A new indole alkaloid in Cuscuta chinensis
Histone specific demethylase 1 (LSD1) was the first discovered histone demethylase, reported by Shi Yang’s research group in 2004. LSD1 can activate or inhibit gene transcription by catalyzing oxidation reactions with flavin adenine dinucleotide (FAD), specifically removing the single and double methyl groups of histone lysine H3K4 and H3K9. LSD1 regulates the expression of related proteins and promotes the growth and metastasis of various tumor cells by altering the methylation status of histones in the promoter regions of genes associated with tumor proliferation and metastasis. Currently, LSD1 has been proven to be an important driver of cancer and a therapeutic target for various tumors. Research has shown that various flavonoids have good inhibitory activity against LSD1, laying the foundation for the discovery of novel anti-tumor lead compounds. However, different flavonoids can exhibit significant differences in LSD1 inhibitory activity, which is closely related to changes in their substituents.

Cuscuta chinensis, belonging to the Convolvulaceae family and the Cuscuta genus, is an annual parasitic herb widely distributed in Northeast, Northwest, and North China of China. Its seeds are commonly used as nourishing Chinese medicine in clinical practice. Dodder seed has a pungent, sweet, and flat taste, which is beneficial to the liver, kidney, and spleen meridians. It has the effects of nourishing the liver and kidneys, consolidating essence and reducing urine, stabilizing pregnancy, improving vision, and stopping diarrhea. Modern pharmacological research has shown that Fructus Cuscutae has significant medicinal value in regulating the reproductive system, anti-aging, immune regulation, cardiovascular and cerebrovascular protection, and lowering blood sugar. The chemical composition of dodder mainly consists of flavonoids, as well as compounds such as lignans, terpenes, and alkaloids. Therefore, in order to further understand the pharmacological substance basis of traditional Chinese medicine Cuscuta chinensis and improve its comprehensive resource utilization efficiency, this study isolated, purified, and structurally identified the chemical components of the methanol part of Cuscuta chinensis, and tested the LSD1 inhibitory activity of flavonoids in it, in order to discover lead compounds with anti-cancer effects.

 

 

This article isolated six monomeric compounds from the methanol extract of Cuscuta chinensis. Among them, compound 1 is a racemic form, a new β – Capolin alkaloid, compounds 2-5 are flavonoids, and compound 6 is a lignan compound. The total flavonoids of Cuscuta chinensis have good in vitro and in vivo anti-tumor activity, but its active ingredients and mechanism of action are not yet clear. Meanwhile, the LSD1 inhibitory activity of dodder has not been reported yet. This article is the first to evaluate the LSD1 inhibitory activity of flavonoids 2 and 5 in Fructus Cuscutae, and the results show that both compounds have strong inhibitory effects on LSD1, laying the foundation for improving the structure-activity relationship of flavonoid LSD inhibitory activity. In addition, dodder is rich in flavonoids, but there are few reports on alkaloid components. This article further enriches the types of alkaloids in traditional Chinese medicine dodder and lays a theoretical foundation for exploring its pharmacological substance basis and better developing and utilizing dodder medicinal materials.