The present world population has reached over 8 billion and is estimated to reach 10 billion by 2050. Due to a number of issues like land scarcity, unfavorable climate change, and insect and pathogen attacks, food production is slowly expanding in an arithmetic trend while the human population is swiftly rising in a geometric progression. Therefore, there will be a huge gap between the increasing population and food production, which is a major emerging problem in the near future. As demand for animal-derive protein is expected to increase at higher rate, insect based nutritional products can be marketed and commercialized as a new source of food. According to the FAO, at least 2 billion people already consume insects as part of their traditional diets. Currently, there are 2,111 edible insect species (1). Insects have historically been consumed by humans in Asia, Africa, and Latin America and have been the subject of extensive scientific study in recent years (2). Among the edible insects, silkworm larvae and pupae are one of the emerging insect-based nutritious food sources with high proteins, oils, polyphenols, vitamins, and chitosan (3). Silkworm eggs contain a high source of sugars, fat, and vitamin B (4). Various stages of silkworm larvae are used in pharmaceuticals (anti diabetic effect) or in food for supplementary nutrition (4). 18 amino acids and a high concentration of essential amino acids, which seem to be beneficial to humans, may be found in protein derived from silkworm pupae (5, 6). Unsaturated fatty acids, notably Omega-3 fatty acids, are abundant in silkworm pupae oil (7). The active compounds found in silkworm pupae have been shown in various experimental investigations to have significant favorable effects on human health. These advantages include antioxidant, anticancer, antibacterial, hepatoprotectant, and immunomodulator characteristics (8). Consequently, silkworms can be used in the near future in the biochemical, health, and food industries (9).

Silkworm is an endopterygote lepidopteran insect having complete metamorphosis with all the four life stages (egg, larva, pupa, and adult). The adults, after mating, lay eggs in batches (DFLs- Disease free layings), eggs, after hatching goes through five larval stages known as instars (I, II, III, IV, V). The larval stage of insect feeds on the host plant vigorously and produces a sericinous material called as silk thread. The late instar larvae produce cocoon by spinning sericigenous material around them called cocoon and pupa is produced inside the cocoon. There are different types of silkworms based on the host plant they feed on like mulberry silkworms, eri silkworms, tasar silkworms, and muga silkworms. Due to their great nutritional content and other medicinal properties, silkworm pupae are thought to be harvested for human consumption (10).

Further, sustainable development goal (SDG) 2 is about creating a world free of hunger by 2030. There were an estimated 720 million to 811 million hungry people in the globe in 2020, an increase of about 161 million over 2019. The number of people going hungry and suffering from food insecurity had been gradually rising between 2014 and the onset of the COVID-19 pandemic. The COVID-19 epidemic has worsened all types of malnutrition, especially among youngsters, and pushed already alarming rates even higher (11). Sustainable development in agriculture is based on increasing crop yields efficiently without putting undue stress on natural resources (12). The foundations of this farming approach, which also attempts to minimize the adversities on the environment, ensure long-term crop acquisition. Reduced chemical use and reliance on complicated machinery are only two examples of how sustainable agriculture strives to reduce its environmental impact (13). It is envisioned that environmental degradation can be avoided if agricultural producers’ commercial interests and customer quality demands are both respected. The circular economy concept is also worth considering in the context of sustainable development because it helps to reduce raw material consumption and trash generated during production by utilizing waste as substrates for subsequent activities (14). In this context, silkworms can be deployed as an alternative proteinaceous food source with lower greenhouse gas emission potential, helping to synergize the SDG target and alleviate the effects of climate change. Furthermore, the silk produced by larval instars, as well as the byproducts of the silk industry, can generate revenues in both impoverished and emerging economies.

This article’s goal is to examine the information on silkworm as a medicinal and food ingredient aligned with current SDGs. This review includes information from the disciplines of pharmacology, biochemistry, nutrition, and biomedicine. With the aim of elucidating the relationship between silkworm stages and health and offering a reference for their pharmaceutical use, the composition, functional mechanisms, and application prospects of silkworm stages (eggs, larvae, pupae, and adults) are explored.

There are several reasons for which silkworm is considered a potential alternative of food source as well as therapeutic option. Global food demand is changing in terms of its composition as a result of rising wages and increased urbanization in developing nations, notably in Asia (8). The rise in meat consumption worldwide is mostly due to increased wealth (15). In 2030, high-income nations’ per capita meat consumption is anticipated to rise by 9%, Consequently, there will be a 48% increase in demand for coarse grain as livestock feed. The consumption of meat is closely tied to the need for grains and protein-rich diets (16). Animals are given around 6 kg of plant protein for every kg of high-quality animal protein generated (17). But, livestock production is a major contributor to global warming, with annual emissions estimated at 7.1 gigatonnes of CO₂-equivalent, or 14.5% of human-induced GHG emissions (18). Therefore, achieving sustainability in the meat industry is a formidable task that calls for a multifaceted and holistic strategy, one that can be accomplished through the investigation of unconventional meat sources (19). By 2050, prices for beef, pigs, and poultry will be higher than they were in 2000 by more than 30% due to the rise in global prices for the most significant agricultural products (20). According to the same study, climate change may make matters worse and lead to an extra 18–21% price increase. When taking into consideration the increased demand for biofuels and declining agricultural production, food shortages may become even more serious: Land and labor productivity increased at a far slower rate (21). Future price increases in food and feed will lead people to look for alternate sources of protein, like silkworm.

About 18% of all greenhouse gas (GHG) emissions that are caused by humans worldwide come from the production of livestock, including the transportation of animals and feed (22). Enteric fermentation results in the production of methane (CH₄), which is then released from manure (6% of world emissions); N₂O is mostly emitted from fertilizer used for feed crops and manure (65% of global emissions). According to a survey of the literature, 1 kilograms of beef has the greatest environmental effect when expressed as CO₂ equivalents (14.8 kg), followed by 1 kg each of pork (3.8 kg) and chicken (1.1 kg) (23). Over all of the world’s anthropogenic atmospheric ammonia emissions, which are to blame for eutrophicating surface waterways and acidifying soils, are produced by agriculture, with cattle contributing nearly two-thirds of this total (22). Ammonia and GHGs may both be produced by insects. In the hindguts of tropical species of termites (Isoptera), scarab beetles, and cockroaches (Blaberidae and Blattinae), methanogenic bacteria can be found (Scarabidae) (24). The majority of commercially raised edible insect species, such as the house cricket (Acheta domesticus), the migratory locust (Locusta migratoria), the yellow mealworm (Tenebrio molitor), and the silkworms do better than traditional cattle in terms of both direct emissions of GHG and ammonia generation (25).

Since a rise in the demand for meat would result in a greater-than-proportional rise in the need for grain and high-protein feeds, feed conversion ratios (FCRs) are particularly crucial. Depending on the type of animal and the methods used to create the meat, FCRs might vary greatly. A very basic computation may be conducted, nevertheless, using average data. The following FCRs were determined using long-term data for the United States: 2.5 for poultry, 5 for pork, and 10 for beef (26). From this study, it is estimated that the FCR for silkworm larva is nearly 7.5, whereas for pupa is 16 (27). Traditional animals and insects have quite different weight ratios that make them edible. The percentage of edible weight is nearly 90%, which is far more than chicken (55%) (28) and beef (40%) (26).

The prevalence of livestock diseases and the emergence of novel, frequently antibiotic-resistant diseases are two additional effects of high-density animal production systems. The worldwide population loses billions of dollars each year due to infectious illnesses that affect cattle, such as foot-and-mouth disease, bovine spongiform encephalopathy (BSE), avian influenza (H5N1), and classical swine fever (29). Additionally, concerns with human health like BSE (29) and cardiovascular disease and cancer have been linked to meat eating in high-income nations (30). Zoonotic illnesses are on the rise and pose serious risks to human health, including the new strain of influenza A (H1N1), which is closely linked to swine influenza A (31). These dangers are anticipated to be quite modest given that insects (silkworms) are taxonomically far more distant from humans than conventional cattle.

Significant worldwide virtual water flows are associated with trading in cattle and livestock products (nearly half of the volume of virtual water flows relates to feed crops) (32). This is due to the fact that animal products, especially livestock with its 22,000 liters kg^–1 produced, have a relatively high virtual water content compared to cereal crops. Due to indirect water inputs like forage and grain feed crops, other sources even claim 43,000 liters (33). A larger amount of meat in the diet causes water scarcity. The numbers for certain edible insect species like silkworm are anticipated to be significantly lower.

The proteomic studies discovered many proteins, including proteins for storing food in silkworm eggs (34). The silkworm eggs contain three main types of glycoproteins namely vitellin, 30 kDa protein, and egg-specific protein (ESP) which account for more than 90% of total (35). Silkworms produce numerous 30 kDa low-molecular-weight proteins, which account for 35% of the total soluble protein in the egg (36). More than thirty genes coding for 30 kDa proteins have been annotated from Bombyx genome. Several additional proteins, including enzymes, proteases, and inhibitors of proteases, were also discovered in the eggs, along with parts of the silkworm energy metabolic system. Enzyme cathepsin B-like acid cysteine proteinase in the eggs of silkworm moth, Antheraea pernyi identified which help in the process of embryogenesis (37). A silkworm egg contains 56% albumin, 19.2% fat, and 7.7% sugar (4). The silkworm eggs contain high amount of protein and vitamins B1, B2. In Romania food industry silkworm eggs are used as Human fort B product (4). Silkworm eggs can be a potential nutritious food for nursing mothers due to presence of omega-3 polyunsaturated fatty acids. This unsaturated fatty acids are precursors of prostaglandins which has significant role in infants nutrition. Consumption of silkworm eggs increases the male sexual power and decreases erectile dysfunction as it increases GSH and nitric oxide synthetase levels in the corpus cavernosum. Silkworm eggs are said to cause heavy drinkers to stop drinking alcohol completely if they eat them (Popular tradition, India). Silkworm eggs are used as embryo inducer, hepatic protector, hypolipidic, and hypoglycemic. The silkworm eggs are also used extensively in transgenic studies (38). The nutritional composition and medicinal uses are mentioned in Figure 1.

It is estimated that 100 grams of the larvae of Bombyx mori consist of 54% protein, 8% fat, 6% fiber, and 6% ash, as well as 390 kcal of energy (39). Due to their high protein content, larvae are fed to younger animals, including reptiles, as a nutritional supplement. Pharmaceutical companies use a complete proteic extract from silkworm larvae possessing anti-diabetic activity, or the food industry uses it an additional nutraceutical (40). According to the research, the silkworm has the greatest potential to drop blood sugar when it is prepared on the third day of the fifth instar, created using the freezing-dry method, and taken as powder as compared to other methods (41). Due to their significant hypoglycemic activity, which is caused by 1-deoxynojirimycin (DNJ), which they obtain by feeding mulberry leaves, silkworms are attracting attention from all over the world. Silkworm DNJ content fluctuates dramatically during its life cycle as a holometabolic insect. DNJ content was analyzed by reverse-phase high-performance liquid chromatography (RP-HPLC) and it was estimated that 3rd day of V instar larvae possesses the highest level of DNJ (1512.46 μg per silkworm) (42). Silkworm has traditionally been used as a diabetic treatment in oriental nations such as China, Korea, and Japan, and several studies have recently proven the silkworm’s blood glucose-lowering impact. Humans can readily digest and absorb silkworm powder. It can also improve the physiological activities of the gastrointestinal tract (43). Cramps, bloating, and other illnesses can be treated using dehydrated silkworm larvae that were killed by the white muscardine disease (44). It is believed that mulberry-eating silkworms have better health benefits than other species. Due to their susceptibility to chemical substances like pesticides, medicines, and heavy metals, silkworms (Bombyx mori) are an excellent model organisms in health safety and ecological pollution evaluation (45). Different profits of the silkworm larva industry are mentioned in Figure 2.

Silkworm pupae contain a wide range of nutrients. The most prevalent constituents are protein, fat, and sugar, as well as minerals, vitamins, polyphenolic compounds, and a variety of other nutrients (46, 47). We have reviewed and summarized them individually here.

In December 2019, the coronavirus epidemic (COVID-19) first appeared. By January 2020, it had extensively spread around the world (111). A novel coronavirus known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is what causes COVID-19. After the genomic sequence of SARS-CoV-2 was published in January 2020, researchers immediately began to produce detection kits and anti-COVID-19 vaccinations (112–114). To promote the development of these technologies, quick and efficient production of target protein molecules is required. In order to create recombinant proteins, the BEVS (baculovirus expression vector system) was created using the BmNPV (Bombyx mori nucleopolyhedrovirus) and silkworm (115, 116). Fetal bovine serum (FBS) is not necessary for the production of recombinant BmNPV when using the silkworm and E. coli recombinant bacmid system (117). The BmNPV-silkworm expression method was used to create the SARS-CoV-2 S protein without the utilization of cultured isolates or FBS (118). Japan developed recombinant protein vaccines based on silkworm insect factories that are particularly adopt at producing difficult-to-express vaccine antigens. Thus, silkworm helped a lot to mankind to fight against deadly disease like COVID-19 and the involved mechanism can be used to combat the forecoming deadly diseases.

Safety is the primary need a person has for any food or medication. Silkworms are often safer for consumption than other well-known high-protein foods like shrimp and fish (119, 120). Silkworms contain a variety of bioactive substances, each of which serves a unique pharmacological function. However, before evaluating if silkworms can be utilized as food or medicine, the safety of their use must be considered. Concerns about safety are raised with regard to both toxicological safety and allergic reactivity. Transgenic silkworms were used in a 28-day feeding trial on rats to test subacute toxicity. Since the study found no negative reactions or fatalities in rats fed with the transgenic silkworms, it demonstrated that these insects were toxicologically safe, at least for rats to consume (121). The researchers also evaluated the safety of silkworm pupae protein by several acute and subacute toxicological investigations (acute toxicity test; teratogenicity test; and 30-day feeding study). The results indicate that neither fatalities nor abnormalities in histology, clinical chemistry, or hemoglobin levels occurred in any of the experimental groups. Rats may consume up to 1.50 g/kg/d of protein, which is generally regarded as safe (50). Triacylglycerols prevent direct ingestion of the oil, despite its great quality and high amount of unsaturated fatty acids. Structured triacylglycerols produced without the use of solvents are more suitable for direct ingestion, according to a study. Currently, research on allergies to silkworm pupae is common. The allergenicity of silkworm pupae has been examined in numerous research, with the most prevalent allergens being 27-kDa glycoprotein, chitinase precursors, paramyosin, and profilin (15, 122, 123). When consuming silkworm pupae, certain people run the risk of experiencing severe allergic reactions like hives, lightheadedness, irritated skin, and sometimes even shock (15, 119, 124). Allergens should be kept to a bare minimum for food and health products, which can favor using silkworm pupae. Many practical techniques or procedures have currently been investigated to lessen or alleviate the allergenicity of silkworm pupae. According to a study, female silkworm pupae raised on mulberry leaves had lower allergen levels, which may indicate a connection between food and sex in the development of silkworm pupae allergens (125). We can control the production of these allergens in the usage or manufacturing of silkworm pupae, even if we cannot totally avoid their production. Additionally, heat during food processing alters the conformation of the allergen and makes chemical modifications that cause the allergen to lose some of its allergenicity (126, 127). For the pre-treatment of silkworm pupae, hydrolysis and fermentation are viable options since they can successfully lower the allergenicity of foods in the food business (128). According to a recent study, treating protein extracts from silkworm pupae with heat, enzymes, and an acid-base solution greatly decreased their allergenicity. The allergens in the pupae are likely to be affected by high pressure, ultrasound, and microwave treatments as well (129). Overall, silkworms are safe to eat or use as medicine. In spite of the fact that allergic reactions can be triggered by allergens in silkworms, a variety of methods can be used to reduce or destroy them.

To sustain the notion that silkworms are edible insects, a cooperative effort by lawmakers, regulators, and law enforcement is required (130). New EU food legislation has made it feasible to legalize the use of edible insects in Europe. However, it’s critical to consider both the producer’s and the consumer’s safety (131). To encourage the growth and use of these products, more detailed and accurate regulations are needed to monitor the production and consumption of insect food products similar to silkworm larvae and pupae. This could protect customers and highlight the relationship between silkworms and human health and well-being (132).

The constituents of silkworms, the mechanisms through which they serve as functional diets and therapeutics are emphasized, and the prospects of silkworm pupae as a nutritional supplement and a medication for the treatment of various diseases are shown in this review. The fact that silkworm larvae and pupae are highly nutritious and can be raised in huge quantities swiftly is one of their key advantages (133). They also carry out a number of bioactive processes. This increases the scope for silkworm application in the pharmaceutical and biological sectors. However, the current examination of the pharmaceutical mechanisms of silkworm is insufficient, and many therapeutical experiments are still restricted to in vitro and animal studies. Clinical experiments must be conducted instantly to confirm the pharmacological properties of silkworm. The production of nutrient-rich food and pharmaceutical products from silkworms is also limited, and the use of silkworm pupae for human consumption is still very much in its infancy (134). According to the studies we have reviewed, silkworms do have huge potential for use in biomedicine. In order to use silkworm pupae as food and to enhance human health, future research should focus on understanding the pharmacological activities of these organisms, both at the molecular scale and in clinical testing.

DM, JK, IS, TB, and VD: conceptualization, writing – original draft preparation, and supervision. KP, AN, MG, NN, and SB: preparation of figures and table. DM, JK, VS, HJ, and DJ: conceptualization, preparation of figures, supervision, and review and editing. All authors read and approved the manuscript.