A minireview of the medicinal and edible insects from the traditional Chinese medicine (TCM)

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TL;DR

This review highlights 12 medicinal insect species from traditional Chinese medicine (TCM) that have been underexplored for their bioactive properties, including mantis egg cases, cicada slough, stink bugs, gallnuts, cockroaches, ground beetles, termites, insect wax, shellac, black ants, gadflies, and mole crickets. These insects have demonstrated a wide range of pharmacological activities such as anti-inflammatory, anticancer, antithrombotic, antioxidant, and immunomodulatory effects, with several compounds and mechanisms identified. The review emphasizes the potential of integrating insect omics (genomics, transcriptomics, proteomics, metabolomics) to accelerate drug discovery from these entomoceuticals, which also serve as nutritional health foods.

Full summary

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**Background:** Insects represent a vast and underexplored source of bioactive compounds for pharmaceutical development. While traditional Chinese medicine (TCM) has documented over 300 medicinal insect species across 13 orders, most remain poorly characterized compared to plant-derived drugs. This narrative review aims to summarize the current knowledge on 12 specific medicinal insect species from TCM that have received relatively more research attention over the past two decades, focusing on their chemical constituents, pharmacological mechanisms, and therapeutic applications.

**Methods:** The authors conducted a literature review of medicinal insect species from TCM, selecting 12 species based on the availability of studies on their chemical structures, pharmacological mechanisms, and pharmacokinetics. The review integrates traditional knowledge from ancient Chinese medical texts (e.g., 'Shennong's Materia Medica Classic', 'Compendium of Materia Medica') with modern scientific findings, including recent advances in insect omics (genome, transcriptome, metabolome, proteome).

**Key Results:** The review details the pharmacological activities and active compounds for each of the 12 insect species:

1. **Mantis egg cases (MECs):** Show immunomodulatory effects by rescuing cyclophosphamide-induced immunosuppression in mice, elevating immunoglobulins (IgM, IgG), cytokines (TNF-α, IL-2, IL-4), and antioxidant enzymes (MDA, SOD, GSH-Px). Compounds N-(3,4-Dihydroxyphenethyl) acetamide and 2,4-di-tert-butylphenol are strong antioxidants. Two serine protease enzymes (MEF and MEF-2) show specific activity at 10.56 U/mg and 155 U/mg, respectively. MEC oil inhibits Staphylococcus aureus and Pseudomonas aeruginosa with MIC of 4 mg/mL.

2. **Cicada slough (CS):** Water extract improved lung pathology in an asthma guinea pig model and normalized serum levels of IL-2, IL-5, TXB2, and 6-Keto-PGF1α. A small peptide (F2-2-2) shows fibrinolytic activity.

3. **Stink bug (Aspongopus chinensis):** Contains approximately 60% unsaturated fatty acids, with oleic acid comprising 44-50%. Shows anticancer activity against HepG2, MCF-7, SGC-7901 cells via cell cycle arrest (G0/G1 phase) and STAT3/Survivin/Bcl signaling. An anticancer mixture (IC50 = 25.462 μg/mL for SGC-7901; 29.003 μg/mL for BGC-823) suppressed tumor growth in a 4T1 xenograft mouse model. Compounds (±)-Aspongopusamide A, Aspongopusamide C, and Aspongamides C inhibit COX-2 with IC50 values of 6.5, 117, and 6.86 μM, respectively.

4. **Chinese gallnut (CG):** Gallotannins account for >50% dry weight. Potent antioxidant activity (EC50 = 1.22 ± 0.01 μg/mL in ethyl acetate; IC50 = 13.13 μg/mL in water for DPPH radicals). Gallic acid comprises 2-4% dry weight. Used in medical toothpastes for oral health.

5. **Cockroach (Periplaneta americana):** Three approved drugs in China: Kangfuxin (KFX) for mucositis and ulcers, Xinmailong (XML) for chronic heart failure, and Ganlong Capsule (GLC) for hepatic fibrosis. Active molecules include adenosine, protocatechuic acid, inosine, and pyroglutamate dipeptides. KFX triggers ERK/p53 apoptotic pathway in SGC-7901 cells.

6. **Ground beetle (Eupolyphaga sinensis):** Contains proteins (21-54 g/100 g dry weight), lipids (33.40 g/100 g dry weight). Ethanol extract (ESWE) inhibits A549 cells via antiangiogenic activity and KDR signaling. Antitumor protein EPS72 (MW ~72 kDa) induces A549 cell apoptosis with low IC50. Two antithrombin-like peptides (ET-I and ET-II) identified. Eupolytin 1 (MW ~26 kDa) shows fibrinolytic and plasminogen-activating activities.

7. **Termite:** Water extract inhibits HIV-1 viral activities. Termitarium contains polysaccharides, sesquiterpenoids, cerebrosides, heteroglycans, isoflavonoids. Termitomyces albuminosus powder (TAP) is safe for human consumption.

8. **Insect wax (Ericerus pela):** Promotes hair growth by upregulating VEGF. Policosanol derived from insect wax (PIW) shows potential for Alzheimer's disease prevention.

9. **Shellac (Kerria spp.):** Shellolic acid A shows antimicrobial activity against B. subtilis (MIC = 0.1 mg/mL).

10. **Black ant (Polyrhachis vicina):** Contains >70% unsaturated fatty acids. Active fraction suppresses MCF-7 (IC50 = 17.91 mg/mL) and MDA-MB-231 (IC50 = 18.73 mg/mL) via EGR1/NKILA/NF-κB axis.

11. **Gadfly (Tabanus spp.):** At least five antithrombotic proteins isolated from salivary glands: thrombostasin, TAP, tablysin-15, vasotab TY, and tablysin 2. Two immunoregulatory peptides (TP1-3 and cecropin-TY1) suppress LPS-stimulated cytokine storm.

12. **Mole cricket (Gryllotalpa spp.):** Contains medicinal amino acids >50% of total amino acids. Four antimicrobial compounds identified: berberine, palmatine, Gryllotalpa A, and Gryllotalpa B. Ethanol extract shows cytotoxic effects on HeLa, Caski, and C-33A cervical cancer cells.

The review also notes that over 400 insect species have been sequenced, with approximately 50 medicinal insect species in the i5K genome database.

**Clinical Implications:** These 12 medicinal insects represent a significant but underexplored reservoir of potential drug candidates for various conditions including cancer, thrombosis, inflammation, infections, and immune disorders. The review highlights the dual role of these insects as both pharmaceuticals and nutritional health foods. However, the authors note that toxicological studies remain insufficient for most of these entomoceuticals, and more in vitro/in vivo toxicity assays are needed before clinical trials. The integration of insect omics approaches promises to accelerate the discovery and development of novel therapeutic agents from these traditional sources.