Pathological pain can be initiated after inflammation and/or peripheral nerve injury. It is a consequence of the pathological functioning of the nervous system rather than only a symptom. In fact, pain is a significant social, health, and economic burden worldwide. Flavonoids are plant derivative compounds easily found in several fruits and vegetables and consumed in the daily food intake. Flavonoids vary in terms of classes, and while structurally unique, they share a basic structure formed by three rings, known as the flavan nucleus. Structural differences can be found in the pattern of substitution in one of these rings. The hydroxyl group (-OH) position in one of the rings determines the mechanisms of action of the flavonoids and reveals a complex multifunctional activity. Flavonoids have been widely used for their antioxidant, analgesic, and anti-inflammatory effects along with safe preclinical and clinical profiles. In this review, we discuss the preclinical and clinical evidence on the analgesic and anti-inflammatory proprieties of flavonoids. We also focus on how the development of formulations containing flavonoids, along with the understanding of their structure-activity relationship, can be harnessed to identify novel flavonoid-based therapies to treat pathological pain and inflammation.

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Therapeutic Potential of Flavonoids in Pain and Inflammation: Mechanisms of Action, Pre-Clinical and Clinical Data, and Pharmaceutical Development.

The consumption of plant-based food is important for health promotion, especially concerning the prevention and management of chronic diseases. Flavonoids are the main bioactive compounds in citrus fruits, with multiple beneficial effects, especially antidiabetic effects. We systematically review the potential antidiabetic action and molecular mechanisms of citrus flavonoids based on in vitro and in vivo studies. A search of the PubMed, EMBASE, Scopus, and Web of Science Core Collection databases for articles published since 2010 was carried out using the keywords citrus, flavonoid, and diabetes. All articles identified were analyzed, and data were extracted using a standardized form. The search identified 38 articles, which reported that 19 citrus flavonoids, including 8-prenylnaringenin, cosmosiin, didymin, diosmin, hesperetin, hesperidin, isosiennsetin, naringenin, naringin, neohesperidin, nobiletin, poncirin, quercetin, rhoifolin, rutin, sineesytin, sudachitin, tangeretin, and xanthohumol, have antidiabetic potential. These flavonoids regulated biomarkers of glycemic control, lipid profiles, renal function, hepatic enzymes, and antioxidant enzymes, and modulated signaling pathways related to glucose uptake and insulin sensitivity that are involved in the pathogenesis of diabetes and its related complications. Citrus flavonoids, therefore, are promising antidiabetic candidates, while their antidiabetic effects remain to be verified in forthcoming human studies.

Citrus Flavonoids as Promising Phytochemicals Targeting Diabetes and Related Complications: A Systematic Review of In Vitro and In Vivo Studies.

Endogenous opiates and behavior: 2014.

Acacetin, a flavone with diverse therapeutic potential in cancer, inflammation, infections and other metabolic disorders.

Quinoa (Chenopodium quinoa Willd.) was known as the “golden grain” by the native Andean people in South America, and has been a source of valuable food over thousands of years. It can produce a variety of secondary metabolites with broad spectra of bioactivities. At least 193 secondary metabolites from quinoa have been identified in the past 40 years. They mainly include phenolic acids, flavonoids, terpenoids, steroids, and nitrogen-containing compounds. These metabolites exhibit many physiological functions, such as insecticidal, molluscicidal and antimicrobial activities, as well as various kinds of biological activities such as antioxidant, cytotoxic, anti-diabetic and anti-inflammatory properties. This review focuses on our knowledge of the structures, biological activities and functions of quinoa secondary metabolites. Biosynthesis, development and utilization of the secondary metabolites especially from quinoa bran were prospected.

Quinoa Secondary Metabolites and Their Biological Activities or Functions.

Evidence of mechanism of action of anti-inflammatory/antinociceptive activities of acacetin.

Emerging evidence proposes a link between immune changes and pain, which is consistent with the inflammation theory and the increased incidence of neurodegenerative diseases. Flavonoids have long been used because of their anti-inflammatory potential activity and they are considered a promising alternative to alleviate neuropathic pain. The aim of this study was to investigate the antihyperalgesic effect of hesperidin and the presence of pro-inflammatory cytokines evaluated at peripheral and central levels in the chronic constriction injury as model of neuropathic pain in rats. Mechanical and thermal hyperalgesia were assessed in the aesthesiometer and plantar tests, respectively, as related to the presence of cytokines concentrations (TNF-α, IL-1β and IL-6) in sciatic nerve and segments of the spinal cord after 15 days chronic constriction injury model in rats receiving vehicle or hesperidin. Antihyperalgesic response of hesperidin (100 mg/kg) was associated to the presence of cytokines mainly at several sections of the spinal cord suggesting not only peripheral but also its involvement in central sensitization in the experimental neuropathic pain.

M. E. González-Trujano

Papers

Evidence of mechanism of action of anti-inflammatory/antinociceptive activities of acacetin.

Pro-inflammatory cytokines involvement in the hesperidin antihyperalgesic effects at peripheral and central levels in a neuropathic pain model.