Five new 8-O-4' type neolignans, named myrifralignan A-E (1-5), together with five known analogues (6-10), were isolated from the seeds of Myristica fragrans Houtt. Their chemical structures were determined using several spectroscopic methods. Compounds 3-10 exhibited potent inhibitory activity against the production of nitric oxide (NO) in the RAW264.7 cell line stimulated by lipopolysaccaride. Myrislignan (7) and machilin D (10) were the most potent inhibitors of NO production amongst these compounds. The IC50 values of myrislignan and machilin D were 21.2 and 18.5 μM. And, their inhibitory activity was more than L-N(6)-(1-iminoethyl)-lysine, a selective inhibitor of inducible nitric oxide synthase (IC50=27.1 μM). Furthermore, real-time PCR analysis revealed that these neolignans could significantly suppress the expression of inducible nitric oxide synthase mRNA. These results demonstrated that the 8-O-4' type neolignans are promising candidates as anti-inflammatory agents.

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Abstract:The blood-brain barrier (BBB) permeability of twelve lignans and three phenolic malabaricones from the seeds of Myristica fragrans (nutmeg) were studied with the MDCK-pHaMDR cell monolayer model. The samples were measured by high-performance liquid chromatography and the apparent permeability coefficients (P app ) were calculated. Among the fifteen test compounds, benzonfuran-type, dibenzylbutane-type and arylnaphthalene-type lignans showed poor to moderate permeabilities with P app values at 10´8-10´6 cm/s; those of 8-O-4 1 -neolignan and tetrahydrofuran-lignan were at 10´6-10´5 cm/s, meaning that their permeabilities are moderate to high; the permeabilities of malabaricones were poor as their P app values were at 10´8-10´7 cm/s. To 5-methoxy-dehydrodiisoeugenol (2), erythro-2-(4-allyl-2,6-dimethoxyphenoxy)-1-(3,4-dimethoxyphenyl)-propan-1-ol acetate (6), verrucosin (8), and nectandrin B (9), an efflux way was involved and the main transporter for 6, 8 and 9 was demonstrated to be P-glycoprotein. The time and concentration dependency experiments indicated the main transport mechanism for neolignans dehydrodiisoeugenol (1), myrislignan (7) and 8 was passive diffusion. This study summarized the relationship between the BBB permeability and structure parameters of the test compounds, which could be used to preliminarily predict the transport of a compound through BBB. The results provide a significant molecular basis for better understanding the potential central nervous system effects of nutmeg.

capsule is an effective Chinese medicine widely used for the treatment of cold and influenza. However, its chemical constituents had not been determined, which entailed a huge obstacle to further pharmacological studies, clinical-safe medication administration, and quality evaluation. To identify the chemical constituents in Fufang Xiling Jiedu capsule, an efficient and systematic approach using ultra-high-performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometry in conjunction with a data mining strategy was adopted in this study. As a result, 145 compounds were qualitatively identified, including 26 phenolic acids, 46 flavonoids, 39 triterpenes, and 34 other compounds, among which 6 were potentially new and 144 were being reported from Fufang Xiling Jiedu capsule for the first time. This research not only provides useful information for quality control of Fufang Xiling Jiedu capsule and its involved single herbs but also serve as basis data for further study of Fufang Xiling Jiedu capsule in vivo. Moreover, it provides a reference for the characterization of the chemical constituents of other Chinese medicine preparations. K E Y W O R D S chemical constituents, data mining strategy, mass spectrometry, traditional Chinese medicine, quadrupole time of flight 1 INTRODUCTION Traditional Chinese medicines (TCMs) have been used to prevent and cure disease in China and other Asian coun-Article Related Abbreviations: FXJC, Fufang Xiling Jiedu capsule; PSMs, plant secondary metabolites; TCM, traditional Chinese medicine; t R , retention time; Q-TOF-MS, quadrupole time-of-flight mass spectrometry tries for centuries [1]. One characteristic of TCMs is the use of several Chinese medicinal materials in one medicine, mostly of herbal but sometimes also of mineral and animal origin. Therefore, it is necessary to conduct a holistic research on the chemical substances of TCM, which, as a whole, plays a multi-targeted, synergistic therapeutic role in the course of medical treatment [2-4]. UHPLC coupled with quadrupole time-of-flight mass spectrometry (Q-TOF-MS) has been developed and widely

Paeonia lactiflora Pall., one of the most famous classical herbal medicine, has been used to treat diseases for over 1200 years. In this research, the functional ingredients were purified by online‐switch two‐dimensional high‐speed counter‐current chromatography combined with inner‐recycling and continuous injection mode. The antioxidant activity was evaluated by investigating the 2,2′‐azobis (2‐amidinopropane) dihydrochloride‐induced oxidant damage in vitro and confirmed through molecular docking. n‐Butanol/ethyl acetate/water (2:3:5, v/v) solvent system was used for the first‐dimensional separation and optimized the sample loading. Two pure compounds and a polyphenol‐enriched fraction were separated. The polyphenol‐enriched fraction was separated with a solvent system n‐hexane/ethyl acetate/methanol/water (2:8:4:6, v/v) with continuous injection mode. Five compounds were successfully separated, including gallic acid (1), methyl gallate (2), albiflorin (3), paeoniflorin (4), and ethyl gallate (5). Their structures were identified by mass spectrometry and NMR spectroscopy. The results from the antioxidant effect showed that albiflorin had stronger antioxidant activity. Molecular docking results indicated that the affinity energy of the identified compounds ranged from ‐3.79 to ‐8.22 kcal/mol and albiflorin showed the lowest affinity energy. Overall, all those findings suggested that the strong antioxidant capacity of albiflorin can be potentially used for the treatment of diseases caused by oxidation.