Pharmacological effects of bioactive agents in earthworm extract: A comprehensive review

Zihan Zhu , Xinyi Deng , Wenqing Xie , Hengzhen Li , Yusheng Li , Zhenhan Deng

Animal Models and Experimental Medicine ›› 2024, Vol. 7 ›› Issue (5) : 653 -672.

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Animal Models and Experimental Medicine ›› 2024, Vol. 7 ›› Issue (5) : 653 -672. DOI: 10.1002/ame2.12465
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Pharmacological effects of bioactive agents in earthworm extract: A comprehensive review

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Abstract

This review compiles information from the literature on the chemical composition, pharmacological effects, and molecular mechanisms of earthworm extract (EE) and suggests possibilities for clinical translation of EE. We also consider future trends and concerns in this domain. We summarize the bioactive components of EE, including G-90, lysenin, lumbrokinase, antimicrobial peptides, earthworm serine protease (ESP), and polyphenols, and detail the antitumor, antithrombotic, antiviral, antibacterial, anti-inflammatory, analgesic, antioxidant, wound-healing, antifibrotic, and hypoglycemic activities and mechanisms of action of EE based on existing in vitro and in vivo studies. We further propose the potential of EE for clinical translation in anticancer and lipid-modifying therapies, and its promise as source of a novel agent for wound healing and resistance to antibiotic tolerance. The earthworm enzyme lumbrokinase embodies highly effective anticoagulant and thrombolytic properties and has the advantage of not causing bleeding phenomena due to hyperfibrinolysis. Its antifibrotic properties can reduce the excessive accumulation of extracellular matrix. The glycolipoprotein extract G-90 can effectively scavenge reactive oxygen groups and protect cellular tissues from oxidative damage. Earthworms have evolved a well-developed defense mechanism to fight against microbial infections, and the bioactive agents in EE have shown good antibacterial, fungal, and viral properties in in vitro and in vivo experiments and can alleviate inflammatory responses caused by infections, effectively reducing pain. Recent studies have also highlighted the role of EE in lowering blood glucose. EE shows high medicinal value and is expected to be a source of many bioactive compounds.

Keywords

antithrombotic / antitumor / bioactive agent / earthworm extract / pharmacological effects

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Zihan Zhu, Xinyi Deng, Wenqing Xie, Hengzhen Li, Yusheng Li, Zhenhan Deng. Pharmacological effects of bioactive agents in earthworm extract: A comprehensive review. Animal Models and Experimental Medicine, 2024, 7(5): 653-672 DOI:10.1002/ame2.12465

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References

[1]

Xin T, Zhang Y, Pu X, Gao R, Xu Z, Song J. Trends in herbgenomics. Sci China Life Sci. 2019;62(3):288-308.

[2]

Liu Z, Chen S, Cai J, et al. Traditional Chinese medicine syndrome-related herbal prescriptions in treatment of malignant tumors. J Trad Chin Med. 2013;33(1):19-26.

[3]

Huang K, Zhang P, Zhang Z, et al. Traditional Chinese Medicine (TCM) in the treatment of COVID-19 and other viral infections: efficacies and mechanisms. Pharmacol Ther. 2021;225:107843.

[4]

Fu Z, Zhang L, Liu X, et al. Comparative proteomic analysis of the sun-and freeze-dried earthworm Eisenia fetida with differentially thrombolytic activities. J Proteome. 2013;83:1-14.

[5]

Gu Y, Zhang J, Sun J, et al. Marker peptide screening and species-specific authentication of Pheretima using proteomics. Anal Bioanal Chem. 2021;413(12):3167-3176.

[6]

Balamurugan M, Parthasarathi K, Ranganathan LS, Cooper EL. Hypothetical mode of action of earthworm extract with hepatoprotective and antioxidant properties. J Zhejiang Univ Sci B. 2008;9(2):141-147.

[7]

Hua Z, Wang YH, Cao HW, Pu LJ, Cui YD. Purification of a protein from coelomic fluid of the earthworm Eisenia foetida and evaluation of its hemolytic, antibacterial, and antitumor activities. Pharm Biol. 2011;49(3):269-275.

[8]

Yang J, Wang T, Li Y, et al. Earthworm extract attenuates silica-induced pulmonary fibrosis through Nrf2-dependent mechanisms. Lab Investig. 2016;96(12):1279-1300.

[9]

Hrzenjak T, Hrzenjak M, Kasuba V, Efenberger-Marinculić P, Levanat S. A new source of biologically active compounds—earthworm tissue (Eisenia foetida, Lumbricus rubelus). Comp Biochem Physiol Comp Physiol. 1992;102(3):441-447.

[10]

Kobayashi H, Ohta N, Umeda M. Biology of lysenin, a protein in the coelomic fluid of the earthworm Eisenia foetida. Int Rev Cytol. 2004;236:45-99.

[11]

Mihara H, Sumi H, Yoneta T, et al. A novel fibrinolytic enzyme extracted from the earthworm, Lumbricus rubellus. Jpn J Physiol. 1991;41(3):461-472.

[12]

Deng Z, Gao S, Xiao X, et al. The effect of earthworm extract on mice S180 tumor growth and apoptosis. Biomed Pharmacother. 2019;115:108979.

[13]

Yang W, Wang W, Ma Y, Yang Q, Li P, Du S. Bioevaluation of Pheretima vulgaris antithrombotic extract, PvQ, and isolation, identification of six novel PvQ-derived fibrinolytic proteases. Molecules. 2021;26(16):4946.

[14]

Verma MK, Pulicherla KK. Enzyme promiscuity in earthworm serine protease: substrate versatility and therapeutic potential. Amino Acids. 2016;48(4):941-948.

[15]

Li W, Li S, Zhong J, Zhu Z, Liu J, Wang W. A novel antimicrobial peptide from skin secretions of the earthworm, Pheretima guillelmi (Michaelsen). Peptides. 2011;32(6):1146-1150.

[16]

Yegnanarayan R, Ismail SA, Shrotri DS. Anti-inflammatory effect of two earthworm potions in carrageenan pedal oedema test in rats. Indian J Physiol Pharmacol. 1988;32(1):72-74.

[17]

Li C, Chen M, Li X, Yang M, Wang Y, Yang X. Purification and function of two analgesic and anti-inflammatory peptides from coelomic fluid of the earthworm, Eisenia foetida. Peptides. 2017;89:71-81.

[18]

Prakash M, Balamurugan M, Parthasarathi K, Gunasekaran G, Cooper EL, Ranganathan LS. Anti-ulceral and anti-oxidative properties of “earthworm paste” of Lampito mauritii (Kinberg) on Rattus norvegicus. Eur Rev Med Pharmacol Sci. 2007;11(1):9-15.

[19]

Deng Z, Gao S, An Y, et al. Effects of earthworm extract on the lipid profile and fatty liver induced by a high-fat diet in Guinea pigs. Ann Transl Med. 2021;9(4):292.

[20]

Deng ZH, Yin JJ, Luo W, et al. The effect of earthworm extract on promoting skin wound healing. Biosci Rep. 2018;38(2):BSR20171366.

[21]

Cooper EL, Hrzenjak TM, Grdisa M. Alternative sources of fibrinolytic, anticoagulative, antimicrobial and anticancer molecules. Int J Immunopathol Pharmacol. 2004;17(3):237-244.

[22]

Hrzenjak TM, Popovic M, Tiska-Rudman L. Fibrinolytic activity of earthworms extract (G-90) on lysis of fibrin clots originated from the venous blood of patients with malignant tumors. Pathol Oncol Res. 1998;4(3):206-211.

[23]

Grdisa M, Popovic M, Hrzenjak T. Glycolipoprotein extract (G-90) from earthworm Eisenia foetida exerts some antioxidative activity. Comp Biochem Physiol A Mol Integr Physiol. 2001;128(4):821-825.

[24]

Goodarzi G, Qujeq D, Elmi MM, Feizi F, Fathai S. The effect of the glycolipoprotein extract (G-90) from earthworm Eisenia foetida on the wound healing process in alloxan-induced diabetic rats. Cell Biochem Funct. 2016;34(4):242-249.

[25]

Azmi N, Hashim P, Hashim DM, Halimoon N, Majid NM. Anti-elastase, anti-tyrosinase and matrix metalloproteinase-1 inhibitory activity of earthworm extracts as potential new anti-aging agent. Asian Pac J Trop Biomed. 2014;4(suppl 1):S348-S352.

[26]

Prakash M, Gunasekaran G. Gastroprotective effect of earthworm paste (Lampito mauritii, Kinberg) on experimental gastric ulcer in rats. Eur Rev Med Pharmacol Sci. 2010;14(3):171-176.

[27]

Chang YM, Kuo WH, Lai TY, et al. RSC96 Schwann cell proliferation and survival induced by Dilong through PI3K/Akt signaling mediated by IGF-I. Evid Based Complement Alternat Med. 2011;2011:216148.

[28]

Chen CT, Lin JG, Lu TW, et al. Earthworm extracts facilitate PC12 cell differentiation and promote axonal sprouting in peripheral nerve injury. Am J Chin Med. 2010;38(3):547-560.

[29]

Bao Y, Peng J, Yang KL, et al. Therapeutic effects of Chinese medicine Di-Long (Pheretima vulgaris) on rheumatoid arthritis through inhibiting NF-κB activation and regulating Th1/Th2 balance. Biomed Pharmacother. 2022;147:112643.

[30]

Luo W, Deng ZH, Li R, et al. Study of analgesic effect of earthworm extract. Biosci Rep. 2018;38(1):BSR20171554.

[31]

Chen H, Takahashi S, Imamura M, et al. Earthworm fibrinolytic enzyme: anti-tumor activity on human hepatoma cells in vitro and in vivo. Chin Med J. 2007;120(10):898-904.

[32]

Nagasawa H, Sawaki K, Fujii Y, et al. Inhibition by lombricine from earthworm (Lumbricus terrestris) of the growth of spontaneous mammary tumours in SHN mice. Anticancer Res. 1991;11(3):1061-1064.

[33]

Zhao R, Ji JG, Tong YP, Chen Q, Pu H, Ru BG. Isolation and identification of proteins with anti-tumor and fibrinolysogen kinase activities from Eisenia foetida. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai). 2002;34(5):576-582.

[34]

Vassalle C, Maltinti M, Sabatino L. Targeting oxidative stress for disease prevention and therapy: where do we stand, and where do we go from here. Molecules. 2020;25(11):2653.

[35]

Ogasawara M, Yoshii K, Wada J, Yamamoto Y, Inouye K. Identification of guanine, guanosine, and inosine for α-amylase inhibitors in the extracts of the earthworm Eisenia fetida and characterization of their inhibitory activities against porcine pancreatic α-amylase. Enzym Microb Technol. 2020;142:109693.

[36]

Nakajima N, Mihara H, Sumi H. Characterization of potent fibrinolytic enzymes in earthworm, Lumbricus rubellus. Biosci Biotechnol Biochem. 1993;57(10):1726-1730.

[37]

Yoshii K, Ogasawara M, Wada J, Yamamoto Y, Inouye K. Exploration of dipeptidyl-peptidase IV (DPP IV) inhibitors in a low-molecular mass extract of the earthworm Eisenia fetida and identification of the inhibitors as amino acids like methionine, leucine, histidine, and isoleucine. Enzym Microb Technol. 2020;137:109534.

[38]

Sun J, Wei Q, Zhou Y, Wang J, Liu Q, Xu H. A systematic analysis of FDA-approved anticancer drugs. BMC Syst Biol. 2017;11(suppl 5):87.

[39]

Popovic M, Hrcenjak TM, Babic T, Kos J, Grdisa M. Effect of earthworm (G-90) extract on formation and lysis of clots originated from venous blood of dogs with cardiopathies and with malignant tumors. Pathol Oncol Res. 2001;7(3):197-202.

[40]

Rayan A, Raiyn J, Falah M. Nature is the best source of anticancer drugs: indexing natural products for their anticancer bioactivity. PLoS ONE. 2017;12(11):e0187925.

[41]

Augustine D, Rao RS, Anbu J, Chidambara Murthy KN. In vitro antiproliferative effect of earthworm coelomic fluid of Eudrilus eugeniae, Eisenia Foetida, and Perionyx excavatus on squamous cell carcinoma-9 cell line: a pilot study. Pharm Res. 2017;9(Suppl 1):S61-S66.

[42]

Kour J, Ali MN, Ganaie HA, Tabassum N. Amelioration of the cyclophosphamide induced genotoxic damage in mice by the ethanolic extract of Equisetum arvense. Toxicol Rep. 2017;4:226-233.

[43]

Yousef MI, Khalil D, Abdou HM. Neuro-and nephroprotective effect of grape seed proanthocyanidin extract against carboplatin and thalidomide through modulation of inflammation, tumor suppressor protein p53, neurotransmitters, oxidative stress and histology. Toxicol Rep. 2018;5:568-578.

[44]

Cherniack EP. Bugs as drugs, part two: worms, leeches, scorpions, snails, ticks, centipedes, and spiders. Altern Med Rev. 2011;16(1):50-58.

[45]

Shafi FAA, Faleh N. Anticancer activity of earthworm powder (Lumbricus terrestris) against MCF-7 and PC-3 cancer cell lines. J Gastrointest Cancer. 2019;50(4):919-925.

[46]

Augustine D, Rao RS, Anbu J, Chidambara Murthy KN. In vitro cytotoxic and apoptotic induction effect of earthworm coelomic fluid of Eudrilus eugeniae, Eisenia foetida, and Perionyx excavatus on human oral squamous cell carcinoma-9 cell line. Toxicol Rep. 2019;6:347-357.

[47]

Mácsik LL, Somogyi I, Opper B, et al. Induction of apoptosis-like cell death by coelomocyte extracts from Eisenia andrei earthworms. Mol Immunol. 2015;67(2 Pt B):213-222.

[48]

Quaglino D, Cooper EL, Salvioli S, et al. Earthworm coelomocytes in vitro: cellular features and “granuloma” formation during cytotoxic activity against the mammalian tumor cell target K562. Eur J Cell Biol. 1996;70(3):278.

[49]

Cooper EL, Cossarizza A, Suzuki MM, et al. Autogeneic but not allogeneic earthworm effector coelomocytes kill the mammalian tumor cell target K562. Cell Immunol. 1995;166(1):113-122.

[50]

Suzuki MM, Cooper EL. Killing of intrafamilial leukocytes by earthworm effector cells. Immunol Lett. 1995;44(1):45-49.

[51]

Ishitsuka R, Yamaji-Hasegawa A, Makino A, Hirabayashi Y, Kobayashi T. A lipid-specific toxin reveals heterogeneity of sphingomyelin-containing membranes. Biophys J. 2004;86(1 Pt 1):296-307.

[52]

Engelmann P, Kiss J, Csongei V, Cooper EL, Nemeth P. Earthworm leukocytes kill HeLa, HEp-2, PC-12 and PA317 cells in vitro. J Biochem Biophys Methods. 2004;61(1–2):215-227.

[53]

Fiołka MJ, Czaplewska P, Macur K, et al. Anti-Candida albicans effect of the protein-carbohydrate fraction obtained from the coelomic fluid of earthworm Dendrobaena veneta. PLoS ONE. 2019;14(3):e0212869.

[54]

Terzić J, Grivennikov S, Karin E, Karin M. Inflammation and colon cancer. Gastroenterology. 2010;138(6):2101-2114.e5.

[55]

Ren M, Yang L, He L, et al. Non-viral gene therapy for melanoma using Lysenin from Eisenia Foetida. Adv Sci (Weinh). 2024;11(17):e2306076.

[56]

Kobayashi H, Ohtomi M, Sekizawa Y, Ohta N. Toxicity of coelomic fluid of the earthworm Eisenia foetida to vertebrates but not invertebrates: probable role of sphingomyelin. Comp Biochem Physiol C Toxicol Pharmacol. 2001;128(3):401-411.

[57]

Fiołka MJ, Rzymowska J, Bilska S, et al. Antitumor activity and apoptotic action of coelomic fluid from the earthworm Dendrobaena veneta against A549 human lung cancer cells. APMIS. 2019;127(6):435-448.

[58]

Czerwonka A, Fiołka MJ, Jędrzejewska K, Jankowska E, Zając A, Rzeski W. Pro-apoptotic action of protein-carbohydrate fraction isolated from coelomic fluid of the earthworm Dendrobaena veneta against human colon adenocarcinoma cells. Biomed Pharmacother. 2020;126:110035.

[59]

Koupenova M, Kehrel BE, Corkrey HA, Freedman JE. Thrombosis and platelets: an update. Eur Heart J. 2017;38(11):785-791.

[60]

Burnett A, Siegal D, Crowther M. Specific antidotes for bleeding associated with direct oral anticoagulants. BMJ. 2017;357:j2216.

[61]

Capodanno D, Mehran R, Valgimigli M, et al. Aspirin-free strategies in cardiovascular disease and cardioembolic stroke prevention. Nat Rev Cardiol. 2018;15(8):480-496.

[62]

Zhao MM, Li M, Han ZL, Wang M, Du LX. Cloning and expression of lumbrokinase gene in Pichia pastoris. Wei Sheng Wu Xue Bao. 2006;46(4):581-585.

[63]

Poniedziałek B, Rosińska J, Rzymski P, Fiołka M. Polysaccharide-protein complex from coelomic fluid of Dendrobaena veneta earthworm exerts a multi-pathway antiplatelet effect without coagulopathy and cytotoxicity. Biomed Pharmacother. 2022;151:113205.

[64]

Chatterjee S, Sharma A, Mukherjee D. PAR-1 antagonists: current state of evidence. J Thromb Thrombolysis. 2013;35(1):1-9.

[65]

Trisina J, Sunardi F, Suhartono MT, Tjandrawinata RR. DLBS1033, a protein extract from Lumbricus rubellus, possesses antithrombotic and thrombolytic activities. J Biomed Biotechnol. 2011;2011:519652.

[66]

Wu Y, Hu S, Ma Y, et al. Novel Pheretima guillelmi-derived antithrombotic protein DPf3: identification, characterization, in vitro evaluation and antithrombotic mechanisms investigation. Int J Biol Macromol. 2020;154:545-556.

[67]

Matsuda T, Murakami M. Relationship between fibrinogen and blood viscosity. Thromb Res. 1976;8(2 suppl):25-33.

[68]

Wu Y, Ma Y, Zhong W, et al. Alleviation of endothelial dysfunction of Pheretima guillemi (Michaelsen)-derived protein DPf3 in ponatinib-induced thrombotic zebrafish and mechanisms explored through ox-LDL-induced HUVECs and TMT-based proteomics. J Ethnopharmacol. 2024;323:117669.

[69]

Wang YH, Li SA, Huang CH, et al. Sirt1 activation by post-ischemic treatment with lumbrokinase protects against myocardial ischemia-reperfusion injury. Front Pharmacol. 2018;9:636.

[70]

Ji H, Wang L, Bi H, et al. Mechanisms of lumbrokinase in protection of cerebral ischemia. Eur J Pharmacol. 2008;590(1–3):281-289.

[71]

Yan XM, Kim CH, Lee CK, Shin JS, Cho IH, Sohn UD. Intestinal absorption of fibrinolytic and proteolytic lumbrokinase extracted from earthworm, Eisenia andrei. Korean J Physiol Pharmacol. 2010;14(2):71-75.

[72]

Matausic-Pisl M, Tomicic M, Micek V, Grdisa M. Influences of earthworm extract G-90 on haematological and haemostatic parameters in Wistar rats. Eur Rev Med Pharmacol Sci. 2011;15(1):71-78.

[73]

Hayashi Y, Miclaus T, Engelmann P, Autrup H, Sutherland DS, Scott-Fordsmand JJ. Nanosilver pathophysiology in earthworms: transcriptional profiling of secretory proteins and the implication for the protein corona. Nanotoxicology. 2016;10(3):303-311.

[74]

Swiderska B, Kedracka-Krok S, Panz T, et al. Lysenin family proteins in earthworm coelomocytes—comparative approach. Dev Comp Immunol. 2017;67:404-412.

[75]

Swiderska B, Kedracka-Krok S, Plytycz B. Data on proteins of lysenin family in coelomocytes of Eisenia andrei and E. fetida obtained by tandem mass spectrometry coupled with liquid chromatography. Data Brief. 2016;9:629-634.

[76]

Ikenouchi J, Suzuki M, Umeda K, et al. Lipid polarity is maintained in absence of tight junctions. J Biol Chem. 2012;287(12):9525-9533.

[77]

Miller ME, Adhikary S, Kolokoltsov AA, Davey RA. Ebolavirus requires acid sphingomyelinase activity and plasma membrane sphingomyelin for infection. J Virol. 2012;86(14):7473-7483.

[78]

Yilmaz N, Yamaji-Hasegawa A, Hullin-Matsuda F, Kobayashi T. Molecular mechanisms of action of sphingomyelin-specific pore-forming toxin, lysenin. Semin Cell Dev Biol. 2018;73:188-198.

[79]

Villarroya-Beltri C, Baixauli F, Gutiérrez-Vázquez C, Sánchez-Madrid F, Mittelbrunn M. Sorting it out: regulation of exosome loading. Semin Cancer Biol. 2014;28:3-13.

[80]

Scott-Fordsmand JJ, Amorim MJB. The curious case of earthworms and COVID-19. Biology (Basel). 2021;10(10):c1043.

[81]

Ueda M, Noda K, Nakazawa M, et al. A novel anti-plant viral protein from coelomic fluid of the earthworm Eisenia foetida: purification, characterization and its identification as a serine protease. Comp Biochem Physiol B Biochem Mol Biol. 2008;151(4):381-385.

[82]

Li F, Wang JH, Zhang JL, Zhong RG, Niu B. Experimental research on anti-respiratory syncytial virus effect in vitro of earthworm coelomic fluid. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2010;24(2):116-118.

[83]

Liu Z, Wang J, Zhang J, Yu B, Niu B. An extract from the earthworm Eisenia fetida non-specifically inhibits the activity of influenza and adenoviruses. J Tradit Chin Med. 2012;32(4):657-663.

[84]

Wang XQ, Chen L, Pan R, Zhao J, Liu Y, He RQ. An earthworm protease cleaving serum fibronectin and decreasing HBeAg in HepG2.2.15 cells. BMC Biochem. 2008;9:30.

[85]

Yang J, Ding X, Zhang Y, Bo X, Zhang M, Wang S. Fibronectin is essential for hepatitis B virus propagation in vitro: may be a potential cellular target? Biochem Biophys Res Commun. 2006;344(3):757-764.

[86]

Liu XY, Liu RX, Hou F, et al. Fibronectin expression is critical for liver fibrogenesis in vivo and in vitro. Mol Med Rep. 2016;14(4):3669-3675.

[87]

Mustafa RG, Dr Saiqa A, Domínguez J, et al. Therapeutic values of earthworm species extract from Azad Kashmir as anticoagulant, antibacterial, and antioxidant agents. Can J Infect Dis Med Microbiol. 2022;2022:6949117.

[88]

Hussain M, Liaqat I, Hanif U, et al. Medicinal perspective of antibacterial bioactive agents in earthworms (Clitellata, Annelida):a comprehensive review. J Oleo Sci. 2022;71(4):563-573.

[89]

Liu YQ, Sun ZJ, Wang C, Li SJ, Liu YZ. Purification of a novel antibacterial short peptide in earthworm Eisenia foetida. Acta Biochim Biophys Sin Shanghai. 2004;36(4):297-302.

[90]

Wang X, Wang X, Zhang Y, Qu X, Yang S. An antimicrobial peptide of the earthworm Pheretima tschiliensis: cDNA cloning, expression and immunolocalization. Biotechnol Lett. 2003;25(16):1317-1323.

[91]

Wu Y, Deng S, Wang X, Thunders M, Qiu J, Li Y. Discovery and mechanism of action of a novel antimicrobial peptide from an earthworm. Microbiol Spectr. 2023;11(1):e0320622.

[92]

Fiołka MJ, Grzywnowicz K, Mendyk E, et al. Antimycobacterial action of a new glycolipid-peptide complex obtained from extracellular metabolites of Raoultella ornithinolytica. APMIS. 2015;123(12):1069-1080.

[93]

Fiołka MJ, Mieszawska S, Czaplewska P, et al. Candida albicans cell wall as a target of action for the protein-carbohydrate fraction from coelomic fluid of Dendrobaena veneta. Sci Rep. 2020;10(1):16352.

[94]

Wang X, Li X, Sun Z. iTRAQ-based quantitative proteomic analysis of the earthworm Eisenia fetida response to Escherichia coli O157:H7. Ecotoxicol Environ Saf. 2018;160:60-66.

[95]

Sara M, Ilyas F, Hasballah K, Nurjannah N, Mudatsir M. The effects of Lumbricus rubellus extract on Staphylococcus aureus colonization and IL-31 levels in children with atopic dermatitis. Medicina (Kaunas). 2023;59(11):2007.

[96]

Balamurugan M, Parthasarathi K, Cooper EL, Ranganathan LS. Anti-inflammatory and anti-pyretic activities of earthworm extract—Lampito mauritii (Kinberg). J Ethnopharmacol. 2009;121(2):330-332.

[97]

Balamurugan M, Parthasarathi K, Cooper EL, Ranganathan LS. Earthworm paste (Lampito mauritii, Kinberg) alters inflammatory, oxidative, haematological and serum biochemical indices of inflamed rat. Eur Rev Med Pharmacol Sci. 2007;11(2):77-90.

[98]

Huang C, Li W, Zhang Q, et al. Anti-inflammatory activities of Guang-Pheretima extract in lipopolysaccharide-stimulated RAW 264.7 murine macrophages. BMC Complement Altern Med. 2018;18(1):46.

[99]

Li XH, Tu XY, Zhang DX, et al. Effects of wuwei dilong decoction on inflammatory cells and cytokines in asthma model Guinea pigs. J Tradit Chin Med. 2009;29(3):220-223.

[100]

Huang CQ, Li W, Wu B, et al. Pheretima aspergillum decoction suppresses inflammation and relieves asthma in a mouse model of bronchial asthma by NF-kappaB inhibition. J Ethnopharmacol. 2016;189:22-30.

[101]

Seo M, Lee JH, Baek M, et al. A novel role for earthworm peptide Lumbricusin as a regulator of neuroinflammation. Biochem Biophys Res Commun. 2017;490(3):1004-1010.

[102]

Bovill JG. Mechanisms of actions of opioids and non-steroidal anti-inflammatory drugs. Eur J Anaesthesiol Suppl. 1997;15:9-15.

[103]

Nalamachu S. An overview of pain management: the clinical efficacy and value of treatment. Am J Manag Care. 2013;19(14 Suppl):s261-s266.

[104]

Schjerning AM, McGettigan P, Gislason G. Cardiovascular effects and safety of (non-aspirin) NSAIDs. Nat Rev Cardiol. 2020;17(9):574-584.

[105]

Darcq E, Kieffer BL. Opioid receptors: drivers to addiction? Nat Rev Neurosci. 2018;19(8):499-514.

[106]

Wang S. Historical review: opiate addiction and opioid receptors. Cell Transplant. 2019;28(3):233-238.

[107]

Bruehl S. Complex regional pain syndrome. BMJ. 2015;351:h2730.

[108]

Hussain T, Tan B, Yin Y, Blachier F, Tossou MC, Rahu N. Oxidative stress and inflammation: what polyphenols can do for us? Oxidative Med Cell Longev. 2016;2016:7432797.

[109]

Rajha HN, Paule A, Aragonès G, et al. Recent advances in research on polyphenols: effects on microbiota, metabolism, and health. Mol Nutr Food Res. 2022;66(1):e2100670.

[110]

Rudrapal M, Khairnar SJ, Khan J, et al. Dietary polyphenols and their role in oxidative stress-induced human diseases: insights into protective effects, antioxidant potentials and mechanism(s) of action. Front Pharmacol. 2022;13:806470.

[111]

Preiss D, Sattar N. Non-alcoholic fatty liver disease: an overview of prevalence, diagnosis, pathogenesis and treatment considerations. Clin Sci (Lond). 2008;115(5):141-150.

[112]

Boden G. Obesity, insulin resistance and free fatty acids. Curr Opin Endocrinol Diabetes Obes. 2011;18(2):139-143.

[113]

Yazici D, Sezer H. Insulin resistance, obesity and lipotoxicity. Adv Exp Med Biol. 2017;960:277-304.

[114]

Prakash M, Gunasekaran G, Elumalai K. Effect of earthworm powder on antioxidant enzymes in alcohol induced hepatotoxic rats. Eur Rev Med Pharmacol Sci. 2008;12(4):237-243.

[115]

Sadek SA, Soliman AM, Marzouk M. Ameliorative effect of Allolobophora caliginosa extract on hepatotoxicity induced by silicon dioxide nanoparticles. Toxicol Ind Health. 2016;32(8):1358-1372.

[116]

Zhang T, Wang C, Song A, et al. Water extract of earthworms mitigates mouse liver fibrosis by potentiating hepatic LKB1/Nrf2 axis to inhibit HSC activation and hepatocyte death. J Ethnopharmacol. 2024;321:117495.

[117]

Ahmed MM, Hammad AA, Orabi SH, et al. Reproductive injury in male rats from acrylamide toxicity and potential protection by earthworm methanolic extract. Animals (Basel). 2022;12(13):1723.

[118]

Jamshidzadeh A, Heidari R, Golzar T, Derakhshanfar A. Effect of Eisenia foetida extract against cisplatin-induced kidney injury in rats. J Diet Suppl. 2016;13(5):551-559.

[119]

Reinke JM, Sorg H. Wound repair and regeneration. Eur Surg Res. 2012;49(1):35-43.

[120]

Guo S, Dipietro LA. Factors affecting wound healing. J Dent Res. 2010;89(3):219-229.

[121]

He M, Xie WQ, Cheng G, et al. The therapeutic effects of earthworm extract on deep second-degree burn wound healing. Ann Palliat Med. 2021;10(3):2869-2879.

[122]

Zhang M, Li X, Liu Y, Ye F, Qiu G. Effects of extract of dilong (pheretima) on the scalded skin in rats. J Tradit Chin Med. 2006;26(1):68-71.

[123]

Yang Y, Hu H, Wang W, et al. The identification of functional proteins from amputated lumbricus Eisenia fetida on the wound healing process. Biomed Pharmacother. 2017;95:1469-1478.

[124]

Hrzenjak M, Kobrehel D, Levanat S, Jurin M, Hrzenjak T. Mitogenicity of the earthworm’s (Eisenia foetida) insulin-like proteins. Comp Biochem Physiol B. 1993;104(4):723-729.

[125]

Grdisa M, Popović M, Hrzenjak T. Stimulation of growth factor synthesis in skin wounds using tissue extract (G-90) from the earthworm Eissenia foetida. Cell Biochem Funct. 2004;22(6):373-378.

[126]

Matausijć-Pisl M, Cupić H, Kasuba V, Mikecin AM, Grdisa M. Tissue extract from Eisenia foetida as a wound-healing agent. Eur Rev Med Pharmacol Sci. 2010;14(3):177-184.

[127]

Yang Y, Sun Y, Zhang N, et al. The up-regulation of two identified wound healing specific proteins-HSP70 and lysozyme in regenerated Eisenia fetida through transcriptome analysis. J Ethnopharmacol. 2019;237:64-73.

[128]

Fu YT, Chen KY, Chen YS, Yao CH. Earthworm (Pheretima aspergillum) extract stimulates osteoblast activity and inhibits osteoclast differentiation. BMC Complement Altern Med. 2014;14:440.

[129]

Wang D, Ruan Z, Zhang R, Wang X, Wang R, Tang Z. Effect of earthworm on wound healing: A systematic review and meta-analysis. Front Pharmacol. 2021;12:691742.

[130]

Song S, Wang Y, Ji K, Liang H, Ji A. Effect of earthworm active protein on fibroblast proliferation and its mechanism. Pharm Biol. 2016;54(4):732-739.

[131]

Li T, Sun Y, Wang J, Zhang C, Sun Y. Promoted skin wound healing by tail-amputated Eisenia foetida proteins via the Ras/Raf/MEK/ERK signaling pathway. ACS Omega. 2023;8(15):13935-13943.

[132]

Mee A, Ali SI, Nabi SU, et al. Modulation of immune cum inflammatory pathway by earthworm granulation tissue extract in wound healing of diabetic rabbit model. Heliyon. 2024;10(3):e24909.

[133]

Wang W, Ye J, Guo Z, et al. A novel glycoprotein from earthworm extract PvE-3: insights of their characteristics for promoting diabetic wound healing and attenuating methylglyoxal-induced cell damage. Int J Biol Macromol. 2023;239:124267.

[134]

Wang XM, Fan SC, Chen Y, Ma XF, He RQ. Earthworm protease in anti-thrombosis and anti-fibrosis. Biochim Biophys Acta Gen Subj. 2019;1863(2):379-383.

[135]

Sun H, Ge N, Shao M, et al. Lumbrokinase attenuates diabetic nephropathy through regulating extracellular matrix degradation in Streptozotocin-induced diabetic rats. Diabetes Res Clin Pract. 2013;100(1):85-95.

[136]

Lai CH, Han CK, Shibu MA, et al. Lumbrokinase from earthworm extract ameliorates second-hand smoke-induced cardiac fibrosis. Environ Toxicol. 2015;30(10):1216-1225.

[137]

Xue Y, Dai HP, Cui A, Niu SJ, Pang BS. Effects of aerosolized earthworm fibrinolytic enzyme on bleomycin induced pulmonary fibrosis in rats. Zhonghua Yi Xue Za Zhi. 2012;92(48):3429-3433.

[138]

Calès P. Apoptosis and liver fibrosis: antifibrotic strategies. Biomed Pharmacother. 1998;52(6):259-263.

[139]

Uhal BD. Apoptosis in lung fibrosis and repair. Chest. 2002;122(6 suppl):293s-298s.

[140]

Li PC, Tien YC, Day CH, et al. Impact of LPS-induced cardiomyoblast cell apoptosis inhibited by earthworm extracts. Cardiovasc Toxicol. 2015;15(2):172-179.

[141]

Wang Q, Duan LX, Xu ZS, Wang JG, Xi SM. The protective effect of the earthworm active ingredients on hepatocellular injury induced by endoplasmic reticulum stress. Biomed Pharmacother. 2016;82:304-311.

[142]

Liao HE, Lai CH, Ho TJ, et al. Cardio protective effects of lumbrokinase and Dilong on second-hand smoke-induced apoptotic signaling in the heart of a rat model. Chin J Physiol. 2015;58(3):188-196.

[143]

Han CK, Kuo WW, Shen CY, et al. Dilong prevents the high-KCl cardioplegic solution administration-induced apoptosis in H9c2 cardiomyoblast cells mediated by MEK. Am J Chin Med. 2014;42(6):1507-1519.

[144]

Huang PC, Shibu MA, Kuo CH, et al. Pheretima aspergillum extract attenuates high-KCl-induced mitochondrial injury and pro-fibrotic events in cardiomyoblast cells. Environ Toxicol. 2019;34(8):921-927.

[145]

Jung CY, Yoo TH. Pathophysiologic mechanisms and potential biomarkers in diabetic kidney disease. Diabetes Metab J. 2022;46(2):181-197.

[146]

LeRoith D, Lesniak MA, Roth J. Insulin in insects and annelids. Diabetes. 1981;30(1):70-76.

[147]

Nongonierma AB, FitzGerald RJ. Features of dipeptidyl peptidase IV (DPP-IV) inhibitory peptides from dietary proteins. J Food Biochem. 2019;43(1):e12451.

[148]

Kwok AJ, Mashar M, Khavandi K, Sabir I. DPP-IV inhibitors: beyond glycaemic control? Trends Cardiovasc Med. 2014;24(4):157-164.

[149]

Kaur N, Kumar V, Nayak SK, Wadhwa P, Kaur P, Sahu SK. Alpha-amylase as molecular target for treatment of diabetes mellitus: a comprehensive review. Chem Biol Drug Des. 2021;98(4):539-560.

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2024 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.

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