Abstract

Tian Hua Fen, a herbal powder extract that contains trichosanthin (TCS), was used as an abortifacient in traditional Chinese medicine. In 1972, TCS was purified to alleviate the side effects. Because of its clinical applications, TCS became one of the most active research areas in the 1960s to the 1980s in China. These include obtaining the sequence information in the 1980s and the crystal structure in 1995. The replication block of TCS on human immunodeficiency virus in lymphocytes and macrophages was found in 1989 and started a new chapter of its development. Clinical studies were subsequently conducted. TCS was also found to have the potential for gastric and colorectal cancer treatment. Studies on its mechanism showed TCS acts as an rRNA N-glycosylase (EC 3.2.2.22) by hydrolyzing and depurinating A-4324 in α-sarcin/ricin loop on 28S rRNA of rat ribosome. Its interaction with acidic ribosomal stalk proteins was revealed in 2007, and its trafficking in mammalian cells was elucidated in the 2000s. The adverse drug reactions, such as inducing immune responses, short plasma half-life, and non-specificity, somehow became the obstacles to its usage. Immunotoxins, sequence modification, or coupling with polyethylene glycerol and dextran were developed to improve the pharmacological properties. TCS has nicely shown the scientific basis of traditional Chinese medicine and how its research and development have expanded the knowledge and applications of ribosome-inactivating proteins.

Highlights

  • Tian Hua Fen, a herbal powder extract that contains trichosanthin (TCS), was used as an abortifacient in traditional Chinese medicine

  • The root tuber has long been used in traditional Chinese medicine (TCM) as an abortifacient called Tian Hua Fen [2]

  • We look back to the sixty-year research and of TCS as an abortifacient, rRNA N-glycosylase, anti-HIV and anti-cancer development agents of TCStoas an abortifacient, reveal the fascinationrRNA

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Summary

From Ancient Prescriptions to Crystallized Protein Powder

Because of the lack of western drugs, Tian Hua Fen was used extensively in China. Because of lack ofabortion westernindrugs, Tian was used extensively in China for sterforthe inducing the 1960s [2].Hua. The herbs crushed to make a liquid extract as a medicated vaginal suppository fever, tetter, and abdominal pain, studies on revising the prescription were carried out. In 1966, researchers in Shanghai further isolated and purified components in Ya Zao and Tian Hua Fen. One death report in clinical application in 1969 alerted researchers again on the impact of ADR. The researchers showed that only Tian Hua Fen could induce abortion in pregnant mice, while Ya Zao only causes muscle festering. In 1982, the precipitated powder was further crystallized in barbitone buffer and came out as the single protein powder of trichosanthin (TCS) [10] The dosage of these developed injections was further lower to 1.2 mg per dose [13], which won the second prize of the National Invention Award. The ing on the damage syncytiotrophoblast cellsanti-early [15] and the selective damage chorionic mechanism on itsofmidterm abortion and pregnancy effects on were reported relying on tissue [16]. of syncytiotrophoblast cells [15] and the selective damage on chorionic tissue [16]

Clinical Application of Tian Hua Fen or TCS as an Abortifacient
Protein and DNA Sequences of TCS
Mechanism of TCS as an rRNA N-glycosylase
Mechanism of TCS as Revealed by Structural Studies
Interaction of TCS with the Ribosome and the Recruitment by Ribosomal P-Protein
Anti-HIV Activity of TCS and Its Related Mechanism
Clinical Study of TCS on AIDS Patients
The Entering of TCS into Cells
Anti-Cancer Properties of TCS
Engineering and TCS-Based Immunotoxins
H-2 Ag-TCS
Findings
Conclusion and Perspectives
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