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Flavonoids Can Exert Larvicidal Effects by Inhibiting a Key Growth-Regulating Enzyme in Mosquitoes
Chemical inhibitors of enzymes that are involved in producing insect steroid hormones could be used to specifically target the development of mosquitoes without affecting other organisms.

Vector-borne infectious diseases are responsible for a sizeable fraction of the global infectious disease burden. Mosquitoes such as A. aegypti, in particular, are important vectors that transmit a number of viral diseases including but not limited to dengue fever, malaria, yellow fever, and Zika. Despite the many efforts and progress in controlling vector-borne diseases, they remain a major cause of morbidity and mortality across tropical regions due to several factors, one of which is insecticide resistance. Wild A. aegypti, for instance, has been shown to be developing insecticide resistance, hence the need for a new countermeasure for targeting this species.

Recently, scientists at the University of Tsukuba have discovered that specific flavonoids can inhibit an enzyme that is involved in the formation of a crucial insect hormone in A. aegypti. Although flavonoids are most commonly associated with nutritional benefits as they are found in almost all fruits and vegetables, studies have suggested another potential health benefit – flavonoids may act as an effective mosquito larvicide that pose fewer environmental hazards.

“Flavonoids – a type of metabolic product from plants, fungi, and other organisms – can interfere with insect development and physiology, and have the ability to kill larvae of A. aegypti,” said senior author of the study, Professor Ryusuke Niwa. “Flavonoids are thought to be relatively safe for the environment, as well as human and animal health.”

In their current study, the researchers sought to uncover the exact mechanism by which flavonoids can kill mosquito larvae. To do this, Prof. Niwa and colleagues examined the activities of several flavonoids in A. aegypti, including daidzein, which has previously been identified as a larvicide for this species. Their results revealed that the larvicidal action of flavonoids works by inhibiting the activity of glutathione S-transferase Noppera-bo (Nobo) in A. aegypti. Nobo is a key enzyme used for biosynthesising the ecdysteroid or insect steroid hormone, ecdysone, in A. aegypti.

In its active form, ecdysone stimulates metamorphosis and regulates moulting in insects. Since ecdysones are crucial to insects’ life cycle, the scientists believe that chemical inhibitors of enzymes involved in producing ecdysteroids, such as Nobo, may be important insect growth regulators (IGRs), which could be used to specifically target the development of insects without compromising other organisms.

“We also discovered that, of the flavonoids we tested, desmethylglycitein (DMG) was the most efficient Nobo inhibitor in this species, even more so than daidzein,” explained Professor Niwa. “DMG showed larvicidal activity against A. aegypti, and indicated promise for DMG-based insecticides in the future.”

With these optimistic results, their findings provide a new avenue for the development of novel IGRs, specifically that of DMG-based IGRs, to help combat insecticide-resistant mosquitoes in a more targeted and environmentally friendly manner.

Source: Inaba et al. (2022). Molecular action of larvicidal flavonoids on ecdysteroidogenic glutathione S-transferase Noppera-bo in Aedes aegypti. BMC Biology, 20, 43.

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