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Review

Volatiles in Berries: Biosynthesis, Composition, Bioavailability, and Health Benefits

by
Inah Gu
,
Luke Howard
and
Sun-Ok Lee
*
Department of Food Science, University of Arkansas, Fayetteville, AR 72704, USA
*
Author to whom correspondence should be addressed.
Appl. Sci. 2022, 12(20), 10238; https://doi.org/10.3390/app122010238
Submission received: 30 August 2022 / Revised: 30 September 2022 / Accepted: 5 October 2022 / Published: 12 October 2022
(This article belongs to the Special Issue Potential Health Benefits of Fruits and Vegetables II)
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Abstract

:
Volatile compounds in fruits are responsible for their aroma. Among fruits, berries contain many volatile compounds, mainly esters, alcohols, terpenoids, aldehydes, ketones, and lactones. Studies for volatile compounds in berries have increased extensively as the consumption of berry products rapidly increased. In this paper, we reviewed biosynthesis and profiles of volatiles in some berries (strawberry, blueberry, raspberry, blackberry, and cranberry) and their bioavailability and health benefits, including anti-inflammatory, anti-cancer, anti-obesity, and anti-diabetic effects in vitro and in vivo. Each berry had different major volatiles, but monoterpene had an important role in all berries as aroma-active components. Volatile compounds were nonpolar and hydrophobic and rapidly absorbed and eliminated from our body after administration. Among them, monoterpenes, including linalool, limonene, and geraniol, showed many health benefits against inflammation, cancer, obesity, and diabetes in vitro and in vivo. More research on the health benefits of volatile compounds from berries and their bioavailability would be needed to confirm the bioactivities of berry volatiles.

1. Introduction

Berries, one of the most common fruits in the human diet (strawberry, blueberry, red raspberry, black raspberry, blackberry, and cranberry in the United States), are rich in minerals, vitamins, dietary fibers, and especially polyphenols and volatiles [1,2,3]. Volatile compounds in berries are responsible for the unique aroma of berries [4]. Fruit volatile compounds are mainly comprised of diverse chemicals, including esters, alcohols, terpenoids, aldehydes, ketones, and lactones [5]. The volatile composition of berries is complex and different by many factors, including the cultivar, ripeness, pre- and post-harvest storage conditions, fruit samples, temperature, and experimental conditions [6,7,8,9,10,11]. Blueberries (Vaccinium ashei) showed linalool increasing and α-terpineol and β-caryophyllene decreasing during the maturation of the blueberry [6]. Full-red harvested strawberries contained more volatile compounds than ¾-red harvested strawberries, regardless of the storage duration [12]. Raspberries (raw, frozen, or frozen for a year) were examined to compare the long-term frozen storage. The changes in volatile composition during long-term frozen storage were negligible except for an increase in α-ionone and caryophyllene [8].
Volatile compounds are small and light molecules (below 250–300 Da) with low polarity and high vapor pressure [13]. Plants synthesize and release volatile compounds to communicate and interact with environments, compensating for the immobility of plants [14]. Volatile compounds play an important role in pollination by attracting pollinators, protecting from pathogens and herbivores, and even communicating with inter- and intra-plants [15]. Volatiles can be divided into primary compounds and secondary compounds. Primary compounds are synthesized during maturation by anabolic or catabolic pathways of the plant [16]. Secondary volatile compounds are produced from tissue disruption by autoxidation or enzyme catalyzing reactions [17,18,19].
A mixture of many different volatile compounds makes a unique aroma. Although a lot of compounds were found as volatile compounds in fruits, only a few compounds have been identified as aroma compounds of fruit flavor based on their quantitative abundance and olfactory thresholds [20]. With the increasing consumption of berries and berry products such as fruits, juice, puree, jams, and other berry ingredients, there have been many studies conducted about identifying aroma volatile compounds of berries for developing consumer acceptability [21] and the studies about the health beneficial effect of berries, especially berry polyphenols. Berry polyphenols are composed of flavonoids, phenolic acids, tannins, stilbenes, lignans, and others and have been shown to possess many health effects, such as antioxidant, anti-inflammatory, and anti-cancer activities [22,23,24]. Unlike berry polyphenols, although there have been extensive analyses of volatile berry composition, there is still a very limited number of studies on the bioavailability and health benefits of berry volatiles. Recently, volatile compounds in plants have been reported to have health-promoting activities such as anti-inflammatory effects [25,26]. Many review articles mainly focused on the composition of berry volatiles and affecting factors such as different locations, ripeness, cultivar/genotypes, harvest and storage conditions, etc., but there is a lack of information about the bioavailability and biological activities of berry volatiles in our body. In this article, the biosynthesis of volatiles in plants, the chemical composition of some berries commonly consumed in the U.S. (blackberry, blueberry, cranberry, raspberry, and strawberry), bioavailability, and the health benefits of volatile compounds that are rich in berries were reviewed.

2. Biosynthesis of Volatiles in Plants

Plant volatiles can be grouped into terpenoids, phenylpropanoids/benzenoids, and fatty acid derivatives based on chemical structure and biochemical synthesis [14,27,28]. Terpenes/terpenoids are the most abundant and diverse family of secondary plant metabolites and essential oils, including more than 30,000 compounds [29,30]. Terpenes are classified by the amount of C5 isoprene units in the structure: isoprene (C5), monoterpenes (C10), sesquiterpenes (C15), diterpenes (C20), and so on, with polyterpenes (C5n where n can be ~30,000) [30]. Monoterpenes and sesquiterpenes are the most abundant terpenes found in essential oils [31]. Although they have diverse chemical structures, they all share common biosynthesis pathways, and they are synthesized in all parts of the plants, such as the leaves, fruits, flowers, stems, and roots [15]. Since terpenes/terpenoids are the major class of berry volatiles, we focused more on the biosynthesis of terpenes, such as monoterpenes and sesquiterpenes, in this review.

2.1. Biosynthesis of Terpenes

All terpenes are synthesized from two universal precursors (C5), isopentenyl diphosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) [32]. A series of condensation reactions of IPP and DMAPP produce prenyl diphosphates, which are precursors of terpenes. Condensation of IPP and DMAPP produces geranyl diphosphate (GPP, C10), the precursor of monoterpenes, by catalyzation of geranyl diphosphate synthase (GDS). Two IPPs and a DMAPP are condensed to the precursor of sesquiterpenes, farnesyl diphosphate (FPP, C15), by farnesyl diphosphate synthase (FDS) [33]. Three IPPs and a DMAPP also produce geranylgeranyl pyrophosphate (GGPP, C20), the precursor of diterpenes. Geranylfarnesyl diphosphate (GFPP, C25) is the recently discovered precursor of sesterterpenes [33]. These prenyl precursors of terpenes are converted to terpenes (iso-, mono-, sesquiterpenes, and so on) by terpene synthases (TPS). Monoterpenes (C10) are one of the major groups of terpenes in essential oils and berries [34]. During the conversion of prenyl precursors to monoterpenes, many different catalytic reactions, including hydroxylation, oxidation, reduction, acetylation, methylation, glycosylation, isomerization, conjugation, and others, occur to modify the structure of monoterpenes and produce many different compounds of terpenes [30,35,36].

2.2. MVA and MEP Pathways

The two precursors of all terpenes, IPP and DMAPP, are generated from two different pathways in different subcellular compartments: the mevalonic acid (MVA) pathway in the cytosol and the 2-methylerythritol 4-phosphate (MEP) pathway (1-deoxy-xylulose-5-phosphate (DOXP) pathway) in plastids (Figure 1) [37]. The MVA pathway generates IPP from acetyl-CoA, while the MEP pathway produces IPP and DMAPP from pyruvate and glyceraldehyde-3-phosphate (GA-3P) [38,39]. In the MVA pathway, there are six enzymatic reactions to generate IPP. Three acetyl-CoA are sequentially condensed, reduced to mevalonate (MVA), then form IPP through two phosphorylations and decarboxylation by mevalonate kinase, phosphomevalonate kinase, and mevalonate diphosphate decarboxylase, respectively [40,41]. Produced IPP in the MVA pathway further forms its allylic isomer, DMAPP, by isopentenyl diphosphate isomerase [42]. In the MEP pathway, seven enzymatic actions are involved in generating IPP and DMAPP [43]. Condensation of pyruvate and GA-3P generates DOXP, and DOXP synthesizes MEP by DOXP reductoisomerase (DXR). Further transformations form 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate (HMBPP) and (E)-4-hydroxy-3-methlbut-2-enyl diphosphate reductase (HDR) catalyzes the conversion of HMBPP to IPP and DMAPP [44]. MVA pathway mainly synthesizes sesquiterpenes, which account for about 28% of total flower terpenes, while the MEP pathway synthesizes more monoterpenes and diterpenes, accounting for about 53% and 1% of total flower terpenes, respectively [45,46]. However, metabolic crosstalk exists between the MVA and MEP pathways, especially from plastids to cytosol [47,48,49].

2.3. Biosynthesis of Other Plant Volatiles

2.3.1. Phenylpropanoids/Benzenoids

Phenylpropanoids/benzenoids are synthesized from the shikimate pathway [31]. The shikimate pathway starts with the condensation of phosphoenolpyruvate and erythrose 4-phosphate [51]. Chorismic acid is formed by the elimination of ring alcohol from shikimic acid, and this forms the phenylpropionic acid skeleton [29]. Cinnamic acid and p-hydroxycinnamic acid undergo many enzymatic reactions to produce volatile compounds, including eugenol and benzyl benzoate [52].

2.3.2. Volatile Fatty Acid Derivatives

Fatty acid-derived volatiles are synthesized via the lipoxygenase pathway [53]. C18 fatty acids, including linoleic acid and linolenic acid, are catalyzed by lipoxygenases and generate 9-hydroperoxy and 13-hydroperoxy derivatives of fatty acids [54]. These two intermediates turn into fatty acid derivatives, including methyl jasmonate and green leaf volatiles. The lipoxygenase pathway also can synthesize oxylipins, isoprene, carotenoid derivatives, indoles, phenolics, methyl salicylate, and aromatic volatile organic compounds [55,56].

2.4. Application of Plant Volatile Biosynthesis

Volatile compounds that are emitted from plants have an important role in many different functions, such as pollinator attraction, direct and indirect defenses against herbivores, insects, and microorganisms, and communication between and within plants [27,57,58]. In addition, natural volatile compounds such as methyl jasmonate, allyl isothiocyanate, and tea tree oil have been used for modulating volatile biosynthesis and controlling the pre- and post-harvest quality of berries [9,59]. Those volatile compounds also suppressed the decay in strawberries and blackberries stored at 10 °C [60]. Sangiorgio et al. found a positive correlation between Lactobacillus, Paenibacillus spp., and norisoprenoids and a negative correlation between Enterobacteriaceae and monoterpenes [61]. From these results, the raspberry microbiome can be selectively chosen for the overall better quality of fruit, including its aroma, shelf-life, and safety [61]. Although there is still more research on the mechanisms required, accumulated results in metabolomic and genomic approaches can be used for making advances in fruit ripeness, quality, and consumer acceptability [62,63,64].

3. The Chemical Composition of Volatile Compounds in Berries

The major volatile compounds identified from five common berries in the U.S. (strawberry, blueberry, raspberry, blackberry, and cranberry) were summarized (Table 1).

3.1. Strawberry

Strawberries (Fragaria spp.) are the most consumed berry fruit for their sweet taste and unique aroma [86]. The consumption of strawberry products, such as jams, juices, and puree, has significantly increased [87,88]. Strawberries are rich in volatile compounds responsible for the strawberry flavor and aroma [89,90]. Volatile compounds in strawberries have been extensively studied, and more than 360 volatile compounds have been identified [91]. These compounds include esters, which were qualitatively and quantitatively dominant, terpenes, furanones, sulfur, lactones, alcohols, and carbonyls. In the study of Lu et al., a total of 42 volatiles were detected, with 19 esters, 10 alcohols, and 6 terpenes being the most abundant in the strawberry samples analyzed [65].
Esters are the most abundant and major aroma volatiles affecting the aroma of strawberries [92]. Among 19 ester compounds, methyl butanoate, methyl hexanoate, ethyl acetate, and hexyl acetate were the major ester compounds [65]. Terpenes are important compounds to the flavor and possess many preferable aroma profiles [93]. Among six terpenes, limonene and α-terpinene were the main compounds in strawberries [65]. Although strawberries contained many alcohol compounds, alcohols did not affect the strawberry flavor notably. In addition, c-decalactone (peach-like aroma) contributes significantly to the strawberry flavor. Hexanal, trans-2-hexenal, and cis-3-hexen-1-ol are responsible for the green, unripe aroma of the strawberry. The furanones 2,5-dimethyl-4-hydroxy-3(2H)-furanone (furaneol) and 2,5-dimethyl-4-methoxy-3(2H)-furanone (mesifurane), which have the sweet, floral, and fruity aroma, are major furans found in strawberries [65].
Summarizing some strawberry volatile studies, volatile components that are consistently considered important aroma compounds include ethyl butanoate, ethyl hexanoate, methyl butanoate, ethyl 3-methylbutanoate, fureneol, and linalool [66,85,94]. Additional compounds that have been reported include 2-heptanone, mesifurane, cis-3-hexenal, ethyl 2-methylpropanoate, 2,3-butanedione, 3-methylbutyl acetate, methyl hexanoate, and ethyl 2-methylbutanoate [67]. Eight different strawberry varieties (Sabrosa, Albion, Sweet Ann, Festival, Fortuna, Ventana, Camarosa, and Rubygem) were examined to investigate the volatile composition [72]. With headspace solid-phase micro-extraction gas chromatography-mass spectrometry (HS-SPME/GC-MS), esters (31 volatiles), especially ethyl hexanoate were detected as major compounds [72]. The most detected compounds were esters (31 compounds), which give fruity and floral characteristics to strawberries [72]. The SPME/GC-MS is one of the most common and effective methods for volatile analysis. SPME fiber samples the volatile compounds from air and thermally desorbs the sample in the injection port of a GC system [95,96]. In Gu et al., 55 volatiles were found in the strawberry extract, with monoterpene being the predominant volatiles (43% of total volatile concentration) [69]. It was followed by acids, esters, furan, aldehydes, alcohol, ketones, and alkylbenzene. Predominant compounds in strawberry extract were myrtenol, butanoic acid, mesifuran, ethyl butanoate, and hexyl butanoate.

3.2. Blueberry

Blueberries (Vaccinium spp.) are the second most popular berry fruit in the U.S. after strawberries [97]. The blueberry market has increased 10–20% annually over the last 5 years [98]. The increased blueberry consumption is due to its well-known health benefits and flavor [99]. Highbush blueberries mainly contained ethyl acetate, (E)-2-hexenal, (E)-2-hexenol, hexanal, (Z)-3-hexenol, linalool, and geraniol [68]. Others, including citronellol, α-terpineol, 2-phenylethanol, and vanillin, were also considered to have the highbush blueberry aroma [81]. A total of 38 aroma volatiles were detected from southern highbush blueberry [74]. There were nine aldehydes, eight esters, seven terpenes, five ketones, two alcohols, two acids, two sulfurs, and three miscellaneous compounds. Aldehydes were the most abundant chemical group within southern highbush blueberry and a major volatile compound group to the blueberry aroma. Hexanal, (Z)-3-hexenal, (E)-2-hexenal, (E,Z)-2,6-nonadienal, and (E,E)-2,4-nonedienal had “fresh green”, “grassy”, and “fruity” aroma characteristics, whereas pentanal, octanal, (E,E)-2,4-hexadienal, and decanal had “fatty” and “citrus” [74]. Esters were the second most abundant in southern highbush blueberry, and they included ethyl propanoate, methyl 2-methylbutanoate, methyl 3-methylbutanoate, ethyl 2-methylbutanoate, ethyl 3-methylbutanoate, (Z)-3-hexyl acetate, (E)-2-hexyl acetate, and geranyl acetate, with “green”, “sweet”, “fruity”, “apple”, “banana”, “pear”, and “floral” aromatic characteristics. Unlike strawberries, apples, and bananas, where esters are the main contributors to the aroma, fewer esters were found in highbush blueberry [66,100]. Terpenes including linalool, citronellol, nerol, and geraniol showed “sweet”, “floral”, “fruity”, “citrus”, and “berry-like”, while 1,8-cineole, dihydrolinalool oxide, and α-terpineol had “woody”, “herbaceous”, and “piney” characteristics. Linalool was one of the major volatiles in southern highbush blueberry. Two alcohols, including (Z)-3-hexenol and 2-heptanol, were aroma active. Only three ketones, including 2-heptanone, 1-octen-3-one, and 2-nonanone with “fruity” “mushroom”, “earthy”, and “cheese-like”, were found to have aroma activity. Furaneol was found in southern highbush blueberries. Furaneol had “sweet”, “candy”, and “caramel” characteristics. In another study, five Vaccinium cultivars (“Biloxi”, “Brigitta Blue”, “Centurion”, “Chandler”, and “Ozark Blue”) were found to have 106 volatile organic compounds [78]. Esters, 25 compounds, were the major compounds and were followed by 18 aldehydes, 16 alcohols, 14 monoterpenes, 7 ketones, 4 acids, 4 hydrocarbons, 3 sesquiterpenes, 1 lactone, and 1 norisoprenoid. Aldehydes, including (E)-2-hexenal, hexanal, (Z)-3-hexenal, hexadienal, or heptenal, are the most abundant, accounting for almost half of the Vaccinium volatile composition. Monoterpenes, including 1,8-cineole and linalool, were also important compounds in the volatile blueberry profile [78]. Even though esters had smaller content compared to others, esters had a unique aroma that characterizes the aroma of blueberry. Among seven ketones identified, 2-heptanone and 6-methyl-5-hepten-2-one were the ones with the highest contents. Octane, ethyl benzene, p-xylene, and mxylene were identified as hydrocarbons. Other volatile compounds in the blueberry aroma profile were hexanoic acid, octanoic acid, nonanoic acid, decanoic acid (acids), d-elemene, (E)-caryophyllene, and caryophyllene oxide (sesquiterpenes), b-damascenone (norisoprenoid), and butyrolactone (lactone). Dymerski et al. conducted identification of volatile blueberry compounds, and alcohol (51.8%), ester (32.8%), and carboxylic acid (6.9%) were mainly detected [101]. Forty-six blueberry volatiles were identified by Gu et al. by using GC-MS [69]. Monoterpenes accounted for 45% of total volatile concentration, with alcohols (17%), aldehydes (8%), C13 norisoprenoids and esters (each 7%), furans (5%), ketones (4%), and others. The major individual blueberry volatiles were linalool, linalool oxide, phenylethyl alcohol, 2-ethylhexanol, α-terpineol, and β-ionone.

3.3. Raspberry

In the Rosaceae family, raspberry (Rubus spp.) is a fruit with an attractive appearance and unique flavor [102,103]. There are red raspberry (Rubus idaeus) and black raspberry (Rubus occidentalis). Different cultivars and varieties of raspberries are grown worldwide, in Europe, North America, and Asia [88]. Raspberries have been reported to contain an aroma impact compound, which is a single compound that has an odor characteristic of raspberry [67]. This compound has been identified as 1-(phydroxyphenyl)-3-butanone and is referred to as raspberry ketone. Approximately 200 volatile compounds were detected in raspberries [76]. Raspberry ketone, α-ionone, β-ionone, linalool, (Z)-3-hexenol, geraniol, nerol, α-terpineol, furaneol, hexanal, β-ocimene, 1-octanol, β-pinene, β-damascenone, ethyl 2-methylpropanoate, (E)-2-hexenal, heptanal, and benzaldehyde have been identified as the raspberry aroma. Among them, α-ionone, β-ionone, geraniol, nerol, linalool, and raspberry ketone especially contributed to the red raspberry aroma. Monoterpene is an important class of fruit volatile organic compounds (VOCs) [104]. This class contains some of the most aroma-active compounds, such as citronellol, nerol, geraniol, α-terpineol, and linalool. The volatile composition of raspberries was identified with 30 compounds, including (Z)-hexenol, hexanal, (E)-2-hexenal, 2-heptanone, δ-octalactone, δ-decalactone, geraniol, α-ionone, β-ionone, and terpinen-4-ol [79]. The main volatile compounds in raspberries include monoterpenes (20%), acids (14%), alcohols (12%), esters (12%), aldehydes (8%), ketones (7%), C-13 norisopernoids (6%), hydrocarbons (6%), lactones (4%), sesquiterpenes (4%), furans (3%), sulfur (3%), and phenols (1%) [105]. Gu et al. identified 78 and 73 volatiles from black and red raspberry extracts, respectively [69]. The major chemical class was monoterpene (61% in black raspberries, 47% in red raspberries) in both raspberries. In black raspberries, (−)-myrtenol, linalool, α-terpineol, 2-ethylhexanol, cuminaldehyde, hexanoic acid, ethyl acetate, and (+)-myrtenol were the major compounds. In red raspberries, myrtenol, butanoic acid, linalool, eugenol, 3-methylbutanoic acid, α-ionone, and vanillin were found as major compounds.

3.4. Blackberry

Blackberries (Rubus spp.) are produced worldwide and consumed mostly as fresh but also as frozen, preserves, jelly, wine, dietary supplements, and others [106]. There have been studies identifying and analyzing the volatile composition of blackberries, but they are still limited. In D’Agostino et al., thirteen Rubus ulmifolius schott blackberries from different locations in Italy and Spain were used to identify the volatile composition by using SPME and GC-MS [80]. They identified a total of 74 volatiles from blackberry samples. Esters and aliphatic alcohols were the major classes, and methylbutanal, ethanol, 2,3-butanedione, trans-2-hexenal, 3-hydroxy-2-butanone, 1-hexanol, 1-octanol, and methylbutanoic acid were mainly found in all samples, which were 76.4% and 65.1% of volatile blackberry profiles from Italy and Spain, respectively. Wang et al. compared the aroma compositions of Chickasaw blackberries grown in Arkansas and Oregon [71]. A total of 84 compounds, including 19 esters, 18 terpenes and terpenoids, 15 alcohols, 13 aldehydes, 4 ketones, 4 acids, 4 lactones, 2 furans, 2 sulfur-containing compounds, 1 pyrazine, and 2 miscellaneous compounds, were identified. Even though they were the same cultivar, climate difference in the two regions strongly affected their blackberry aroma. The most attributing aromas of Chickasaw from Oregon were ethyl butanoate, linalool, methional, trans,cis-2,6-nonadienal, cis-1,5-octadien-3-one, and 2,5-dimethyl-4-hydroxy-3(2H)-furanone. However, the most potent aromas in Chickasaw from Arkansas were ethyl butanoate, linalool, methional, ethyl 2-methylbutanoate, β-damascenone, and geraniol. In sensory evaluations, Oregon samples were evaluated to have green, fruity, citrus, and watermelon aromas, while Arkansas samples were to have cinnamon, piney, floral, sweet, and caramel aromas [71]. Qian and Wang also investigated the volatile compositions of Marion and Thornless Evergreen blackberries by using GC-MS [73]. Acids (53.83%) and alcohols (24.25%) were the most abundant compounds in Marion, while alcohols (46.62%) were the most abundant in Thornless Evergreen. Thornless Evergreen blackberries showed much more amounts of volatiles (27.33 ppm) compared to Marion blackberries (8.62 ppm). The most abundant individual volatiles were acetic, hexanoic, decanoic, and 2/3-methylbutanoic acids, ethanol, and linalool for Marion, and 2-heptanol, octanol, α-pinene, hexanol, p-cymen-8-ol, and nopol for Thornless Evergreen. Based on odor activity values (OAVs), the most potent odorants were ethyl hexanoate, β-ionone, linalool, 2-heptanone, 2-undecanone, α-ionone, and hexanal for Marion, and ethyl hexanoate, 2-heptanone, ethyl 2-methylbutanoate, 2-heptanol, 3-methylbutanal, α-pinene, limonene, p-cymene, linalool, t-2-hexenal, myrtenol, hexanal, 2-methylbutanal, and sabinene [73]. Sixty-one volatiles were identified from volatile blackberry extract: 24 monoterpenes, 12 alcohols, 6 esters, 4 ketones, 4 C13 norisoprenoids, 3 furans, 2 acids, a lactone, and a phenolic [69]. Acids (57%) accounted for the highest concentration, followed by alcohols (18%), esters (10%), monoterpenes (10%), and others. Major individual compounds were butanoic acid, hexanoic acid, 4-methyl-1-pentanol, myrtenol, 2-ethylhexanol, isophorone, limonene, and 4-terpineol. Morin et al. identified a total of 80 volatiles in volatile extracts from three blackberry genotypes: Natchez and two University of Arkansas breeding lines, A2528T and A2587T [70]. Monoterpenes, alcohols, and esters were the predominant chemical classes in the three genotypes. As individual volatile compounds, ethyl acetate and α-terpineol were found to be the major volatiles in all three genotypes.

3.5. Cranberry

Cranberries (Vaccinium spp.) are native to North America, and production has been highly increased due to their well-known health benefits of cranberries [107]. The unique cranberry aroma is developed during ripening [75]. In 1981, Hirvi et al. detected 70 volatile compounds from European (Vaccinium oxycoccus, L.) and American cranberries (Vaccinium macrocarpon, Ait.) [82]. In this study, benzyl alcohol accounted for 29.2% and 21.6% in European and American cranberries, respectively. α-terpineol was 13% and 9.7% of total volatiles in European and American cranberries, respectively. Ruse et al. identified 21 volatiles from fresh cranberries [77]. Common volatile compounds detected from wild (Vaccinium oxycoccus L.) and different cultivars of cranberries (Vaccinium macrocarpon Ait., ‘Early Black’, ‘Ben Lear’, ‘Steven’, Bergman’ and ‘Pilgrim’) were 4-penten-2-ol, 3-cis-hexenyl formate, benzaldehyde, α-1-terpineol, butyric acid, and benzyl alcohol. Zhu et al. analyzed the cranberry (Vaccinium macrocarpon Ait.) volatile composition of four cultivars (‘Early Black’, ‘Howes’, ‘Searles’, and ‘McFarlin’) by using GC-MS and GC-olfactometry (GC-O) [75]. A total of 33-36 volatiles were detected as odor-active compounds by GC-O. Hexanal, pentanal, (E)-2-heptenal, (E)-2-hexenal, (E)-2-octenal, (E)-2-nonenal, ethyl 2-methylbutyrate, β-ionone, 2-methylbutyric acid, and octanal were mainly contributing to the cranberry aroma. Khomych et al. detected 54 aromatic compounds in cranberry juice [84]. Twenty-three alcohols (41.2% of total concentration) were predominant in cranberry juice, followed by eight acids (40.7%), ten aldehydes (1.7%), five ketones (2.2%), five ethers (1.4%), three lactones, and each heterocyclic and unidentified compound (less than 1% each). Among alcohols, benzyl alcohol was the major volatile, accounting for 23.1% of total volatile concentration. Moore et al. detected 23 cranberry volatiles by using GC-MS [83]. In terms of total volatile concentration, Monoterpene (84%) was predominantly contained in cranberries, followed by aldehyde (8%) and alcohols (3%). The major volatile compounds were α-terpineol, linalool oxide, eucalyptol, trans-2-decanal, and 2-octanal. In cranberry volatile extract, 35 volatiles were found: 16 monoterpenes, 8 alcohols, 6 aldehydes, 2 esters, 2 ketones, and an acid [81]. Monoterpenes (60%) were predominant in total volatile concentration. α-terpineol, eucalyptol, 2-methylbutyric acid, ethyl benzoate, citronellol, and linalool were the major individual volatile compounds in cranberry.

4. Bioavailability of Berry Volatiles

The definition of bioavailability by the U.S. Food and Drug Administration (FDA) is “the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action” [108]. More proper meaning is the part of ingested compound reaching the systemic circulation and specific site where it is available in the body [109]. Investigating the bioavailability of a compound is important to find the clinical relevance of the health-promoting activities of the bioactive compound in our body [110]. Thus, it is necessary to study the absorption, distribution, metabolism, and excretion of bioactive compounds.
Bioavailability can be variable due to many different factors, including chemical structure, physical state, solubility, route of administration, and distribution via biotransformation and excretion [111,112]. Based on solubility, volatile compounds and essential oils are relatively more nonpolar hydrophobic compounds than polyphenols that are more polar hydrophilic nutraceuticals [113,114]. Regarding the route of administration, volatile compounds are more suitable for pulmonary administration through inhalation, while polyphenols are normally administrated orally [115]. Oral administration generally takes, on average, 30–90 min of action, while inhalation of gaseous compounds takes, on average, only 2–3 min [116]. The bioavailability of volatiles is largely affected by volatility, instability, and hydrophobicity [117].
Although there are many types of research conducted about the identification and quantification of berry volatiles, information is still lacking on the bioavailability of berry volatiles in animals and humans [118]. In this review, bioavailability studies of essential oils and herbal medicinal products that contain volatiles commonly present in berries were selected to estimate the bioavailability of volatile berry compounds. Unfortunately, the studies found are limited and mostly include animal models.
Most of the bioavailability studies of essential oils showed that the volatile compounds in essential oils are rapidly absorbed and eliminated after pulmonary, dermal, and oral administration [115]. The compounds were mostly metabolized and eliminated within an hour of elimination half-life through the kidney after phase-II conjugation or CO2 exhalation.
In Igimi et al., the absorption, distribution, and excretion of d-limonene, a monoterpene in many essential oils but also found in black raspberries and blackberries, were investigated in rats [119]. 14C-labeled d-limonene was orally administered to 21 male Wistar rats. The maximum radioactivity was obtained 2 h after administration in blood and 1–2 h after administration in tissues. High radioactivity in the liver, kidney, and blood became not significant after 48 h. The excretion of d-limonene was 60% in urine, 5% in feces, and 2% in expired CO2 in 48 h. About 25% of administered d-limonene was eliminated in bile in 24 h in bile duct cannulated rats. Biotransformation studies of (+)-limonene in humans showed that the main metabolites of biotransformation were perillic acid, dihydroperillic acid, and limonene-10-ol, and their glucuronides, perillyl alcohol, p-mentha-1,8-dien-carboxylic acid, cis- and trans-dihydroperillic acid, limonene, 1,2-diol and limonene-8,9-diol [120].
Dermal application of α-pinene on humans (ointment) and mice (bath) resulted in rapid absorption in plasma, reaching maximum plasma levels in 10 min of application [115]. Inhalation of α-pinene in humans resulted in 61% absorption of α-pinene [115]. However, only 4–6% of α-pinene was found to be absorbed in the blood. In α-pinene dermal and pulmonary administration studies [115], the half-life was short in the α-phase (5 min) and longer in the β-phase (26–38 min). α- and β-pinene in humans were metabolized to trans- and cis-verbenol, respectively, and they were further hydroxylated to diols. In rabbits, trans-verbenol was major, and myrtenol and myrtenic acid were minor metabolites of α-pinene, while cis-verbenol was the major metabolite of β-pinene [121]. In a recent open-label, single-arm study, ten male subjects consumed Mastiha oil (1 mL) containing rich monoterpenes, and blood samples were collected at 0–24 h after Mastiha oil administration [122]. Mastiha oil contained α-pinene (82.2%), myrcene (8.5%), and β-pinene (2.4%) as the major terpenes and also had linalool and limonene (0.8% each). In subjects’ blood samples, the three major terpenes were detected. Myrcene reached its peak at 2.2 h (966.6 μg/L), and α-pinene and β-pinene reached their peaks at 3.8 (914.8 μg/L) and 3.6 h (18 μg/L), respectively [122].
Linalool, one of the major berry volatile compounds, was metabolized to dihydrolinalool, tetrahydrolinalool, and 8-hydroxylinalool, then further oxidized to 8-carboxylinalool by cytochrome P450 (CYP). Metabolites derived by CYP formed glucuronide conjugates [123]. Oral administration of α-terpineol to rats resulted in the metabolization of alpha-terpineol to p-menthane-1,2,8-triol. The major biotransformation occurred in 1,2-double bound with allylic methyl oxidation and reduction [124].

5. Health Benefits of Berry Volatiles

Despite the sensory properties of fruits and vegetables, there are studies demonstrating that the role of aroma compounds is more than their odor impact [18,125]. Recently, volatile compounds in plants have been reported to have health-promoting activities, including anti-inflammatory [25,126], anti-cancer [26], anti-obesity, and anti-diabetic effects [127]. However, since there are not many studies on the health-promoting effects of berry volatiles, studies of volatile compounds from essential oils and other fruits and plants that berries commonly contain were used to review the potential health benefits of volatile compounds in berries (Figure 2).

5.1. Inflammation

Infection, inflammation, or any cellular damage/stimuli are detected by macrophages and dendritic cells through pattern recognition receptors (PRRs) with pathogen-associated molecular patterns and danger-associated molecular patterns [128,129]. Toll-like receptors and intracellular nucleotide-binding domain leucine-rich-repeat-containing receptors recognize these stimuli and stimulate signal transductions, mitogen-activated protein kinases (MAPKs) [130,131,132]. MAPK signal transduction pathways include extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 and regulate downstream protein kinases and transcription factors [133]. Stimulated signal transductions activate pro-inflammatory transcription factors, such as nuclear factor kappa-B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) [132]. NF-κB regulates the production of pro-inflammatory cytokines and chemokines, including interleukin (IL)-1ß, IL-6, nitric oxide (NO), prostaglandin (PGE) 2, and tumor necrosis factor (TNF)-α [134,135]. NF-κB is activated by IκB kinase (IKK) phosphorylating NF-κB-inhibitory protein (IκBα), and translocating into the nucleus, promoting transcription of pro-inflammatory mediators [136]. Nrf2 is another transcription factor related to oxidative damage and inflammation [137]. During the cascade of inflammatory responses, reactive oxidative stress (ROS) increases oxidative stress on cells, leading to the autophagy of cells [138,139]. However, recent studies found that volatile compounds in plants, especially terpenes, mitigate inflammation by suppressing many different inflammatory processes [140,141]. In this section, the effects of volatile compounds rich in berries against inflammation in different steps of inflammatory processes were summarized (Table 2).

5.1.1. Modulation of Pro-Inflammatory Mediators

Many volatile compounds in plants showed anti-inflammatory effects by reducing the level of pro-inflammatory mediators and cytokines, such as NO, PGE2, cyclooxygenase (COX-2), TNF-α, and interleukins [69,83,142,145,146,147,150,151,152,153,154,159,160]. Amorim et al. indicated that the essential oils obtained from Citrus species and limonene demonstrated a significant anti-inflammatory effect by reducing cytokine production, including NO, TNF-α, and IL-1β [142]. The essential oils of citrus fruit peel contain abundant monoterpenes such as limonene, geranial, β-pinene, and γ-terpinene, which are one of the major volatile compounds in berries [159]. In Rehman et al., d-limonene at 5% and 10% doses mixed in a diet given to rats for 20 days effectively reduced doxorubicin-induced COX-2, inducible nitric oxide synthase (iNOS), and NO [160]. In an ulcerative colitis rat model, rats (n = 8/group) fed d-limonene (50 and 100 mg/kg) for 7 days showed anti-inflammatory effects by suppressing the level of iNOS, COX-2, and PGE2 [145]. In lipopolysaccharide (LPS)-induced RAW264.7 cells, 125–1000 μg/mL of rheosmin (raspberry ketone) isolated from pine needles exerted an anti-inflammatory activity with reduced NO, PGE2, iNOS, and COX-2 production [147]. In the LPS-induced murine macrophage RAW264.7 cell model, α-terpineol treatment (1.16 μg/mL) before and after LPS stimulation showed significant inhibition on the level of NO [83]. In a mouse model of carrageenan-induced peritonitis, oral administration of γ-terpinene 1 h before intraperitoneal carrageenan injection significantly attenuated the TNF-α and IL-1β production [146]. In a triple transgenic Alzheimer’s mouse model, oral administration of 25 mg/kg linalool, every 48 h for 3 months, markedly decreased the production of iNOS, COX-2, and IL-1β [150]. Mice administered 2.6 and 5.2 mg/kg linalool before injecting endotoxin remarkably suppressed the nitrate/nitrite, IL-1β, IL-18, TNF-α, and interferon (IFN)-γ production [151]. Oral linalool administration (15 and 30 mg/kg) also lowered iNOS levels in lung tissues in mice with allergic asthma [152]. Intraperitoneal injection of 10, 20, and 40 mg/kg linalool two hours before cigarette smoke exposure for five days ameliorated the lung inflammation by suppressing the level of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-8, and monocyte chemoattractant protein (MCP)-1) [153]. Linalool (40–120 μg/mL) attenuated the LPS-induced inflammation on RAW264.7 cells with the suppressed level of TNF-α and IL-6 [154]. In the LPS-stimulated mouse macrophage RAW264.7 cell model, 1 h pretreatment of volatile extracts (50-fold dilution) from blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry significantly reduced production in NO, PGE2, and COX-2 [69]. Blackberry, blueberry, cranberry, and volatile strawberry extracts also effectively suppressed LPS-induced TNF-α and IL-6 production.

5.1.2. Regulation of Inflammatory Transcription Factors and Signal Transduction

NF-κB is a crucial target for anti-inflammation since it is one of the main transcription factors regulating pro-inflammatory mediators [161]. Linalool significantly reduced the NF-κB activation in mice with endotoxin injection [151], cigarette smoke-induced acute lung inflammation [153], and airway allergic inflammation [152]. Limonene (25–75 mg/kg) intraperitoneal injection 1 h before LPS administration down-regulated the phosphorylation of IκBα, NF-κB p65, p38 MAPK, JNK, and ERK in LPS-induced acute lung injury mice [143]. In Rehman et al., d-limonene also suppressed NF-κB activation in a doxorubicin-stimulated inflammation rat model [160]. Limonene and myrcene attenuated the IL-1β-induced inflammation by suppressing NF-κB and JNK activation in human chondrocytes [144]. Terpinen-4-ol inhibited NF-κB in the dextran sulfate sodium (DSS)-increased experimental colitis in mice [148]. Terpinen-4-ol also attenuated the LPS-stimulated IκBα and NF-κB p65 phosphorylation in acute lung injury mice [149]. In Wu et al., linalool increased nuclear translocation of Nrf2 in mice with pneumonia infected by Pasteurella multocida [155]. Linalool (162–648 μM), one of the major berry volatiles, reduced LPS-stimulated inflammation on BV2 microglia cells through Nrf2/HO-1 signaling pathway [156]. α-Pinene in coniferous trees and rosemary oils suppressed the MAPK and NF-κB activation in LPS-induced macrophages [157]. In LPS-induced RAW264.7 murine macrophage cells, volatile extract (50-fold dilution) from blackberry, black raspberry, blueberry, and cranberry significantly suppressed the NF-κB activation by down-regulating phosphorylation of NF-κB p65 and IκBα [69].

5.1.3. Attenuation of Oxidative Stress and Autophagy

A disparity between the production and elimination of ROS causes oxidative stress. Excessively produced ROS can damage tissues, increasing inflammatory responses and leading to cell death, such as necrosis and apoptosis [162]. There have been many examinations of the antioxidant activities of volatile compounds in plants against oxidative stress in vitro. α-terpinene, γ-terpinene, and linalool showed antioxidant activities in 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS), chelating power, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and oxygen radical absorbance capacity (ORAC) assays [163]. α-pinene, 1,8-cineole, and d-limonene remarkably ameliorated the formation of ROS in H2O2-stimulated oxidative stress [158].

5.2. Cancer

Kim et al. demonstrated that geraniol inhibits human prostate cancer cell PC-3 proliferation in in vitro and in vivo xenograft mice models [164]. Geraniol at 0.5 and 1 mM significantly suppressed the cell growth of PC-3 by increasing cell cycle arrest and apoptosis. Balb/C nude mice inoculated with PC-3 cells took intratumoral geraniol injection daily for 38 days at 0, 12, 60, or 300 mg/kg. The mice treated with 60 or 300 mg/kg geraniol showed significantly decreased tumor volume and weight. Injection of geraniol at 20 mg/kg also sensitized the chemotherapeutic agent Docetaxel (2 mg/kg) in the xenograft mice model. In Lee et al., geraniol inhibited prostate cancer growth by a down-regulating E2F8 transcription factor and inducing G2/M phase cell cycle arrest [165]. In gastric adenocarcinoma AGS cells, geraniol showed cytotoxicity by inhibiting the JNK/ERK signaling pathway [166]. Lavender essential oil, its active compounds linalool and linalyl acetate [167], and ethyl acetate fraction of Ajwa dates [168] also inhibited PC-3 cell proliferation by increasing apoptosis and cell cycle arrest. Linalool also reduced tumor growth in PC-3 xenograft mice [167] and the 22Rv1 xenograft mice model [169]. Ethyl acetate exerted an anti-proliferative activity on human breast cancer MCF7 and SKBR3 cells [170] and human cervical cancer HeLa cells [171]. α-terpineol [172] and linalool [173] also showed strong cytotoxicity on HeLa cells with apoptosis and cell cycle arrest. In human acute myeloid leukemia U937 cells [173], human oral cancer cells [174,175], and lung adenocarcinoma A549 cells [176], linalool significantly suppressed the cell growth. D-limonene [177] and d-limonene-rich blood orange volatile oils [178] inhibited the proliferation of lung cancer A549 and H1299 cells and human colon adenocarcinoma cells SW480 and HT-29 cells, respectively. Limonene (9 μM) significantly reduced the proliferation of human bladder cancer cell T24 after 24 h, showing induced apoptosis with increased G2/M cell cycle arrest and apoptotic markers (Bax, and cleaved caspase-3, 8, and 9) [179]. In Yu et al., d-limonene induced apoptosis and autophagy-related genes in a lung cancer model [177]. In an acetic acid-induced gastric ulcer rat model, 7-day oral administration of (-)-myrtenol at 50–100 mg/kg increased the healing of the ulcer [180]. Myrcene640 μM) significantly decreased the proliferation of SCC9 oral cancer cells after 24 h [181]. Myrcene also showed increased apoptosis with the concentration of 5–20 μM and significantly suppressed the migration of SCC9 cells at 10 μM myrcene treatment. The effects of volatile compounds rich in berries on cancer models were summarized in Table 3.

5.3. Obesity

A high-fat diet for obese humans and animals can increase endothelial dysfunction. It can lead to many other severe cardiovascular diseases and metabolic disorders. In Wang et al., geraniol was examined for the effect on endothelial function in high-fat diet (HFD)-fed mice [182]. Forty mice were fed HFD for 8 weeks, while 20 mice had a normal diet. Then, HFD-fed mice were randomly assigned to intraperitoneal geraniol treatment (20 mice) or vehicle treatment (20 mice) group for 6 weeks. As a result, geraniol protected and improved HFD-induced endothelial dysfunction in HFD-fed mice by reducing aortic NADPH oxidases and ROS production. In Sousa et al., α-terpineol enantiomers were examined for their effect on the biological markers in HFD-induced obese rats [183]. Six weeks of daily α-terpineol supplementation (50–100 mg/kg of diet) suppressed pro-inflammatory cytokines (TNF-α and IL-1β), serum thiobarbituric acid reactive substances (TBARS), and recovered insulin sensibility. In Li et al., Microcapsules of d-limonene-rich sweet orange essential oil (SOEO) were orally administered to HFD-induced obese rats for 15 days [184]. SOEO microcapsules decreased the body weight in obese rats by protecting the gut barrier, increasing Bifidobacterium, and reducing low-grade inflammation. While white adipocytes store the excessive energy in triglyceride forms, brown adipocytes burn the calories in heat form by non-shivering thermogenesis [185]. Lone and Yun showed that limonene increased 3T3-L1 adipocytes browning through the activation of the β3-adenergenic receptor and ERK signaling pathway [185]. In Ayala-Ruiz et al., male Wister rats (n = 6 per group) were administered with control, high-fat-sucrose diet (HFSD) and 0.6 mL of corn oil, HFSD with 1,8-cineole (0.88 mg/kg), limonene (0.43 mg/kg), α-terpineol (0.32 mg/kg), or the mixture of three terpenes per gavage for 15 weeks [186]. Rats fed with HFSD with terpenes significantly reduced weight gain compared to the ones with only HFSD. In addition, all terpenes suppressed the fat deposition, serum glucose levels, and triacylglycerol levels. The effects of volatile compounds rich in berries against obesity were summarized (Table 4).

5.4. Diabetes

In Bacanlı et al., streptozotocin (STZ) (60 mg/kg) was injected into Wistar rats to induce type 1 diabetes [187]. Diabetic rats were orally treated with d-limonene (50 mg/kg body weight) for 28 days. D-limonene treatment significantly reduced DNA damage and induced the level of antioxidant enzymes (catalase, superoxide dismutase, and total glutathione). D-limonene also altered hepatic enzyme and lipid profile, suggesting the potential of d-limonene being protective against diabetes in the liver and kidney in rats. D-limonene showed potential antihyperglycemic activities [188,189] and reduced lipid peroxidation with increased antioxidant activity [190]. In El-Bassossy et al., geraniol (150 mg/kg) was orally treated in STZ-induced obese rats for 7 weeks [191]. Geraniol significantly reduced systolic cardiac function related to diabetes by alleviating oxidative stress. Geraniol treatment also reduced GLUT 2 transporter [192], hyperglycemia [193], diabetic nephropathy [194], and improved impaired vascular reactivity [195] in STZ-induced diabetic rats. Linalool also exerted a reduction in fasting blood glucose level, insulin resistance, glycation oxidative stress [196], and nephropathic changes in kidneys [197] on STZ-induced diabetic rats. Xuemei et al. investigated the effect of myrtenol on STZ-induced gestational diabetes mellitus (GDM) in rats [198]. GDM is diabetes that occurs only during pregnancy. Twenty-five mg/kg of STZ was injected into the pregnant rats to induce GDM. Myrtenol (50 mg/kg) was orally administered for 2 weeks. Myrtenol oral administration helped decrease blood glucose levels and pro-inflammatory markers. It also increased high-density lipoprotein (HDL) and antioxidant status in diabetic pregnant rats. The effects of volatile compounds rich in berries against diabetes were summarized in Table 5.

6. Conclusions

As berry consumption through the fruit and products, including berry-flavored water, juice, and others, have rapidly increased, many studies about monitoring and improving overall berry quality, including flavor, aroma, appearance, shelf-life, and safety, were conducted to target consumer acceptability. However, the beneficial health effects of berry volatiles have not been extensively studied. In this article, we looked into the biosynthesis of plant volatiles, volatile composition, and possible bioavailability and health benefits of some berry volatiles were reviewed. Major terpene volatiles were synthesized via MVA and MEP pathways. Major chemical classes in berries were esters, alcohols, terpenoids, aldehydes, ketones, and lactones. Berries had different profiles of volatiles, but monoterpene showed a crucial role in characterizing the unique berry aroma in all five berries. Volatile compounds were nonpolar and hydrophobic and rapidly absorbed and eliminated from our body after administration. Among them, monoterpenes, including linalool, limonene, and geraniol, showed many health benefits associated with inflammation, cancer, obesity, and diabetes in vitro and in vivo, suggesting potential health beneficial effects of berry volatiles. More research on animal and human models of the health benefits of berry volatiles and bioavailability would be needed to confirm their bioactivities.

Author Contributions

Conceptualization, L.H. and S.-O.L.; writing—original draft preparation, I.G.; writing—review and editing, S.-O.L., L.H. and I.G.; supervision, S.-O.L. and L.H.; funding acquisition, L.H. and S.-O.L. All authors have read and agreed to the published version of the manuscript.

Funding

The work was supported by the Arkansas Biosciences Institute.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

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Figure 1. Biosynthetic pathways of volatile terpenes in plants (adopted and modified from Nagegowda [50]). AACT = acetoacetyl-CoA thiolase; AcAc-CoA = acetoacetyl-CoA; CDP-ME = 4-(cytidine 50-diphospho)-2-C-methyl-D-erythritol; CDP-ME2P = 4-(cytidine 50-diphospho)-2-C-methyl-D-erythritol phosphate; CMK = CDP-ME kinase; DMAPP = dimethylallyldiphosphate; DOXP=1-deoxy-D-xylulose 5-phosphate; DXR = DOXP re-ductoisomerase; DXS = DOXP synthase; FDS = farnesyl diphosphate synthase; FPP = farnesyl diphosphate; GA-3P = glyceraldehyde-3-phosphate; GDS = geranyl diphosphate synthase; GGDS = geranyl geranyl diphosphate synthase; GGPP = geranyl geranyl di-phosphate; GPP = geranyldiphosphate; HDR = (E)-4-hydroxy-3-methylbut-2-enyl di-phosphate reductase; HDS = (E)-4-hydroxy-3-methylbut-2-enyl diphosphate synthase; HMBPP = (E)-4-hydroxy-3-methylbut-2-enyl diphosphate; HMG-CoA = 3-hydroxy-3-methylglutaryl-CoA; HMGR = HMG-CoA reductase; HMGS = HMG-CoA synthase; IDI = isopentenyl diphosphateisomerase; IPP = isopentenyl diphosphate; ISPS = isoprene synthase; MCT = 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase; MDS = 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase; ME-2,4cPP = 2-C-methyl-D-erythritol 2,4-cyclodiphosphate; MEP = 2-C-methyl-D-erythritol 4-phosphate; MVD = mevalonate diphosphate decar-boxylase; MVK = mevalonate ki-nase; PMK = phosphomevalonate kinase; TPS=terpene synthase. Names of the enzymes are in gray.
Figure 1. Biosynthetic pathways of volatile terpenes in plants (adopted and modified from Nagegowda [50]). AACT = acetoacetyl-CoA thiolase; AcAc-CoA = acetoacetyl-CoA; CDP-ME = 4-(cytidine 50-diphospho)-2-C-methyl-D-erythritol; CDP-ME2P = 4-(cytidine 50-diphospho)-2-C-methyl-D-erythritol phosphate; CMK = CDP-ME kinase; DMAPP = dimethylallyldiphosphate; DOXP=1-deoxy-D-xylulose 5-phosphate; DXR = DOXP re-ductoisomerase; DXS = DOXP synthase; FDS = farnesyl diphosphate synthase; FPP = farnesyl diphosphate; GA-3P = glyceraldehyde-3-phosphate; GDS = geranyl diphosphate synthase; GGDS = geranyl geranyl diphosphate synthase; GGPP = geranyl geranyl di-phosphate; GPP = geranyldiphosphate; HDR = (E)-4-hydroxy-3-methylbut-2-enyl di-phosphate reductase; HDS = (E)-4-hydroxy-3-methylbut-2-enyl diphosphate synthase; HMBPP = (E)-4-hydroxy-3-methylbut-2-enyl diphosphate; HMG-CoA = 3-hydroxy-3-methylglutaryl-CoA; HMGR = HMG-CoA reductase; HMGS = HMG-CoA synthase; IDI = isopentenyl diphosphateisomerase; IPP = isopentenyl diphosphate; ISPS = isoprene synthase; MCT = 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase; MDS = 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase; ME-2,4cPP = 2-C-methyl-D-erythritol 2,4-cyclodiphosphate; MEP = 2-C-methyl-D-erythritol 4-phosphate; MVD = mevalonate diphosphate decar-boxylase; MVK = mevalonate ki-nase; PMK = phosphomevalonate kinase; TPS=terpene synthase. Names of the enzymes are in gray.
Applsci 12 10238 g001
Applsci 12 10238 g002 550
Figure 2. Potential bioactivities of berry volatiles. COX-2 = cyclooxygenase-2; ERK = extracellular signal-regulated kinase; IL-1β = interleukin-1β; IL-6 = interleukin-6; JNK = c-Jun N-terminal kinase; MAPK = mitogen-activated protein kinase; NF-κB = nuclear factor kappa B; NO = nitric oxide; Nrf2 = nuclear factor erythroid 2-related factor 2; PGE2 = prostaglandin 2; TNF-α = tumor necrosis factor-α; ↓ = decrease.
Figure 2. Potential bioactivities of berry volatiles. COX-2 = cyclooxygenase-2; ERK = extracellular signal-regulated kinase; IL-1β = interleukin-1β; IL-6 = interleukin-6; JNK = c-Jun N-terminal kinase; MAPK = mitogen-activated protein kinase; NF-κB = nuclear factor kappa B; NO = nitric oxide; Nrf2 = nuclear factor erythroid 2-related factor 2; PGE2 = prostaglandin 2; TNF-α = tumor necrosis factor-α; ↓ = decrease.
Applsci 12 10238 g002
Table
Table 1. The major volatile compounds in berries.
Table 1. The major volatile compounds in berries.
CompoundStrawberryBlueberryRaspberryBlackberryCranberry
Esters
Methyl butanoate[65,66]
Methyl hexanoate[65,66,67]
Ethyl acetate[65][68][69][70]
Hexyl acetate[65]
Ethyl butanoate[66,69] [71]
Ethyl hexanoate[66,72] [73]
Ethyl 2-methylbutanoate[67][74] [71,73][75]
Ethyl 2-methylpropanoate[67] [76]
3-methylbutylacetate[67]
Hexyl butanoate[69]
Ethyl propanoate [74]
Methyl 2-methylbutanoate [74]
Methyl 3-methylbutanoate [74]
Ethyl 3-methylbutanoate [74]
(Z)-3-hexyl acetate [74]
(E)-2-hexyl acetate [74]
Geranyl acetate [74]
3-cis-hexenyl formate [77]
Ethyl benzoate [69]
Ketones
2-heptanone[67][74,78][79][73]
2,3-butanedione[67] [80]
1-octen-3-one [74]
2-nonanone [74]
6-methyl-5-hepten-2-one [74]
Raspberry ketone [76]
β-damascenone [76][71]
3-hydroxy-2-butanone [80]
2-undecanone [73]
Isophorone [69]
Terpenes
Limonone[65][74] [69,73]
α-terpinene[65]
Linalool[65,66][69,74,78][67,76][71,73][69]
Nerolidol[66]
Myrtenol[69] [69][69,73]
Geraniol [68,74][76,79][71]
Citronellol [74,81] [69]
α-terpineol [69,74,81][69,76][70][69,77,82,83]
Nerol [74][76]
Eucalyptol (1,8-cineolo) [74,78] [69,83]
Dihydrolinalool oxide [74]
δ-elemene [78]
(E)-caryophyllene [78]
Caryophyllene oxide [78]
Linalool oxide [69] [83]
β-ionone [69][76,79][73][75]
α-ionone [69,76,79][73]
β-pinene [76]
Terpinen-4-ol [79][69]
α-pinene [73]
p-cymene [73]
Sabinene [73]
Acids
Butanoic acid[69] [69][77]
Hexanoic acid [78][69][69,73]
Octanoic acid [78]
Nonanoic acid [78]
Decanoic acid [78] [73]
3-methylbutanoic acid [69][73]
2-methylbutanoic acid [73,80][69,75]
Acetic acid [73]
Alcohols
Cis-3-hexen-1-ol[65]
(E)-2-hexenol [68]
(Z)-3-hexenol [68][76]
2-phenylethanol [81]
(Z)-3-hexenol [74]
2-heptanol [74] [73]
Phenylethyl alcohol [69]
2-ethylhexanol [69][69][69]
1-octanol [76][73,80]
(Z)-hexenol [79]
Ethanol [73,80]
1-hexanol [73,80]
p-cymen-8-ol [73]
Nopol [73]
4-methyl-1-pentanol [69]
4-penten-2-ol [77]
Benzyl alcohol [77,82,84]
Aldehydes
Hexanal[65,85][68,74,78][76,79][73][75]
Trans-2-hexenal[65] [73,80]
Cis-3-hexenal[67]
(E)-2-hexenal [68,74,78][76,79] [75]
Vanilllin [81][69]
(Z)-3-hexenal [74,78]
(E,Z)-2,6-nonadienal [74]
(E,E)-2,4-nonedienal [74]
Pentanal [74] [75]
Octanal [74] [75]
(E,E)-2,4-hexadienal [74]
Decanal [74]
Hexadienal [78]
Heptanal [78][76]
Benzaldehyde [76] [77]
cuminaldehyde [69]
Methylbutanal [80]
Methional [71]
Trans,cis-2,6-nonadienal [71]
3-methylbutanal [73]
2-methylbutanal [73]
(E)-2-heptenal [75]
(E)-2-octenal [75]
(E)-2-nonenal [75]
Trans-2-decanal [83]
2-octanal [83]
Surfurs
methanethiol[66]
Norisoprenoids
β-damascenone [78]
Cis-1,5-octadien-3-one [71]
Furanones
Furaneol[65,66][74][76][71]
Mesifurane[65,66,67,69]
Hydrocarbons
Octane [78]
Ethyl benzene [78]
p-xylene [78]
Mxylene [78]
Β-ocimene [76]
Lactones
γ-decalactone[65]
Butyrolactone [78]
δ-octalactone [79]
δ-decalactone [79]
Table
Table 2. The effect of volatile compounds rich in berries on inflammation models.
Table 2. The effect of volatile compounds rich in berries on inflammation models.
Volatile CompoundInflammation ModelEffectReferences
LimoneneCarrageenan-induced mice subcutaneous air pouch mice modelIFN-γ, IL-1β, NO, and TNF-α production↓[142]
LimoneneLPS-induced acute lung injury mice modelNF-κB and MAPK activation↓
(IκBα, NF-κB p65, ERK, JNK, and p38 MAPK phosphorylation↓)		[143]
D-limoneneDoxorubicin-induced rat modelCOX-2, iNOS, NO, PGE2, and TNF-α production↓
NF-κB activation↓		[144]
D-limoneneUlcerative colitis rat modelCOX-2, iNOS, PGE2↓[145]
Limonene, myrceneIL-1β-induced human chondrocyte modelJNK and p38 phosphorylation↓
NF-κB activation↓		[146]
RheosminLPS-induced RAW264.7 cellsCOX-2, iNOS, NO, and PGE2 production↓[147]
α-terpineolLPS-induced RAW264.7 cellsNO production↓[83]
γ-terpineneCarrageenan-induced peritonitis mice modelIL-1β and TNF-α production↓[146]
Terpinen-4-olDSS-induced colitis mice modelNF-κB activation↓[148]
Terpinen-4-olLPS-induced acute lung injury mice modelIL-1β and TNF-α production↓
IκBα and NF-κB p65 phosphorylation↓		[149]
LinaloolAged triple transgenic Alzheimer’s mice modelCOX-2, IL-1β, and iNOS production↓
P38 MAPK production↓		[150]
LinaloolEndotoxin-induced mice modelIFN-γ, IL-1β, IL-18, NO, and TNF-α production↓
TLR4 expression↓
NF-κB activation↓		[151]
LinaloolOvalbumin-induced pulmonary inflammation mice modeliNOS and MCP-1 production↓
MAPK and NF-κB activation↓		[152]
LinaloolCigarette smoke-induced acute lung inflammation mice modelIL-1β, IL-6, IL-8, MCP-1, and TNF-α production↓
NF-κB activation↓		[153]
LinaloolLPS-induced RAW264.7 cellsIL-6 and TNF-α production↓[154]
LinaloolPasteurella multocida-induced lung inflammation mice modelIL-6 and TNF-α production↓
Nrf2 nuclear translocation↑		[155]
LinaloolLPS-induced BV2 microglia cellsIL-1β, NO, PGE2, and TNF-α production↓
NF-κB activation↓
Nrf2 nuclear translocation↑
HO-1 expression↑		[156]
α-pineneLPS-induced mouse peritoneal macrophagesCOX-2, IL-6, iNOS, NO, and TNF-α production↓
MAPK and NF-κB activation↓		[157]
α-pinene, 1,8-cineoleH2O2-stimulated U373-MG cells (human astrocytoma cell line)ROS formation↓[158]
Berry volatile extractsLPS-induced RAW264.7 cellsCOX-2↓, IL-6↓, NO↓, PGE2↓, TNF-α↓
IκBα and NF-κB p65 phosphorylation↓		[69]
COX-2 = cyclooxygenase-2; ERK = extracellular signal-regulated kinase; HO-1 = heme oxygenase-1; IFN-γ = interferon-γ; IκBα = IκB kinase phosphorylating NF-κB-inhibitory protein; IL-18 = interleukin-18; IL-1β = interleukin-1β; IL-6 = interleukin-6; iNOS = inducible nitric oxide synthase; JNK = c-Jun N-terminal kinase; MAPK = mitogen-activated protein kinase; MCP-1 = monocyte chemoattractant protein-1; NF-κB = nuclear factor kappa B; NO = nitric oxide; Nrf2 = nuclear factor erythroid 2-related factor 2; PGE2 = prostaglandin 2; ROS = reactive oxidative stress; TLR4 = toll-like receptor 4; TNF-α = tumor necrosis factor-α; ↑ = increase; ↓ = decrease.
Table
Table 3. The effect of volatile compounds rich in berries on cancer models.
Table 3. The effect of volatile compounds rich in berries on cancer models.
Volatile CompoundCancer ModelEffectReferences
GeraniolHuman prostate cancer PC-3 cells, in vitro and in vivo xenograft mice modelCell proliferation↓
Cell cycle arrest and apoptosis↑
Tumor volume and weight↓
Docetaxel sensitization↑		[164]
GeraniolHuman prostate cancer PC-3 cellsE2F8 transcription factor↓
G2/M phase cell cycle arrest↑		[165]
GeraniolGastric adenocarcinoma AGS cellsERK, JNK, p38 MAPK activation↓
Apoptosis↑		[166]
Linalool, linalyl acetateHuman prostate cancer PC-3 and DU145 cells, PC-3 cell-transplanted xenograft mice modelApoptosis and G2/M phase cell cycle arrest↑
Tumor growth↓		[167]
LinaloolHuman prostate cancer 22Rv1 cellsCell proliferation↓
Apoptosis↑		[169]
LinaloolHuman leukemia U937 cells and human cervical adenocarcinoma HeLa cellsApoptosis and cell cycle arrest↑[173]
LinaloolHuman oral cancer OECM1 and KB cellsCell proliferation↓
Apoptosis and sub-G1 phase cell cycle arrest↑		[174]
[175]
Linalool, 1,8-cineoleHuman lung adenocarcinoma A549 cellsCell proliferation↓
Cell cycle arrest↑
No apoptosis		[176]
Ethyl acetateHuman prostate cancer PC-3 cellsApoptosis and S phase cell cycle arrest↑
Oxidative stress↑
Mitochondrial membrane potential (MMP)↓		[168]
Ethyl acetateHuman breast cancer MCF7 and SKBR3 cellsSub G1 phase cell cycle arrest↑
ROS production↑
MMP↓		[170]
Ethyl acetateHuman cervical cancer HeLa cellsApoptosis and G2/M phase cell cycle arrest↑[171]
α-terpineolHuman cervical cancer HeLa cellsApoptosis and G1 phase cell cycle arrest↑[172]
D-limoneneLung cancer A549 and H1299 cellsTumor growth↓
Apoptosis and autophagy-related gene expression↑		[177]
LimoneneHuman bladder cancer T24 cellsCell proliferation↓
Apoptosis and G2/M cell cycle arrest↑
Bax, cleaved caspase-3, 8, and 9 expression↑
Bcl-2 expression↓		[179]
MyrceneOral cancer SCC9 cellsApoptosis↑
Cell migration↓		[181]
ERK = extracellular signal-regulated kinase; JNK = c-Jun N-terminal kinase; MAPK = mitogen-activated protein kinase; ROS = reactive oxidative stress; ↑ = increase; ↓ = decrease.
Table
Table 4. The effect of volatile compounds rich in berries on obesity models.
Table 4. The effect of volatile compounds rich in berries on obesity models.
Volatile CompoundObesity ModelEffectReferences
GeraniolHigh-fat diet (HFD)-fed miceAortic NADPH oxidases, ROS production↓[182]
α-terpineolHFD-induced obese ratsIL-1β and TNF-α↓
Serum TBARS↓
Insulin sensibility↑		[183]
D-limonene-rich sweet orange essential oilHFD-induced obese ratsBody weight↓
Relative abundance of Bifidobacterium↑		[184]
LimoneneMouse preadipocytes 3T3-L1Adipocyte browning↑[185]
Limonene, α-terpineol, 1,8-cineoleHigh-fat-sucrose diet (HFSD)-fed ratsBody weight↓
Fat deposition↓
Serum glucose level↓
Triacylglycerol level↓		[186]
IL-1β = interleukin-1β; NADPH = nicotinamide adenine dinucleotide phosphate; ROS = reactive oxidative stress; TBARS = thiobarbituric acid reactive substances; TNF-α = tumor necrosis factor-α; ↑ = increase; ↓ = decrease.
Table
Table 5. The effect of volatile compounds rich in berries on diabete models.
Table 5. The effect of volatile compounds rich in berries on diabete models.
Volatile CompoundDiabetes ModelEffectReferences
D-limoneneStreptozotocin-induced diabetic rat modelDNA damage↓
Antioxidant enzyme activities↑		[187]
D-limoneneStreptozotocin-induced diabetic rat modelAntihyperglycemic activities↑[188]
Limonene, linaloolStreptozotocin-induced diabetic rat modelBlood glucose level↓
Antioxidant enzyme activities↑		[189]
D-limoneneStreptozotocin-induced diabetic rat modelLipid peroxidation↓
Antioxidant activity↑		[190]
GeraniolStreptozotocin-induced diabetic rat modelOxidative stress↓[191]
GeraniolStreptozotocin-induced diabetic rat modelGLUT2 expression↓
Kidney glucose release↓		[192]
GeraniolStreptozotocin-induced diabetic rat modelInsulin resistance↓
Plasma glucose level↓		[193]
GeraniolStreptozotocin-induced diabetic rat modelRedox balance↑
Lipid peroxidation↓		[194]
GeraniolStreptozotocin-induced diabetic rat modelVasoconstriction↓[195]
LinaloolStreptozotocin-induced diabetic rat modelNF-κB and TGF-β1 expression↓[197]
MyrtenolStreptozotocin-induced gestational diabetic pregnant rat modelBlood glucose level↓
Pro-inflammatory markers↓
HDL and antioxidant activity↑		[198]
HDL = high-density lipoprotein; NF-κB = nuclear factor kappa B; TGF-β1 = Transforming growth factor beta-1; ↑ = increase; ↓ = decrease.
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Gu, I.; Howard, L.; Lee, S.-O. Volatiles in Berries: Biosynthesis, Composition, Bioavailability, and Health Benefits. Appl. Sci. 2022, 12, 10238. https://doi.org/10.3390/app122010238

AMA Style

Gu I, Howard L, Lee S-O. Volatiles in Berries: Biosynthesis, Composition, Bioavailability, and Health Benefits. Applied Sciences. 2022; 12(20):10238. https://doi.org/10.3390/app122010238

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Gu, Inah, Luke Howard, and Sun-Ok Lee. 2022. "Volatiles in Berries: Biosynthesis, Composition, Bioavailability, and Health Benefits" Applied Sciences 12, no. 20: 10238. https://doi.org/10.3390/app122010238

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