant effect on cartilage protection for post traumatic OA compared with saline treatment. Elisa results showed A2M reduced the concentration of MMP-13 in synovial fluid compared with HA treatment group and other groups. RT-qPCR indicated that supplemental intra-articular A2M inhibits catabolism and enhances anabolic metabolism, while there was no significant difference in the expression of OA-related genes between ACLT+HA group and ACLT+S group. Conclusion: In rat model, intra-articular injection of A2M had obvious protective effects on cartilage degeneration compared with HA treatment. Major indexes of joint degeneration decreased, providing strong evidence for its intra-articular inhibitory effect. Meanwhile, we found no significant alleviation of articular cartilage pathogenesis in HA treated group, which suggests that the efficacy of HA is questionable and possibly transient, although it is extensively used to improve syndromes.

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“…MMP-13 induces the degradation of proteoglycan and type II collagen; thus, it is used as an important indicator of cartilage damage. [34][35][36] Higher type II collagen levels and lower MMP-13 levels in the A2M injection group than in the other groups; thus, the protective effect of A2M injection was con rmed. In addition, we examined sGAG concentrations in synovial uid in each group.…”

Section: Discussionmentioning

confidence: 99%

Intra-articular Injection of Hyaluronic Acid and Alpha-2-Macroglobulin to Ameliorate Knee Posttraumatic Osteoarthritis: A Rat Model

Wang

Huangfu

Chen

et al. 2022

Preprint

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Background Posttraumatic osteoarthritis (PTOA) correlates with a dramatic increase in multiple inflammatory factors after joint injury. There is a broad spectrum proteinase inhibitor known as alpha-2-macroglobulin (A2M) that plays an important role in protecting against inflammatory injury. Endogenous A2M is abundant in serum but insufficient in synovial fluid due to its large molecular weight and has a limited effect on articular cartilage inflammation. We hypothesize that intra-articular injection of A2M has a better clinical effect than the commonly used hyaluronic acid (HA) injection therapy. Furthermore, A2M could be a safer method than alternative treatments because it is a native substance in the human body. Method The in vivo effects of A2M and HA on cartilage degeneration were evaluated in rats with surgery-induced anterior cruciate ligament transection (ACLT) OA. One hundred rats were randomly divided into four groups (N = 25/group): (a) sham surgery + saline (Sham + S), (b) ACLT + A2M, (c) ACLT + HA, or (d) ACLT + saline (ACLT + S). Intra-articular injections of A2M were given immediately and 3 days after surgery, and then 20 µl was injected each weekly in each joint. The animals were sacrificed 12 weeks after surgery. Indian ink staining, safranin O staining and immunohistochemical staining were performed to assess cartilage damage. The extent of OA progression was graded by the Osteoarthritis Research Society International Osteoarthritis Cartilage Histopathology Assessment System (OOCHAS) (OA score = Grade × Stage; range, 0 to 24). The concentrations of matrix metalloproteinase-13 (MMP-13) and sGAG in synovial fluid lavage were measured by ELISA and spectrophotometric quantitative determination. OA-related gene expression was quantified by qPCR. Results Indian ink staining showed that the articular cartilage surface in rats treated with A2M was relatively intact compared with that in the animals treated with ACLT plus saline or HA injection, but there was no significant difference between the ACLT + HA group and the ACLT + S group. Histological staining indicated that early intra-articular injection of A2M attenuated OA pathogenesis in the rat ACLT model compared with that in animals treated with saline and HA. However, intra-articular injection of HA did not significantly protect cartilage against posttraumatic OA compared with saline treatment. The ELISA results showed that A2M reduced the concentration of MMP-13 in synovial fluid compared with that in the HA treatment group and other groups. RT–qPCR indicated that intra-articular A2M inhibited catabolism and enhanced anabolic metabolism, while there was no significant difference in the expression of OA-related genes between the ACLT + HA group and the ACLT + S group. Discussion In rat model, intra-articular injection of A2M had obvious protective effects against cartilage degeneration compared with HA treatment. The inflammatory factor MMP-13 provides strong evidence for this inhibitory effect. Moreover, we found no significant alleviation of articular cartilage pathogenesis in the HA-treated group, which suggests that the efficacy of HA is questionable and possibly transient, although it is still extensively used in clinical practice.

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Theobromine mitigates IL-1β-induced oxidative stress, inflammatory response, and degradation of type II collagen in human chondrocytes

Cited by 24 publications

References 33 publications

Protective Effect of Cocoa Bean Shell against Intestinal Damage: An Example of Byproduct Valorization

Protective Effect of Cocoa Bean Shell against Intestinal Damage: An Example of Byproduct Valorization

Hyaluronic Acid versus Alpha-2-Macroglobulin Intra-Articular Injections for Amelioration of Knee Posttraumatic Osteoarthritis: A Rat Model

Intra-articular Injection of Hyaluronic Acid and Alpha-2-Macroglobulin to Ameliorate Knee Posttraumatic Osteoarthritis: A Rat Model

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