Stachydrine and Synephrine, a Pair of Bioactive Equilibrists in Four Chinese Herbs from <em>Citrus</em> Genus

Abstract

Four Chinese herbs Zhishi, Zhiqiao, Qingpi and Chenpi from Citrus genus were widely used for treating various cardiovascular and gastrointestinal diseases. Although many pharmacological functions of these herb decoctions can be clarified from the bioactivities of identified ingredients, some of them remain confusing. To clarify the reasons of those confusing functions, depending on the extended structure-activity relationships of cholinergic and anti-cholinergic agents, here a simple method for quickly discovering possible choline analogs was established using a specific TLC method, and then stachydrine and choline were first identified from these Citrus herb decoctions based on their NMR and HRMS data. After this, two TLCS methods were first established respectively for the quantitatively analyses of stachydrine and choline, and the contents of both two ingredients and synephrine in 39 samples were determined using the valid TLCS and HPLC methods, respectively. The results showed the contents of stachydrine were 2.4 times to those of synephrine in Zhiqiao while about 1/3 to 2/3 in Zhishi, Qingpi and Chenpi. Simultaneously, the contents of stachydrine, choline and synephrine in these herbs present similar changing trends along with the delay of harvest time. However, the contents of synephrine decrease most rapidly, while those of stachydrine decrease most slowly. Based on these above, comparing with the pharmacological activities and pharmacokinetics reported of stachydrine and synephrine, it indicated that stachydrine and synephrine can be considered as a pair of bioactive equilibrists, especially in the cardio-cerebrovascular protection from these citrus herbs. Simultaneously, it confirmed that stachydrine should play an important role in the pharmacological functions, especially in dual-directionally regulating the uterus and various beneficial effects on cardio-cerebrovascular system, kidney and liver, of these citrus herbs.