Pharmacological activity and NMR solution structure of the leech peptide HSTX-I

McMahon, Kirsten L.; Tay, Bryan; Deuis, Jennifer R.; Tanaka, Brian S.; Peigneur, Steve; Jin, Aihua; Tytgat, Jan; Waxman, Stephen G.; Dib‐Hajj, Sulayman D.; Vetter, Irina; Schroeder, Christina I.

doi:10.1016/j.bcp.2020.114082

Cited by 3 publications

(2 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The leech peptide HSTX-I exerts significant analgesic function by specifically inhibiting Nav1.8 and 1.9 channels [ 28 ]. However, another study suggested that HSTX-I was not a useful lead for development of analgesic Nav1.8 and 1.9 modulators [ 29 ]. The specific inhibitors of Nav1.9 channels need further study.…”

Section: Structure and Function Of Nav19 Channelsmentioning

confidence: 99%

The influence of Nav1.9 channels on intestinal hyperpathia and dysmotility

2023

View full text Add to dashboard Cite

The Nav1.9 channel is a voltage-gated sodium channel. It plays a vital role in the generation of pain and the formation of neuronal hyperexcitability after inflammation. It is highly expressed in small diameter neurons of dorsal root ganglions and Dogiel II neurons in enteric nervous system. The small diameter neurons in dorsal root ganglions are the primary sensory neurons of pain conduction. Nav1.9 channels also participate in regulating intestinal motility. Functional enhancements of Nav1.9 channels to a certain extent lead to hyperexcitability of small diameter dorsal root ganglion neurons. The hyperexcitability of the neurons can cause visceral hyperalgesia. Intestinofugal afferent neurons and intrinsic primary afferent neurons in enteric nervous system belong to Dogiel type II neurons. Their excitability can also be regulated by Nav1.9 channels. The hyperexcitability of intestinofugal afferent neurons abnormally activate entero-enteric inhibitory reflexes. The hyperexcitability of intrinsic primary afferent neurons disturb peristaltic waves by abnormally activating peristaltic reflexes. This review discusses the role of Nav1.9 channels in intestinal hyperpathia and dysmotility.

show abstract

Section: Structure and Function Of Nav19 Channelsmentioning

confidence: 99%

The influence of Nav1.9 channels on intestinal hyperpathia and dysmotility

2023

View full text Add to dashboard Cite

show abstract

“…For example, the sylvestin peptide (43 amino acids long, molecular weight 4790.4 Da), isolated and purified from the forest leech ( Haemadipsa sylvestris ), can prolong activated partial thromboplastin time (APTT) without affecting prothrombin time (PT) by inhibiting the biological activities of kallikrein and blood coagulation factor XIIa (FXIIa), thus showing potential in the treatment of ischemic stroke [ 28 ]. Similarly, the HSTX-I peptide, isolated from salivary gland secretions of H. sylvestris , can exert a significant analgesic function by inhibiting voltage-gated sodium (NaV) channels (NaV1.8 and NaV1.9) [ 29 , 30 ]. In addition, the neuropeptide Y-HS (36 amino acids long), isolated and purified from H. sylvestris , contains an amidated C-terminus and exhibits significant inhibitory effects on the production of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-6 (IL-6), and monocyte chemotactic protein-1 (MCP-1) [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Isolation and Characterization of Poeciguamerin, a Peptide with Dual Analgesic and Anti-Thrombotic Activity from the Poecilobdella manillensis Leech

Wang

Chen

et al. 2023

IJMS

View full text Add to dashboard Cite

When Poecilobdella manillensis attacks its prey, the prey bleeds profusely but feels little pain. We and other research teams have identified several anticoagulant molecules in the saliva of P. manillensis, but the substance that produces the paralyzing effect in P. manillensis is not known. In this study, we successfully isolated, purified, and identified a serine protease inhibitor containing an antistasin-like domain from the salivary secretions of P. manillensis. This peptide (named poeciguamerin) significantly inhibited elastase activity and slightly inhibited FXIIa and kallikrein activity, but had no effect on FXa, trypsin, or thrombin activity. Furthermore, poeciguamerin exhibited analgesic activity in the foot-licking and tail-withdrawal mouse models and anticoagulant activity in the FeCl3-induced carotid artery thrombosis mouse model. In this study, poeciguamerin was found to be a promising elastase inhibitor with potent analgesic and antithrombotic activity for the inhibition of pain and thrombosis after surgery or in inflammatory conditions.

show abstract

Therapeutic Potentials of Medicinal Leech in Chinese Medicine

Wu,

Zhou,

Wang

et al. 2024

Am. J. Chin. Med.

View full text Add to dashboard Cite

The use of medicinal leeches in clinical therapy has been employed for a long time, as it was originally recognized for exerting antithrombin effects. These effects were due to the ability of the leech to continuously suck blood while attached to human skin. According to Chinese Pharmacopoei, leeches used in traditional Chinese medicine mainly consist of Whitmania pigra Whitman, Hirudo nipponia Whitman, and Whitmania acranulata, but the latter two species are relatively scarce. The main constituents of leeches are protein and peptide macromolecules. They can be categorized into two categories based on their pharmacological effects. One group consists of active ingredients that directly target the coagulation system, such as hirudin, heparin, and histamine, which are widely known. The other group comprises protease inhibitor components like Decorsin and Hementin. Among these, hirudin secreted by the salivary glands of the leech is the most potent thrombin inhibitor and served as the sole remedy for preventing blood clotting until the discovery of heparin. Additionally, leeches play a significant role in various traditional Chinese medicine formulations. In recent decades, medicinal leeches have been applied in fields including anti-inflammatory treatment, cardiovascular disease management, antitumor treatment, and many other medical conditions. In this review, we present a comprehensive overview of the historical journey and medicinal applications of leeches in various medical conditions, emphasizing their pharmaceutical significance within traditional Chinese medicine. This review offers valuable insights for exploring additional therapeutic opportunities involving the use of leeches in various diseases and elucidating their underlying mechanisms for future research.

show abstract

Pharmacological activity and NMR solution structure of the leech peptide HSTX-I

Cited by 3 publications

References 38 publications

The influence of Nav1.9 channels on intestinal hyperpathia and dysmotility

The influence of Nav1.9 channels on intestinal hyperpathia and dysmotility

Isolation and Characterization of Poeciguamerin, a Peptide with Dual Analgesic and Anti-Thrombotic Activity from the Poecilobdella manillensis Leech

Therapeutic Potentials of Medicinal Leech in Chinese Medicine

Contact Info

Product

Resources

About