Avocado/soybean Unsaponifiables Research Articles

Periodontal host-modulation therapy with avocado/soybean unsaponifiables in rats with arthritis.

The aim of this study was to evaluate the effect of the avocado/soybean unsaponifiables (ASU) in the treatment of induced periodontitis in rats with experimental arthritis. Sixty rats were randomly assigned to 4 groups according to the type of treatment and the systemic condition of the animals: CTR-S: healthy animals in which saline solution (SS) was administered; ASU-S: healthy animals in which ASU (0.6 mg/kg) was administered; AR/ASU-S: animals with induced arthritis in which ASU was administered; AR-S: animals with induced arthritis in which SS was administered. Periodontitis was induced by ligatures, maintained for 15 days. Subsequently, the treatment was performed by scaling with hand instruments. The SS and ASU were administered daily by gavage until euthanasia of the animals that occurred at 7, 15 or 30 days after the scaling procedure (N.=5 animals/group). Bone resorption, inflammatory infiltrate composition, and osteoclastogenesis were assessed. The AR-S group had greater bone loss, smaller amounts of fibroblasts and larger amounts of inflammatory cells than all other groups. In addition, the AR-S group had greater osteoclastogenesis in relation to the healthy animal groups. The use of ASU improved the healing pattern after treatment for experimental periodontitis in animals with arthritis reducing the periodontal bone loss.

Exploring Future Horizons in Osteoarthritis Relief: Unveiling the Potential of Slow-Acting Drugs and Innovative Medications

Introduction: 
 The existing treatment options for osteoarthritis (OA) fall short of addressing the significant challenges this disease imposes on patients in today's society. It markedly diminishes the quality of life of those affected and is one of the leading causes of disability. While conventional pharmacological interventions such as non-steroidal anti-inflammatory drugs (NSAIDs) and opioids effectively address pain, they are not intended to halt disease progression and are associated with potential health risks. Symptomatic Slow-Acting Drugs for Osteoarthritis (SYSADOA) and innovative medications, rooted in our expanding understanding of OA pathogenesis, offer promising prospects for discovering improved treatment modalities.
 
 State of knowledge: 
 The evolving understanding of OA's etiology highlights the necessity for tailored treatments that consider distinct disease phenotypes. This review critically examines SYSADOA, specifically focusing on chondroitin sulfate, glucosamine, and avocado-soybean unsaponifiables, as agents designed to address the underlying pathology of OA. Chondroitin sulfate demonstrates potential disease-modifying effects, however with conflicting study results that underscore the extent of its efficacy. Glucosamine exhibits varying disease-modifying effects, with short-term trials demonstrating more promising outcomes in pain reduction. Avocado-soybean unsaponifiables show promise in alleviating knee OA pain, yet their impact on hip OA symptoms remains inconclusive. The review extends its scope to novel drugs with potential disease-modifying effects, exploring proteinase inhibitors, fibroblast growth factors, Wnt-signaling pathway inhibitors, senolytic agents, anti-nerve growth factor agents, and transforming growth factor-β.
 
 Conclusions: 
 Although preliminary studies indicate potential for certain novel agents, challenges and adverse effects necessitate further investigation through rigorous, high-quality research.

From misconceptions to reasonable osteoarthritis patients therapy

Osteoarthritis (OA) is a painful and disabling disease that affects millions of people around the world. OA is the most common form of arthritis and is characterized by joint pain and stiffness, leading to a decrease in functional activity and loss of quality of life. Approaches to OA therapy are constantly being revised, as new molecules appear, data on drugs/molecules already in use, including data on adverse events, new randomized controlled trials results, new methods of adjunctive therapy become available. OA therapy and prevention, drugs with chondroprotective properties are prescribed according to the opinion of European experts (2019): chondroitin sulfate (CS), glucosamine sulfate (GS), diacerein, avocado soybean unsaponifiables, hyaluronic acid (HA) for intra-articular administering. Only CS and GS have proven effectiveness and the level of recommendations A1, they are included in clinical recommendations and standards of the Ministry of Health of the Russian Federation (MHRF), and international recommendations according to which CS and GS should be used for a long time (up to 6 months). The article focuses on the analysis of erroneous statements regarding the classification, composition and mechanisms of action of different drugs of this group. Differences in terminology of drug groups are given, such as: chondroprotectors, symptomatic slow acting drugs for osteoarthritis (SYSADOAs), disease-modifying osteoarthritis drugs, between which an equal sign cannot be placed. Based on the analysis, a conclusion was made about erroneous attitudes towards some SYSADOAs: 1) according to the Anatomical Therapeutic Chemical Classification, the active substances CS, GS, diacerein and HA are classified as nonsteroidal anti-inflammatory drugs due to their antiinflammatory activity; 2) quite often, drugs based on bioactive concentrate of small sea fish and glycoaminoglycan-peptide complex do not belong to SYSADOAs according to any of the existing generally recognized classifications, they do not contain a sufficient amount of active substances (CS or peptides), there is no proper level of evidence, they are not included in the recommendations of international medical communities and MHRF clinical recommendations and standards. In Russia, physicians must follow MHRF clinical guidelines and standards for OA therapy.

Beneficial effects of arthrocen on neuroinflammation and behavior like depression in stroke in a murine model.

Stroke is a considerable reason for death, disability, socioeconomic loss, and depression in the world. Notably, many attempts to the reduction of the complications of poststroke injuries like depression have failed so far. In this study, we aimed to evaluate the anti-inflammatory effect of arthrocen, avocado/soybean unsaponifiables (ASU), in the poststroke injuries like depression improvement in a mice model. We examined the antidepressant-like effect of arthrocen using the forced swimming test and tail suspension test in mice subjected to stroke. Furthermore, immunohistochemistry of proinflammatory cytokines, IL-10 and TNF-α, and neural cell count were performed in the ischemic brain hippocampus of mice. Oral arthrocen reduced significantly (p< .001) the immobility time in the forced swimming test and tail suspension test in the stroke animals. Also, immunohistochemistry analysis of the hippocampus indicated significantly (p< .01) the reduction of IL-10 and TNF-α cytokines production. Nissl staining showed a significant (p< .0001) increase in the number of viable neurons in stroke mice receiving arthrocen. In conclusion, our data revealed the antidepressant activity of arthrocen in the stroke mice which may be the result of its anti-inflammatory and neuroprotective role.

Comparison of Chondrogenesis Induction by TGF-β3, Kartogenin and Avocado/ soybean Unsaponifiables Between Laboratory and Animal Models

Background and Objectives Cartilage tissue engineering, by using stem cells, scaffolding and appropriate growth factors, seek to produce natural cartilage tissue to replace damaged tissue and solve the problems that exist in the treatment of cartilage damage. This study aims to compare chondrogenic differentiation of adipose-derived stem cells under the influence of the transforming growth factor beta 3 (TGF-β3), Kartogenin, and avocado/soybean unsaponifiables (ASU) on the fibrin scaffold in the laboratory and animal models. Subjects and Methods In this experimental laboratory study, after extraction of stem cells from human adipose tissue, induction of chondrogenic differentiation was done for 14 days on the fibrin scaffold in laboratory. The cells differentiated in the fibrin scaffold were transplanted subcutaneously under the skin of male rats for two weeks. Then, comparison of histological and immunohistochemical studies was performed in both laboratory and animal models. Results A significant increase in the density of Toluidine blue dye accumulation was observed in TGF-β3, Kartogenin and ASU groups in the animal model compared to the laboratory model. Immunohistochemical results for the collagen type X accumulation in the TGF-β3 group showed a significant increase in the animal model compared to the laboratory model. In the Kartogenin and ASU groups, the accumulation of collagen type Χ showed a significant decrease in the animal model compared to the laboratory model. Conclusion The implantation of differentiated cartilage cells in laboratory before subcutaneous transfer to the skin can help mature and complete the characteristics of the constructed cartilage.

Composition Analysis and Pharmacological Activity of Avocado/Soybean Unsaponifiable Products Used in the Treatment of Osteoarthritis.

Objective: Avocado/soybean unsaponifiables (ASUs) are commonly used to treat OA symptoms. However, there are many ASU mixtures on the market with differing compositions and pharmacological activities. This study aimed to compare the composition and pharmacological activity of seven commercially available ASU products on human osteoarthritis chondrocytes. Methods: The contents of the lipidic part of ASUs were characterized by gas chromatography analysis using a VARIAN 3400 chromatograph. The pharmacological activity of the ASU products was tested on human osteoarthritis chondrocytes cultured in alginate beads. Their effects were evaluated on aggrecan, interleukin (IL)-6 and -8, and matrix metalloproteases (MMP)-3 using immunoassays and on nitric oxide through measurement of nitrite via spectrometry. Results: PIASCLEDINE-ExpASU® showed a specific profile with the presence of chromatographic peaks corresponding to an alkyl furan fraction and alkyl triols. PIASCLEDINE-ExpASU®, Persemax, Insaponifiable 300, Arthrocen, and Arthocare contained quantifiable amounts of tocopherol, while tocopherol was undetectable in Avovida and Saponic. Squalene was found only in PIASCLEDINE-ExpASU®. The abundance of sterols varied depending on the product. PIASCLEDINE-ExpASU® was the most active of the tested ASU products in inhibiting nitric oxide, IL-6, and IL-8 production by chondrocytes. With the exception of Saponic and Persemax, all the ASU mixtures either slightly or significantly increased aggrecan production. MMP-3 levels were significantly decreased by Insaponifiable 300 and PIASCLEDINE-ExpASU® and significantly increased by Saponic. Conclusion: The composition of PIASCLEDINE-ExpASU® is different to that of the other evaluated ASU mixtures. This specific composition explains its better pharmacological activity, including the higher inhibitory effect on pro-inflammatory and pro-catabolic factors. Our findings are helpful in providing a basis for understanding the symptomatic effect of PIASCLEDINE-ExpASU® in patients with osteoarthritis.

Evaluation Avocado Soybean Unsaponifiables Loaded in Poly (lactic-co-glycolic) Acid/Avocado Soybean Unsaponifiables-Fibrin Nanoparticles Scaffold (New Delivery System) is an Effective Factor for Tissue Engineering.

Background:Growth factors and chemical stimulants have key role in cartilage tissue engineering, but these agents have unfavorable effects on cells. Avocado soybean unsaponifiables (ASU) has chondroprotective and anti-inflammatory effects. In this study, fibrin2nanoparticles (FNP)/ASU, as a new delivery system, with stem cells applied for cartilage tissue engineering in poly (lactic-co-glycolic) acid (PLGA) scaffold.Materials and Methods:FNP/ASU prepared by freeze milling and freeze drying. NFP/ASU was characterized by dynamic light scattering (DLS). PLGA-NFP/ASU scaffold was fabricated and assessed by scanning electron microscope (SEM). Human adipose-derived stem cells (hADSCs) were seeded on scaffold and induced for chondrogenesis. After 14 days, cell viability and gene/protein expression evaluated.Results:The results of DLS and SEM indicated that nanoparticles had high quality. The expression of type II collagen and SOX9 and aggrecan (ACAN) genes in differentiated cells in the presence of ASU was significantly increased compared with the control group (P and lt; 0.01), on the other hand, type I collagen expression was significantly decreased and western blot confirmed it.Conclusions:This study indicated FNP/ASU loaded in PLGA scaffold has excellent effect on chondrogenic differentiation of hADSCs and tissue engineering.

EFFICACY OF HERBAL AND NATURALLY-DERIVED DIETARY SUPPLEMENTS FOR THE MANAGEMENT OF KNEE OSTEOARTHRITIS: A MINI-REVIEW

Knee osteoarthritis (OA) accounts for approximately 85% of the burden of OA worldwide. Knee OA is a whole joint disorder involving structural alterations in the hyaline articular cartilage, subchondral bone, ligaments, capsule, synovium, and periarticular muscles. The complex knee OA pathogenesis includes mechanical, inflammatory, and metabolic factors, eventually leading to the synovial joint’s structural destruction and failure. This review aims to present an overview of current knowledge on dietary supplements, such as glucosamine, chondroitin, methylsulfonylmethane, diacerein, avocado-soybean unsaponifiables, curcuminoids, as well as boswellic acids. Results originating from several small studies with natural products in managing knee OA are encouraging. However, additional well-designed placebo-controlled clinical trials are required.

Impact of Fibrin on the Chondrogenic Avocado Soybean Unsaponifiables on Poly (Lactic-co-Glycolic) Acid Scaffold

Synthetic and naturally derived-biodegradable polymers have been applied extensively for scaffold fabrication for cartilage tissue engineering. Human adipose-derived stem cells (hADSCs) seeded in poly (lactic-co-glycolic) acid (PLGA) and PLGA/fibrin scaffolds and cultured in chondrogenic media containing Soybean Unsaponifiables (ASU). All constructs were cultured for 14 days. Cell viability was measured by MTT assay. Chondrogenic differentiation markers, including type II collagen (Coll II), Aggrecan (AGG), and SOX9, were detected by real-time PCR. Hypertrophic and Fibrous differentiation was also analyzed using gene expression type X (Coll X) and Ι (Coll Ι) collagen. The MTT results on the 14th day showed that the viability of hADSCs in the PLGA group was higher than the PLGAL/Fibrin group, but it was not significant. Real-time PCR results demonstrated that SOX9, Coll II, and AGG gene expression in the PLGA and PLGA/Fibrin groups are higher than the control group. The real-time PCR results indicated that Coll X in the PLGA/Fibrin group is lower than the PLGA and control groups. Also, Coll I gene expression in the PLGA group was higher in contrast with the control group. Administrating fibrin with a PLGA scaffold can induce chondrogenesis in hADSCs on chondrogenic media containing ASU.

Avocado-Soybean Unsaponifiables: A Panoply of Potentialities to Be Exploited.

Avocado and soybean unsaponifiables (ASU) constitute vegetable extracts made from fruits and seeds of avocado and soybean oil. Characterized by its potent anti-inflammatory effects, this ASU mixture is recommended to act as an adjuvant treatment for osteoarthritic pain and slow-acting symptomatic treatment of hip and knee osteoarthritis; autoimmune diseases; diffuse scleroderma and scleroderma-like states (e.g., morphea, sclerodactyly, scleroderma in bands). Besides, it was reported that it can improve the mood and quality of life of postmenopausal women in reducing menopause-related symptoms. This article aims to summarize the studies on biological effects of the avocado–soybean unsaponifiable, its chemical composition, pharmacotherapy as well as applications in autoimmune, osteoarticular and menopausal disorders. Finally, we will also discuss on its safety, toxicological and regulatory practices.

Avocado/Soybean Unsaponifiables, Glucosamine and Chondroitin Sulfate Combination Inhibits Proinflammatory COX-2 Expression and Prostaglandin E2 Production in Tendon-Derived Cells.

Tendinopathy, a common disorder in man and horses, is characterized by pain, dysfunction, and tendon degeneration. Inflammation plays a key role in the pathogenesis of tendinopathy. Tendon cells produce proinflammatory molecules that induce pain and tissue deterioration. Currently used nonsteroidal anti-inflammatory drugs are palliative but have been associated with adverse side effects prompting the search for safe, alternative compounds. This study determined whether tendon-derived cells' expression of proinflammatory cyclooxygenase (COX)-2 and production of prostaglandin E2 (PGE2) could be attenuated by the combination of avocado/soybean unsaponifiables (ASU), glucosamine (GLU), and chondroitin sulfate (CS). ASU, GLU, and CS have been used in the management of osteoarthritis-associated joint inflammation. Tenocytes in monolayer and microcarrier spinner cultures were incubated with media alone, or with the combination of ASU (8.3 μg/mL), GLU (11 μg/mL), and CS (20 μg/mL). Cultures were next incubated with media alone, or stimulated with interleukin-1β (IL-1β; 10 ng/mL) for 1 h to measure COX-2 gene expression, or for 24 h to measure PGE2 production, respectively. Tenocyte phenotype was analyzed by phase-contrast microscopy, immunocytochemistry, and Western blotting. Tendon-derived cells proliferated and produced extracellular matrix component type I collagen in monolayer and microcarrier spinner cultures. IL-1β-induced COX-2 gene expression and PGE2 production were significantly reduced by the combination of (ASU+GLU+CS). The suppression of IL-1β-induced inflammatory response suggests that (ASU+GLU+CS) may help attenuate deleterious inflammation in tendons.

Efficacy and safety of avocado-soybean unsaponifiables for the treatment of hip and knee osteoarthritis: A systematic review and meta-analysis of randomized placebo-controlled trials.

We performed a systematic review and meta-analysis from randomized controlled trials to examine the efficacy and safety of avocado-soybean unsaponifiables (ASU) in patients with hip or knee osteoarthritis (OA). Medline, SCOPUS, Web of Science, and Google Scholar databases were searched for randomized placebo-controlled trials. Original studies were randomized placebo-controlled trials evaluating the effect of orally administered ASU on knee or hip OA symptoms using the Lequesne index, visual analog scale (VAS) and/or joint space width (JSW). Meta-analysis was conducted using a random-effects model and generic inverse variance method. Heterogeneity was tested using the I2 statistic index. Avocado-soybean unsaponifiables therapy had a significant reduction on pain by VAS assessment (weighted mean difference [WMD]: -9.64mm, 95% CI: -17.43, -1.84; P=.02; I2 =92%). A subanalysis according to the type of OA showed that ASU significantly decreased both VAS and Lequesne index in knee OA (WMD: -17.36, 95% CI: -25.91, -8.82; P<.0001; I2 =87% and WMD: -2.33, 95% CI: -2.88, -1.78; P<.00001; I2 =18%, respectively) but not in hip OA. Finally, ASU supplementation showed no significant differences for adverse events compared to placebo (relative risk: 1.02, 95% CI: 0.83, 1.25; P=.88; I2 =0%). Results of this meta-analysis suggest a beneficial effect of ASU treatment in symptomatic knee OA but not in hip OA. Additionally, adverse events were similar in patients receiving ASU therapy or placebo.

Mitigation of Antibiotic-Inducted Toxicity in Equine Chondrocytes by Soybean/Glucosamine/Chondroitin Combination

Objectives The aim of this study was to evaluate the effect of amikacin (AK) and enrofloxacin (EF) at concentrations consistent with those obtained by intra-articular and intravenous regional limb perfusion on both cytotoxicity and prostaglandin E2 (PGE2) production by equine chondrocytes. This study also determines if PGE2 production could be reduced by avocado/soybean unsaponifiables (ASU), glucosamine (GLU) and chondroitin sulphate (CS). Study Design Chondrocytes were grown in monolayer from the articular cartilage of 12 horses and treated with clinically relevant concentrations of AK and EF, with or without the combination of ASU + GLU + CS. Positive controls consisted of chondrocytes that were activated with lipopolysaccharide (LPS). Chondrocyte response was evaluated using both MTT cytotoxicity assay and immunoassay for PGE2 production. Results Amikacin and EF generated a dose-dependent cytotoxicity. Amikacin induced 90% cell death at a concentration of 25 mg/mL. Enrofloxacin induced 90% cell death at 1.0 mg/mL and 98% cell death at 10 mg/mL (p &lt; 0.05). Amikacin failed to induce PGE2 production at any of the concentrations studied. In contrast, EF and the positive control (LPS) induced PGE2 production at all concentrations. Induction of PGE2 by EF at all concentrations was significantly reduced (p &lt; 0.05) by pre-treatment with ASU + GLU + CS. Conclusions and Clinical Relevance Horses receiving commonly used dosages of AK and EF may benefit from administration of ASU + GLU + CS.

What factors affect the effectiveness of long - term analgesic therapy for osteoarthritis? Data analysis of the multi - center 3-month PARACELSUS study

There are factors that can affect the effectiveness of treatment of osteoarthritis (OA). Aim to identify factors affecting the effectiveness of long - term analgesic therapy in OA. Materials and methods. The study included 6448 patients (70.9% female and 29.1% male), middle age 57.8±10.2 years, with severe pain [≥40 mm on the visual analog scale]. All patients received the preparation of avocado - soybean unsaponifiables (ASU) 300 mg/day. For pain relief at the beginning and during the study, the drug Ketoprofen lysine salt (KLS) 320 mg/day was used. The efficiency criterion was pain reduction ≥50% and satisfaction with treatment ≥4 on a 5-point scale. The influence of a number of factors on the result of treatment was evaluated. Results. For 3 months of treatment, the pain decreased from 63.7±12.0 to 14.2±11.7 mm VAS. The result was evaluated as "good" or "excellent" 81.7% of patients. Adverse reactions were rare. In total, a good response to therapy was noted in 87.4% of patients. Gender, body mass index ≥30 kg/m2, type 2 diabetes mellitus, poor effect of non - steroidal anti - inflammatory drugs (NSAIDs) and Symptomatic Slow-Acting Drugs in Osteoarthritis (SYSADOA) in history did not affect the result. The effect was lower in persons >65 years [odds ratio (OR) 0.418; 95% confidence interval (CI) 0.342-0.509, p2 by Kellgren-Lawrence (OR 0.556; 95% CI 0.298-0.738, p.

Dietary Ingredients as an Alternative Approach for Mitigating Chronic Musculoskeletal Pain: Evidence-Based Recommendations for Practice and Research in the Military.

ObjectiveApproximately 55–76% of Service members use dietary supplements for various reasons, including pain and related outcomes. This work evaluates current research on dietary ingredients for chronic musculoskeletal pain to inform decisions for practice and self-care, specifically for Special Operations Forces personnel.MethodsA steering committee convened to develop research questions and factors required for decision-making. Key databases were searched through August 2016. Eligible systematic reviews and randomized controlled trials were assessed for methodological quality. Meta-analysis was applied where feasible. GRADE was used to determine confidence in the effect estimates. The committee made evidence-informed judgments and recommendations for practice and self-care use.ResultsNineteen eligible dietary ingredients were assessed for quality, efficacy, and safety. Avocado soybean unsaponifiables, capsaicin, curcuma, ginger (as a food source), glucosamine, melatonin, polyunsaturated fatty acids, and vitamin D were conditionally recommended as their benefits outweighed risks, but there was still some uncertainty about the trade-offs. No recommendations were made for boswellia, ginger (as a dietary supplement), rose hip, or s-adenosyl-L-methionine. Recommendations were made against the use of collagen, creatine, devil’s claw, l-carnitine, methylsulfonylmethane, pycnogenol, willow bark extract, and vitamin E. Research priorities were developed to address gaps precluding stronger recommendations.ConclusionsCurrently the scientific evidence is insufficiently robust to establish definitive clinical practice guidelines, but processes could be established to track the impact of these ingredients. Until then, providers have the evidence needed to make informed decisions about the safe use of these dietary ingredients, and future research can address existing gaps.

Conditional Recommendations for Specific Dietary Ingredients as an Approach to Chronic Musculoskeletal Pain: Evidence-Based Decision Aid for Health Care Providers, Participants, and Policy Makers.

Approximately 55-76% of Service members use dietary supplements for various reasons; although such use has become popular for a wide range of pain conditions, decisions to use supplements are often driven by information that is not evidence-based. This work evaluates whether the current research on dietary ingredients for chronic musculoskeletal pain provides sufficient evidence to inform decisions for practice and self-care, specifically for Special Operations Forces personnel. A steering committee convened to develop research questions and factors required for decision-making. Key databases were searched through August 2016. Eligible systematic reviews and randomized controlled trials were assessed for methodological quality. Meta-analysis was applied where feasible. GRADE was used to determine confidence in the effect estimates. A decision table was constructed to make evidence-informed judgments across factors required for decision-making, and recommendations were made for practice and self-care use. Nineteen dietary ingredients were included. Conditional evidence-based recommendations were made for the use of avocado soybean unsaponifiables, capsaicin, curcuma, ginger, glucosamine, melatonin, polyunsaturated fatty acids, and vitamin D. In these cases, desirable effects outweighed undesirable effects, but there was uncertainty about the trade-offs, either because the evidence was low quality or because benefits and downsides were closely balanced. The evidence showed that certain dietary ingredients, when taken as part of a balanced diet and/or as a supplement (e.g., pill, tablet, capsule, cream), may alleviate musculoskeletal pain with no to minimal risk of harm. This finding emphasizes and reinforces the critical importance of shared decision-making between Operators and their health care providers.

Safety of Symptomatic Slow-Acting Drugs for Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis.

BackgroundSymptomatic slow-acting drugs for osteoarthritis (SYSADOAs) are an important drug class in the treatment armamentarium for osteoarthritis (OA).ObjectiveWe aimed to re-assess the safety of various SYSADOAs in a comprehensive meta-analysis of randomized placebo-controlled trials, using, as much as possible, data from full safety reports.MethodsWe performed a systematic review and random-effects meta-analyses of randomized, double-blind, placebo-controlled trials that assessed adverse events (AEs) with various SYSADOAs in patients with OA. The databases MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL) and Scopus were searched. The primary outcomes were overall severe and serious AEs, as well as AEs involving the following Medical Dictionary for Regulatory Activities (MedDRA) system organ classes (SOCs): gastrointestinal, cardiac, vascular, nervous system, skin and subcutaneous tissue, musculoskeletal and connective tissue, renal and urinary system.ResultsDatabase searches initially identified 3815 records. After exclusions according to the selection criteria, 25 studies on various SYSADOAs were included in the qualitative synthesis, and 13 studies with adequate data were included in the meta-analyses. Next, from the studies previously excluded according to the protocol, 37 with mainly oral nonsteroidal anti-inflammatory drugs (NSAIDs) permitted as concomitant medication were included in a parallel qualitative synthesis, from which 18 studies on various SYSADOAs were included in parallel meta-analyses. This post hoc parallel inclusion was conducted because of the high number of studies allowing concomitant anti-OA medications. Indeed, primarily excluding studies with concomitant anti-OA medications was crucial for a meta-analysis on safety. The decision for parallel inclusion was made for the purpose of comparative analyses. Glucosamine sulfate (GS), chondroitin sulfate (CS) and avocado soybean unsaponifiables (ASU; Piascledine®) were not associated with increased odds for any type of AEs compared with placebo. Overall, with/without concomitant OA medication, diacerein was associated with significantly increased odds of total AEs (odds ratio [OR] 2.22; 95% confidence interval [CI] 1.58–3.13; I2 = 52.8%), gastrointestinal disorders (OR 2.85; 95% CI 2.02–4.04; I2 = 62.8%) and renal and urinary disorders (OR 3.42; 95% CI 2.36–4.96; I2 = 17.0%) compared with placebo. In studies that allowed concomitant OA medications, diacerein was associated with significantly more dermatological disorders (OR 2.47; 95% CI 1.42–4.31; I2 = 0%) and more dropouts due to AEs (OR 3.18; 95% CI 1.85–5.47; I2 = 13.4%) than was placebo. No significant increase in serious or severe AEs was found with diacerein versus placebo.ConclusionsGS and CS can be considered safe treatments for patients with OA. All eligible studies on ASU included in our analysis used the proprietary product Piascledine® and allowed other anti-OA medications; thus, the safety of ASU must be confirmed in future studies without concomitant anti-OA medications. Given the safety concerns with diacerein, its usefulness in patients with OA should be assessed, taking into account individual patient characteristics.Electronic supplementary materialThe online version of this article (10.1007/s40266-019-00662-z) contains supplementary material, which is available to authorized users.

A Comparison between Avocado-Soybean Unsaponifiables and Celecoxib on Serum Levels of Cartilage Oligomeric Matrix Protein in Patients with Knee Osteoarthritis

Background/objectives: Cartilage oligomeric matrix protein (COMP) as a marker of cartilage destruction. We aimed to compare the effect of a mixture of avocado-soybean unsaponifiables versus celecoxib on the serum level of COMP in patients with knee osteoarthritis.Methods: This was a randomized controlled trial and the patients with knee osteoarthritis were recruited from those who attended Imam Reza Hospital, Mashhad, Iran. The patients were divided randomly into two groups; Group 1 (n=30) received avocado+soybean mixture (300 mg daily) and group 2 (n=30) received celecoxib (200 mg/day) for 2 months. At the enrollment and then every month up to 2 months, the patients' venous blood samples were collected to measure serum COMP.Results: The total number of patients was 60 (male 38%, female 62%) with a mean age 56±7 years. Before treatment, the serum levels of COMP were 14.5±1.4 unit/liter (U/L) and 13.9±1.4 U/L in avocado+soybean mixture and celecoxib groups, respectively (P=0.052). After the first month the serum levels of COMP were 12.3±1.5 U/L and 12.8±1 U/L in avocado+soybean mixture and celecoxib groups, respectively (P

Anti-Inflammatory Effect of Carprofen Is Enhanced by Avocado/Soybean Unsaponifiables, Glucosamine and Chondroitin Sulfate Combination in Chondrocyte Microcarrier Spinner Culture.

Osteoarthritis is a painful, chronic joint disease affecting man and animals with no known curative therapies. Palliative nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used but they cause adverse side effects prompting the search for safer alternatives. To address this need, we evaluated the anti-inflammatory activity of avocado/soybean unsaponifiables (ASU), glucosamine (GLU), and chondroitin sulfate (CS) with or without the NSAID carprofen. Canine chondrocytes were propagated in microcarrier spinner culture and incubated with (1) control medium, (2) ASU (8.3 µg/mL) + GLU (11 µg/mL) + CS (20 µg/mL) combination for 24 hours; and/or carprofen (40 ng/mL). Cultures were next incubated with control medium alone or IL-1β (10 ng/mL) for another 24 hours. Production of PGE2, IL-6, IL-8, and MCP-1 (also known as CCL-2) were measured by ELISA. Chondrocytes proliferated in microcarrier spinner culture and produced type II collagen and aggrecan. Stimulation with IL-1β induced significant increases in PGE2, IL-6, IL-8, and MCP-1 production. The increases in production were suppressed by carprofen as well as [ASU+GLU+CS]. The combination of carprofen and [ASU+GLU+CS] reduced PGE2 production significantly more than either preparation alone. The inhibitory effect of carprofen on IL-6, IL-8, and MCP-1 production was significantly less than that of [ASU+GLU+CS], whereas the combination did not reduce the production of these molecules significantly more than [ASU+GLU+CS] alone. The potentiating effect of [ASU+GLU+CS] on low-dose carprofen was identified in chondrocyte microcarrier spinner cultures. Our results suggest that the combination of low-dose NSAIDs like carprofen with [ASU+GLU+CS] could offer a safe, effective management for joint pain.

Avocado soybean unsaponifiables ameliorates cartilage and subchondral bone degeneration in mono-iodoacetate-induced knee osteoarthritis in rats.

Osteoarthritis (OA), the most common type of arthritis, is a disabling progressive disease mainly affecting the elderly and is becoming a major public health problem. Current therapies for OA provide only palliative pain relief and therapeutic candidates that are able to slow the progression of structural deterioration is a major unmet need for this disorder. Avocado soybean unsaponifiables (ASU) has proven its safety and effectiveness in clinical studies of knee osteoarthritis (OA); however, whether ASU exerts structure-modifying effects is still to be elucidated. There are limited studies that have explored the underlying mechanisms of ASU's beneficial effects in animal models of OA. To this end, this study is the first to evaluate the effects of ASU in a rat model of mono-iodoacetate (MIA)-induced knee OA. OA was induced in rats by knee intra-patellar injection of MIA. Oral administration of ASU (27.5 mg/kg per day for 3 weeks) was initiated 3 weeks after MIA injection. We analysed the knee samples using light and electron microscopy. In addition, we used immunohistochemistry to investigate the expression of inducible nitric oxide synthase (iNOS), tumour necrosis factor-α (TNF-α), and matrix metalloproteinase-13 (MMP-13) in OA cartilage and subchondral bone. ASU significantly attenuated the synovium, cartilage, and subchondral degeneration. In addition, it reduced the expression of TNF-α and MMP-13 in OA cartilage and the expression of iNOS in both OA cartilage and subchondral bone. These results provide evidence of the structure-modifying abilities of ASU via its anti-oxidative and anti-inflammatory properties, in addition to its ability to modulate MMP-13 activity. This work suggests that ASU can be used as a potential disease-modifying treatment for OA.