Antioxidant, Anti-Inflammatory and Cytotoxic Activity of Phenolic Compound Family Extracted from Raspberries (Rubus idaeus): A General Review

Abstract

Raspberries (Rubus idaeus) possess a wide phenolic family profile; this serves the role of self-protection for the plant. Interest in these compounds have significantly increased, since they have been classified as nutraceuticals due to the positive health effects provided to consumers. Extensive chemical, in vitro and in vivo studies have been performed to prove and validate these benefits and their possible applications as an aid when treating several chronic degenerative diseases, characterized by oxidative stress and an inflammatory response. While many diseases could be co-adjuvanted by the intake of these phenolic compounds, this review will mainly discuss their effects on cancer. Anthocyanins and ellagitannins are known to provide a major antioxidant capacity in raspberries. The aim of this review is to summarize the current knowledge concerning the phenolic compound family of raspberries, and topics discussed include their characterization, biosynthesis, bioavailability, cytotoxicity, antioxidant and anti-inflammatory activities.

Keywords: anti-inflammatory activity; antioxidant activity; cytotoxicity; phenolic compounds; raspberry.

Figure 1

Phenolic family compound basic skeletal structure and their classification in subclasses as stated by [50]. There are two major groups: flavonoids and non-flavonoids. Flavonoids have six subclasses: anthocyanidins, flavonols, flavanones, flavanols, flavones and isoflavones. Anthocyanidins become anthocyanins when sugars are linked in their chemical structures. Non-flavonoids are subdivided into four subclasses: stilbenes, tannins, coumarins and phenolic acids. Tannins are categorized into condensed, hydrolysable and complex. For phenolic acids, a more specified classification is to divide them into three groups: hydroxybenzoic, hydroxyphenylacetic and hydroxycinnamic acids. Created using licensed BioRender (2022).

Figure 2

Biosynthesis of the phenolic compound family in the plant cell through the shikimate, phenylpropanoid and flavonoid pathways. The shikimate pathway begins with the reaction of erythrose 4-phosphate and phosphoenolpyruvate (PEP) to produce dehydroshikimate. With this precursor, the enzyme shikimate dehydrogenase (SDH) can catalyze the production of ellagitannins, gallotannins and phenylalanine. The phenylpropanoid pathway begins with the condensation of phenylalanine and acetate by the action of the phenylalanine ammonia lyase enzyme (PAL). Consequently, p-coumaryl CoA is produced by the action of the cinnamate 4-hydoxylase enzyme (C4H) and 4-coumarate CoA ligase (4CL). The precursor of the flavonoid pathway is p-coumaryl CoA, which reacts with three molecules of Malonyl CoA to later produce multiple phenolic family compounds, such as anthocyanins and stilbenes. The enzymes involved in the flavonoid pathway are the following: chalcone synthase (CHS), stilbene synthase (SS), chalcone isomerase (CHI), flavanone 3-hydroxylase (F3H), flavanone 3′-hydroxylase (F3′H), flavanone 3′5′-hydroxylase (F3′5′H), dihydroflavonol 4-reductase (DFR) and anthocyanidin synthase (ANS). Created using licensed BioRender (2022).

Figure 3

Absorption, metabolism and mechanisms of ellagitannins and anthocyanins in the human body. The gut microbiota plays an important role for their metabolism. First, ellagitannins are transformed into ellagic acid prior to interacting with the gut microbiota. The final metabolites produced in ellagitannin metabolism are urolithins, and their concentrations will vary between individuals. Urolithin-A, isourolithin-A and urolithin-B are the final derivatives from ellagitannins, which can be quantified as plasma and urine. On the other hand, the anthocyanin final metabolites are sulfate, glucuronide, glycine and methyl derivatives. Both ellagitannins and anthocyanins are stable until reaching the small and large intestines, where they will interact with the intestinal microbiota of the host. For anthocyanins, only low amounts do not interact with the gut microbiota, because they are absorbed directly into the small intestine. Abbreviation: dehydroxylation (DHO). Created using licensed BioRender (2022).