Natural Products in Honey Bee Gut Parasite: History
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Contributor:
Hesham R. El-Seedi
,
Aida A. Abd El-Wahed
,
Yahya Al Naggar
,
Aamer Saeed
,
Jianbo Xiao
,
Hammad Ullah
,
Syed G. Musharraf
,
Mohammad H. Boskabady
,
Wei Cao
,
Zhiming Guo
,
Maria Daglia
,
Abeer El Wakil
,
Kai Wang
,
Shaden A. M. Khalifa

Honey bees (Apis mellifera L.) are a highly valuable natural resource, and are of great importance to the human population and the whole ecosystem. They play a critical role as pollinators of agricultural crops, wild flora, and natural vegetation, and are an effective biological monitor of environmental contaminants, acting as collectors for airborne particulates and dust deposited on the surfaces on which they land. Honey bees are also source of honey, royal jelly, propolis, bee pollen, bee bread, venom, and wax.

  • honey bees
  • nosemosis
  • essential oils
  • plant extracts
  • active compounds

1. Natural Products in Control of Nosema Disease

1.1. Essential Oils

A study conducted by Bravo and his collaborators on the essential oils (EOs) of Cryptocarya alba indicated the presence of 39 compounds, including three major components, α-terpineol, eucalyptol, and monoterpene β-phellandrene. A group of infected bees received EO C. alba at a range of doses (1, 2, 3, and 4 µg/bee), a further group received fumagillin syrup (240 µg/bee) as a positive control, and infected bees without treatment were included as a negative control group. The results showed that 4 μg EO/bee was the most effective dose, exhibiting an 80% spore inhibition rate, similar to that of fumagillin. On the other hand, EOs had no toxicity on A. mellifera  [1]. EOs from several plants, such as lemon balm (Melissa officinalis), summer savory (Satureja hortensis), peppermint (Mentha piperita), and coriander (Coriander sativum), have demonstrated anti-nosemosis activity and enhanced the longevity of infected honey bees. Six groups of five bees each (experimental modules) were administered the product (Supresor 1, which is a mixture of essential oils derived from melliferous medicinal herbs) at different concentrations of 1 mL, 2 mL, 5 mL, 10 mL, and 50 ml per liter of syrup, with a positive control (infected non-treated), in addition to two negative control groups (uninfected, treated). The result reported no toxicity against bees, even at the elevated concentration of 10 mL (2000 mg etheric oil) per liter of syrup [2], and the optimal dose detected was 5 mL per liter of sugar syrup.

1.2. Plant Extracts

The ethanolic extracts of Artemisia dubia and Aster scaber have anti-nosemosis functions, seen as a reduction in spores of 77%, at a concentration of 100 μg/mL [3]. Aqueous extract of A. dubia and A. scaber at 1 μg/mL decreased spore levels by 76%. Butanol and ethyl acetate extracts displayed less activity than aqueous extract [4]. Extracts of six adaptogenic plants, including Ginkgo biloba, Panax ginseng, Eleutherococcus senticosus, Garcinia cambogia, Camellia sinensis, and Schisandra chinensis, were tested. The extract of E. senticosus root exhibited the strongest effect against nosema [5]. Another study proved the anti-nosemosis activity of aqueous extracts of nest carton produced from a jet-black ant nest (Lasius fuliginosus) with no toxicity on healthy bees. Additionally, the extract of birch carton decreased the number of spores by 97.97% [6].
Administration of the ethanolic extract of Laurus nobilis L. (Lauraceae) was carried out on infected bees to test its effects against N. ceranae. Syrup was enriched with 1% or 10% plant extract, and a control group was fed only on 60% (w/v) sucrose syrup without spores. The result showed that 10% L. nobilis extract inhibited 10% N. ceranae, while 1% L. nobilis extract was more effective for nosema inhibition after 19 days of treatment than 10%, and caused death of infected bees [7]. When applied at the time of infection or as a preventative measure, the water extract of Agaricus blazei mushroom was effective in reducing the number of N. ceranae spores without causing any side effects. Regardless of the presence of nosema infection, A. blazei increased the expression of the majority of immune-related genes, such as abaecin, hymenoptaecin, defensin, and vitellogenin. Daily food consumption did not differ between the groups, indicating that the extract was well-tolerated and acceptable [8][9]. The defatted seed meals (DSMs) from Brassica nigra and Eruca sativa, with a known quantity of various glucosinolates, were added for 8 days to feed the infected bees. The concentrations were 2% and 4%, leading to an inhibition of N. ceranae, as well as potential nutraceutical benefits, as reflected on the bee lifespan [10].
The effects of methanolic extracts of Chilean native plant leaves ((2%, 4%, 8%, and 16%), Aristotelia chilensis, Ugni molinae, and Gevuina avellana) and propolis (Biobío (BB) and Los Ríos (LR) regions) on N. ceranae infection were also investigated. It was found that 88% propolis and U. molinae extracts are sufficient for the treatment of infection. The survival rate mean values were 6.62, 8.88, and 7.61, respectively, for the two extracts and the infected control [11]. Another study on the effects of ethanolic propolis extract on the longevity and spore load of N. ceranae-infected worker bees indicated that propolis caused a significant reduction in nosema spore load compared to control [12]. The highest survival rate was found in the negative control group with 89%, followed by the 70% in propolis group, with values of 86% of the uninfected samples. The 50% propolis group demonstrated a 54% survival rate, whereas the 70% propolis group had 32%, and the 49% ethanol extract group had 27%. The no-treatment group showed 10% survival in the infected samples [13]. When honey bees were given propolis ethanol extract before or after infection, mortality, infectivity, and N. ceranae infection rates were significantly lower than those of the positive control [14].
The use of the herbal supplements NOZEMAT HERB® and NOZEMAT HERB PLUS® resulted in a statistically significant reduction of N. ceranae spore load [15].
ApiHerbfi and Api-Bioxalfi dietary supplements that were used also as anti-N. ceranae therapies. Both therapies decreased the prevalence of infections and resulted in a reduction of the amount of N. ceranae, where ApiHerb had a higher impact [16].

1.3. Isolated Compounds from Natural Products

The anti-microsporidian activity of sulphated polysaccharides of algae was reported in an in vitro assay, where they decreased parasite load and increased the survival of infected bees [17]. Similarly, phenolic compounds isolated from aqueous extract of A. dubia and A. scaber, namely chlorogenic acid, 3,4-dicaffeoylquinic acid (3,4-DCQA), 3,5-dicaffeoylquinic acid (3,5-DCQA), 4,5-dicaffeoylquinic acid (4,5-DCQA), and coumarin, were screened for their anti-nosema effect and toxicity to bees via in vitro and in vivo assays. The results showed that coumarin, chlorogenic acid, and 4,5-DCQA have more potent anti-nosema effects and are less toxic to bees than the other two compounds. Chlorogenic acid and coumarin showed outstanding anti-nosema activities, even at the lowest concentration (10 µg/mL) [18]. Another study on ten compounds (oregano oil, thymol, carvacrol, trans-cinnamaldehyde, tetrahydrocurcumin, sulforaphane, naringenin, embelin, allyl sulfide, hydroxytyrosol) and (chitosan, poly I:C) was aimed at controlling N. ceranae infections. The infected bees were fed on (166.7, 100, 100, and 50 µg/mL) of the compounds and fumagillin (PC), respectively, in 50% sugar syrup and 4 μL/mL ethanol or distilled water to determine the best dose response. Sulforaphane had the highest effect on spores, with a reduction of up to 64% [19]. Chitosan and peptidoglycan, both natural compounds, inhibited N. ceranae spore multiplication. Additionally, chitosan and peptidoglycan promote foraging for both pollen and non-pollen without impairing hygienic behavior [20].
In nature, porphyrins are a class of heterocyclic macrocycle organic substances. The consumption of a diet high in sucrose-protoporphyrin amide [PP(Asp)2] syrup significantly inhibited the growth of microsporidia, reduced mortality in infected honey bees, and prevented the spread of the microsporidia. Additionally, their exosporium layers, which were noticeably deformed, demonstrated the morphological changes. Given that they significantly reduce spore numbers, porphyrins are promising candidates for treating microsporidiosis, especially nosemosis, in honey bees [21].
Thymus vulgaris is the source of the naturally occurring essential oil ingredient thymol (3-hydroxy-p-cymene). Thymol improved honey bee health by increasing bee survival, immune-related gene levels, and oxidative stress parameter values, as well as decreasing nosema spore loads. However, when applied to nosema-free bees, thymol caused certain honey bee health problems, such as reduced bee longevity and induction of oxidative stress and, thus, beekeepers must take caution when applying it [22].
A dietary amino acid and vitamin complex has the potential to protect honey bees from the immunosuppression caused by N. ceranae. When compared to the control, the supplements significantly lowered the number of nosema spores. It also affected the expression of immune-related genes in honey bees infected with N. ceranae [23].

2. Safety of Natural Products as Treatments of Nosemosis

The natural products are safe when consumed in reasonable quantities. “GRAS” is an acronym for the phrase Generally Recognized as Safe, designated by FDA for natural products [24]. Furthermore, toxicity could be applied to adult workers, larvae, eggs, queens, bees’ enzyme activities, and their energy reserves [25], and to avoid any adverse impact of hosts during the first hour, the mortality must be less than 20% at 72 h [26]. Ariana and his colleagues concluded that a spray of 2% thyme, spearmint, and savory essential oil has no harmful effect on honey bees compared to dillsun essence, which caused 12% honey bee mortality [27]. Another study estimated that an essential oil of Citrus paradisi and C. sinensis reduced Paenibacillus, and at the tested concentrations of 2.34 mg/L, 2.08 mg/L, 1.82 mg/L, 1.56 mg/L, and 1.30 mg/L, had no mortality of honey bees [28]. Screening the toxicity activity of 13 crude plant extracts, Piper ribesioides and P. sarmentosum were found to be highly toxic to bees but Thunbergia laurifolia, Allium sativum, Cymbopogon citratus, and Senna alata had no toxic effect on adult bees, even those exposed to a high concentration [29]. In addition, the metabolites produced by Lactobacillus johnsonii, mainly consisting of lactic acid, did not cause bee mortality after 72 h of exposure by oral administration, even in high doses (60 µL of bacterial metabolite produced 10% mortality) [30]. Thymol is among the main chemical constituents of thymus essential oils, which, when applied to other plants, can help in the reduction of bee diseases. For bees infected with nosema, candies containing 0.12 mg/g thymol can decrease bee mortality and increase bee survival [31]. Administration of syrup enriched with 1% or 10% L. nobilis leaf extracts is effective inhibiting in vivo development of nosema in bees, depending on the dosage applied. The concentration of 10% was more effective than 1% and acted in a shorter time frame, but caused higher mortality [32].

This entry is adapted from the peer-reviewed paper 10.3390/ani12213062

References

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  2. Mitrea, I.L. “In vitro” studies on using natural essential oils in treatment of Nosemosis in honey bees: Determination of the therapeutic dose. Sci. Work. Ser. C Vet. Med. 2017, 63, 165–170.
  3. Kim, J.H.; Park, J.K.; Lee, J.K. Evaluation of antimicrosporidian activity of plant extracts on Nosema ceranae. J. Apic. Sci. 2016, 60, 167–178.
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  5. Ptaszynska, A.A.; Zaluski, D. Extracts from Eleutherococcus senticosus (rupr. et Maxim.) maxim. roots: A new hope against honeybee death caused by nosemosis. Molecules 2020, 25, 4452.
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  12. Mura, A.; Pusceddu, M.; Theodorou, P.; Angioni, A.; Floris, I.; Paxton, R.J.; Satta, A. Propolis consumption reduces Nosema ceranae infection of European honey bees (Apis mellifera). Insects 2020, 11, 124.
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