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Research progress on extraction, purification and medical

pharmacological activities of tetrodotoxin

2
2
2
1*
1
LIN Xiaoyu ，CAI Shuilin ，LIN Yifen ，SU Yongchang ，XU Min ，LIU Zhiyu 2*
(1. College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China;
2. Key Laboratory of Cultivation and High-value Utilization of Marine Organisms in
Fujian Province, Fisheries Research Institute of Fujian, Xiamen 361013, China)
Abstract: [Background] Tetrodotoxin (TTX) is a natural weak alkaline toxin with a unique structure and
strong toxicity. It causes nerve palsy and produces a strong central analgesic effect by specifically blocking
voltage-gated sodium channels. Because of its significant pharmacological value, it has become a hot spot in
natural product research. Although its potential is huge, its practical application is still restricted by its complex
preparation process and narrow safety window. [Objective] This paper aims to systematically clarify the rela-
tionship among TTX extraction, purification, medical pharmacological activities and safety from the perspect-
ive of translational medicine, and to provide a strategic reference for breaking through the bottleneck of TTX re-
search in the field of fisheries. [Progress] In this paper, the key progress of TTX in extraction, purification and
functional activity research is reviewed. TTX extraction has developed from the traditional constant temperat-
ure water bath method to ultrasonic-assisted extraction, and purification technology has evolved from column
chromatography and membrane separation to high-resolution high-performance liquid chromatography-mass
spectrometry (HPLC-MS) and immunomagnetic bead systems, which has significantly improved the purity and
recovery rate of TTX. Functional activity studies have shown that TTX has potential application value in anal-
gesia, anti-arrhythmia, inhibition of tumor metastasis and local anesthesia by blocking sodium ion channels. In
recent years, drug delivery systems such as liposomes and nanoparticles have been used for the encapsulation
and controlled release of TTX, which can effectively reduce toxicity and prolong efficacy, providing a new idea
for its safe medicinal use. [Conclusion] TTX has great medicinal potential, but the difficulty of extraction and
purification makes it “difficult to produce”, and the narrow safety window makes it “difficult to apply”. In the
future, it will be necessary to explore low-cost, industrialized extraction and purification processes, and to devel-
op targeted drug delivery systems, so as to gradually realize the high-value application of TTX and the interdis-
ciplinary combination of “fishery resources-clinical application”.
Key words: tetrodotoxin (TTX); extraction; purification; activities