Curcumin exerts chondroprotective effects against osteoarthritis by promoting AMPK/PINK1/Parkin-mediated mitophagy.

Conflicting evidence exists concerning the effects of nutrient intake in osteoarthritis (OA). A systematic literature review and meta-analysis were performed using PubMed, EMBASE, and Cochrane Library up to November 2021 to assess the effects of nutrients on pain, stiffness, function, quality of life, and inflammation markers. We obtained 52 references including 50 on knee OA. Twelve studies compared 724 curcumin patients and 714 controls. Using the standardized mean difference, improvement was significant with regard to pain and function in the curcumin group compared to placebo, but not with active treatment (i.e., nonsteroidal anti-inflammatory drugs, chondroitin, or paracetamol). Three studies assessed the effects of ginger on OA symptoms in 166 patients compared to 164 placebo controls. Pain was the only clinical parameter that significantly decreased. Vitamin D supplementation caused a significant decrease in pain and function. Omega-3 and vitamin E caused no changes in OA parameters. Herbal formulations effects were significant only for stiffness compared to placebo, but not with active treatment. A significant decrease in inflammatory markers was found, especially with ginger. Thus, curcumin and ginger supplementation can have a favorable impact on knee OA symptoms. Other studies are needed to better assess the effects of omega-3 and vitamin D.

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A Meta-Analysis of the Impact of Nutritional Supplementation on Osteoarthritis Symptoms

Background: The endoplasmic reticulum (ER) is a multi-functional organelle responsible for cellular homeostasis, protein synthesis, folding and secretion. It has been increasingly recognized that the loss of ER homeostasis plays a central role in the development of autoimmune inflammatory disorders, such as rheumatic diseases. Purpose/Main contents: Here, we review current knowledge of the contribution of ER stress to the pathogenesis of rheumatic diseases, with a focus on rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We also review the interplay between protein folding and formation of reactive oxygen species (ROS), where ER stress induces oxidative stress (OS), which further aggravates the accumulation of misfolded proteins and oxidation, in a vicious cycle. Intervention studies targeting ER stress and oxidative stress in the context of rheumatic diseases are also reviewed. Conclusions: Loss of ER homeostasis is a significant factor in the pathogeneses of RA and SLE. Targeting ER stress, unfolded protein response (UPR) pathways and oxidative stress in these diseases both in vitro and in animal models have shown promising results and deserve further investigation.

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Endoplasmic Reticulum Stress, Oxidative Stress, and Rheumatic Diseases

Despite its broad range of biological activities, use of curcumin is limited because of poor bioavailability. Here we report a novel curcumin formulation, Curcuwin Ultra+ (CU+), with superior bioavailability as compared to 95% turmeric extract (TUR 1800). A randomized, double-blind, three-treatment, crossover oral bioavailability study was conducted in 24 healthy volunteers under fasting conditions. Subjects received a single dose of CU+ 250 mg, 500 mg and 1900 mg of TUR1800 as per randomization schedule and blood samples were collected at 4 h and 0 h before dosing, and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24 h post dose. Total curcuminoids were measured as curcumin, demethoxycurcumin, bisdemethoxycurcumin, and tetrahydrocurcumin using a validated LC–MS/MS method. CU+ achieved a significantly higher (p < 0.05) maximum plasma concentration (Cmax) and total systemic exposure (AUC0–6 and AUC0–12) for total curcuminoids as compared to TUR 1800. We observed 101 and 100 times higher Cmax respectively for 250 and 500 mg doses of CU+ as compared to 1900 mg of TUR1800. Similarly, AUC0–6 was 144 and 149 times higher whereas AUC0–12 was 99 and 113 times higher respectively for 250 and 500 mg doses of CU+ as compared to 1900 mg dose of TUR1800. Further, CU+ showed 40% faster absorption (p < 0.05). No safety issues were observed. CU+, which is designed for increased absorption and protection of curcuminoids from intestinal degradation, demonstrated superior bioavailability as compared to TUR1800 at considerably smaller doses. Additional clinical studies will help to demonstrate the impact of its increased bioavailability on efficacy. CTRI/2020/10/028508 (Clinical Trials Registry—India). 

https://link.springer.com/content/pdf/10.1007/s12325-022-02081-w.pdf

Superior Bioavailability of a Novel Curcumin Formulation in Healthy Humans Under Fasting Conditions

Owing to their water insolubility, low stability, and poor absorption, anti-inflammatory curcuminoids (CUN) are difficult to be extracted and delivered to the action site. As a result, therapeutic hydrophobic deep eutectic solvents (HDESs), containing menthol and fatty acids (capric, caprylic, and oleic acids), are being developed for CUN solubilization and delivery. In this study, the anti-inflammatory effects of various combinations of HDESs with CUN and curcumin (CUR) were investigated on RAW264.7 macrophage cells. The results showed that CUN can be solubilized using the HDESs. The HDESs of oleic acid (OLA) : menthol (1 : 2, 1 : 1, and 2 : 1 molar ratios) exhibited anti-inflammatory effects, and OLA : menthol (1 : 1 molar ratio) increased the anti-inflammatory effects of CUR. The cytotoxicity of CUN and CUR was also lowered when combined with some OLA : menthol HDESs. The combination of OLA, menthol, and CUR entirely suppressed NO secretion without significant cytotoxicity. These results clearly indicate the potential of HDESs to solubilize CUN and impart anti-inflammatory properties. Furthermore, these solvents could replace organic solvents for CUN extraction, with the added benefit of being therapeutic, biodegradable, and safe for human consumption.

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Therapeutic hydrophobic deep eutectic solvents of menthol and fatty acid for enhancing anti-inflammation effects of curcuminoids and curcumin on RAW264.7 murine macrophage cells

Objective To assess the efficacy and safety of Curcuma longa Extract and curcumin supplements on osteoarthritis (OA). Methods The databases such as Pubmed and Cochrane Library were searched to collect the article about Curcuma longa Extract and curcumin in the treatment of OA. Then, randomized controlled trials (RCTs) were selected and their data was extracted. Finally, the RevMan5.3 was utilized for risk of bias assessment and meta-analysis, the STATA15.0 were utilized for publication bias assessment, and GRADE tool were used for the evidence quality assessment of primary outcomes. Results A total of 15 RCTs involving 1621 participants were included. (1) Compared with placebo, Curcuma longa Extract and curcumin (C.) can decrease the VAS and WOMAC score-pain, the WOMAC score-function and the WOMAC score-stiffness. In terms of adverse events, Curcuma longa Extract and curcumin are comparable to those of placebo. (2) Compared with NSAIDs, Curcuma longa Extract and curcumin have similar effects on joint pain, function and stiffness. The incidence of adverse events in Curcuma longa Extract and curcumin was lower. (3) Compared with the NSAIDs group, C.+NSAIDs can also decrease the VAS and WOMAC score-pain, the WOMAC score-function and the WOMAC score-stiffness. In terms of adverse events, the addition of Curcuma longa Extract and curcumin to NSAIDs did not increase adverse events. Conclusion Curcuma longa Extract and curcumin may be a safer and effective supplement for OA patients. It is recommended to use Curcuma longa Extract and curcumin supplement for OA patients for more than 12 weeks.

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The efficacy and safety of Curcuma longa extract and curcumin supplements on osteoarthritis: a systematic review and meta-analysis.

Objective To explore the efficacy of antioxidative stress therapy on oxidative stress levels in rheumatoid arthritis (RA) by a systematic review and meta-analysis of randomized controlled trials. Methods Chinese and English databases such as PubMed, Embase, China National Knowledge Infrastructure (CNKI), and China Biomedical Literature were searched, mainly searching for clinical randomized controlled trials of antioxidant therapy for rheumatoid arthritis. The search time is from the establishment of the database to July 2021. Two researchers independently carried out literature search, screening, and data extraction. The bias risk tool provided by the Cochrane Collaboration was used to evaluate the bias risk of all the included literature, and the RevMan 5.3 software was used for meta-analysis. Results A total of 24 RCTs (28 records) and 1277 participants were included. The time span of randomized controlled trials (RCTs) is from 1986 to 2020. These RCTs involve 14 types of antioxidants or antioxidant therapies, and these therapies have varying degrees of improvement on oxidative stress in RA patients. The summary results showed that the MDA in the experiment group is lower (SMD -0.82, 95% CI -1.35 to -0.28, P = 0.003). The difference of TAC, SOD, NO, GPx, CAT, and GSH between two groups was of no statistical significance (TAC (SMD 0.27, 95% CI -0.21 to 0.75, P = 0.27), SOD (SMD 0.12, 95% CI -0.16 to 0.40, P = 0.41), NO (SMD -2.03, 95% CI -4.22 to 0.16, P = 0.07), GPx (SMD 0.24, 95% CI -0.07 to 0.54, P = 0.13), CAT (SMD 2.95, 95% CI -2.6 to 8.51, P = 0.30), and GSH (SMD 2.46, 95% CI -0.06 to 4.98, P = 0.06)). For adverse events, the summary results showed that the difference was of no statistical significance (RR 1.16, 95% CI 0.79 to 1.71, P = 0.45). In addition, antioxidant therapy has also shown improvement in clinical efficacy indexes (number of tender joints, number of swollen joints, DAS28, VAS, and HAQ) and inflammation indexes (ESR, CRP, TNF-α, and IL6) for RA patients. Conclusion The existing evidence shows potential benefits, mainly in reducing MDA and increasing TAC and GSH in some subgroups. However, more large samples and higher quality RCTs are needed to provide high-quality evidence, so as to provide more clinical reference information for the antioxidant treatment of RA.

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The Efficacy of Antioxidative Stress Therapy on Oxidative Stress Levels in Rheumatoid Arthritis: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Aim. Probiotics are considered to be bone metabolism regulators, and their efficacy as an adjuvant treatment option for osteoporosis is still controversial. The purpose of this study is to compare the available data from randomized controlled trials (RCT) of probiotics in the treatment of osteoporosis and osteopenia. Methods. As of June 2021, databases such as Medline, Embase, Web of Science, and Central Cochrane Library have been used for English-language literature searches and CNKI and China Biomedical Database have been used for Chinese-language literature searches. RevMan 5.3 was used for bias risk assessment, heterogeneity detection, and meta-analysis. This research has been registered in PROSPERO (CRD42020085934). Results. This systematic review and meta-analysis included 10 RCTs involving 1156. Compared with the placebo, the absolute value of lumbar spine’s BMD was not statistically significant (WMD 0.04 (−0.00, 0.09), , random effect model), while the percentage of lumbar spine’s BMD was higher (SMD 1.16 (0.21, 2.12), , random effect model). Compared with the control group, the percentage of total hip’s BMD was not statistically significant (SMD 0.52 (−0.69, 1.73), , random effect model). The safety analysis showed that, compared with control group, the adverse events in the experimental group were not statistically significant (RR 1.02 (0.92, 1.12), , fixed effect model). Conclusion. Probiotics may be safety supplements to improve the lumbar spine’s BMD of patients with osteoporosis and osteopenia. More large-sample, random-controlled, high-quality RCTs are needed to further verify the effectiveness and safety of probiotics in intervening osteoporosis or osteopenia.

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The Improving Effect and Safety of Probiotic Supplements on Patients with Osteoporosis and Osteopenia: A Systematic Review and Meta-Analysis of 10 Randomized Controlled Trials.

Wensa Hao

Papers

The efficacy and safety of Curcuma longa extract and curcumin supplements on osteoarthritis: a systematic review and meta-analysis.

The Efficacy of Antioxidative Stress Therapy on Oxidative Stress Levels in Rheumatoid Arthritis: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

The Improving Effect and Safety of Probiotic Supplements on Patients with Osteoporosis and Osteopenia: A Systematic Review and Meta-Analysis of 10 Randomized Controlled Trials.