The Development of Naringin for Use against Bone and Cartilage Disorders

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Abstract

Bone and cartilage disorders are the leading causes of musculoskeletal disability. There is no absolute cure for all bone and cartilage disorders. The exploration of natural compounds for the potential therapeutic use against bone and cartilage disorders is proving promising. Among these natural chemicals, naringin, a flavanone glycoside, is a potential candidate due to its multifaceted pharmacological activities in bone and cartilage tissues. Emerging studies indicate that naringin may promote osteogenic differentiation, inhibit osteoclast formation, and exhibit protective effects against osteoporosis in vivo and in vitro. Many signaling pathways, such as BMP-2, Wnt/β-catenin, and VEGF/VEGFR, participate in the biological actions of naringin in mediating the pathological development of osteoporosis. In addition, the anti-inflammatory, anti-oxidative stress, and anti-apoptosis abilities of naringin also demonstrate its beneficial effects against bone and cartilage disorders, including intervertebral disc degeneration, osteoarthritis, rheumatoid arthritis, bone and cartilage tumors, and tibial dyschondroplasia. Naringin exhibits protective effects against bone and cartilage disorders. However, more efforts are still needed due to, at least in part, the uncertainty of drug targets. Further biological and pharmacological evaluations of naringin and its applications in bone tissue engineering, particularly its therapeutic effects against osteoporosis, might result in developing potential drug candidates.

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Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies

Gary Williamson, Claudine Manach, Christine Morand … (2005)

Polyphenols are abundant micronutrients in our diet, and evidence for their role in the prevention of degenerative diseases is emerging. Bioavailability differs greatly from one polyphenol to another, so that the most abundant polyphenols in our diet are not necessarily those leading to the highest concentrations of active metabolites in target tissues. Mean values for the maximal plasma concentration, the time to reach the maximal plasma concentration, the area under the plasma concentration-time curve, the elimination half-life, and the relative urinary excretion were calculated for 18 major polyphenols. We used data from 97 studies that investigated the kinetics and extent of polyphenol absorption among adults, after ingestion of a single dose of polyphenol provided as pure compound, plant extract, or whole food/beverage. The metabolites present in blood, resulting from digestive and hepatic activity, usually differ from the native compounds. The nature of the known metabolites is described when data are available. The plasma concentrations of total metabolites ranged from 0 to 4 mumol/L with an intake of 50 mg aglycone equivalents, and the relative urinary excretion ranged from 0.3% to 43% of the ingested dose, depending on the polyphenol. Gallic acid and isoflavones are the most well-absorbed polyphenols, followed by catechins, flavanones, and quercetin glucosides, but with different kinetics. The least well-absorbed polyphenols are the proanthocyanidins, the galloylated tea catechins, and the anthocyanins. Data are still too limited for assessment of hydroxycinnamic acids and other polyphenols. These data may be useful for the design and interpretation of intervention studies investigating the health effects of polyphenols.

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Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies

Aiyong Cui, Huizi Li, Dawei Wang … (2020)

Background Knee osteoarthritis (OA) is a major cause of disability in the elderly, however, there are few studies to estimate the global prevalence, incidence, and risk factors of knee OA. Methods For this study, we searched PUBMED, EMBASE and SCOPUS from inception to April 4, 2020, without language restriction. We identified eligible studies with information on the prevalence or incidence of knee OA in population-based observational studies and extracted data from published reports. We did random-effects meta-analysis to generate estimates. This study was registered with PROSPERO (CRD42020181035). Findings Out of 9570 records identified, 88 studies with 10,081,952 participants were eligible for this study. The pooled global prevalence of knee OA was 16⋅0% (95% CI, 14⋅3%-17⋅8%) in individuals aged 15 and over and was 22⋅9% (95% CI, 19⋅8%-26⋅1%) in individuals aged 40 and over. Correspondingly, there are around 654⋅1 (95% CI, 565⋅6–745⋅6) million individuals (40 years and older) with knee OA in 2020 worldwide. The pooled global incidence of knee OA was 203 per 10,000 person-years (95% CI, 106–331) in individuals aged 20 and over. Correspondingly, there are around annual 86⋅7 (95% CI, 45⋅3–141⋅3) million individuals (20 years and older) with incident knee OA in 2020 worldwide. The prevalence and incidence varied substantially between individual countries and increased with age. The ratios of prevalence and incidence in females and males were 1⋅69 (95% CI, 1⋅59–1⋅80, p<0⋅00) and 1⋅39 (95% CI, 1⋅24–1⋅56, p<0⋅00), respectively. Interpretation Our study provides the global prevalence (16⋅0% [95% CI, 14⋅3%-17⋅8%]) and incidence (203 per 10,000 person-years [95% CI, 106–331]) of knee OA. These findings can be used to better assess the global health burden of knee OA. Further prospective cohort studies are warranted to identify modifiable risk factors for providing effectively preventive strategies in the early stages of the disease. Funding This work was supported by grants from the 10.13039/501100001809 National Natural Science Foundation of China (nos. 81772384 and 81572174).

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Immunopathogenesis of Rheumatoid Arthritis.

Gary S. Firestein, Iain McInnes (2017)

Rheumatoid arthritis (RA) is the most common inflammatory arthropathy. The majority of evidence, derived from genetics, tissue analyses, models, and clinical studies, points to an immune-mediated etiology associated with stromal tissue dysregulation that together propogate chronic inflammation and articular destruction. A pre-RA phase lasting months to years may be characterized by the presence of circulating autoantibodies, increasing concentration and range of inflammatory cytokines and chemokines, and altered metabolism. Clinical disease onset comprises synovitis and systemic comorbidities affecting the vasculature, metabolism, and bone. Targeted immune therapeutics and aggressive treatment strategies have substantially improved clinical outcomes and informed pathogenetic understanding, but no cure as yet exists. Herein we review recent data that support intriguing models of disease pathogenesis. They allude to the possibility of restoration of immunologic homeostasis and thus a state of tolerance associated with drug-free remission. This target represents a bold vision for the future of RA therapeutics.