Functional dyspepsia (FD) is a widely prevalent gastrointestinal disorder throughout the world, whereas the efficacy of current treatment in the Western countries is limited. As the symptom is equivalent to the traditional Chinese medicine (TCM) term “stuffiness and fullness,” FD can be treated with Zhi-zhu Wan (ZZW) which is a kind of Chinese patent medicine. However, the “multi-component” and “multi-target” feature of Chinese patent medicine makes it challenge to elucidate the potential therapeutic mechanisms of ZZW on FD. Presently, a novel system pharmacology model including pharmacokinetic parameters, pharmacological data, and component contribution score (CS) is constructed to decipher the potential therapeutic mechanism of ZZW on FD. Finally, 61 components with favorable pharmacokinetic profiles and biological activities were obtained through ADME (absorption, distribution, metabolism, and excretion) screening in silico. The related targets of these components are identified by component targeting process followed by GO analysis and pathway enrichment analysis. And systematic analysis found that through acting on the target related to inflammation, gastrointestinal peristalsis, and mental disorder, ZZW plays a synergistic and complementary effect on FD at the pathway level. Furthermore, the component CS showed that 29 components contributed 90.18% of the total CS values of ZZW for the FD treatment, which suggested that the effective therapeutic effects of ZZW for FD are derived from all active components, not a few components. This study proposes the system pharmacology method and discovers the potent combination therapeutic mechanisms of ZZW for FD. This strategy will provide a reference method for other TCM mechanism research.

In-depth research on processing can promote the globalization of processed herbs. The purpose of this study is to propose an improved strategy for processing effect investigation. Frankincense and processed frankincense were used as research subjects. First, high-speed countercurrent chromatography (HSCCC) and preparation high-performance liquid chromatography (PHPLC) techniques were used for major compounds isolation and minor compounds concentration. Processed frankincense was subjected to two stepwise solvent systems, namely, n-hexane:ethanol:water (6:5:1) and n-hexane:methyl-acetate:acetonitrile:water (4:4:3:4), to yield 12 fractions, and 18 compounds were further separated. Second, a comprehensive metabolomic analysis conducted by ultrahigh-performance liquid-chromatography/electrospray-ionization mass spectrometry (UHPLC-Qtof-MS) coupled with multivariate statistics was performed to fully characterize the chemical components and discover the potential biomarkers between frankincense and processed frankincense. In total, 81 metabolites, including the 18 separated compounds, were selected as potential biomarkers between frankincense and processed frankincense among 153 detected compounds for their VIP values of greater than one. The tirucallane-type compounds and components with 9,11-dehydro structures clearly occurred at high levels in the processed frankincense, while lupine-type compounds and those with 11-keto structures were significantly higher in frankincense. Then, a network pharmacology model was constructed to decipher the potential mechanisms of processing. Intestinal absorption properties prediction indicated the possibility of processing-related absorption enhancement. A systematic analysis of the constructed networks showed that the C-T network was constructed with 18 potential biomarkers and 69 targets. TNF and IL-1β were among the top-ranked and were linked by 8 and 7 pathways, which were mainly involved in inflammation. The arachidonic acid metabolism pathway exhibited the highest number of target connections. Finally, the prediction was validated experimentally by an intestinal permeability and efficacy assay. The experiments provided convincing evidence that processed frankincense harbored stronger inhibition effects toward TNF-α-, IL-1β- and arachidonic acid-induced platelet aggregation. The processing procedure leads to changes of the chemical metabolites, which triggers the enhancement of absorption and cure efficiency. The global change of the metabolites, absorption and pharmacological effects of processing were depicted in a systematic manner.

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Boswellic acids (BAs), as the main components of frankincense, exhibit notable anti-inflammatory properties. However, their pharmaceutical development has been severely limited by their poor oral bioavailability. Traditional Chinese medicinal processing, called Pao Zhi, is believed to improve bioavailability, yet the mechanism is still completely unclear. Previous research suggested that the bioavailability of a drug can be influenced by physical properties. This paper was designed to investigate the physical properties of frankincense and processed frankincense, including the surface morphology, particle size, polydispersity index (PDI), zeta potential (ZP), specific surface area, porosity, and viscosity. The differences in the intestinal absorption characteristics and equilibrium solubilities between frankincense and processed frankincense were determined by an ultra-high-performance liquid chromatography coupled with a triple quadrupole electrospray tandem mass spectrometry (UHPLC-TQ-MS) analysis method. The results showed that vinegar processing can alter the surface morphology, decrease the particle size and PDI, raise the absolute values of the ZP, specific surface area and porosity, and drop the viscosity of frankincense. Meanwhile, the rates of absorption and dissolution of the main BAs were increased after the processing of frankincense. The present study proves that the physical properties were changed after processing, in which case the bioavailability of frankincense was enhanced.