A Comprehensive Survey of Phenolic Constituents Reported in Monofloral Honeys around the Globe

The aim of this review is to provide a comprehensive overview of the large variety of phenolic compounds that have to date been identified in a wide range of monofloral honeys found globally. The collated information is structured along several themes, including the botanical family and genus of the monofloral honeys for which phenolic constituents have been reported, the chemical classes the phenolic compounds can be attributed to, and the analytical method employed in compound determination as well as countries with a particular research focus on phenolic honey constituents. This review covers 130 research papers that detail the phenolic constituents of a total of 556 monofloral honeys. Based on the findings of this review, it can be concluded that most of these honeys belong to the Myrtaceae and Fabaceae families and that Robinia (Robinia pseudoacacia, Fabaceae), Manuka (Leptospermum scoparium, Myrtaceae), and Chestnut (Castanea sp., Fagaceae) honeys are to date the most studied honeys for phenolic compound determination. China, Italy, and Turkey are the major honey phenolic research hubs. To date, 161 individual phenolic compounds belonging to five major compound groups have been reported, with caffeic acid, gallic acid, ferulic acid and quercetin being the most widely reported among them. HPLC with photodiode array detection appears to be the most popular method for chemical structure identification.


Introduction
Honey is a stored food of honeybees (Apis mellifera) that originates from plant nectar and is converted to honey with the aid of enzymes secreted from the glands of worker bees. Inside a colony, forager bees with full honey sacs transfer nectar into honeycombs and then flutter their wings to hasten the decrease in nectar moisture before worker bees seal the cells for storage [1]. Honeys are classified either as monofloral/unifloral or polyfloral/multifloral, the former being derived from a predominant botanical species, thus from mainly one type of nectar with only minor, if any, nectar contributions from other botanical sources. Polyfloral honeys, on the other hand, are linked to several botanical sources, none of which predominate [2].
Honey has been extensively used throughout history, not only as a food and food sweetener but also for medicinal purposes, which are associated, for example, with its antimicrobial and/or antioxidant properties [2][3][4][5]. However, honey's potential health benefits can vary considerably due to the diversity of nectar collected by bees as they move The literature search yielded a total of 130 original research articles that detail phenolic compounds identified in monofloral honeys in various countries around the globe. Since most studies analysed more than one monofloral honey, this review captures the published data for a total of 556 monofloral honeys. Their predominant botanical sources can be attributed to a total of 51 plant families; 90 of the reported monoflorals originated from members of the Fabaceae family, 88 from Myrtaceae, 56 from Lamiaceae, 41 from Ericaceae, 34 from Rutaceae, 33 from Fagaceae and 30 from Asteraceae. Thus, these seven plant families appear to be the most common botanical sources of honeys for which phenolic constituents have to date been reported in the literature.
The reviewed reports were further categorised into 159 monofloral groups taking into account not only the botanical family, but also the common name and/or the genus or species of the honeys' botanical origin. It was found that 23 of these monofloral groups belonged to the Myrtaceae family, 17 were Fabaceae, 14 Lamiaceae, 12 Asteraceae and 9 belonged to the Rosaceae family.
It could also be determined from this grouping that Robinia honey (Robinia pseudoacacia, Fabaceae), which has been reported in 36 research papers, is the most studied honey with respect to phenolic constituents. This is followed by Manuka honey (Leptospermum scoparium, Myrtaceae) with 29 research papers, Chestnut honey (Castanea sp., Fagaceae) with 28, Linden honey (Tilia sp., Malvaceae) with 25, Rape honey (Brassica sp., Brassicaceae) and Heather honey (Calluna vulgaris and Erica sp. (L.) Hull, Ericaceae) with 24 each, Eucalyptus honey (Eucalyptus sp., Myrtaceae) with 21, Thyme honey (Thymus sp., Lamiaceae) and Buckwheat honey (Fagopyrum sp., Polygonaceae) with 16 reports each, and Sunflower honey (Helianthus sp., Asteraceae) with 15 reports on phenolic profiling. This grouping, based on the botanical origin of the honeys, was also used to structure the overview on  (Table 1). The collated information was further used to create two groups of monofloral honeys-the first group containing high-frequency monoflorals (HFMs), where there are four or more studies reporting on their phenolic constituents (31 monofloral honey groups), and the second group, referred to as other monoflorals (OMs), having three or less studies dedicated to their phenolic composition (128 monofloral honey groups). To date, worldwide research efforts on phenolic constituents have mainly focused on the 31 monofloral honey groups referred to as HFMs in this review. The identification of the HFMs was also used in the construction of the regional maps of honey research shown in Section 3.3. Figure 1 presents the distribution of research on phenolic constituents in honeys across 37 countries. Countries that have yielded a high number of papers on phenolic honey constituents can be considered current 'hot spots' for this type of research. China leads the global research efforts with 76 reports on phenolic constituents in monofloral honeys, 76% of which were locally sourced. There were 74 papers originating from Italy with 89% of the reported samples being local honeys, and 45 reports from Turkey, all of which reported on Turkish honeys. Spain was also found to be a hotspot for research on phenolic honey constituents with 44 papers from this country, just under half of them (41%) reporting on locally sourced honeys. A total of 25 studies were carried out in Poland, with the vast majority (92%) investigating Polish honeys, 23 reports came from New Zealand (with 91% of the investigated honeys being local), 21 from Australia and 20 from Malaysia, both of which had 95% of the reported honeys sourced locally.

Regional Hotspots of Honey Phenolics Research
The distribution of studies on the phenolic constituents of honeys was further divided into four subregions to ascertain the most prevalent monoflorals studied in the respective geographical subregions of Australia and New Zealand; Asia; the Americas, and Africa and Europe.  detail the most frequently studied honeys in the four respective regions, with colour coding used for each region also conveying information on the respective popularity of honey phenolics research. The pie chart included in the maps allows assessing which monofloral honey species these regional research efforts were focused on.           honey phenolic constituents were carried out in Australia, 10 of which are focused on various Eucalyptus honeys (Myrtaceae). Within the region, Manuka (Leptospermum scoparium, Myrtaceae) honeys are the most studied, with 11 reports on their phenolic constituents, followed by Kanuka (Kunzea ericoides, Myrtaceae) and Clover honeys (Trifolium sp., Fabaceae), each with 4 reports, and Jelly bush honey (Leptospermum polygalifolium, Myrtaceae) and Rewarewa honey (Knightia excelsa, Proteaceae), with two reports each. Figure 2 details the most frequently studied honeys in the Australia and New Zealand region.

Asia
To date, research on honey phenolic constituents has been carried out in seven countries in Asia, namely Bangladesh, China, India, Malaysia, Saudi Arabia, Thailand and the United Arab Emirates. A total of 126 reports have been produced in the region, hotspots of research on honey phenolics being China with 76 studies, Malaysia with 20 and the United Arab Emirates with 11. Considering the botanical origin of the honeys studied in the region, 26 belong to the Fabaceae family, 17 are Myrtaceae, 10 Rhamnaceae and 8 each are Lamiaceae and Sapindaceae. The phenolic constituent profile of Gelam honey (Melaleuca cajuputi, Myrtaceae) appears to be the most studied in the region with seven reports, followed by that of New Zealand Manuka honey (Leptospermum scoparium), Rape honey (Brassica sp., Brasicaceae), Longan honey (Dimocarpus longan, Sapindaceae), Robinia honey (Robinia pseudoacacia L., Fabaceae) and Wild Jujube honey (Ziziphus spina-csisti, Rhamnaceae), which have been addressed in six reports each. Furthermore, the phenolic profile of Acacia honeys from Acacia mangium (Fabaceae) and Acacia tortilis (Fabaceae), Buckwheat honey (Fagopyrum esculentum, Polygonaceae) and Linden honey (Tilia sp., Malvaceae) have also been discussed in five studies each. Figure 3 details the most frequently studied honeys in the Asia region with respect to phenolic profile, and it visually conveys the importance of China for honey phenolic research in the region. Not only do the researchers in China report on a relatively large number of monofloral honeys, more than half of the honeys studied can be considered HFMs based on the reports generated. Thus, in many respects, China's research efforts strongly influence what constitutes, seen through a global lense, a HFM honey.

The Americas
In the Americas region, Argentina, Brazil, Chile and the United States can be considered honey phenolics research hotspots with a total of 35 published studies reporting on the phenolic constituents of monofloral honeys from 16 plant families, 7 each from Fabaceae and Myrtacea. Most studies (15 reports) were carried out in the United States, 9 in Brazil and 8 in Argentina. Interestingly, within the Americas, the New Zealand Manuka honey (Leptospermum scoparium, Myrtaceae) was the most studied, with four individual reports, followed by three studies on the phenolic constituents of Eucalypt honey (Eucalyptus sp., Myrtaceae) and two each on Azara honey (Azara sp., Salicaceae), Schinus honey (Schinus terebinthifolius, Anacardiaceae) and Tupelo honey (Nyssa aquatica, Nyssaceae). Figure 4 details the most frequently studied honeys in the Americas and it can be seen that, with the exception of the United States, honey phenolic research in this vast region is mainly focused on regionally important honeys classified as OMs in this review, and have, on a global scale, not yet attracted considerable research attention.

Africa and Europe
Research on phenolic constituents in honey has been reported from 24 countries in the Africa and Europe region, totalling 351 reports on monofloral honeys from 31 families. Italy leads the region with 74 reports, followed by Turkey with 45, Spain with 44, and Poland with 25. Honeys of the Fabaceae family were researched the most (53 papers), followed by honeys from the Lamiaceae (47), Ericaceae (39), Myrtaceae (33), Fagaceae (32), Rutaceae (25), Asteraceae (23), Malvaceae (21), Brassicaceae (18) and Pinaceae (13) families. Of these, the Robinia honey (Robinia pseudoacacia L., Fabaceae) appears to be the most studied with  Figure 5 details the most frequently studied honeys in Africa and Europe. From the pie charts, it can be seen that most of the European countries appear to contribute research on HFMs and also tend to have a broader research focus than the African countries. It is also evident that Robinia (Robinia pseudoacacia L., Fabaceae) honey seems to attract a lot of research interest across Europe, reflected in the high number of individual research reports on this monofloral honey. Table 1 summarises the 170 compounds, 161 of them phenolic in nature, reported from the 159 monofloral honey groups covered by this literature review. Based on existing phenolic compound classifications with minor modifications, the compounds are grouped into five chemical classes, namely simple phenols (two groups), polyphenols, a miscellaneous and an 'other phenolics' group as well as non-phenolics [23][24][25][26][27][28]. Simple phenols include phenolic acids, which are chemically defined as carboxylic acid derivatives of phenols and are generally grouped into two subclasses, hydroxylcinnamic derivatives (HCAD group) and hydroxylbenzoic acids derivatives (HBAD group). A total of 20 HCADs and 21 HBADs were reported from honeys around the globe, making them the most common phenolic constituent class in honeys identified to date. Polyphenols, on the other hand, are a group of compounds which are characterized by the existence of more than one phenol unit or building block per molecule and can further be subdivided into two classes, tannins and flavonoids (flavonoid group) with the former being further grouped into hydrolysable and condensed tannins and the latter being divided, for example, into flavones, flavonols, flavanones, dihydroflavonols, chalcones, aurones, isoflavonoids, bioflavonoids [23,26].
Among the reported compounds, caffeic acid (HCAD) is the most prevalent in honeys having been identified in 118 of the 159 investigated monofloral honeys. Gallic acid (HBAD) came in second with 106 reports, followed by p-coumaric acid (HCAD) with 104, ferulic acid (HCAD) with 103 and quercetin (flavonol) with 102 reports.
When analysing the reported honey constituents along the honeys' respective botanical classification, it was found that 93, or 55%, of the identified, mostly phenolic compounds in honey have been found in Robinia honey (Robinia pseudoacacia, Fabaceae), 76 (45%) in Chestnut honey (Castanea sativa Mill., Fagaceae), 75 (44%) in Manuka honey (Leptospermum scoparium, Myrtaceae), 69 (41%), respectively, in various Eucalyptus honeys (Eucalyptus sp., Myrtaceae), Rape honey (Brassica sp. Brassicaceae) and Linden honey (Tilia sp., Malvaceae), and 63 (37%) in Sunflower honey (Helianthus annuus, Asteraceae). Chemically, flavonoids can be classified as polyphenols as they possess at least one hydroxyl substituent in their structure. They are made up of a flavane nucleus of 15 carbon atoms (C 6 -C 3 -C 6 ) and are diphenyl-propanoids. The C 6 and C 3 moieties are arranged to form two fused rings in which the first is an oxygen-containing heterocycle and the second one is a benzene ring constituting a phenylchromane nucleus (2,3-dihydro-2phenylchroman-4-one). To the base skeleton of the phenylchromane, a second phenyl substituent is linked and, according to the bond position (C2, C3, C4), flavanes, isoflavanes, and neoflavanes, respectively, can be distinguished [26]. These groups usually share a common chalcone precursor and are therefore biogenetically and structurally related [27]. On the other hand, as seen in Figure 6, on the basis of the substitution patterns of the three rings, several subclasses of flavonoids can be identified (e.g., flavones, flavonols, flavanones, flavanonols, isoflavanonoids, flavan-3-ols, and anthocyanidins) [26]. Other natural products such as chalcones and aurones also contain a C 6 -C 3 -C 6 backbone and are thus considered minor flavonoids [27,28]. Flavonoids may exist as both aglycones and prenylated and methyl ethers, and in glycosylated forms incorporating sugar residues that can be linked to several positions of the three rings in form of both O-and C-glycosides [26]. Flavonoids are synthesised in all parts of a plant and play an important role in providing color, fragrance and taste to fruits, flowers and seeds, making them attractants for insects, birds, and mammals, which aid in pollen and seed transmission [29,[159][160][161][162]. However, plants also release numerous chemicals such as flavonoids to deter insects and other predators [159,160]. Aside from that, the strong light absorbance of flavonoids in the ultra-violet region also allows them to act as a protective screen against harmful UV-B Seventy percent of the reported flavonoids in honey were found as aglycones, probably due to the action of amylase in bee saliva, which can rapidly cleave glycosidic linkages to liberate flavonoid aglycones from the respective glycosides [29].   Aca, Api, Chr, Chr-2 -ME, Chr-6-ME, Genk, Lut, Tec, Gal, Gal-5-ME, Isor, Kaem, Kaem-ME, Kaem-8-ME, Myr, Quer, Quer-3,3-DME, Quer-3,7-DME, Quer-3-ME, Querc, Rham, Rut, Hest, Nar, Pinoc, Pinob, pinob-3-O-pent, Pinob-5-ME, C, CG, EC, Gene, Leptosin, Pinob Chal      Flavonoids are synthesised in all parts of a plant and play an important role in providing color, fragrance and taste to fruits, flowers and seeds, making them attractants for insects, birds, and mammals, which aid in pollen and seed transmission [29,[159][160][161][162]. However, plants also release numerous chemicals such as flavonoids to deter insects and other predators [159,160]. Aside from that, the strong light absorbance of flavonoids in the ultra-violet region also allows them to act as a protective screen against harmful UV-B radiation [29,162]. They also function as signal molecules, allopathic compounds, phytoalexins, detoxifying agents and antimicrobial defensive compounds [162]. Flavonoids, along with other phenolic compounds are responsible for the organoleptic characteristics of honey [3]. In honey, they originate not only from the nectar but, to an extent, also from plant pollen and plant resins collected by bees. Flavonoids can thus be considered as markers for the botanical and geographical origins of honeys [163] and have associated biological and pharmacological activities such as antioxidant [27,162,164,165], antimicrobial [164], anticancer [164,166,167], anti-inflammatory [162,164], antiallergic [164], antithrombotic [164], cardioprotective [164], hepatoprotective [164,168] neuroprotective [164], antimalarial [161], antileishmanial [161], anticholinesterase [162], anti-Alzheimer's disease [169], antiulcer [164], antiatherosclerotic [164], antidiabetic [164], estrogenic effect [27], steroid-genesis modulators [162], vasorelaxant effect [164], improved blood flow [170], the inhibition of cholesterol absorption [171], countering antibiotic resistance [162], and protection from damage by ultraviolet B radiation [172].
Based on the findings of this study, the vast majority of monofloral honeys included in this review (82%) were reported to contain flavonoids, 89 different types in total. Robinia honey (Robinia pseudoacacia, Fabaceae) was found to contain 53 of the identified flavonoids in honey. 35 flavonoids, respectively, have to date been identified in Eucalyptus honey (Eucalyptus sp., Myrtaceae) and Linden honey (Tilia sp., Malvaceae), 34 in Chestnut honey (Castanea sativa Mill., Fagaceae) and 32 each in Manuka (Leptospermum scoparium, Myrtaceae) and Rape (Brassica sp. Brassicaceae) honeys.

Flavones
Flavones are a subclass of flavonoids that contain a double bond between C2 and C3 in the flavonoid skeleton, no substituent on the C3 position and the C4 position is oxidised (Figure 7). Along with flavonols, flavones are the primary pigments in white-and cream-colored flowers and act as copigments with anthocyanins in blue flowers. They also act as UV-B protectants in plants as they absorb in the 280-315 nm range [173]. Table 2. Flavones reported in monofloral honeys (see Figure 7 for general structure).  Based on the findings of this comprehensive review, at least one flavone has to date been reported to be present in 64% of the monofloral honeys, with Robinia honey (Robinia pseudoacacia, Fabaceae) containing nine different flavones. Chrysin has been found to be the most common flavone, reported to be present in 83 monofloral honeys, followed by apigenin in 74, luteolin in 69, tectochrysin in 16 and acacetin in 15 honeys. Table 2 shows all the flavones that have to date been identified in monofloral honeys and the number of honeys in which they were identified.

Flavones
Flavones are a subclass of flavonoids that contain a double bond between C2 and C3 in the flavonoid skeleton, no substituent on the C3 position and the C4 position is oxidised (Figure 7). Along with flavonols, flavones are the primary pigments in white-and creamcolored flowers and act as copigments with anthocyanins in blue flowers. They also act as UV-B protectants in plants as they absorb in the 280-315 nm range [173].  Table 2). Table 2. Flavones reported in monofloral honeys (see Figure 7 for general structure).   Table 2).

Flavonols
Flavonols are naturally yellow in color (flavus is Latin for yellow) and are present in plant and fungi [174]. They are also known as 3-hydroxyflavones, the only difference to flavones being the hydroxyl group at C3 position. Flavonols are frequently found as O-glycosides, with glycosidation occuring mainly at the 3-position of the Cring ( Figure 8) [175]. Flavonols are primarily accrued in the epidermal cells of plant tissues and serve as a protection against solar radiation, especially UV-B. They also play an important role, along with xanthophylls, in protecting the photosynthetic apparatus in situ from excess solar radiation and are known to moderate drought-related oxidative damage because of their strong radical scavenging activity [176]. Table 3. Flavonols reported in monofloral honeys (see Figure 8 for general structure).    Based on the findings of this comprehensive review, at least one flavone has to date been reported to be present in 64% of the monofloral honeys, with Robinia honey (Robinia pseudoacacia, Fabaceae) containing nine different flavones. Chrysin has been found to be the most common flavone, reported to be present in 83 monofloral honeys, followed by apigenin in 74, luteolin in 69, tectochrysin in 16 and acacetin in 15 honeys. Table 2 shows all the flavones that have to date been identified in monofloral honeys and the number of honeys in which they were identified.

Flavonols
Flavonols are naturally yellow in color (flavus is Latin for yellow) and are present in plant and fungi [174]. They are also known as 3-hydroxyflavones, the only difference to flavones being the hydroxyl group at C3 position. Flavonols are frequently found as Oglycosides, with glycosidation occuring mainly at the 3-position of the C-ring (Figure 8) [175]. Flavonols are primarily accrued in the epidermal cells of plant tissues and serve as a protection against solar radiation, especially UV-B. They also play an important role, along with xanthophylls, in protecting the photosynthetic apparatus in situ from excess solar radiation and are known to moderate drought-related oxidative damage because of their strong radical scavenging activity [176].
Based on the findings of this review, more than 74% of the honeys were found to contain at least one of the 42 reported flavonols. Acacia honey (Robinia pseudoacacia, Fabaceae) has the highest number of published studies reporting on its flavonols, followed by Eucalyptus honey (Eucalyptus sp., Myrtaceae) with 17 studies. Quercetin is the most commonly isolated flavonol reported to be present in 102 monofloral honey groups, followed by kaempferol in 89 honeys, galangin in 66, rutin in 58, myricetin in 54, and isorhamnetin in 43 monofloral honeys. Table 3 shows all the flavonols that have to date been identified in monofloral honeys and the number of monofloral honey groups for which they were reported.  Table 3). Table 3. Flavonols reported in monofloral honeys (see Figure 8 for general structure).   Table 3).

R3
Based on the findings of this review, more than 74% of the honeys were found to contain at least one of the 42 reported flavonols. Acacia honey (Robinia pseudoacacia, Fabaceae) has the highest number of published studies reporting on its flavonols, followed by Eucalyptus honey (Eucalyptus sp., Myrtaceae) with 17 studies. Quercetin is the most commonly isolated flavonol reported to be present in 102 monofloral honey groups, followed by kaempferol in 89 honeys, galangin in 66, rutin in 58, myricetin in 54, and isorhamnetin in 43 monofloral honeys. Table 3 shows all the flavonols that have to date been identified in monofloral honeys and the number of monofloral honey groups for which they were reported.

Flavanones
Flavanones, also referred to as dihydroxyflavones, are characterised by the lack of a double bond between C2 and C3 in the C-ring of the flavonoid skeleton, resulting in a chiral center at C2 (Figure 9) [177]. The chirality creates an angle between the B-ring relative to the A-C rings. This variation in the molecule's structural orientation impacts flavanones' interactions with biological receptors, in turn influencing their bioactivities [178,179]. Table 4. Flavanones reported in monofloral honeys (see Figure 9 for general structure).  Based on the findings of this review, 62% of the honeys were reported to contain at least one of the 11 flavanones that to date have been isolated from honeys. Robinia honey (Robinia pseudoacacia, Fabaceae) has been found to contain nine of these flavanones. Pinocembrin has been identified in 64 monofloral honeys, followed by naringenin found in 54 and hesperitin in 49 honeys, respectively. Table 4 shows all the flavanones that have to date been identified in monofloral honeys and the number of honeys they have been reported to be present in.  Table 4). Table 4. Flavanones reported in monofloral honeys (see Figure 9 for general structure). Flavanonols, which are also known as dihydroflavonols, are 3-hydroxy derivatives of flavanones ( Figure 10) [180]. This review found that the presence of at least one of the seven flavanonols that have to date been isolated in honey, was reported for 32% of the  Table 4).

R5
Based on the findings of this review, 62% of the honeys were reported to contain at least one of the 11 flavanones that to date have been isolated from honeys. Robinia honey (Robinia pseudoacacia, Fabaceae) has been found to contain nine of these flavanones. Pinocembrin has been identified in 64 monofloral honeys, followed by naringenin found in 54 and hesperitin in 49 honeys, respectively. Table 4 shows all the flavanones that have to date been identified in monofloral honeys and the number of honeys they have been reported to be present in.

Flavanonols
Flavanonols, which are also known as dihydroflavonols, are 3-hydroxy derivatives of flavanones ( Figure 10) [180]. This review found that the presence of at least one of the seven flavanonols that have to date been isolated in honey, was reported for 32% of the monofloral honeys. Four of these seven flavanonols were identified in Robinia honey (Robinia pseudoacacia, Fabaceae). Pinobanksin is the most prevalent flavanonol, reported to be present in 49 honeys. Table 5 shows all the flavanonols that that have to date been identified in monofloral honeys and the number of monofloral honeys in which they were found.  Table 5). Table 5. Flavanonols reported in monofloral honeys (see Figure 10 for general structure).

Flavan-3-ols
Flavan-3-ols or flavanols are also known as catechins. They are characterised by the absence of a double bond between C2 and C3 as well as the absence of a carbonyl on C4 of ring C. As a result, flavan-3-ols feature two chiral carbons and can form four possible diastereomers [181,182]. They exist in both monomeric (catechins) and in polymeric (proanthocyanidins) forms. The monomeric form can vary in its degree of hydroxylation at position 5 and 7 on ring A and at positions 3′, 4′ and 5′ on ring B. C3 of ring C usually carries a hydroxyl group or is esterified with gallic acid (gallate) (Figure 11) [183]. The polymeric form, also known as condensed tannin, features dimers, trimers, oligomers and polymers of flavan-3-ol units linked by C-C bonds either at 4-6 (A-type proanthocyanidins) or 4-8 (B-type proanthocyanidins). They are also classified as procyanidins when derived from catechin, epicatechin and their gallic esters [183].
Seven flavan-3-ols have to date been identified in honeys with at least one flavan-3ol reported to be present in just over a third (34.6%) of the monofloral honey groups. Five different flavan-3-ols have been identified in Sage honey (Salvia officinalis L., Lamiaceae), making it the honey with the highest number of reported flavan-3-ols. Catechin and epicatechin are the most prevalent flavan-3-ols in honeys, being present in 29 and 24 honeys, respectively. Table 6 shows all the flavan-3-ols that have to date been identified in monofloral honeys and the number of honeys for which their presence has been reported.  Table 5). Table 5. Flavanonols reported in monofloral honeys (see Figure 10 for general structure).

Flavan-3-ols
Flavan-3-ols or flavanols are also known as catechins. They are characterised by the absence of a double bond between C2 and C3 as well as the absence of a carbonyl on C4 of ring C. As a result, flavan-3-ols feature two chiral carbons and can form four possible diastereomers [181,182]. They exist in both monomeric (catechins) and in polymeric (proanthocyanidins) forms. The monomeric form can vary in its degree of hydroxylation at position 5 and 7 on ring A and at positions 3 , 4 and 5 on ring B. C3 of ring C usually carries a hydroxyl group or is esterified with gallic acid (gallate) (Figure 11) [183]. The polymeric form, also known as condensed tannin, features dimers, trimers, oligomers and polymers of flavan-3-ol units linked by C-C bonds either at 4-6 (A-type proanthocyanidins) or 4-8 (B-type proanthocyanidins). They are also classified as procyanidins when derived from catechin, epicatechin and their gallic esters [183]. Table 6. Flavan-3-ols reported in monofloral honeys (see Figure 1 for general structure). Seven flavan-3-ols have to date been identified in honeys with at least one flavan-3-ol reported to be present in just over a third (34.6%) of the monofloral honey groups. Five different flavan-3-ols have been identified in Sage honey (Salvia officinalis L., Lamiaceae), making it the honey with the highest number of reported flavan-3-ols. Catechin and epicatechin are the most prevalent flavan-3-ols in honeys, being present in 29 and 24 honeys, respectively. Table 6 shows all the flavan-3-ols that have to date been identified in monofloral honeys and the number of honeys for which their presence has been reported.
Seven flavan-3-ols have to date been identified in honeys with at least one flavan-3ol reported to be present in just over a third (34.6%) of the monofloral honey groups. Five different flavan-3-ols have been identified in Sage honey (Salvia officinalis L., Lamiaceae), making it the honey with the highest number of reported flavan-3-ols. Catechin and epicatechin are the most prevalent flavan-3-ols in honeys, being present in 29 and 24 honeys, respectively. Table 6 shows all the flavan-3-ols that have to date been identified in monofloral honeys and the number of honeys for which their presence has been reported. Figure 11. Basic flavan-3-ol structure (see 73-80 in Table 6).

Isoflavonoids
The structure of isoflavonoids is somewhat different to that of other flavonoids in so far that ring B is connected to C3 of ring C instead of C2 ( Figure 12) [184]. Seven isoflavonoids have to date been identified in honey. They do not appear to be a particularly common honey constituent class as only 17% of the monofloral honeys covered by this review were found to contain them. Amonst them, Robinia honey (Robinia pseudoacacia, Fabaceae) was reported to contain six different isoflavonoids. Genistein is the most common identified isoflavonoid in honeys with 23 reports, followed by formononetin with 8 reports. Table 7 shows all the isoflavonoids that have to date been identified in monofloral honeys and the number of honeys they have been found in.  Table 6). Legend: -H-hydride, -O-H-hydroxide, -O-Gall-gallate, and # no further structural information provided.

Isoflavonoids
The structure of isoflavonoids is somewhat different to that of other flavonoids in so far that ring B is connected to C3 of ring C instead of C2 ( Figure 12) [184]. Seven isoflavonoids have to date been identified in honey. They do not appear to be a particularly common honey constituent class as only 17% of the monofloral honeys covered by this review were found to contain them. Amonst them, Robinia honey (Robinia pseudoacacia, Fabaceae) was reported to contain six different isoflavonoids. Genistein is the most common identified isoflavonoid in honeys with 23 reports, followed by formononetin with 8 reports. Table 7 shows all the isoflavonoids that have to date been identified in monofloral honeys and the number of honeys they have been found in.  Table 7). Table 7. Isoflavonoids reported in honeys (see Figure 12 for general structure).

Aurones and Chalcones
Due to their bright yellow color, the word aurones is derived from the Latin word aurum for gold. Aurones are considered a minor class of flavonoids. They also contain 15 carbon atoms, arranged in the general structure С6-С3-С6 (Figure 13). They occur in  Table 7). Table 7. Isoflavonoids reported in honeys (see Figure 12 for general structure).

Aurones and Chalcones
Due to their bright yellow color, the word aurones is derived from the Latin word aurum for gold. Aurones are considered a minor class of flavonoids. They also contain 15 carbon atoms, arranged in the general structure C 6 -C 3 -C 6 ( Figure 13). They occur in hydroxylated, methoxylated or glycosylated forms [185]. The word chalcone, on the other hand, is derived from the Greek word chalcos, meaning bronze, reflecting the typical colour of most natural chalcones [186]. Chalcones are α,β-unsaturated ketones (trans-1,3-diaryl-2propen-1-ones) consisting of two aromatic rings attached to an α,β-unsaturated carbonyl system with a variety of substituents (Figure 8) [187]. Aurones and chalcones were only identified in 3% and 4%, respectively, of the monfloral honeys covered by this review. Table 8 details these compounds and the number of monofloral honey groups that were found to contain them. hydroxylated, methoxylated or glycosylated forms [185]. The word chalcone, on the other hand, is derived from the Greek word chalcos, meaning bronze, reflecting the typical colour of most natural chalcones [186]. Chalcones are α,β-unsaturated ketones (trans-1,3-diaryl-2-propen-1-ones) consisting of two aromatic rings attached to an α,β-unsaturated carbonyl system with a variety of substituents (Figure 8) [187]. Aurones and chalcones were only identified in 3% and 4%, respectively, of the monfloral honeys covered by this review. Table 8 details these compounds and the number of monofloral honey groups that were found to contain them. Figure 13. Structure of leptosin (88, Table 8) and of pinobanksin chalcone (89, Table 8).

Hydroxycinnamic Acid and its Derivatives
Hydroxycinnamic acid and its derivatives (HCADs) are phenolic acids that are prevalent in plants [188]. They can be considered hydroxy metabolites of cinnamic acid featuring a C6-C3 backbone ( Figure 14) [189,190].
A high proportion, 88%, of the monfloral honey groups covered by this review were reported to contain at least 1 of the 20 HCADs that have to date been identified in honeys. Robinia honey (Robinia pseudoacacia, Fabaceae) had the highest number of HCADs, 15 in total, while 12 HCADs each were reported for Rape (Brassica sp., Brassicaceae) and Sunflower (Helianthus annuus, Asteraceae) honeys. Among the HCADs, caffeic acid appears to be the most prevalent, having been reported in 117 of the honeys, followed by p-coumaric acid in 103, ferulic acid in 102, chlorogenic acid in 85 and t-cinnamic acid in 57 honeys. Table 9 shows all the HCADs that have to date been identified in monofloral honeys and the number of honeys in which they were found to be present.  Table  9). Table 9. Hydroxycinnamic acid and its derivatives reported in monofloral honeys (see Figure 14 for general structure).  Table 8) and of pinobanksin chalcone (89, Table 8).

Hydroxycinnamic Acid and Its Derivatives
Hydroxycinnamic acid and its derivatives (HCADs) are phenolic acids that are prevalent in plants [188]. They can be considered hydroxy metabolites of cinnamic acid featuring a C6-C3 backbone ( Figure 14) [189,190].

Hydroxycinnamic Acid and its Derivatives
Hydroxycinnamic acid and its derivatives (HCADs) are phenolic acids that are prevalent in plants [188]. They can be considered hydroxy metabolites of cinnamic acid featuring a C6-C3 backbone ( Figure 14) [189,190].
A high proportion, 88%, of the monfloral honey groups covered by this review were reported to contain at least 1 of the 20 HCADs that have to date been identified in honeys. Robinia honey (Robinia pseudoacacia, Fabaceae) had the highest number of HCADs, 15 in total, while 12 HCADs each were reported for Rape (Brassica sp., Brassicaceae) and Sunflower (Helianthus annuus, Asteraceae) honeys. Among the HCADs, caffeic acid appears to be the most prevalent, having been reported in 117 of the honeys, followed by p-coumaric acid in 103, ferulic acid in 102, chlorogenic acid in 85 and t-cinnamic acid in 57 honeys. Table 9 shows all the HCADs that have to date been identified in monofloral honeys and the number of honeys in which they were found to be present.  Table  9). Table 9. Hydroxycinnamic acid and its derivatives reported in monofloral honeys (see Figure 14 for general structure).   Table 9).

OR1
A high proportion, 88%, of the monfloral honey groups covered by this review were reported to contain at least 1 of the 20 HCADs that have to date been identified in honeys. Robinia honey (Robinia pseudoacacia, Fabaceae) had the highest number of HCADs, 15 in total, while 12 HCADs each were reported for Rape (Brassica sp., Brassicaceae) and Sunflower (Helianthus annuus, Asteraceae) honeys. Among the HCADs, caffeic acid appears to be the most prevalent, having been reported in 117 of the honeys, followed by p-coumaric acid in 103, ferulic acid in 102, chlorogenic acid in 85 and t-cinnamic acid in 57 honeys. Table 9 shows all the HCADs that have to date been identified in monofloral honeys and the number of honeys in which they were found to be present.

Hydroxybenzoic Acid and Its Derivatives
Hydroxybenzoic acid and its derivatives (HBADs) are phenolic metabolites featuring the general structure C6 ± C1 (Figures 15 and 16) [191,192]. Of the monofloral honey groups covered by this review, 90% have been reported to contain at least one of the 21 HBADs that have to date been identified in honeys. Chestnut honey (Castanea sativa Mill., Fagaceae) and Manuka honey (Leptospermum scoparium, Myrtaceae) are reported to contain 16 of the HBADs, while Rape honey (Brassica sp., Brassicaceae) and Clover honey (Trifolium sp., Fabaceae) contain 15 each. Gallic Acid is the most prevalent HBAD with 105 reports, followed by syringic acid with 85, p-hydroxybenzoic acid with 79, vanillic acid with 66 and protocatechuic acid with 57. Table 10 shows all the HBADs that have to date been identified in monofloral honeys and the number of honeys which were found to contain them. Table 9. Hydroxycinnamic acid and its derivatives reported in monofloral honeys (see Figure 14 for general structure).

Hydroxybenzoic Acid and its Derivatives
Hydroxybenzoic acid and its derivatives (HBADs) are phenolic metabolites featuring the general structure C6 ± C1 ( Figure 15) [191,192]. Of the monofloral honey groups covered by this review, 90% have been reported to contain at least one of the 21 HBADs that have to date been identified in honeys. Chestnut honey (Castanea sativa Mill., Fagaceae) and Manuka honey (Leptospermum scoparium, Myrtaceae) are reported to contain 16 of the HBADs, while Rape honey (Brassica sp., Brassicaceae) and Clover honey (Trifolium sp., Fabaceae) contain 15 each. Gallic Acid is the most prevalent HBAD with 105 reports, followed by syringic acid with 85, p-hydroxybenzoic acid with 79, vanillic acid with 66 and protocatechuic acid with 57. Table 10 shows all the HBADs that have to date been identified in monofloral honeys and the number of honeys which were found to contain them.  Table  10). Table 10. Hydroxybenzoic acid and its derivatives reported in monofloral honeys (see Figure 15 for general structure).   Table 10).

Non-Phenolic Compounds
Nine non-phenolic compounds were also reported in 26.7% of the monofloral honey groups covered by this review. Manuka honey (Leptospermum scoparium, Myrtaceae) was reported to contain 6 of the 9 non-phenolic compounds, 5 were identified in Kanuka honey (Kunzea ericoides, Myrtaceae) and 4 in Eucalyptus honey (Eucalyptus sp., Myrtaceae). Absiscic acid, which has been detected in 36 honeys, is the most commonly reported non-phenolic honey constituent. Figure 22 and Table 16 detail the different non-phenolic compounds identified to date in the monofloral honeys.  Nine non-phenolic compounds were also reported in 26.7% of the monofloral honey groups covered by this review. Manuka honey (Leptospermum scoparium, Myrtaceae) was reported to contain 6 of the 9 non-phenolic compounds, 5 were identified in Kanuka honey (Kunzea ericoides, Myrtaceae) and 4 in Eucalyptus honey (Eucalyptus sp., Myrtaceae). Absiscic acid, which has been detected in 36 honeys, is the most commonly reported nonphenolic honey constituent. Figure 22 and Table 16 detail the different non-phenolic compounds identified to date in the monofloral honeys.  Table 16).  Table 17 details the different analytical methods found in this review for the detection of phenolic compounds in the monofloral honeys. It is evident that the phenolic compounds were mostly identified by high-performance liquid chromatography (HPLC) (67%) using either UV, UV-Vis, UV-UV, photodiode array (DAD or PDA), DAD-UV, electron capture (ECD), or EDC-UV as detectors. Almost one-quarter (24%) of the reports indicated the use of liquid chromatography coupled with mass spectrometry (LC-MS),  Table 16).  Table 17 details the different analytical methods found in this review for the detection of phenolic compounds in the monofloral honeys. It is evident that the phenolic compounds were mostly identified by high-performance liquid chromatography (HPLC) (67%) using either UV, UV-Vis, UV-UV, photodiode array (DAD or PDA), DAD-UV, electron capture (ECD), or EDC-UV as detectors. Almost one-quarter (24%) of the reports indicated the use of liquid chromatography coupled with mass spectrometry (LC-MS), 5% used a combination of HPLC, LC-MS and/or gas chromatography coupled with mass spectrometry (GC-MS), 1% of the analyses used gas chromatography coupled with mass spectrometry (GC-MS) and high-performance thin-layer chromatography (HPTLC), respectively, and finally, less than 1% used fluorescence spectroscopy to identify the phenolic compounds. Table 17. Analytical methods used in phenolic compound analysis for monofloral honeys.

Method
No. of Reports

Conclusions
This review investigated 130 original research articles that detailed the phenolic compounds identified in 556 monofloral honeys. The honeys from 51 botanical families were grouped into 159 monofloral groups. Most of the monofloral honeys belonged to the Myrtaceae and Fabaceae families. The Robinia honey (Robinia pseudoacacia, Fabaceae), Manuka honey (Leptospermum scoparium, Myrtaceae) and Chestnut honey (Castanea sp., Fagaceae) were the most studied monofloral honeys for their phenolic constituents. China, Italy and Turkey were the major hubs the honey phenolic research. A total of 161 phenolic compounds were reported in the honeys and these were classified in this review into five major compound groups, namely flavonoids, hydroxycinnamic acid and its derivatives (HCAD), hydroxybenzoic acid and its derivatives (HBAD), miscellaneous or 'other phenolics', as well as nine non-phenolics which were mainly used as marker compounds for specific monofloral honeys. Hydroxycinnamic acid derivatives (HCAD) and hydroxybenzoic acid derivatives (HBAD) were the most prevalent phenolic constituents in the monofloral honeys, with caffeic acid, gallic acid, ferulic acid, and quercetin being the most reported phenolic compounds. Robinia honey (Robinia pseudoacacia, Fabaceae), Chestnut honey (Castanea sativa Mill., Fagaceae), and Manuka honey (Leptospermum scoparium, Myrtaceae) were the monofloral honeys for which the highest number of phenolic compounds has to date been identified. Most of these phenolic compounds were detected and structurally identified using HPLC.
The information compiled in this review can serve as a guide for future research into the identification of phenolic compounds in honey. It illustrates which geographical locations are very active in phenolics research in honey. It also provides information for which monofloral honeys worldwide phenolic compounds have already been determined. Moreover, it also details the specific phenolic constituents that have to date been detected in monofloral honeys and the analytical methods used to identify them. In doing so, it assists with the identification of common or ubiquitous phenolic honey constituents and those that to date have only been found in specific monofloral honeys or honeys derived from particular botanical families.