Quercetin (Que) and its derivatives are naturally occurring phytochemicals with promising bioactive effects. The antidiabetic, anti-inflammatory, antioxidant, antimicrobial, anti-Alzheimer's, antiarthritic, cardiovascular, and wound-healing effects of Que have been extensively investigated, as well as its anticancer activity against different cancer cell lines has been recently reported. Que and its derivatives are found predominantly in the Western diet, and people might benefit from their protective effect just by taking them via diets or as a food supplement. Bioavailability-related drug-delivery systems of Que have also been markedly exploited, and Que nanoparticles appear as a promising platform to enhance their bioavailability. The present review aims to provide a brief overview of the therapeutic effects, new insights, and upcoming perspectives of Que.

Therapeutic Potential of Quercetin: New Insights and Perspectives for Human Health.

Apoptosis of chondrocytes are the main initiator of osteoarthritis (OA) and can be explained by oxidative stress and endoplasmic reticulum (ER) stress, thus the pharmacological interventions aimed at inhibiting of these pathways may be a promising approach for the management of OA. Quercetin is a member of the flavonoid family and has antioxidant and anti-inflammatory properties in degenerative diseases. However, its effects and potential mechanisms on the pathological process of OA are not very clear. The present study aimed to investigate the protective effects of quercetin on OA and the underlying mechanisms. The tert-butyl hydroperoxide (TBHP)-stimulated rat chondrocytes and destabilization of the medial meniscus OA rat model was used to explore the protective effects of quercetin. Our results showed that quercetin treatment can attenuate oxidative stress, ER stress, and associated apoptosis. Moreover, quercetin inhibited ER stress through activating the sirtuin1/adenosine monophosphate-activated protein kinase (SIRT1/AMPK) signaling pathway. The protective effects of quercetin were also observed in OA rat model which is evidenced by abolished cartilage degeneration and decreased chondrocytes apoptosis in the knee joints. Our results suggested that quercetin is a promising treatment for OA.

Quercetin attenuates oxidative stress-induced apoptosis via SIRT1/AMPK-mediated inhibition of ER stress in rat chondrocytes and prevents the progression of osteoarthritis in a rat model

The role of flavonoids in autoimmune diseases: Therapeutic updates

Rheumatoid arthritis (RA) is a prototypical autoimmune disorder mainly characterized by joint inflammation and cartilage destruction Neutrophils actively take part in the initiation and progression of RA Neutrophils express inflammatory mediators, including cytokines and chemokines Aberrant formation of neutrophil extracellular traps (NETs) has been demonstrated in the pathogenesis of RA Thus, neutrophils are regarded as important therapeutic targets in RA treatment Quercetin is one of the major flavonoids found in fruits and vegetables Previous studies have demonstrated that quercetin is a potential agent for the treatment of RA However, the underlying antiarthritic mechanism of quercetin has not been investigated clearly In this study, we analyzed the therapeutic mechanism of quercetin for RA Our results showed that quercetin ameliorates inflammation in RA mice by inhibiting neutrophil activities Quercetin inhibited neutrophil infiltration and reduced the plasma levels of inflammatory cytokines Quercetin promoted the apoptosis of activated neutrophils In addition, quercetin inhibited NET formation by suppressing autophagy These findings suggest that quercetin may be an alternative agent for the treatment of RA by inhibiting neutrophil activities

Quercetin alleviates rheumatoid arthritis by inhibiting neutrophil inflammatory activities.

Comparative oncology clinical trials play an important and growing role in cancer research and drug development efforts. These trials, typically conducted in companion (pet) dogs, allow assessment of novel anticancer agents and combination therapies in a veterinary clinical setting that supports serial biologic sample collections and exploration of dose, schedule and corresponding pharmacokinetic/pharmacodynamic relationships. Further, an intact immune system and natural co-evolution of tumour and microenvironment support exploration of novel immunotherapeutic strategies. Substantial improvements in our collective understanding of the molecular landscape of canine cancers have occurred in the past 10 years, facilitating translational research and supporting the inclusion of comparative studies in drug development. The value of the approach is demonstrated in various clinical trial settings, including single-agent or combination response rates, inhibition of metastatic progression and randomized comparison of multiple agents in a head-to-head fashion. Such comparative oncology studies have been purposefully included in the developmental plan for several US FDA-approved and up-and-coming anticancer drugs. Challenges for this field include keeping pace with technology and data dissemination/harmonization, improving annotation of the canine genome and immune system, and generation of canine-specific validated reagents to support integration of correlative biology within clinical trial efforts.

Improving human cancer therapy through the evaluation of pet dogs.

Therapeutic effect of quercetin in collagen-induced arthritis

Osteosarcoma is the most common paediatric primary bone malignancy. The major cause of death in osteosarcoma is drug-resistant pulmonary metastasis. Previous studies have shown that thioredoxin reductase 2 is a driver of metastasis in osteosarcoma and can be inhibited by auranofin (AF). Moreover, studies have shown that AF significantly reduces pulmonary metastases in xenotransplant models. Here, we describe a phase I/II study of AF in canine osteosarcoma, a well-recognized spontaneous model of human osteosarcoma. We performed a single-arm multicentre pilot study of AF in combination with standard of care (SOC) (amputation + carboplatin). We recruited 40 dogs to the trial and used a historical SOC-only control group (n = 26). Dogs >15 kg received 9 mg AF q3d PO and dogs <15 kg received 6 mg q3d. Follow-up occurred over at least a 3-year period. Auranofin plus SOC improved overall survival (OS) (P = .036) in all dogs treated. The improved outcome was attributable entirely to improved OS in male dogs (P = .009). At the time of writing, 10 dogs (25%) survive without measurable disease in the treatment group with survival times ranging between 806 and 1525 days. Our study shows that AF improves OS in male dogs when combined with SOC. Our findings have translational relevance for the management of canine and human osteosarcoma. Our data justify a larger multicentre phase 2 trial in dogs and a phase I/II trial in human patients with refractory disease at the time of initial surgery.

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Guy Bird

Papers

Therapeutic effect of quercetin in collagen-induced arthritis

Auranofin improves overall survival when combined with standard of care in a pilot study involving dogs with osteosarcoma.