Citation: El-Seedi, H.R.; El-Wahed, A.A.A.; Naggar, Y.A.; Saeed, A.; Xiao, J.; Ullah, H.; Musharraf, S.G.; Boskabady, M.H.; Cao, W.; Guo, Z.; et al. Insights into the Role of Natural Products in the Control of the Honey Bee Gut Parasite (Nosema spp.). Animals 2022, 12, 3062. https:// doi.org/10.3390/ani12213062 Academic Editors: María Shantal Rodríguez-Flores, Olga Escuredo and M. Carmen Seijo Received: 22 September 2022 Accepted: 3 November 2022 Published: 7 November 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). animals Review Insights into the Role of Natural Products in the Control of the Honey Bee Gut Parasite (Nosema spp.) Hesham R. El-Seedi 1,2,3,4, *, Aida A. Abd El-Wahed 5 , Yahya Al Naggar 6 , Aamer Saeed 7 , Jianbo Xiao 8 , Hammad Ullah 9 , Syed G. Musharraf 10 , Mohammad H. Boskabady 11,12 , Wei Cao 13,14 , Zhiming Guo 15 , Maria Daglia 1,9 , Abeer El Wakil 16 , Kai Wang 17 and Shaden A. M. Khalifa 18, * 1 International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China 2 Pharmacognosy Group, Department of Pharmaceutical Biosciences, Biomedical Centre, Uppsala University, P.O. Box 591, SE-751 24 Uppsala, Sweden 3 International Joint Research Laboratory of Intelligent Agriculture and Agri-Products Processing (Jiangsu University), Jiangsu Education Department, Nanjing 210024, China 4 Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Koom 32512, Egypt 5 Department of Bee Research, Plant Protection Research Institute, Agricultural Research Centre, Giza 12627, Egypt 6 Zoology Department, Faculty of Science, Tanta University, Tanta 31527, Egypt 7 Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan 8 Department of Analytical Chemistry and Food Science, University of Vigo, 36310 Vigo, Spain 9 Department of Pharmacy, University of Napoli Federico II, 80131 Naples, Italy 10 H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan 11 Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad 13131-99137, Iran 12 Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad 13131-99137, Iran 13 College of Food Science and Technology, Northwest University, Xi’an 710069, China 14 Bee Product Research Center of Shaanxi Province, Xi’an 710065, China 15 School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China 16 Department of Biological and Geological Sciences, Faculty of Education, Alexandria University, Alexandria 215260, Egypt 17 Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Beijing 100093, China 18 Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE-106 91 Stockholm, Sweden * Correspondence: hesham.el-seedi@farmbio.uu.se (H.R.E.-S.); shaden.khalifa@regionstockholm.se (S.A.M.K.); Tel.: +46-(700)-434-343 (H.R.E.-S.) Simple Summary: The most significant pollinators of crops globally are thought to be honey bees. Unfortunately, bee loss is an issue brought on by a variety of circumstances, such as pesticide use, poor nutrition, parasitic mites, and climate change. The spore-forming unicellular fungi Nosema apis and N. ceranae cause nosemosis, a serious microsporidian disease of adult European honey bees. The disease has an effect on honeybee productivity and reproduction. Antibiotic fumagillin is still used in some countries for the treatment of Nosema sp. infection. However, using fumagillin has adverse effects on human health, as well as on honey bee physiology. Therefore, there are trends to develop non-antibiotic alternatives with already existing therapeutics. The present work attempts to emphasize the natural compounds now available for treating nosemosis. Abstract: The honey bee is an important economic insect due to its role in pollinating many agricultural plants. Unfortunately, bees are susceptible to many pathogens, including pests, parasites, bacteria, and viruses, most of which exert a destructive impact on thousands of colonies. The occurrence of resistance to the therapeutic substances used against these organisms is rising, and the residue from these chemicals may accumulate in honey bee products, subsequently affecting the human health. There is current advice to avoid the use of antibiotics, antifungals, antivirals, and other drugs in bees, and therefore, it is necessary to develop alternative strategies for the treatment of bee diseases. In this context, the impact of nosema diseases (nosemosis) on bee health and the negative insults of existing drugs are discussed. Moreover, attempts to combat nosema through the use Animals 2022, 12, 3062. https://doi.org/10.3390/ani12213062 https://www.mdpi.com/journal/animals