From ancient leech to direct thrombin inhibitors and beyond: New from old

Montinari, Maria Rosa; Minelli, Sergio

doi:10.1016/j.biopha.2022.112878

Cited by 21 publications

(12 citation statements)

References 69 publications

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“…Typical hematophagous animals, including leeches and ticks, contain biologically active compounds in their secretions, especially in the saliva. The components of the salivary glands of leeches and ticks are relatively well studied, and classical active peptides, such as hirudin, have been used widely [25,26]. As bloodsuckers, the buccal glands of lampreys are considered a source of diverse bioactive proteins, from which various anticoagulant-and immune-related proteins, such as RGD (Arg-Gly-Asp) motif toxin and cysteine-rich secretory protein (CRISP), have been identified in recent years [14,27].…”

Section: Discussionmentioning

confidence: 99%

Peptidomics Analysis Reveals the Buccal Gland of Jawless Vertebrate Lamprey as a Source of Multiple Bioactive Peptides

et al. 2023

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Various proteins with antibacterial, anticoagulant, and anti-inflammatory properties have been identified in the buccal glands of jawless blood-sucking vertebrate lampreys. However, studies on endogenous peptides in the buccal gland of lampreys are limited. In this study, 4528 endogenous peptides were identified from 1224 precursor proteins using peptidomics and screened for bioactivity in the buccal glands of the lamprey, Lethenteron camtschaticum. We synthesized four candidate bioactive peptides (VSLNLPYSVVRGEQFVVQA, DIPVPEVPILE, VVQLPPVVLGTFG, and VPPPPLVLPPASVK), calculated their secondary structures, and validated their bioactivity. The results showed that the peptide VSLNLPYSVVRGEQFVVQA possessed anti-inflammatory activity, which significantly increased the expression of anti-inflammatory factors and decreased the expression of inflammatory factors in THP-1 cells. The peptide VVQLPPVVLGTFG showed antibacterial activity against some gram-positive bacteria. The peptide VSLNLPYSVVRGEQFVQA possessed good ACE inhibitory activity at low concentrations, but no dose-related correlation was observed. Our study revealed that the buccal glands of the jawless vertebrate lamprey are a source of multiple bioactive peptides, which will provide new insights into the blood-sucking mechanism of lamprey.

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Section: Discussionmentioning

confidence: 99%

Peptidomics Analysis Reveals the Buccal Gland of Jawless Vertebrate Lamprey as a Source of Multiple Bioactive Peptides

et al. 2023

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“…In 1904, Jacoby, a German pharmacologist named the term “hirudin” to refer to the leech head extract produced through a patented purification technology [ 49 ], which started the commercial production of hirudin. The emergence of commercial hirudin preparations has encouraged pharmacological research on its mechanism of action.…”

Section: Hirudinmentioning

confidence: 99%

Hirudin in the Treatment of Chronic Kidney Disease

Liu,

Cao,

Zhang

2024

Molecules

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Chronic kidney disease (CKD) is a common public health concern. The global burden of CKD is increasing due to the high morbidity and mortality associated with it, indicating the shortcomings of therapeutic drugs at present. Renal fibrosis is the common pathology of CKD, which is characterized by glomerulosclerosis, renal tubular atrophy, and renal interstitial fibrosis. Natural hirudin is an active ingredient extracted from Hirudo medicinalis, which has been found to be the strongest natural specific inhibitor of thrombin. Evidence based on pharmacological data has shown that hirudin has important protective effects in CKD against diabetic nephrology, nephrotic syndrome, and renal interstitial fibrosis. The mechanisms of hirudin in treating CKD are mainly related to inhibiting the inflammatory response, preventing apoptosis of intrinsic renal cells, and inhibiting the interactions between thrombin and protease-activated receptors. In this review, we summarize the function and beneficial properties of hirudin for the treatment of CKD, and its underlying mechanisms.

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“…Hirudin has a molecular weight of approximately 7000 daltons and contains approximately 65 amino acid sites (Fritsma 2012; Müller et al 2020). Hirudin is the most potent natural thrombin inhibitor found to date, binding to thrombin and forming an extremely stable non-covalent complex (Mousa et al 2021; Montinari and Minelli 2022). Compared to anticoagulants such as warfarin and heparin, hirudin causes fewer bleeding side effects (Chen et al 2021).…”

Section: Introductionmentioning

confidence: 99%

Comparative genomics of three non-hematophagous leeches (Whitmaniaspp.): focusing on antithrombotic genes

Zhao,

Huang,

Tang

et al. 2024

Preprint

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Leeches are well known for their blood-feeding habits and are widely used for medicinal purposes as they secrete various antithrombotic substances. However, some leeches such as Whitmania spp. exhibit non-hematophagous feeding habits and their significance for medicinal use is debated. In this study, we provide chromosome-level genomes of two non-hematophagous leeches Whitmania acranulata and Whitmania laevis, and combined with our previous results of Whitmania pigra, we systematically analyzed the similarities and differences on the genomes and especially their antithrombotic genes among the three non-hematophagous Whitmania leeches. For W. acranulata, W. laevis, and W. pigra, the genome size (181.72 Mb, 173.87 Mb, and 173.56), the percentage of repeat sites (29.55%, 28.28%, and 27.02%), and the number of protein-coding genes (27,068, 23,805, and 24,156) were close to each other, respectively. In contrast, both the total number of the antithrombotic genes (100, 63, and 79), and the detailed constitutes of different antithrombotic gene families were obviously different among the three leeches. There were also massive genetic variations among the members within each antithrombotic gene/protein family. RNA-Seq-based gene expression estimation showed that the expression profiles of the antithrombotic gene families were apparently different among the three leeches. This is the most comprehensive comparison of the genomes and antithrombic biomacromolecules for the Whitmania leeches to date. Our results will greatly facilitate the evolutionary research and application of leech derivatives for medical and pharmaceutical purposes of thrombosis.

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From ancient leech to direct thrombin inhibitors and beyond: New from old

Cited by 21 publications

References 69 publications

Peptidomics Analysis Reveals the Buccal Gland of Jawless Vertebrate Lamprey as a Source of Multiple Bioactive Peptides

Peptidomics Analysis Reveals the Buccal Gland of Jawless Vertebrate Lamprey as a Source of Multiple Bioactive Peptides

Hirudin in the Treatment of Chronic Kidney Disease

Comparative genomics of three non-hematophagous leeches (Whitmaniaspp.): focusing on antithrombotic genes

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