Recent advances in developing insect natural products as potential modern day medicines

Abstract

Except for honey as food, and silk for clothing and pollination of plants, people give little thought to the benefits of insects in their lives. This overview briefly describes significant recent advances in developing insect natural products as potential new medicinal drugs. This is an exciting and rapidly expanding new field since insects are hugely variable and have utilised an enormous range of natural products to survive environmental perturbations for 100s of millions of years. There is thus a treasure chest of untapped resources waiting to be discovered. Insects products, such as silk and honey, have already been utilised for thousands of years, and extracts of insects have been produced for use in Folk Medicine around the world, but only with the development of modern molecular and biochemical techniques has it become feasible to manipulate and bioengineer insect natural products into modern medicines. Utilising knowledge gleaned from Insect Folk Medicines, this review describes modern research into bioengineering honey and venom from bees, silk, cantharidin, antimicrobial peptides, and maggot secretions and anticoagulants from blood-sucking insects into medicines. Problems and solutions encountered in these endeavours are described and indicate that the future is bright for new insect derived pharmaceuticals treatments and medicines.

Figure 1

Schematic showing approximate evolutionary relationship of spiders, silkworms, bees, wasps, and ants mentioned in this review. Figure from Tara D. Sutherland, Sarah Weisman, Andrew A. Walker, and Stephen T. Mudie, “The Coiled Coil Silk of Bees, Ants, and Hornets,” Biopolymers volume 97, Issue 6, pp. 446–454, 2012 (DOI 10.1002/bip.21702) published by John Wiley and Sons with permission.

Figure 2

Evaluation in vivo of the effect of α-melittin nanoparticles on the inhibition of melanoma development. (a) Tumor volume over time showing that only the α-melittin nanoparticle group was significantly inhibited. (b) Comparative sizes and (c) volumes of the excised tumors between different groups after 13 days growth. Means ± SD, n = 5, **P < 0.01. Reprinted with permission from C. Huang, H. Jin, and Y. Qian et al., “Hybrid melittin cytolytic peptide-driven ultrasmall lipid nanoparticles block melanoma growth in vivo,” ACS Nano, volume 7, number 7, 5791-5800, 2013. (DOI: 10.1021/nn400683s). Copyright (2013) American Chemical Society.

Figure 3

Effects of cantharidin on cell viability and morphological changes of human colorectal cancer cells. (a) Cells treated with 0, 5, 10, 20, or 40 μM cantharidin for 0, 24, 48, and 72 h and then harvested for determination of cell viability. (b) Cells exposed to 20 μM cantharidin for 24 h and then examined for morphological changes under phase-contrast microscopy. Data represent the mean ± SD of three experiments. From Huang et al., “Cantharidin induces G2/M phase arrest and apoptosis in human colorectal cancer colo 205 cells through inhibition of CDK1 activity and caspase-dependent signaling pathways,” International Journal of Oncology, volume 38, pp. 1067-1073, 2011. Reprinted with permission of Spandidos Publications 2013.

Figure 4

Showing newly washed final instar Lucilia sericata larvae prior to incubation for production of extracorporeal secretions. Photograph by kind permission of Mr. I.F. Tew, Swansea University.

Figure 5

Comparison of mechanism of thrombin recognition by anophelin with other substrates and inhibitors. Thrombin is represented by an orange ellipse, with exosites in blue and the active site in red. Anophelin inhibitor binds to thrombin in a reverse orientation relative to the other molecules, such that the N-terminal portion recognises exosite I, whereas the C-terminal acidic segment binds to the active site of thrombin. From original Figure 4 of Ana C. Figueiredo, Daniele de Sanctis, Ricardo Gutiérrez-Gallego, Tatiana B. Cereija, Sandra Macedo-Ribeiro, Pablo Fuentes-Prior, and Pedro José Barbosa Pereira, “Unique thrombin inhibition mechanism by anophelin, an anticoagulant from the malaria vector” which appeared in Proceedings of the National Academy of Sciences of the United States of America.” Volume, 109, Issue 52, pages E3649 to E3658, 2013 (doi: 10.1073/pnas.1211614109). Reprinted with permission of PNAS.