IngredientsEupolyphaga sinensis Walker is a medicinal insect belonging to the order Blattodea, family Corydiidae (formerly classified under Polyphagidae). It is also called Steleophaga plancyi (Boleny) and is widely distributed in Southeast Asian countries, including Thailand, India, Malaysia, and China. It is known by several Chinese common names including Tubiechong, Tuyuan, Dibiechong, Dibie, and Zhechong.
There are 2 genera and 5 species in the Polyphagidae family: (1) Steleophaga plancyi (Boleny), found in Beijing, Hebei, Henan, Shaanxi, Gansu, Qinghai, and Hunan province in China; (2) Eupolyphaga sinensis Walker, widely distributed in China; (3) Eupolyphaga yunnanensis (Chopard), produced in Yunnan and Vietnam; (4) Eupolyphaga thibetana Chopard, produced in Tibet; and (5) Eupolyphaga everistiana, found on Mount Everest. In China, at least four species of ground beetles belonging to the family Corydiidae are compiled into traditional Chinese medicinal prescriptions, including Eupolyphaga sinensis Walker, E. thibetana, E. everestians, and Polyphaga plancyi, among which ESW is the most widely exploited.
The species was originally described based on female morphology, being a member of Polyphaga, while the males were described as a separate species, Homoegamia sinensis. Only the females are used in medicine. In Chinese medicine, the term "Tubiechong" denotes the dried female insects of Eupolyphaga sinensis Walker or Polyphaga plancyi Bolivar.
Common names and synonyms:
Eupolyphaga sinensis Walker (Blattaria: Polyphagidae) is a traditional medicinal insect and has been included in the list of traditional Chinese medicine in the Pharmacopoeia of the People's Republic of China.
For commercial use, they are bred and raised artificially; once mature, they are collected, boiled in water, and dried either in the sun or by baking. ESW has been artificially bred since the 1970s, and its breeding has become an industry. In some countries, such as China and Thailand, the ground beetle has been officially recommended as a healthy food with high contents of proteins (21–54 g/100 g dry weight), lipids (33.40 g/100 g dry weight), essential fatty acids, vitamins, and a variety of beneficial minerals (1–7 g/100 g dry weight).
When used as a medicine, ESW has various forms of application; the methods of administration consist of fresh application, dry grinding, and making decoctions, with oral and topical being the most frequently used. Tubiechong could be prepared in different ways depending on what was being treated; preparation methods include grinding, frying, water extraction, and rice wine extraction, with water or rice wine extraction being the most common method. In modern research contexts, preparations studied include dried whole insect powder, lyophilized powder, aqueous extracts, 70% ethanol extracts, and enzymatic hydrolysates yielding isolated peptide fractions.
ESW was first recorded in the Shennong Bencao Jing (Divine Farmer's Classic of Materia Medica) of the Han Dynasty, and was noted to have the effects of "breaking blood and stasis" and promoting the reunion of fractured bones. In China, ESW was first recorded as a drug in Shen Nong Ben Cao Jing (originating in the third century AD).
Tubiechong alone or its derived formulas are applied in clinical treatment of various diseases. It is mainly used to treat postpartum blood stasis and bone injury, as recorded in the Compendium of Materia Medica. A later generation's book, Bencao Jing Shu, stated that it had great effect on treating traumatic injury and reuniting tendons and bones.
Within traditional Chinese medicine, E. sinensis was historically used to treat a variety of ailments, such as bruises, fractures, amenorrhea, postpartum blood stasis, and used as a pain reliever. It was used to promote blood circulation and remove stasis, as well as facilitate the healing of tendons and bones. Clinical practice commonly involves the treatment of injuries, fractures, amenorrhea, postpartum stasis, tumors, and various other diseases.
ES is traditionally known as a drug that regulates blood circulation by removing "static blood," a pathological product of blood stagnation that may become a pathogenic factor in TCM theory. There are claims by TCM physicians that Tubiechong can reduce and treat tumors via actions on blood vessels, and the apparent effect on blood vessels is why it was prescribed for the ailments it was (and still is).
The "Xiayuxue decoction" (XYXD) is a traditional Chinese medicine compound composed of three natural medicines: Rheum officinale Baill., Prunus persica (L.) Batsch, and Eupolyphaga sinensis Walker. It is derived from the famous traditional Chinese medical classics Jingui Yaolue (Essentials from the Golden Cabinet) and has been used for thousands of years. In the Guidelines for the Diagnosis and Treatment of Primary Liver Cancer issued by China's Health Commission, XYXD was applied in the treatment of primary liver cancer.
Another prominent classical formula is the Dahuang Zhechong Pill (Dà Huáng Zhè Chóng Wán). Dahuang Zhechong pills (also known as "Rhubarb and Eupolyphaga Pills" or "Rhubarb and Ground Beetle Pills") are a classic Chinese medicine formula originally described in Essentials from the Golden Cabinet. The action of this medicinal formula includes dispelling blood stasis and promoting new blood, with original indications of severe deficiency due to exhaustion or lesions from the five labors. It is also recorded as able to break up blood clots, stimulate blood circulation, slow intermediate reactions, and alleviate deficiency syndrome.
The most widely used 34 kinds of Chinese patent medicine containing Tubiechong were included in the Chinese Pharmacopoeia (2020 Edition) for the treatment of traumatic injury, low back pain, cardiovascular disease, tumors or masses and nodules, cervical spondylopathy, osteoarthritis, and psoriasis. Other derived formulas have been used in the clinical treatment of various diseases such as blood stasis, hepatic cirrhosis, cyclomastopathy, chronic active hepatitis, nephropathy, gynecological diseases, and cancer.
Chemical studies have demonstrated that Eupolyphaga sinensis Walker contains a variety of bioactive substances, including proteins, peptides, amino acids, fatty acids, nucleosides, alkaloids, polysaccharides, fat-soluble vitamins, and mineral elements. The fact that protein is the main component of E. sinensis has been established in previous experiments.
Proteins and their enzymatic hydrolysis products (bioactive peptides) are the most pharmacologically characterized class of compounds in ESW. Metabolomics identified 31 compound types in both female and male ESW, including lipids, amino acids, and fatty acids. The relative percentages of lipids and lipid molecules, amino acids and their derivatives in both female and male ESW exceeded 10%. The female ESW also contained organic heterocyclic compounds, benzene and substituted derivatives. Twenty-five types were detected in ESI- mode, and the relative percentages of fatty acids in both male and female ESW exceeded 20%.
A particularly significant protein is Eupolytin1: as reported in the Compendium of Materia Medica, the insect of Eupolyphaga sinensis Walker has been used as a traditional anti-thrombosis medicine without bleeding risk for several hundred years. Researchers have identified a fibrin(ogen)olytic protein (Eupolytin1) containing both fibrin(ogen)olytic and plasminogen-activating (PA) activities from the beetle. Using a thrombus animal model, Eupolytin1 was proved to contain strong and rapid thrombolytic ability and safety in vivo, which were better than that of urokinase.
Another characterized anticoagulant peptide is P9: a novel anticoagulant peptide (P9) containing 9 amino acids was isolated from the hydrolysate of aqueous extracts of ESW. P9 synthesized by solid-phase synthesis showed 70% inhibition of thrombin, prolonging thrombin time to 17 s and activated partial thromboplastin time to 33 s; molecular docking and spectroscopy demonstrated that P9 could inhibit thrombin activity by binding to the active site of thrombin and altering the secondary structure of thrombin.
E. sinensis walker polypeptides (EPs) were extracted through enzymatic hydrolysis, revealing 15 types of amino acids, with hydrophobic amino acids (HAAs) accounting for 46.7%.
The isolated polysaccharide ESPS has been structurally characterized. ESPS was found to be composed of rhamnose, fucose, arabinose, xylose, glucose, and galactose in a molar ratio of 7.4:3.1:13.9:9.3:39.7:26.5, with a mean molecular weight (Mw) of 2.14 × 10⁴ Da; the main chain of ESPS was mainly composed of →4)-α-D-Glcp-(1→ and →3)-β-D-Galp-(1→, with side chains connected through the O-6 atom of glucose and O-4 and O-6 atoms of galactose.
A variety of compounds in Tubiechong have been identified, including 37 volatile oil components, 17 ethyl acetate extracts, 7 alkaloid components, among others. Preliminary physical and chemical reactions revealed the presence of organic acids, triterpenes or saponins, esters, lactones, coumarins, and their glycosides. Top expressed components in ESW include phosphatidic acid (22:0/a-15:0), lysophosphatidylcholine (16:0/0:0), phenylalanine, hypoxanthine, uric acid, and others, dominated by amino acids and fatty acids.
Female ESW exhibited significantly higher levels of 8 bioactive compounds, 15 small peptides, and 13 prostaglandins compared to male ESW, which contribute to immunity enhancement, antithrombotic effects, and improved bone metabolism. In general, the content of pharmacologically active components in female ESW was higher than that in male ESW. This finding provides a scientific basis for the traditional pharmacopeial requirement to use only female specimens.
ESW has been utilized as a traditional antithrombotic agent in Eastern countries to mitigate bleeding risks. Prior research has identified a bifunctional antithrombotic protein in insects which exhibits both direct plasminogen and plasminogen activator activities. The peptide P9 acts by directly binding to and inhibiting thrombin — the final enzyme in the coagulation cascade — blocking its conversion of fibrinogen to fibrin.
The therapeutic effects of Eupolyphaga sinensis Walkers in thrombosis and blood stasis have been clinically validated, with anticoagulant peptides as key components; however, their pharmacological mechanisms remain not fully understood. By offering a novel approach to fibrinolysis, Eupolyphaga sinensis Walker may play a pivotal role in the development of innovative, safer antithrombotic therapies in modern clinical practice.
ES regulates the cell cycle, tumor suppressor genes and proteins, immune-related biomarkers, and antioxidant molecules.
In CML cell line studies: the 70% ethanol extract effectively inhibited K562 (human chronic myeloid leukemia) cell proliferation and induced G2-M phase arrest accompanied by up-regulation of cyclin B1 and cdc2, and down-regulation of cyclin D1, cyclin E1, cdc25c, and p53. It inhibited EGF secretion and EGFR kinase activity. Western blotting analysis indicated it also inhibited the phosphorylation of EGFR and activation of its downstream signaling molecules AKT and ERK. These results suggested that the antitumor mechanism of E. sinensis Walker involved altering the cell cycle and inhibiting EGFR phosphorylation in the EGFR signaling pathway.
In lung cancer cell studies: the 70% ethanol extract was demonstrated to inhibit the autophosphorylation of KDR, and downregulate the subsequent activation of AKT and extracellular signal-regulated kinase (ERK)1/2 in A549 cells. The antitumor mechanism of the extract was through inhibiting angiogenesis, functioning by interrupting the autophosphorylation of KDR and subsequently AKT and ERK1/2.
In HCC studies: ESW extract (ESWE) inhibits HCC growth by downregulating the signaling of PKCβ, Akt, m-TOR, Erk1/2, MEK-2, Raf, and JNK-1, while also increasing cyclin D1 protein levels and decreasing amounts of cyclin E, cyclin B1, and cdc2 cycle proteins.
Eupolyphaga sinensis Walker ethanol extract enhances Th1-type cytokines (TNF-α and IFN-γ) production and induces cell apoptosis in H22 HCC bearing mice.
In cyclophosphamide-induced immunosuppressed mice, ESW lyophilized powder notably increased the immune organ index, mononuclear macrophage function, and the level of natural killer (NK) cells; delayed-type hypersensitivity (DTH) was also improved. Levels of superoxide dismutase (SOD) and catalase (CAT) were enhanced, while malondialdehyde (MDA) and nitrogen monoxide (NO) were reduced. CD3⁺ T cells, CD4⁺ T cells, and the CD4⁺/CD8⁺ ratio were all increased.
Active peptides (APE) from ESW significantly reduced the accumulation of fat, oxidative stress levels, and serum pro-inflammatory cytokine levels in hyperlipidemic rats. Untargeted metabolomic analysis showed that the mechanism of the hypolipidemic effect was mainly related to tryptophan metabolism, phenylalanine metabolism, arginine biosynthesis, and purine metabolism. APE significantly downregulated the mRNA expression of SREBP-1, SREBP-2, and HMGCR. The hypothesis is that APE ameliorates hyperlipidemia by modulating amino acid metabolism, mediating the SREBP/HMGCR signaling pathway, and reducing oxidative stress and inflammation levels.
The ESPS polysaccharide significantly inhibited the production of HBsAg, HBeAg, and HBV DNA in the supernatants of HepG2.2.15 cells in a dose-dependent manner; HBV RNA and core protein expression were also decreased by ESPS. In vivo studies using HBV transgenic mice further revealed that ESPS (20 and 40 mg/kg/2 days) significantly reduced the levels of HBsAg, HBeAg, and HBV DNA in serum, as well as HBV DNA and HBV RNA in mouse liver. It is suggested that polysaccharide ESPS may activate innate immunity and exert antiviral effects via TLR4. Notably, the downregulation of HNF4α in liver tissue implied that ESPS may inhibit HBV through reducing the activity of the HBV core promoter.
Extracts from Eupolyphaga sinensis Walker exhibit a broad spectrum of biological activities, such as anticoagulant and antithrombotic effects, anti-tumor properties, antioxidant activity, immune regulation, blood lipid modulation, and liver protection.
The most robustly characterized anticoagulant mechanisms have been established in vitro and in preclinical animal models. In an in vivo study, peptide P9 was able to reduce the intensity of phenylhydrazine-induced cardiac staining in thrombosed zebrafish with antithrombotic activity. The results suggest that peptides originated from ESW hydrolysates could exert an anticoagulant effect and are likely to be a potential source of bioactive peptides with anticoagulant activity. The therapeutic effects of ESW in thrombosis and blood stasis have been clinically validated, with anticoagulant peptides as key components. The scoping review identified preclinical studies of coagulopathy as among the most frequently studied conditions. In the preclinical studies, coagulopathy was studied most frequently, followed by hyperviscosity, hyperlipidemia, inflammation, neoplasm, ischemic brain injury, and atherosclerosis.
Evidence strength: The antithrombotic and anticoagulant effects are substantiated at the biochemical and preclinical levels. Specific anticoagulant proteins and peptides have been isolated and characterized. Well-designed, large-scale human RCTs specifically assessing ESW as a standalone intervention for thrombotic diseases are absent from the published English-language literature reviewed.
Clinically, Tu Bie Chong is often used to treat trauma, bone pain, and cardiovascular diseases related to blood stasis. Tu Bie Chong is particularly effective in bone disease treatment. The 2020 edition of the Chinese Pharmacopoeia includes 34 proprietary Chinese medicines containing Tu Bie Chong, of which 16 are used to treat bone diseases or bruises. In 1992, researchers used rabbit fracture models to verify the effect of gavage administration of dried Tubiechong powder in promoting fracture healing.
Traumatic injury was the most frequently studied disease/condition in the clinical studies identified in the 2022 scoping review. However, the clinical evidence base consists largely of Chinese-language studies and case series. A total of 151 studies were identified in the scoping review, of which 51 were included; there were 14 studies on extracted or dried whole ES, 15 on ES-derived compounds, and 22 on ES-containing prescriptions.
Evidence strength: Preclinical data (animal fracture models) consistently support bone-healing properties. The scoping review noted that clinical studies exist but called for further mechanistic studies based on therapeutic effects in clinical settings.
ES was most commonly used for cancer-related diseases, followed by those related to endocrine function and immunity in the 2022 scoping review of 51 included studies.
Key preclinical findings include:
Evidence strength: Evidence is entirely preclinical (in vitro cell lines and animal tumor models). Overall, ES is a beneficial medicinal insect that can treat various diseases, including cancer and immune diseases; however, further mechanistic studies based on its therapeutic effects in clinical settings are required. No controlled human clinical trials evaluating ESW as a standalone anticancer intervention have been identified in the published literature.
Based on the theory of traditional Chinese medicine, blood stasis stagnating in the liver can lead to liver diseases; DHZCP has therefore been extensively used to treat various liver diseases, particularly hepatitis and hepatic fibrosis.
The Dahuang Zhechong Pill effectively inhibits hepatic fibrosis by modulating the intestinal microbiota and metabolites, as well as enhancing intestinal barrier function. The anti-HBV activity of the ESPS polysaccharide has been demonstrated in cell culture (HepG2.2.15 cells) and in HBV transgenic mouse models, but has not been confirmed in human clinical trials.
Evidence strength: Hepatoprotective and antifibrotic effects for ESW-containing formulas have been studied in preclinical models and in clinical use within China for compound formulas. The contribution of ESW specifically, versus other components of multi-herb formulas, is difficult to isolate from existing published evidence.
Research has confirmed that the active peptide AR-9 from Eupolyphaga steleophaga can mitigate lipid and hepatic lipid accumulation in hyperlipidemic rats by restoring gut microbiota and its metabolites, thereby ameliorating hyperlipidemia and reducing levels of triglycerides, total cholesterol, and low-density lipoprotein. The results showed that APE significantly reduced the accumulation of fat, oxidative stress levels, and serum pro-inflammatory cytokine levels in preclinical rat studies.
Evidence strength: Antihyperlipidemic activity is supported by preclinical rat studies using active peptide fractions. No human clinical trial data for lipid-lowering effects were identified in the reviewed sources.
The in vivo study was designed to elucidate the immuno-enhancement effects of ESL (lyophilized powder) in immunosuppressed mice induced by cyclophosphamide. Mice were treated with three doses of ESL (0.5, 1.0, and 2.0 g/kg). ESL notably increased the immune organ index, mononuclear macrophage function, and the level of natural killer cells. All these findings suggest that ESL could effectively improve immune functions via modulating oxidative systems and innate immune cells.
Evidence strength: Immunomodulatory effects have been demonstrated in mouse models with specific dose ranges reported. Human clinical trial data are lacking.
The polysaccharide fraction ESPS has been studied for anti-hepatitis B virus activity. ESPS has been isolated and characterized, and its anti-HBV activity and regulatory pathways have been investigated in vitro and in vivo. The preclinical results were described in the Mechanisms section above. Evidence strength: Preclinical only (cell and transgenic mouse model); no human studies reported.
The pharmacological activities of Tubiechong and its various extracts have been evaluated, including anticoagulant and antithrombotic, anticancer, bone repair, immunomodulation, analgesia, antioxidant, antihyperlipidemic, antimicrobial, and protective and repair functions for damage to the liver, heart, brain, and skin.
Based on the reviewed evidence, the body systems for which scientific or traditional evidence exists include:
The following dosages appear in the peer-reviewed literature and reflect experimental or pharmacopeial usage, not prescriptive clinical recommendations:
No standardized, validated human clinical dosage recommendations were identified in the English-language peer-reviewed literature reviewed. Dosages used in human-level applications in China exist within the context of compound formulas and are governed by the Chinese Pharmacopoeia for those specific patent medicines.
The pharmacological activities of Tubiechong and its various extracts have been extensively evaluated. As an edible insect, its safety has been confirmed by acute toxicity tests and 30-day feeding trials. ES has long been used as a food source as they are rich in proteins, vitamins, essential amino acids, minerals, and essential fatty acids.
Patients with allergies or a history of allergies may be more susceptible to adverse drug events (ADEs). Studies suggest that animal herbs may be main allergens. Chinese patent medicines containing Ground Beetle (Eupolyphaga/Tubiechong), such as the Dahuang Zhechong pill, have been found to cause a high proportion of skin symptoms in ADEs. These reactions present as dermatological adverse events and have been noted in clinical risk assessments of Chinese patent medicines containing insect-derived ingredients.
The traditional TCM literature, reflected in Chinese Pharmacopoeia-listed formulas, consistently marks ESW-containing formulas as contraindicated during pregnancy. Functions include activating blood circulation to remove blood stasis and promoting menstruation; ESW-containing products are not to be administered to pregnant women. This contraindication reflects the potent blood-activating and stasis-resolving properties of ESW, which are considered to carry risk of uterine stimulation in traditional medicine.
Based on metabolomics technology, the pharmacokinetic characteristics of Eupolyphaga Steleophaga (EuS) combined with Rhei Radix et Rhizoma acting on acute liver injury were explored using HPLC-MS/MS and ¹H NMR methods; models of acute liver injury were established to find the pharmacokinetic parameters of components in the RhRR-EuS combination. Pharmacokinetic results showed there were different levels of bimodal phenomenon in different groups, and the absorption of free anthraquinone in RhRR increased after compatibility with EuS. This finding indicates that ESW can alter the pharmacokinetics of co-administered herbal compounds, specifically enhancing absorption of anthraquinone constituents from rhubarb (Rheum), which could have clinical relevance in multi-herb formulations.
Given the documented anticoagulant and fibrinolytic activity of ESW proteins and peptides, the therapeutic effects of ESW in thrombosis and blood stasis, with anticoagulant peptides as key components, a plausible additive or synergistic interaction risk exists when ESW-containing preparations are co-administered with conventional anticoagulant or antiplatelet drugs (e.g., warfarin, aspirin, heparin). This concern follows from the mechanism of action rather than specific interaction trials; no dedicated drug–herb interaction studies for ESW and conventional anticoagulants were identified in the reviewed sources.
Despite promising potential, challenges such as low bioavailability, difficulties in peptide identification, pharmacological evaluation, and toxicity assessment persist for ESW-derived compounds. Previous research on the chemical composition of ESW was fragmented and superficial. Articles focused on female ESW and targeted large molecules such as proteins or polypeptides that cannot be directly absorbed by the human body. This limitation restricts understanding of other potentially significant components, such as small peptides, lipids, or low-molecular-weight compounds, which may play crucial roles in ESW's therapeutic effects.
The overall body of scientific evidence for Eupolyphaga sinensis Walker is characterized by:
Health conditions that Eupolyphaga sinensis may help support.
Body systems that Eupolyphaga sinensis may help support.
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