Insects are one of the most abundant and diverse animal groups on earth, among which holometabolous insects are an extremely unique category. They undergo complete metamorphosis, experiencing four stages in their lifecycle: egg, larva, pupa, and adult, with significant differences in morphology, ecology, and behavior between the larval and adult stages. Holometabolous insects are widely distributed in various ecosystems, including forests, grasslands, deserts, and other habitats, playing a crucial role in maintaining ecological balance and ecosystem functionality.

The venom of holometabolous insects serves as an essential physiological bioactive substance, exhibiting various biological effects such as antibacterial, anti-tumor, and analgesic properties. Moreover, the venom can also influence the physiology and behavior of the host, inducing itchiness, paralysis, and other symptoms. Therefore, studying the chemical composition and attack mechanisms of venom from holometabolous insects is of great significance for gaining a deeper understanding of their ecological and physiological characteristics, exploring new medical and agricultural applications.

This review will focus on the chemical composition and attack mechanisms of venom from holometabolous insects. By extracting and isolating venom from various holometabolous insects and utilizing multiple analytical methods, the main chemical constituents in the venom have been identified. Additionally, this review explores the action mechanisms, targets, and pathways of the venom components. It is hoped that the research findings in this review can provide valuable references and insights for a deeper understanding of the action mechanisms and potential applications of venom from holometabolous insects.

1 Chemical Composition Analysis of Insect Venom

The analysis of venom chemical composition involves multiple aspects, including extraction and isolation, physical and chemical property analysis, and structural identification and analysis. These studies are significant for gaining a deeper understanding of the chemical constituents and action mechanisms of venom, as well as for discovering novel bioactive substances and developing new applications.

1.1 Extraction and separation methods of venom

The extraction and separation of insect venom form the basis of research on venom chemical composition. Traditional extraction methods include electrical stimulation, manual squeezing, centrifugation, and others, but they suffer from issues such as low efficiency and small extraction yields. In recent years, several new extraction and separation methods have been widely applied in venom research, such as solid phase microextraction, mass spectrometry imaging, and high-performance liquid chromatography. These methods offer advantages such as high extraction efficiency and excellent separation effects, enabling more accurate extraction and separation of chemical constituents from the venom.

1.2 Physical and chemical property analysis of venom components

The analysis of the physical and chemical properties of venom components is an essential aspect of venom research, including parameters such as color, density, pH value, and conductivity. These parameters can provide vital reference information for subsequent chemical composition analysis. Additionally, preliminary analysis and identification of the chemical constituents in the venom can be achieved by determining its ultraviolet absorption spectrum, fluorescence spectrum, and other physical and chemical properties.

1.3 Structure identification and analysis of venom components

The structure identification and analysis of venom components are the focal points of research on venom chemical composition. Traditional methods for structure identification include mass spectrometry analysis, nuclear magnetic resonance analysis, and infrared spectroscopy analysis. In recent years, with the advancement of genomics and proteomics technologies, an increasing number of venom components have been identified and further studied using techniques such as gene cloning and protein expression. The development of these new technologies has enabled more in-depth and accurate research on the structure and function of venom components (Zeng et al., 2019).

2 Attack Mechanism of Venoms

2.1 Functions and mechanisms of action of venom components

2.1.1 Functions of venom components

Proteins and peptides are the most common bioactive components in venom, and they serve various functions. Enzymes in the venom can break down proteins and other large biomolecules, enabling digestion or exerting an attack effect. Some venom components also exhibit biological effects such as antimicrobial, anti-tumor, analgesic, coagulation, and hemolytic activities, which can have rapid and effective impacts on the target of the attack (Müller, 2010).

2.1.2 The mechanism of action of venom components

The mechanisms of venom component action refer to the process of interaction between bioactive components in the venom and molecules or cells within the host organism. Venom components typically interact with receptors, enzymes, ion channels, and other structures present in the host organism, leading to physiological effects. Enzymes in the venom can bind to proteins or other large biomolecules within the host organism, enabling digestion or exerting an attacking effect. Additionally, small organic compounds in the venom can also interact with molecules within the host organism.

In conclusion, research on the functions and mechanisms of venom components is significant for gaining a deeper understanding of the biological significance and applications of venom. With the continuous development of biotechnology and analytical techniques, an increasing number of venom components have been identified and extensively studied, providing a theoretical and experimental basis for discovering novel bioactive substances and developing new applications. In the future, as we delve further into the study of venom components and their mechanisms of action, it will aid in the discovery of more bioactive constituents within venom and open up further possibilities for applications in biomedicine and agriculture.

2.2 The target and pathway of action in venom

2.2.1 Target of action in venom

Protein toxins are one of the most common components found in insect venom, and they exert their biological toxicity by interacting with ion channels and receptors in the insect's nervous system. For instance, sodium channel toxins can interfere with nerve transmission by blocking sodium ion channels on the insect's neuron membrane, leading to paralysis and death. On the other hand, potassium channel toxins can impact nerve excitability and muscle contraction by modulating potassium ion channels on the insect's neuron membrane, resulting in paralysis and death of the insect.

In addition, insect venom also contains various enzymes and hormone-like molecules. For instance, proteases can break down protein structures within the insect, leading to cell death and tissue damage. On the other hand, hormone-like molecules can regulate the insect's growth and development processes, affecting its reproductive ability and survival success rate. Besides the mentioned targets, insect venom can also interact with other biomolecules within the insect, such as lipids and nucleic acids, thereby influencing the insect's metabolic and immune response processes, and other physiological functions.

In conclusion, the various components in insect venom can act on multiple targets within the insect's body, leading to a series of physiological and behavioral changes, thereby exerting their effects in insect predation, defense, and reproduction, among other aspects.

2.2.2 Action pathways of venom

The action pathways of venom components refer to the biological pathways through which bioactive components in the venom interact with molecules or cells within the host organism. These action pathways can be categorized into several aspects, including neurotransmitter release pathways, ion channel pathways, enzymatic pathways, and immune pathways.

In the neurotransmitter release pathway, venom components can influence the release of neurotransmitters and neuronal activity, leading to abnormal nerve transmission and spasms. In the ion channel pathway, venom components can impact the activity of ion channels within the host organism, resulting in changes in cell membrane potential and abnormal cell function. In the enzymatic pathway, venom components can affect the activity and function of enzymes within the host organism, leading to the breakdown and digestion of proteins and other large biomolecules. In the immune pathway, venom components can influence the function of the host organism's immune system, causing disruptions in immune responses. The study of venom action pathways is significant for gaining a deeper understanding of the biological significance and applications of venom.

With the continuous development of biotechnology and analytical techniques, an increasing number of venom components have been identified and extensively studied, providing a theoretical and experimental basis for discovering novel bioactive substances and developing new applications. In the future, as research on the targets and action pathways of venom components deepens, it will aid in the discovery of more bioactive constituents within venom, offering new possibilities for applications in biomedicine and agriculture.

2.3 The effects of venom on host physiology and behavior

2.3.1 The effect of venom on host physiology

The impact of venom components on the host's physiology is mainly manifested in the following aspects. In the nervous system, venom components can affect the functionality of the host's nervous system, leading to abnormal nerve transmission and either inhibition or excitation of neuronal activity. In the circulatory system, venom components can influence the functionality of the host's cardiovascular system, resulting in cardiovascular abnormalities. Regarding the immune system, venom components can affect the functionality of the host's immune system, leading to immune response irregularities and immune system suppression. In the digestive system, venom components can impact the functionality of the host's digestive system, causing digestive dysfunction. For example, the venom of bees (Figure 1) contains a protein called "insulin-like growth factor" (IGF), which can stimulate the host's immune system, but may also lead to allergic reactions. The venom of ants (Figure 2) can cause inflammation, itching, and pain on the host's skin. Among them, the venom of fire ants contains a chemical substance called "salmonella toxin," which can induce symptoms such as fever, diarrhea, and vomiting.

All of the aforementioned aspects represent the main manifestations of how venom components impact the host's physiology. This influence is of vital importance for the host's survival and health. Therefore, the study of the effects of venom components on host physiology holds significant significance.

2.3.2 The effect of venom on host behavior

The effects of venom components on the host's behavior are primarily manifested in the following aspects. In terms of pain perception, venom components can cause pain and discomfort in the host, leading to changes in the host's behavior. Regarding mobility, venom components can influence the host's ability to move, resulting in restricted behavior. On the emotional front, venom components can affect the host's emotions and behavior, leading to unstable or abnormal behavior. The impact of venom on host physiology and behavior is an important aspect of venom research.

Studying the impact of venom on the host provides a better understanding of the biological significance and potential applications of venom, and it offers a theoretical and experimental basis for applied research. The effects of venom on the host are not limited to the aspects mentioned above; it can also potentially cause reproductive health issues and disruptions in hormone levels in the host. Additionally, venom can trigger allergic reactions and shock (Valentine, 1984; Bilo and Bonifazi, 2009), and in severe cases, it can even lead to death. Therefore, the impact of venom on host physiology and behavior is a complex and crucial research area. In-depth investigations into the mechanisms of venom components and the factors influencing their effects are necessary to strengthen the regulation and prevention of venom, ensuring public health and ecological safety.

3 The Potential of Venom in Medical and Agricultural Applications

3.1 Pharmacological effects of venom components

Venom is a natural biological resource with various pharmacological effects. Its components include proteins, peptides, enzymes, small organic molecules, and others, each possessing diverse biological and pharmacological properties. Consequently, the pharmacological study of venom components serves as a crucial foundation for the medical applications of venom (Walker et al., 2016).

In recent years, an increasing body of research has shown that insect venom components exhibit significant anti-cancer activity (Cao et al., 2019). Certain peptides and small organic molecules found in some insect venoms also possess anti-tumor activity, and neurotoxins can induce apoptosis in tumor cells. Certain protein toxins in insect venom can target cancer cells, leading to apoptosis and cell death. Moreover, some small organic molecules present in insect venom have demonstrated anti-cancer effects, such as certain alkaloids found in venom (Schmidt, 1982).

In-depth research on the anti-cancer components in insect venom can provide important scientific evidence for the development of novel anti-cancer drugs. Compared to traditional chemical drugs, the anti-cancer components in insect venom exhibit higher specificity and lower side effects, which can better protect the health of patients. Additionally, these components can serve as means of chemical prevention and adjunctive therapy, offering more options for cancer patients. For instance, bee venom (Figure 3) contains a protein called "melittin", which has demonstrated anti-cancer properties in research. Studies have shown that melittin can induce apoptosis in tumor cells and inhibit tumor cell proliferation and metastasis.

In addition to its anti-cancer effects, venom components also possess various pharmacological properties, such as anti-inflammatory, anticoagulant, and antimicrobial activities (Wang et al., 2009). Venom components can also be used in the preparation of antimicrobial drugs and immunomodulators. For instance, an enzyme called "HyAL4" found in mosquito saliva is used for the treatment of skin diseases. HyAL4 can degrade hyaluronic acid in skin tissues, promoting wound healing and skin regeneration (Figure 4).

The pharmacological study of venom components is a crucial foundation for the medical applications of venom. By isolating, purifying, and structurally identifying venom components, we can gain insights into their mechanisms of action and pharmacological effects. Based on this knowledge, we can further investigate the toxicity and side effects of venom components and develop safe and effective drugs. Moreover, exploring the potential applications of venom components in treating other diseases is also possible.

In conclusion, venom components exhibit a wide range of pharmacological effects, laying the groundwork and prospects for venom's medical applications. However, it is essential to remain vigilant about regulating and preventing venom to ensure public health and ecological safety. In the future, as research on venom components and their mechanisms of action deepens, the potential applications of venom in the medical field will continue to expand and evolve.

3.2 The application prospects of venom in agricultural pest control

Traditional methods of agricultural pest control often have certain limitations, such as the generation of pesticide residues, environmental pollution, and potential harm to human health and ecosystems. However, employing venom for agricultural pest control offers advantages such as being environmentally friendly, non-toxic, and sustainable.

The application prospects of venom in agricultural pest control are very extensive (Han et al., 2010, Advances in the study of novel insecticides: insect toxins, pp. 80-86). For example, venom from parasitic wasps contains parasitoids that can paralyze pests without causing death, making it suitable for developing soft insecticides. Products using this approach have been used to control cotton bollworms, vegetable moths, and other pests. Neurotoxic peptides found in wasp venom can cause paralysis in the central nervous system of pests, making it a potential insecticide for controlling aphids, leafhoppers, and other pests. Additionally, the venom from bees and ants has also shown promising effects in controlling certain pests (Pan et al., 2004).

The application of venom in agricultural pest control is not only limited to individual venom components but can also involve the preparation of composite pesticides by combining different venom components. Venom holds extensive prospects in agricultural pest control, not only in terms of individual venom components but also in the preparation of composite pesticides through the combination of different venom components. With further research into venom components and their mechanisms of action, the application prospects of venom in agricultural pest control will continue to expand and deepen. However, it is important to pay attention to the regulation and prevention of venom to ensure public health and ecological safety. In the future, the application prospects of venom in agricultural pest control will be even broader and promising, providing more sustainable, environmentally friendly, and efficient pest control solutions for agricultural production.

4 Conclusion and Prospects

The chemical composition of the venom of completely metamorphosed insects is very complex, containing a variety of substances such as proteins, enzymes, peptides, small organic molecules, and so on. These components play important roles in insect attacks, such as inhibiting the host immune system, destroying host cell membranes, and damaging the host nervous system. In addition, the types and amounts of venom components may vary depending on factors such as the species of the insect, its habitat, and its food.

Currently, there are still some limitations in the research on the venom of completely metamorphosed insects. For instance, the isolation and identification of venom components still present certain technical difficulties, and the study of the mechanisms and interactions of venom components is not yet sufficiently in-depth. Future research can employ more advanced techniques, such as gene editing, mass spectrometry, and proteomics, to further explore the chemical structure, mechanisms, and interactions of venom components, providing a more scientific basis for the application of venom in fields such as medicine and agriculture.

The study of venom in completely metamorphosed insects is not only beneficial for understanding their evolution and ecological characteristics but also holds significant practical implications. For example, research on venom components can provide a basis for the development of new drugs and novel pesticides. The investigation of the mechanisms of venom components can offer new insights and approaches for the treatment and prevention of diseases. Additionally, the study of venom components can provide important scientific evidence for biodiversity conservation and the maintenance of ecological balance.

Author’s contribution

GTX was responsible for the literature review, data compilation, and writing of the initial draft of this review. GTX also participated in discussions and revisions of the manuscript. GTX served as the lead author of this review, contributing to both the writing and editing of the paper. Author read and approved the final manuscript.

Acknowledgement

Author would like to express her gratitude to Ms. Xuan Jia for her guidance and valuable feedback throughout the writing process of this review. The illustrations used in this review are sourced from the internet. If there are any concerns regarding copyright or the need for permission to use these images, please contact the author to ensure proper attribution and respect for the rights. Thank you for your understanding and support.

References

Bilo M.B., and Bonifazi F., 2009, The natural history and epidemiology of insect venom allergy: clinical implications, Clinical & Experimental Allergy, 39(10): 1467-1476.

https://doi.org/10.1111/j.1365-2222.2009.03324.x

Cao L., Liang S., and Shen Y., 2019, Venom peptides from the assassin bug Agriosphodrus dohrni exhibit antimicrobial activity and show selective cytotoxicity against human cancer cells, Exp. Biol. Med. (Maywood), 244(7): 547-555.

Müller U.R., 2010, Insect venoms, Anaphylaxis, 95: 141-156.

https://doi.org/10.1159/000315948

Pan J., Yu H., Chen X.X., and He J.H., 2004, An outline of the study on venom of parasitic wasps, Zhongguo Shengwu Fangzhi Xuebao (Chinese Journal of Biological Control), 20(3): 150-155.

Schmidt J.O., 1982, Biochemistry of insect venoms, Annual Review of Entomology, 27(1): 339-368.

https://doi.org/10.1146/annurev.en.27.010182.002011

Valentine M.D., 1984, Insect venom allergy: diagnosis and treatment, Journal of allergy and clinical immunology, 73(3): 299-304.

https://doi.org/10.1016/0091-6749(84)90397-X

Walker A.A., Weirauch C., Fry B.G., and King G.F., 2016, Venoms of heteropteran insects: a treasure trove of diverse pharmacological toolkits, Toxins (Basel), 8(12): 43.

https://doi.org/10.3390/toxins8020043

Wang W.L., Shi X.J., Mi X.Y., and Hou T.Y., 2009, The development in spider toxins research and application, Xiandai Shengwu Yixue Jinzhan (Progress in Modern Biomedicine), 9(15): 2989-2991, 2988.

Zeng X., Liu B., and Fang Q., 2019, Molecular cloning and functional characterization of a venom protein from the spider, Ornithoctonus huwena, which induces apoptosis in insect cells, Toxicon, 59: 1-9.