Poeciguamerin: A Novel Analgesic and Antithrombotic Peptide from Poecilobdella manillensis


Poecilobdella manillensis is a species of leech that has garnered interest in the scientific and medical communities for its anticoagulant properties. Anticoagulants are substances that help prevent blood clotting, making them valuable for surgeries and conditions requiring improved blood flow. The anticoagulant properties of Poecilobdella manillensis are primarily due to substances present in its saliva. When the leech feeds on the blood of a host, it secretes saliva containing a complex mixture of proteins and peptides, some of which have potent anticoagulant effects. These substances serve the leech by ensuring that the blood of their host remains fluid enough for them to ingest, but they also have potential applications in human medicine. These anticoagulant compounds have several potential medical applications. They can be used to treat or prevent diseases related to blood clotting, such as thrombosis, where blood clots form in blood vessels and can lead to heart attacks or strokes. They are also used in surgeries to reduce the risk of postoperative blood clots and to promote healing in reconstructive surgeries by improving blood flow to tissues. There is extensive research into the anticoagulant properties of Poecilobdella manillensis and other leeches and scientists are seeking to identify and synthesize these compounds for medical use. Understanding how these substances work at a molecular level, researchers can develop new, more effective medicine.   A new study published in International Journal of Molecular Science led by Professors Ren Lai and Zilei Duan from the Kunming Institute of Zoology, Chinese Academy of Sciences and conducted by Chaoming Wang, Mengrou Chen, Xiaoyu Lu, Shuo Yang, Min Yang, and Yaqun Fang, the researchers conducted a comprehensive study to isolate, purify, and characterize a novel peptide from the salivary gland secretions of Poecilobdella manillensis, subsequently named poeciguamerin. This peptide displayed potent analgesic and anticoagulant activities, with a specific inhibitory action against elastase, a notable advancement in the quest for new therapeutic agents.  The team initial step involved collecting P. manillensis salivary gland secretions, followed by a multi-stage purification process using gel filtration chromatography, reverse-phase high-performance liquid chromatography, and fast protein liquid chromatography. This meticulous process led to the isolation of poeciguamerin, a peptide which they found to significantly inhibit elastase activity. The authors used Edman degradation method and mass spectrometry, and determined the amino acid sequence of poeciguamerin, identifying it as a serine protease inhibitor containing an antistasin-like domain. This structural elucidation was critical for understanding the functional capabilities of poeciguamerin, particularly its interactions with various proteases. They evaluated the peptide’s inhibitory effects against a panel of proteases, including elastase, FXIIa, kallikrein, FXa, trypsin, and thrombin. Poeciguamerin demonstrated a dose-dependent inhibition of elastase activity, slight inhibition of FXIIa and kallikrein activities, but no significant effect on the other tested proteases. These findings indicated a selective inhibitory profile, particularly relevant to its analgesic and anticoagulant activities. They also used mouse models to test the analgesic efficacy of poeciguamerin through foot-licking and tail-withdrawal assays. The authors showed the peptide to have significant analgesic effects, reducing pain behaviors in mice injected with elastase in their paws and exhibiting thermal pain upon tail immersion in hot water. These results confirmed the peptide’s potential as an effective pain management agent. Moreover, the authors assessed the antithrombotic property of poeciguamerin was assessed using a FeCl3-induced carotid artery thrombosis model in mice. Poeciguamerin was found to inhibit thrombus formation in a dose-dependent manner, akin to the effect observed with sodium heparin, a known anticoagulant. This demonstrated the peptide’s capacity to act as an anticoagulant.

In conclusion, the discovery of poeciguamerin by Professors Ren Lai, Zilei Duan, and their team as a promising candidate for developing new treatments for pain and thrombosis represents a significant milestone in the field of natural product research and pharmaceutical development. The dual analgesic and anticoagulant properties of poeciguamerin position it as a candidate for the development of novel treatments for pain and thrombosis, addressing a significant need in clinical medicine. The authors’ findings highlight the potential of natural bioactive peptides as sources of new therapeutic agents, reinforcing the importance of biodiversity in medical research. Moreover, the elucidation of its structural and functional properties paves the way for further studies aimed at exploiting its therapeutic potential, contributing to the advancement of pain management and anticoagulant therapies.

In a statement to Medicine Innovates, the authors said “In addition, we have isolated and identified peptides or small molecules with antithrombotic (Poecistasin[1], PGE1[2], sylvestin[3], bdellin-HM-2[4]), analgesic (HSTXs[5]), antimicrobial (RK-22[6]) and antiinflammatory (Neuropeptide Y[7], HMEI-A[8]) activities from Poecilobdella manillensis and Haemadipsa sylvestris.”

Poeciguamerin: A Novel Analgesic and Antithrombotic Peptide from Poecilobdella manillensis - Medicine Innovates

About the author

Dr. Zilei Duan, Associate Professor, Kunming Institute of Zoology, Chinese Academy of Sciences. His major research interest focuses on the pathogenesis of diseases (ulcerative colitis, Alzheimer’s disease, COVID-19) and drug discovery (antibacterial, antiviral, antithrombotic and  analgesic related drugs), which were published in Cell Res, Sci Bull, Cell Mol Life Sci, PNAS, Front Microbiol, Int J Mol Sci, etc.

About the author

Prof. Ren Lai, Principal Investigator, Associate Director, Kunming Institute of Zoology, Chinese Academy of Sciences, Winner of National Outstanding Youth Foundation, Ten Thousand Talent Program, Science and Technology Leader in Yunnan Province, Director of CAS Engineering Laboratory for Natural Active, Director of Natural Bio-active Peptide Engineering Laboratory of Yunnan Provincial Development and Reform Commission and Deputy Editor of J Venom Res. His research is mainly focused on peptideomics and proteomics of natural medicines, functions and mechanisms of bioactive peptides and proteins, structural modification of native peptides/proteins and drug research and development. More than 250 papers have been published in Immunity, Chem Rev, Nat Immunol, Cir Res, Nat Commun, FASEB J, Sci Adv, Plos Biology, Blood, Cell Res, and PNAS. He has applied for more than 120 patents. He is winner of Second National Technology and Invention Award, Innovation Award, First Yunnan Province Natural Science Award. He has directed more than 70 graduate students.


Wang C, Chen M, Lu X, Yang S, Yang M, Fang Y, Lai R, Duan Z. Isolation and Characterization of Poeciguamerin, a Peptide with Dual Analgesic and Anti-Thrombotic Activity from the Poecilobdella manillensis Leech. Int J Mol Sci. 2023 ;24(13):11097. doi: 10.3390/ijms241311097.

Go To Int J Mol Sci.

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