Biological Properties of Latex, Aqueous Extracts and Bee Products of Euphorbia officinarum L.: A Short Review

Euphorbia officinarum L. is a Moroccan endemic plant known as “Tikiout” and “Daghmus” that can also be found in Mauritania, Western Sahara, and Algeria. In the present review, “Euphorbia officinarum”, “metabolites” “hemisynthesis” were the keywords used for the research in the Web search engine Google Scholar and in the database Web of Science. Triterpenes, phytosterols and ingol diterpenes were isolated and identified in the latex of Moroccan E. officinarum. More than sixty triterpenes were obtained by hemisynthesis from natural triterpenes. Some of these derivatives had insecticidal and antimicrobial activity (phytopathogenic bacteria). The total phenol content and the antioxidant and anti-α-glucosidase activities were dependent on the time and temperature of extractions and also on the plant solvent ratio. The antioxidant activity of monofloral honey of E. officinarum origin was attributed to the phenol fraction (this fraction, previously isolated from honey samples, had better activity than the entire honey).


Introduction
Euphorbiaceae family encloses 6000 species of plants, and genus Euphorbia is the largest in the spurge family. Euphorbia are succulent plants that may be found from Africa to the Canary Islands, in Madagascar, India, and the Americas and even Australia [1]. Euphorbia officinarum L. (Figure 1) is a Moroccan endemic plant known as "Tikiout" and "Daghmus". This species can also be found in Mauritania, Western Sahara, and Algeria [1] (Figure 2). E. officinarum belonging to the Euphorbia genus has the presence of a milky white latex, which has been studied not only for its chemical characterization but also due to its biological properties [2]. Generally, this latex has been used since ancient times in folk medicine although containing harmful compounds. The term Euphorbia was named in honour of "Euphorbus", the physician of King Juba II of Mauritania, who paid attention to the medicinal properties of E. officinarum, for the first time [3]. There is one infra-specific taxon of the species Euphorbia officinarum L. (E. officinarum subsp. echinus (Hook.f. & Coss.) Vindt) [4].
Since ancient times, E. officinarum has been used in folk medicine, although currently it has been determined that this is obsolete, at least for some ailments. For example, there are still descriptions that the milky sap of this species is used in earache and as emetic in Buxar district, India [5], although this utilization as emetic has already been considered outdated [6]. Anti-diabetic utilization of E. officinarum is particularly cited in diverse places in Morocco and almost always under powder obtained from aerial parts of E. officinarum subsp. echinus. Some local examples of its use include Agadir Ida Outanane region (Southwest Morocco) [7], Tata Province [8], Chtouka and Tiznit (western Anti-Atlas) [9], Since ancient times, E. officinarum has been used in folk medicine, although cu it has been determined that this is obsolete, at least for some ailments. For exampl are still descriptions that the milky sap of this species is used in earache and as em Buxar district, India [5], although this utilization as emetic has already been con outdated [6]. Anti-diabetic utilization of E. officinarum is particularly cited in places in Morocco and almost always under powder obtained from aerial parts ficinarum subsp. echinus. Some local examples of its use include Agadir Ida Outan Since ancient times, E. officinarum has been used in folk medicine, although currently it has been determined that this is obsolete, at least for some ailments. For example, there are still descriptions that the milky sap of this species is used in earache and as emetic in Buxar district, India [5], although this utilization as emetic has already been considered outdated [6]. Anti-diabetic utilization of E. officinarum is particularly cited in diverse places in Morocco and almost always under powder obtained from aerial parts of E. officinarum subsp. echinus. Some local examples of its use include Agadir Ida Outanane region (Southwest Morocco) [7], Tata Province [8], Chtouka and Tiznit (western Anti-Atlas) [9], multiple regions [10] and under decoction in Beni Mellal-Khenifra [11]. E. officinarum L. is also used as anti-diabetic, according to different authors [10][11][12][13].
E. officinarum in a mixture with other plants (Opuntia ficus-barbarica, Zea mays and Ziziphus lotus) and honey has been used in the treatment of pyelonephritis and cystitis, in Algeria E. officinarum in a mixture with other plants (Opuntia ficus-barbarica, Zea mays and Ziziphus lotus) and honey has been used in the treatment of pyelonephritis and cystitis, in Moroccan Sahara [14]; the flowers and roots of Euphorbia officinarum subsp. echinus are also reported in the treatment of pyelonephritis in Central Morocco [15]. E. officinarum subsp. echinus has also been reported in the treatment of wounds, skin infections and abscesses in diverse places in Morocco [16][17][18] and by the Sahrawi refugees in Algerian refugee camps [19]. Although Idm'hand et al. [18] had noted the utilization of that species in the treatment of skin diseases, their work indicated that the specific treatment purpose of E. officinarum subsp. echinus was the elimination of helminths.
In Morocco, the root powder of E. officinarum subsp. echinus has also been reported in the treatment of cancer, although not specifying which type [16,20,21]. Through ethnobotanical interviews and vegetation surveys in a Saharan Moroccan village, Blanco and Carrière [22] reported that E. officinarum subsp. echinus use presented a Smith Salience index: N: total number of informants; L i : size of the list for the informant i; R a : rank of appearance of the ethnospecies and frequency of 0.239 and 38%, respectively. Other uses have also been described for E. officinarum, such as for respiratory and circulatory systems [23], and as gum-resin for headache, paralysis and apoplexy [24]. In Morocco, E. officinarum subsp. echinus aerial parts may be chopped and cooked as a vegetable salad [25,26], despite its relative high toxicity [2].

Biosynthesis of Diterpenes, Triterpenes and Sterols
Terpenoids are assembled from C5 units (isoprene-like), and the number of repetitions of this unit, followed by cyclization reactions, rearrangements and oxidation of the terpene skeleton determine the huge diversity of structures (more than 80,000) [30]. Nevertheless and concerning the biosynthesis of these natural compounds, they have as central intermediates the isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP). Two distinct pathways generate these C5 precursors: the meva-

Biosynthesis of Diterpenes, Triterpenes and Sterols
Terpenoids are assembled from C 5 units (isoprene-like), and the number of repetitions of this unit, followed by cyclization reactions, rearrangements and oxidation of the terpene skeleton determine the huge diversity of structures (more than 80,000) [30]. Nevertheless and concerning the biosynthesis of these natural compounds, they have as central intermediates the isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP). Two distinct pathways generate these C 5 precursors: the mevalonate pathway (MVA), which occurs in cytosol, and the deoxyxylulose-5-phosphate (DXP), more recently known as methyl-D-erythritol-4-phosphate (MEP), which occurs in plastids ( Figure 5) [31]. The MVA pathway provides cytosolic metabolites, such as C 30 triterpenes and their saponin derivatives, and C 27 -C 29 steroids, plus some C 15 sesquiterpenes, whereas MEP provides C 10 monoterpenes, C 20 diterpenes, C 40 tetraterpenes (carotenoids), some C 15 sesquiterpenes and the prenyl side chains of chlorophyll and plastoquinones [31]. These terpenes can then undergo oxygenation through the activity of cytochrome P 450 monooxygenases (P 450 ), followed by the introduction of other functional groups, originating more than 80,000 natural products [30].
Many studies have demonstrated that species of the family Euphorbiaceae are producers of unique diterpenoids, isolated from milky latices, which belong to the macrocylic diterpenes with diverse skeletons (jatrophane, lathyrane, terracinolide, ingenane, pepluane, paraliane, and segetane) ( Figure 6) [32]. All skeletons have geranyl geranyl-diphosphate as precursor, as casbene is the precursor of the macrocyclic and polycyclic diterpenes ( Figure 6) and then proceed through intermediates such as jolkinol C [32].
Although the biological properties of those lathyrane diterpenes have not been evaluated, Vela et al. [34] in their review work noted that terpenes belonging to this group have biological properties with clinical potential (cytotoxicity, multidrug resistant reversal ability, antiviral and anti-inflammatory properties, and capability to induce neural progenitor cell proliferation or differentiation into neurons).
Although the biological properties of those lathyrane diterpenes have not been evaluated, Vela et al. [34] in their review work noted that terpenes belonging to this group have biological properties with clinical potential (cytotoxicity, multidrug resistant reversal ability, antiviral and anti-inflammatory properties, and capability to induce neural progenitor cell proliferation or differentiation into neurons).
As far as we know there are not any biosynthetic studies on the diterpenes, triterpenes and sterols in Euphorbia officinarum, only a hypothesis for the biosynthetic pathway of the spirotriterpene, 3S,4S,5R,7S,9R,14R-3,7-dihydroxy-4,14-dimethyl-7    Obtusifoliol is a phytosterol, which means the presence of an extra one-carbon on the side-chain, attached at C24 and the substrate for alkylation is cycloartenol ( Figure 9) [36]. Generally, the substrate for the biosynthesis of phytosterols is cycloartenol, whereas in fungi it is lanosterol [36]. However, in E. lathyris, Forestier et al. [37] reported lanosterol synthase in the cytoplasm of laticifers, in combination with cycloartenol synthase and Obtusifoliol is a phytosterol, which means the presence of an extra one-carbon on the side-chain, attached at C 24 and the substrate for alkylation is cycloartenol ( Figure 9) [36]. Generally, the substrate for the biosynthesis of phytosterols is cycloartenol, whereas in fungi it is lanosterol [36]. However, in E. lathyris, Forestier et al. [37] reported lanosterol synthase in the cytoplasm of laticifers, in combination with cycloartenol synthase and butyrospermol synthases. Therefore, further studies are needed in order to better understand the role of cycloartenol and lanosterol in the biosynthesis of phytosterols in Euphorbiaceae.
Molecules 2022, 27, 7200 10 of 25 butyrospermol synthases. Therefore, further studies are needed in order to better understand the role of cycloartenol and lanosterol in the biosynthesis of phytosterols in Euphorbiaceae. Figure 9. Schematic biosynthesis of obtusifoliol (adapted from [36]).
Beyond the production of triterpenoid derivatives obtained by hemisynthesis from triterpenoids isolated from the latex of E. officinarum, the same Moroccan team and others also from Morocco started to test the biological properties of the derivatives obtained or new derivatives along with the determination of their respective biological activities, with the purpose of obtaining compounds with better biological activities than the natural triterpenoids. This will fill the gap in studies on biological attributes of the natural triterpenes from E. officinarum latex or their derivatives-a gap that exists despite their known interesting pharmacological properties, including anti-inflammatory, antimicrobial and antiplasmodial activities [51].
Beyond the insecticidal and antiparasitic activities aforementioned for some terpene derivatives obtained after hemisynthesis of terpenes isolated from E. officinarum latex, other biological activities have been reported. For example, Smaili et al. [58] reported that 3βacetoxy-norlup-20-one (31) and 3-chloro-4α,14α-dimethyl-5α-cholest-8-ene (64), obtained by hemisynthesis from lupeol acetate (2) and 4α,14α-dimethyl-5α-cholest-8-en-3β-ol (9), respectively, were able in vitro to greatly reduce conidia formation and germination of Verticillium dahlia, and Fusarium oxysporum fsp. melonis, both causal agents of wilt, and Penicillium expansum, which is responsible for post-harvest rot that infects diverse fruits (e.g., tomato and apple). Such results indicate that those two derivatives act as fungistatic compounds [58]. The antibacterial activities of these derivatives were also evaluated in vitro. The phytopathogenic bacteria used were Agrobacterium tumefaciens, causal agent of crown gall disease, P. syringae pv. tabaci and P. syringae pv. syringae, which cause wild fire disease of tobacco, and diseases of various monocot and dicot plants, respectively. The results showed that compound 3-chloro-4α,14α-dimethyl-5α--cholest-8-ene (64) was more effective in inhibiting the growth of P. syringae pv. tabaci and P. syringae pv. syringae, even being similar to the positive control used (chloramphenicol). Concerning Erwinia amylovora, the causal agent of fire blight disease of pear and apple trees, 3-chloro-4α,14α-dimethyl-5α-cholest-8-ene (64) was also the only one of these compounds that showed antibacterial activity but at a moderate level and significantly lower than that recorded with the positive control [58].
Since 3β-acetoxy-norlup-20-one (31) and 3-chloro-4α,14α-dimethyl-5α-cholest-8-ene (64) were able to reduce in vitro conidia formation and germination of Verticillium dahlia, one of the most important vascular diseases reported on tomato plants, Smaili et al. [59] studied the effect of two triterpene derivatives [4α,14α-dimethyl-5α-cholest-7,9-dien-3β-ol (44) and 3β-tosyloxy4α,14α-dimethyl-5α-cholest-7,9-diene (65)], obtained after oxidation of 4α,14α-dimethyl-5α-cholest-8-en-3β-ol (9) isolated from E. officinarum latex, on the protection of tomato plants against V. dahliae in a greenhouse as well as in tomato plants derived from seeds that germinated in the presence of low concentrations of those two triterpenic derivatives. The results showed that they were able to significantly reduce disease severity at 10 µg/mL (e.g., reduction of leaf alteration index and of stunting index ranged from 52 to 68% and from 43 to 67%, respectively, while vessel discoloration was reduced by at least 95%) [59]. Moreover, the compounds were also able to elicit H 2 O 2 accumulation before and after fungal inoculation, and enhance peroxidase and polyphenol oxidase activities. According to Smaili et al. [59], induction of protection against plant diseases by triterpenes of plant origin was reported for the first time.
Previously, Smaili et al. [58] concluded that 3-chloro-4α,14α-dimethyl-5α-cholest--8ene (64) was effective in inhibiting the growth of P. syringae pv. tabaci in in vitro studies. Later, Smaili et al. [60] treated seeds of Nicotiana benthamiana with three hemisynthetic triterpenes, including 3β-acetoxy-norlup-20-one (31) and 3-chloro-4α,14α-dimethyl-5α--cholest-8-ene (64) derived from the latex of E. officinarum, in order to evaluate their ability to enhance resistance to P. syringae pv. tabaci. Smaili et al. [60] observed that soaking seeds in the triterpene derivatives did not harm germination and significantly reduced the diameter of the lesions in inoculated leaves, when compared to the control; bacterial growth was also significantly reduced in plants previously treated with the triterpenic derivatives by at least 0.54 logarithmic units when compared to the control. At the same time, the mock-inoculated leaves of plants that germinated in the presence of the triterpenic derivatives showed enhanced ascorbate peroxidase and catalase activities (two antioxidant enzymes). An increase of guaiacol peroxidase and polyphenol oxidase inoculated plants with P. syringae pv. tabaci was observed when pre-treated with the triterpenic derivatives.
Continuing the study on the effect of some triterpene derivatives obtained from triterpene isolated from E. officinarum latex, Smaili et al. [61] evaluated the effect of direct application of the 3β-acetoxy-norlup-20-one (31) and 3-chloro-4α,14α-dimethyl--5α-cholest-8-ene (64) on the growth of tomato seedlings under normal conditions or in the presence of the pathogens V. dahliae and Agrobacterium tumefaciens. After foliage spraying with these two derivatives, the authors observed a significant improvement of growth rate, fresh weight, dry weight and leaf area, an increased content of chlorophylls a and b, carotenoids, proline, and the activity of nitrate reductase (an enzyme which is correlated with growth and plant yield) [61]. In the presence of the infection by V. dahliae, triterpene derivatives reduced leaf alteration indexes induced by V. dahliae, particularly for 3-chloro-4α,14α-dimethyl-5αcholest-8-ene (64). The browning index of the vessels caused by this phytopathogen was also much reduced, with the percentage of protection being 97-99% [61]. The diameter of lesions caused by the oncogenic strain C58 of A. tumefaciens was also reduced when pre-treated with those triterpenic derivatives. Moreover, these compounds also induced H 2 O 2 accumulation and increased the activity of several antioxidant enzymes such as catalase, ascorbate peroxidase, and guaiacol peroxidase [61]. According to these results, Smaili et al. [61] concluded that the two derivatives are able to mediate resistance of tomato plant against bacterial and fungal diseases through improvement of antioxidant defences.
So far, diverse hemisynthesized triterpenoids obtained from isolated triterpenes of E. officinarum latex have been demonstrated to possess insecticidal and antimicrobial activities. Daoui et al. [48] have as purpose the improvement of these biological activities using in silico studies based on 3D molecular modelling techniques applied on 27 semisynthetic triterpene derivatives obtained from triterpenes isolated from E. officinarum and E. resinifera latices. To achieve this objective, Daoui et al. [48] have developed the three dimensional quantitative structure property relationships (3D-QSAR) based on Comparative Molecular Similarity Indices Analysis (CoMSIA) and Comparative Molecular Field Analysis (CoMFA) techniques. Such an approach enabled the authors to design 38 new derivatives and also to predict their pLD 50 (log 10 [1/LD 50 ]), where LD 50 is the amount of sample which causes the death of 50% of the living beings of a group. Studies taking into account the absorption, distribution, metabolism, excretion (ADME), and toxicity (ADME-Tox) of the designed molecules led the authors to select four molecules as promising antibacterial and insecticidal molecules. The molecular docking test predicting the referential interactions that occur between the molecular structures and the receptors made it possible to find 3 molecules (66), (67), (68) (Figure 10) that were able to inhibit the MurE (PDB code: 1E8C) and EcR (PDB code: 1R20) proteins involved in the process of antibacterial and insecticidal activities and had greater stability than the reference molecule 24-methylen-elemo-lanosta-2,8,24trien-7,11-dione (69) inside the MurE and EcR receptors pocket. The reference used was a triterpene derivative obtained through chemical modifications of the major component of E. resinifera, α-euphorbol (70) [53]. According to Daoui et al. [48], such observations may permit adoption of these molecules as references for the synthesis of insecticidal and antimicrobial activities.

Extracts and Bee Products from Euphorbia Origin
Although E. officinarum is used in folk medicine as antidiabetic or in the treatment of diseases of the respiratory and circulatory systems, pyelonephritis, treatment of wounds, skin infections and abscesses, headache, paralysis, apoplexy, among other ailments (see Introduction), very few works can be found that confirm these abilities. In fact, only the antimicrobial and insecticidal activities of triterpene derivatives from E. offcinarum latex have been extensively evaluated (see previous Section). Nevertheless, some works start to approach other attributes of E. officinarum extracts or their monofloral honeys. For example, El-Hawary et al. [33] tested the cytotoxic potential of fifteen Euphorbia species and concluded that methanolic extracts of the aerial parts of E. officinarum presented the highest activity against human colon adenocarcinoma (CACO2) cell line (IC 50 = 7.2 µM). Chemical analysis through liquid chromatography-high resolution electrospray ionization mass spectrometry (LC-HR-ESIMS) and dereplication strategies using the Dictionary of Natural Products (DNP) database, followed by chemotaxonomic filtration, resulted in the characterization of 44 natural compounds from the 15 Euphorbia studied. For E. officinarum, two compounds were characterized but without activity (3β,7α-dihydroxy-4α,14α-dimethyl-5α-cholest-8en-11-one (10) (Figure 2) and 8-methoxyingol 7,12-diacetate 3-phenylacetate (3) (Figure 3). After an orthogonal partial least square discrimination analysis (OPLS-DA), the authors concluded that the metabolite highly correlated with the CACO2 cytotoxicity was at m/z [M] + 281.272 (time retention = 29.16), and was not yet isolated and identified in this species.
Beyond the antimicrobial and insecticidal activities of the derivatives obtained from natural triterpenes of the E. officinarum latex, Daoubi et al. [2] demonstrated that 8-methoxyingol 7,12-diacetate 3-phenylacetate (3) (Figure 3) was able to induce both G 0 /G 1 cell-cycle arrest and human immunodeficiency virus type 1-long terminal repeat (HIV-1-LTR) promoter activation in a concentration-dependent manner, in the leukaemia cell line Jurkat-LTR-green fluorescent protein (Jurkat-LTR-GFR). According to these results, Daoubi et al. [2] suggested that 8-methoxyingol 7,12-diacetate 3-phenylacetate may be important for the development of therapies against HIV-latency. In fact, to eradicate HIV-1 has been difficult since the virus can be in reservoirs of latently infected cells and within them, the proviral DNA is integrated in the host's genome but it does not actively replicate. In such a situation, the virus remains invisible to the host immune system and is not affected by antiviral drugs [62].
In the work developed by Boutoub et al. [63], they compared the antioxidant activity of aqueous plant extracts and monofloral honey of E. officinarum origin. They demonstrated that the ability of plant extracts for scavenging some free radicals such as 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) of plant extracts was more than 20 times greater than the activity of honey; likewise, the capacity for scavenging superoxide radical anions or antiacetylcholinesterase and anti-lipoxygenase were approximately 10 times higher in the plant extracts than in the honey samples. However" the detailed chemical composition was not reported, only the total phenol, and in this case all aqueous extracts had higher amounts of these metabolites than the honey samples. The extraction conditions (time, temperature and plant solvent ratio) were determinant of the total concentration of phenols as well the antioxidant activity and inhibition of the α-glucosidase activity of the E. officinarum aqueous extracts [64]. The same team [65] also concluded that the activities found for honey samples could be attributed to the phenol fraction since the phenols extracts isolated from the monofloral honey of E. officinarum origin had better activities than the entire honey. In this case, Boutoub et al. [65] presented a preliminary chemical composition of the extracts (gallic acid (1), p-hydroxybenzoic acid (2), caffeic acid (3), p-coumaric acid (4), abscisic acid (5), luteolin (6), quercetin (7), apigenin (8), naringenin (9) and kaempferol (10)) ( Figure 11) [65]. The authors [63,65] studied monofloral honey because in Morocco the Euphorbia honey is considered the most precious by the consumers but it has been scarcely studied, although the physico-chemical and palynological characteristics, generally needed for honey characterisation, have already been found [63,[66][67][68][69]. Many times, beekeepers labelled the honey as being only of Euphorbia origin, although three honey types of this genus are produced (E. officinarum subsp. echinus, E. resinifera and E. regis-jubae) [48,70]. The work of Abderrahim et al. [71] demonstrated the antioxidant, synergistic antimicrobial and burn wound healing activities of monofloral honey of Euphorbia origin (without any specification of the species) mixed with Allium sativum. This mixture had higher wound healing activity, since shorter epithelialization and wound contraction time was observed, as well as better histological recovery of the treated tissues [71]. group were only found in the latex of E. resinifera and E. officinarum. However, the ingol diterpenes found in propolis of this work were those isomers characteristic of the E. resinifera latex. Such results may indicate the utilization of latex of E. resinifera by bees for making propolis, but also from E. officinarum, since obtusifoliol is generally present in the E. officinarum latex. p-hydroxybenzoic acid was reported in this propolis sample, being also observed in honey of E. officinarum and E. resinifera origins [65].

Conclusions
Euphorbia officinarum is geographically limited to Morocco, Western Sahara, Algeria and Mauritania. This species has been used in folk medicine in various ways: as anti-diabetic; in the treatment of skin diseases, although later it was concluded that the main treatment purpose was the elimination of helminths; when associated with other Another beeproduct is propolis, a plant-derived product that bees collect from resins and exudates from diverse parts of the plants, and subsequently transport to the hive, mixing it with beeswax. Bees use propolis to protect the hive against intruders and pathogenic microorganisms [72]. The detailed chemical composition and antimicrobial activity of propolis from a semi-arid region of Morocco were evaluated by Chimshirova et al. [72]. Fifteen compounds were isolated and identified, some of them being already reported as constituents of plants in the genus Euphorbia, particularly the macrocyclic diterpenes and triterpenoids, as well as other groups of known compounds (e.g., coumarins, phenolic acids) and new ones (e.g., 29-norlanost-3β-hydroxy-8-ene-7,11-dione). The macrocyclic diterpenes, particularly ingol diterpenes containing a phenylacetyl group were only found in the latex of E. resinifera and E. officinarum. However, the ingol diterpenes found in propolis of this work were those isomers characteristic of the E. resinifera latex. Such results may indicate the utilization of latex of E. resinifera by bees for making propolis, but also from E. officinarum, since obtusifoliol is generally present in the E. officinarum latex. p-hydroxybenzoic acid was reported in this propolis sample, being also observed in honey of E. officinarum and E. resinifera origins [65].

Conclusions
Euphorbia officinarum is geographically limited to Morocco, Western Sahara, Algeria and Mauritania. This species has been used in folk medicine in various ways: as anti-diabetic; in the treatment of skin diseases, although later it was concluded that the main treatment purpose was the elimination of helminths; when associated with other plants (Opuntia ficus-barbarica, Zea mays and Ziziphus lotus) and honey, in the treatment of pyelonephritis and cystitis. So far, fifteen compounds (diterpenes, triterpenes and sterols) have been isolated and identified in the E. officinarum latex from Morocco. The E. officinarum honey is considered the most precious; nevertheless, many times it is mixed with other Euphorbiaceae honeys. The chemical composition of the phenolic fraction of the monofloral honey was found to include ten compounds. More than seventy hemisynthesized compounds were obtained from some triterpenes of E. officinarum in order to obtain compounds with higher insecticide and antimicrobial activity. The in silico studies indicated that three hemisynthesized compounds were able to inhibit proteins involved in the process of antibacterial and insecticidal activities and also presented great stability inside the protein receptors pocket. They are, therefore, of interest for possible adoption as references for the synthesis of antibacterial drugs and insecticides.
This review shows an insufficiency of knowledge on the chemical composition of latex, flowers and other organs of E. officinarum, and the need for further investigation. Greater insight into the relationship between the chemical structures of the natural compounds or normalized extracts and biological properties is also needed. A possible relationship of the chemical composition of flowers and that of honey is another field requiring investigation. Since honey is appreciated by consumers and in order to increase the commercial value of a monofloral E. officinarum honey, it would be important to find one or more specific markers for this type of honey. Since many hemisynthesized compounds have been obtained, it is necessary to assay more biological activities of such compounds and not only antimicrobial and insecticidal activities.

Data Availability Statement:
The data is contained within the manuscript.

Conflicts of Interest:
The authors declare no conflict of interest.