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

Abstract

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.

Synthesis, In Silico and In Vitro Evaluation of Some Flavone Derivatives for Acetylcholinesterase and BACE-1 Inhibitory Activity

“…During the last few years, flavonoids, including flavones, have attracted much interest because of their diverse bioactivities [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. Recent studies have indicated the abilities of flavones in inhibiting many enzymes [ 25 , 26 , 27 , 28 , 29 ], especially AChE [ 30 ] and BACE-1 [ 31 , 32 ].…”

Anti-toxicity test of Peperomia pellucida steeping on liver function in diabetic-induced rat

“…This will repair liver cell damage. Phenolic compounds work as free radical scavengers, through the H + donor from hydroxyl groups (OH) in flavonoids against free radical compounds to form stable molecules (Ferraz et al, 2020;Mutee et al, 2010;Saryono et al, 2017). Previous studies showed that flavonoids in herb plants are useful for chelating free radicals by increasing endogenous antioxidant enzymes, reducing free radicals, and donating atoms.…”

Biological activity and flavonoid profile of five species of the Bursera genus

“…five Bursera species in this study ( Table 5). The antioxidant activity of other Bursera species have been associated with lignans (Nieto-Yañez 2017, Marcotullio et al 2018) and phenols (Martinez-Elizalde et al 2018) Flavonoids such as hesperidin, apigenin, luteolin and quercetin, have anti-inflammatory and analgesic effects (Ferraz et al 2020). In a previous work, anti-inflammatory effects have been reported with an average effective dose (ED 50 ) of B. excelsa (0.26 ± 0.01 mg/ear), B. galeottiana (0.23 ± 0.02 mg/ear) and B. schlechtendalii (0.25 ± 0.02 mg/ear) from bark using chloroform extracts (Acevedo et al 2015).…”