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Along with definite clinical effects, traditional Chinese medicine (TCM) has increasingly gained worldwide attention. Quality control marker (Q-marker) is always used to confirm the primary effects of herbs or TCM. Thus, the characterization of the metabolism features and subsequently induced effects are essential to reveal the functional consequences. In this work, a strategy by integrating metabolite profiling of a Q-marker and network pharmacology was proposed and applied to explore the potential function of herbs, and prim-O-glucosylcimifugin, the Q-marker of Radix Saposhnikoviae, was used as an example. As a result, 35 metabolites were characterized in rats' plasma, urine, feces, heart, liver, spleen, lung, kidney, and brain. Among them, M13/M17/M20/M23/M24/M28 were the primary metabolites, and 23 metabolites were reported for the first time. It was found that major metabolic pathways of prim-O-glucosylcimifugin were hydroxylation, dehydrogenation, hydrogenation and glucuronidation. In addition to the above metabolic reactions, methylation, hydrogenation, glycosylation, isomerization, sulfation, and other S-conjunctions were found in prim-O-glucosylcimifugin for the first time. Meanwhile, targets of prim-O-glucosylcimifugin and its major metabolites targeted additional 125 targets with functions of MAPK signaling pathway, proteoglycans in cancer, pathways in cancer, bladder cancer, colorectal cancer, serotonergic synapse and natural killer cell-mediated cytotoxicity. Among them, the depression of inflammation by MAPK signaling pathway might be the core mechanism for prim-O-glucosylcimifugin to treat respiratory tract infections. The above results provided vital information for understanding the metabolism and functional mechanism of prim-O-glucosylcimifugin in the treatment of respiratory tract infections, and a new insight for revealing the pharmacological mechanism of the complex system was also provided.

Food additives are widely used in our daily life, and the side-effects caused by them have gained extensive attention around the world. Notably, constituent-oriented metabolites, in some sense, always contribute to pharmacological changes, inducing toxicity, therapeutic effects, etc. Characterization of the metabolites and their potential functions is of great importance to the practical applications. In this work, an integrated strategy by combining metabolite profiling and network pharmacology was applied to characterize the metabolic features and reveal pharmacological changes of neohesperidin dihydrochalcone (NHDC) in vivo to demonstrate its pharmacological mechanism and potential functions. As a result, a total of 19 metabolites (3 in plasma, 19 in urine, 8 in feces, 3 in heart, 5 in liver, 0 in spleen, 1 in lung, 2 in kidneys and 2 in brain) were screened and 18 of them were characterized for the first time. Phase I metabolic reactions of hydrolysis and phase II reactions of glucuronidation, sulfation, glutamylation, N-butyryl glycylation and lactylation were the main metabolic reactions of NHDC in vivo. Moreover, the results analyzed by network pharmacology revealed that, in addition to common pathways (steroid hormone biosynthesis) of NHDC, metabolites' targets were involved in pathways in cancer, ovarian steroidogenesis, proteoglycans in cancer, PI3K-Akt signaling pathway and progesterone-mediated oocyte maturation, indicating that these functional changes might result in potential novel functions or other side-effects, such as a disorder of steroid hormones. Our work provided the metabolic features and functional modifications of NHDC in vivo for the first time, and meaningful information for further pharmacological validations or potential functions is supplied.

Elucidating the therapeutical basis and functional mechanism of traditional Chinese medicine (TCM) is still a challenge faced by researchers since the effects of TCM are always achieved by the interactions of multiple components and multiple targets. In this study, an integrated strategy using a combination of chemical profiling, network pharmacology and in vitro experimental validation was applied to profile the trace constituents of TCM and characterize their functional mechanism, and Rhizoma coptidis (RC) was used as an example. As a result, a total of 55 compounds were identified or tentatively characterized in the water extract of RC, including 22 organic acids, 17 alkaloids, 8 lignans, 2 flavonoids, 4 phenylethanoid glycosides, and 2 other types of compounds. Meanwhile, a potential novel compound (compound 41) – one of the alkaloids – was found and characterized. Notably, organic acids in RC were systematically characterized for the first time. Moreover, the pharmacological targets of the 46 main constituents of RC were predicted using the network pharmacological method, and 234 of them were involved in diabetes mellitus (DM). KEGG analysis indicated that the Rap1 signaling pathway, the cAMP signaling pathway, the PI3K–Akt signaling pathway, and inflammatory mediator regulation of TRP channels were the core signaling pathways for RC in the treatment of DM. Further, the anti-inflammatory effects of RC, correlated with inflammatory mediator regulation of TRP channels, were confirmed by using the LPS-induced RAW 264.7 cell model. Meanwhile, the downstream pathway (NF-kB) of TRP channels was validated by western blot. Our work comprehensively provided the material basis and potential pharmacological mechanism of RC against inflammation in DM; in the meantime, a new insight for elucidating the functional mechanism of TCM was also supplied.

Two new xanthones, oxisterigmatocystins J and K (1–2), and two new anthraquinones, versicolorins D and E (3–4), were isolated from solid cultures of the fungus Penicillium sp. DWS10-P-6, together with twelve known compounds (5–16). Their structures, including their absolute configurations, were characterized on the basis of extensive 1D NMR, 2D NMR, MS and CD spectral data. The cytotoxic activities of compounds 1–12 against HL-60, MDA-MB-231 and PC-3 cells were also evaluated. Compounds 4 and 5 showed significant cytotoxic activity against the HL-60 cell line with IC50 values of 1.65 μM and 1.05 μM, respectively.