Amelioration of human osteoarthritis symptoms with topical ‘biotherapeutics’: a phase I human trial

Abstract

Osteoarthritis (OA) treatments presently rely on analgesics, which manage pain but fail to restore imbalances between catabolic and anabolic processes that underlie OA pathogenesis. Recently, biologic (biotherapeutic) drugs, which alter the activity of catabolic agents such as nitric oxide and inflammatory cytokines in ways, allowing tissue regeneration, were evaluated for efficacy in OA treatment. These studies failed to demonstrate dramatic abatement of OA symptoms by these drugs, but suggested strategies by which biologic agents might be used to treat OA. The present review summarizes current understanding of OA pathogenesis and evolving treatments. Preliminary evaluations of a novel biotherapeutic strategy are presented here. Twenty OA patients receiving sour topical cherry seed extract (SCE), an inducer of heme oxygenase-1 (HO-1), a major physiological protectant against oxidative stress exhibited significantly decreased joint pain and activation of CD4+ T cells expressing inflammatory cytokines (p<0.05), significantly decreased peripheral blood C-reactive protein (CRP), and increased leukocyte HO-1 (p<0.05) in comparison with ten placebo-treated patients. SCE inhibits joint-damaging inflammatory mediator production. This agent therefore meets the main criterion for classification as a "biotherapeutic," or "biologic" agent. The negligible toxicity and low cost of such materials make them promising contributors to OA treatment, sustainable within resource limitations of a wide range of patients.

Endothelin-1-induced hypertrophic alterations and heme oxygenase-1 expression in cardiomyoblasts are counteracted by beta estradiol: in vitro and in vivo studies

“…For this reason, naturally occurring, generally regarded as safe (GRAS) formulations which interact additively or synergistically with β-E to decrease its effective dosage, are of potentially enormous clinical value. Recently, HO-1 inducers have been recognized as being valuable for treatment of cardiovascular, lung, neurological, and kidney disorders (Haines et al 2012 ), along with osteoarthritis as described above (Mahmoud et al 2015 ).…”

Protective Effect of Prunus Cerasus (Sour Cherry) Seed Extract on the Recovery of Ischemia/Reperfusion-Induced Retinal Damage in Zucker Diabetic Fatty Rat

“…The results of previous work by the authors of this report suggest that sour cherry seed extract may have potential for the prevention and treatment of I/R-associated pathologies, including diabetes-related ocular disease: previously Bak et al [ 17 ], and later Czompa et al [ 18 ], demonstrated the protective effect of SCSE on ischemic-reperfused rat myocardium; Juhasz et al [ 4 ] confirmed a cardioprotective effect in hypercholesterolemic rabbits; and Szabo et al [ 19 ] proved protection in ischemic-reperfused retina. The extract was further studied toxicologically [ 20 ], which enabled the use of SCSE even in human studies [ 21 , 22 ]. These results are very promising and make SCSE a potential candidate for future drug development and further studies, such as the present one, to analyze the wide spectrum of effects the extract may exert.…”

Effect of Black Tea Consumption on Intracellular Cytokines, Regulatory T Cells and Metabolic Biomarkers in Type 2 Diabetes Patients

“…The authors of the present report have previously demonstrated that activation of endogenous antioxidant defenses with widely available, non‐toxic phytochemicals dramatically inhibits pathological expression of inflammatory cytokines by CD3+ CD4+ T cells in human cells (Mahmoud et al ., ; Mahmoud et al ., ; Csiki et al ., ), and dramatically abates symptoms of osteoarthritis in a human population (Mahmoud et al ., ); moreover, animal studies have recently revealed that tea polyphenols significantly inhibit tissue damage and symptoms of obesity; and obesity‐associated arthritis, by alteration of representation by CD3+ CD4+ T cells activated to express inflammatory cytokines (Byun et al ., ). Therefore, the outcome shown in Fig.…”