Study on the Chemical Components of Phthalides in Chuanxiong Stem and Leaf
Ligusticum chuanxiong Hort. is a dried rhizome of the Umbelliferae family plant Ligusticum chuanxiong Hort. It is a famous authentic medicinal herb produced in Sichuan, with the effects of promoting blood circulation, removing blood stasis, promoting qi circulation, relieving depression, dispelling wind and relieving pain. It is clinically used to treat headaches, liver depression and qi stagnation, as well as various stasis syndromes. However, its traditional medicinal parts are dried rhizomes, and the aboveground parts (stems and leaves) that account for 75% of the fresh weight of the whole plant are often discarded, which not only causes resource waste and environmental pollution, but also hinders the sustainable utilization of traditional Chinese medicine resources. The stems and leaves of Ligusticum chuanxiong have been called as the “Suiwu” in ancient times. The “Shennong’s Classic of Materia Medica” records that “it is mainly used to cough, calm nerves, ward off evil, eliminate poisonous insects, cure ghosts, remove three pests, and take a long time to pass the spirit”. In the main production areas of Ligusticum chuanxiong, Dujiangyan Irrigation Project and Pengzhou, Sichuan, people have the habit of eating the tender leaves of Ligusticum chuanxiong to prevent cardiovascular and cerebrovascular diseases. Among them, benzophenone compounds, as the main active ingredients of Chuanxiong, have significant regulatory effects on cardiovascular, cerebrovascular, and nervous systems. Some studies speculate that they are the main material basis for Chuanxiong’s treatment of blood stasis syndrome or cardiovascular and cerebrovascular diseases. Vasodilation is currently the main treatment for cardiovascular diseases such as coronary heart disease, angina pectoris, and myocardial infarction. Previous studies have shown that ligustilide and ligustilide A have vasodilatory activity. Therefore, investigating the vasodilatory activity of benzophenone components is of great significance for clarifying the efficacy and application of Ligusticum chuanxiong and its above ground parts.

The research team first discovered benzophenone compounds that can dilate blood vessels from the stems and leaves of Ligusticum chuanxiong in the early stage. Based on the previous research, this article further explores the benzophenone compounds, studies their vasodilation effects and preliminary mechanisms, and explores the structure-activity relationship. This article further enriches the benzophenone component library of Chuanxiong stem and leaf, and preliminarily explores the structure-activity relationship of benzophenone components in vasodilation, providing reference for the development and utilization of Chuanxiong and its aboveground parts.

According to incomplete statistics, the number of cardiovascular disease patients in China has reached 290 million, ranking first in the world. At present, the main treatment for cardiovascular diseases is drug therapy, such as vasodilators. By promoting vasodilation and improving hemodynamic effects, it can not only be used for the treatment of hypertension, but also an important means of treating cardiovascular and cerebrovascular diseases. The blood-brain barrier is the main factor affecting the treatment of cerebrovascular diseases. Studies have shown that benzophenone drugs can penetrate the blood-brain barrier, which may be the pharmacological substance basis for Chuanxiong’s “ascending head” to treat headaches. Previous studies have shown that ligustilide A and ligustilide can relax KC1 induced vasoconstriction (pd24.42, 4.43) without endothelial dependence. Gaoben lactone, as its main phthalein component, is limited in further application due to its instability. Therefore, its derivatives should also receive more attention.

In this experiment, 15 phthalein compounds were isolated from the petroleum ether parts of Chuanxiong stems and leaves, including 9 monophthalides and 6 phthalein dimers. Among them, Angelica sinensis lactone A (1), new dimeric ligustilide (15), tea ligustilide D (2), Z-6-hydroxy-7-methoxy-glycoside (8), (3S, 3aR) -3-hydroxyethyl-3a, 4,5,6-tetrahydrophthalic acid (12), (3S, 3ar, 10R) – (-) -10-hydroxyphthalic acid (13) were isolated from Chuanxiong for the first time; And for the first time, single crystal diffraction was performed on compounds 1 and 2 to further determine their structures. This article briefly analyzes the effects of hydroxyl substitution and optical isomerism on the vasodilation of phthalic anhydride, providing a reference for further enriching the structural types of phthalic anhydride and in-depth studying the structure-activity relationship. It also provides direction for finding novel vasodilator lead compounds. Previous mechanistic studies have found that the activity of ligustilide is related to the inhibition of voltage dependent calcium channels (VDCC) and receptor operated calcium channels (ROCC) mediated Ca2+influx and release, and it is speculated that it may be related to the L-type voltage-gated calcium channel Cav1.2 target. This article preliminarily verified through laser confocal experiments that the vasodilation effect of benzophenone components may be caused by affecting the opening of ion channels and inhibiting calcium ion influx, but the specific mechanism still needs further research. Through the study of the chemical composition of above ground biological resources of Chuanxiong, the chemical composition library of Chuanxiong stems and leaves has been further enriched, laying the foundation for the discovery of vasodilator compounds and providing scientific basis for the prevention of cardiovascular and cerebrovascular diseases in folk consumption of Chuanxiong tender leaves.