Rapid Screening of Forskolin-Type Diterpenoids of Blumea aromatica DC Using Ultra-High-Performance Liquid Chromatography Tandem Quadrupole Time-of-Flight Mass Spectrometry Based on the Mass Defect Filtering Approach.

The discovery of new active compounds of natural products tends to be increasingly more challenging due to chemical complexity and unpredictable matrices. Forskolin is an active natural labdane-type diterpenoid ingredient widely used worldwide for the treatment of glaucoma, heart failure, hypertension, diabetes, and asthma, and is expected to be a promising anticancer, anti-inflammation, and anti-HIV agent. In recent years, demand for forskolin in the medicine market has increased dramatically. However, natural forskolin originates exclusively from traditional Indian herb medicine Coleus forskohlii (Willd.) Briq. In a previous study, we isolated a series of diterpenoids including an 8,13-epoxy-14ene labdane carbon skeleton from Blumea aromatica DC. In order to identify alternative plant resources, a novel and effective strategy was proposed for the screening of potential forskolin-type diterpenoids (FSKD) compounds obtained from B. aromatica, using the mass defect filtering (MDF) strategy via ultra-high-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) approach. Within a narrow, well-defined mass defect range, the strategy developed could significantly improve the detection efficiency of selected FSKD compounds by filtering out certain major or moderate interference compounds. Additionally, the MS/MS cleavage behavior and the characteristic diagnostic ions of the FSKD compounds were proposed to be used in aiding structural identification of the filtration compounds. As a result, a total of 38 FSKD of B. aromatica were filtered out and tentatively identified. To the best of our knowledge, it was the first time that these forskolin-type diterpenoids were identified in B. aromatica, which significantly expands our understanding of the chemical constituents of Blumea species, and allows B. aromatica to be used as a potential alternative plant resource that contains these forskolin-type active compounds. The strategy proposed was proven efficient and reliable for the discovery of novel compounds of herbal extracts.

Aromatin D-J: Seven previously undescribed labdane diterpenoids isolated from Blumea aromatica.

Blumea aromatica is a traditional Chinese medicine used for treating various diseases such as rheumatoid arthritis, eczema, and pruritus. Previous studies on B. aromatica used a mass defect-filtering strategy via the ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and reported the presence of several labdane diterpenoids (LADs). To determine the actual structures of these LADs and investigate their biological activities, seven previously undescribed LADs (aromatin D-J) were isolated from the whole B. aromatica herb. The structures of these isolated compounds were characterized using high-resolution mass spectrometry and extensive 1D and 2D NMR analyses. In addition, the absolute configurations of these compounds were determined by comparing the experimental and calculated electronic circular dichroism (ECD) spectra as well as using X-ray crystallographic analysis. All isolated compounds were evaluated for their ability to activate adenylate cyclase by measuring the levels of cyclic adenosine 3',5'-monophosphate (cAMP) in rat ventricular tissue. Aromatin E, F, and J showed moderate activities with an increase in cAMP levels by 67%, 69%, and 64%, respectively, compared with the control group.