Study on the dynamic variation of the secondary metabolites in Viscum coloratum using targeted metabolomics.

Viscum coloratum (Kom.) Nakai is a well-known medicinal plant. However, the optimal harvest time for V. coloratum is unknown. Few studies were performed to analyze compound variation during storage and to improve post-harvest quality control. Our study aimed to comprehensively evaluate the quality of V. coloratum in different growth stages, and determine the dynamic variation of metabolites. Ultra-performance liquid chromatography tandem mass spectrometry was used to quantify 29 compounds in V. coloratum harvested in six growth periods, and the associated biosynthetic pathways were explored. The accumulation of different types of compounds were analyzed based on their synthesis pathways. Grey relational analysis was used to evaluate the quality of V. coloratum across different months. The compound variation during storage was analyzed by a high-temperature high-humidity accelerated test. The results showed that the quality of V. coloratum was the hightest in March, followed by November, and became the lowest in July. During storage, compounds in downstream steps of the biosynthesis pathway were first degraded to produce the upstream compounds and some low-molecular-weight organic acids, leading to an increase followed by a decrease in the content of some compounds, and resulted in a large gap during the degradation time course among different compounds. Due to the rapid rate and large degree of degradation, five compounds were tentatively designated as "early warning components" for quality control. This report provides reference for better understanding the biosynthesis and degradation of metabolites in V. coloratum and lays a theoretical foundation for rational application of V. coloratum and better quality control of V. coloratum during storage.

The effect of compatibility of Aconiti Radix and honey on the pharmacokinetics of five Aconitum alkaloids in rat plasma.

Aconiti Radix [Chuanwu (CW)] is widely used to treat chronic and intractable diseases due to its remarkable curative effect. CW has been combined with honey for thousands of years to reduce toxicity and enhance efficacy. This study first determined the compatibility mechanism of CW with honey using a comparative pharmacokinetic concept. We developed and validated a simple, sensitive, specific, and accurate UHPLC-MS/MS method to simultaneously determine five Aconitum alkaloids in rat plasma after the oral administration of CW decoction and CW-honey concentrated solution. Pharmacokinetic parameters were significantly different between the two groups (P < 0.01 and P < 0.05). Compared with the CW group, Cmax and AUC0 → t decreased in the CW-honey group for three diester-diterpenoid alkaloids (hypaconitine, mesaconitine, and aconitine); Tmax and T1/2 were prolonged. However, Cmax and AUC0 → t increased in the CW-honey group for two monoester-diterpenoid alkaloids (benzoylaconine and benzoylmesaconine); Tmax was shortened, and T1/2 was prolonged. These findings suggest that honey affected the pharmacokinetic behaviors of five Aconitum alkaloids. We speculate that the detoxification and synergism of honey might result from reducing the toxicity of diester-diterpenoid alkaloids and promoting the biological activity of monoester-diterpenoid alkaloids in vivo. This study provides a theoretical basis for the clinical use of CW combined with honey.

Penctrimertone, a bioactive citrinin dimer from the endophytic fungus Penicillium sp. T2-11.

Penctrimertone (1), a novel citrinin dimer bearing a 6/6/6/6 tetracyclic ring scaffold, along with two known compounds xerucitrinic acid A (2) and citrinin (3) were isolated from the endophytic fungus Penicillium sp. T2-11. Their structures were unequivocally established by a comprehensive interpretation of the spectroscopic data, with the stereochemistry for 1 was defined by a combination of TDDFT-ECD calculations and the DP4+ probability analysis based on NMR chemical shift calculations. Bioassays revealed that compound 1 exhibited noticeable antimicrobial activities and moderate cytotoxicity. A plausible biosynthetic pathway of 1 was also proposed.

Peniterester, a carotane-type antibacterial sesquiterpene from an artificial mutant Penicillium sp. T2-M20.

Peniterester (1), a new tricyclic sesquiterpene, together with 6 known compounds (2-7) were isolated from the secondary metabolites of an artificial mutant Penicillium sp. T2-M20 which was obtained from the parental strain Penicillium sp. T2-8 via UV irradiation as well as nitrosoguanidine (NTG) induction. Peniterester was only produced by the mutant T2-M20 on the basis of LC-MS analysis. Meanwhile, the results of in vitro bioactivities screening indicated that peniterester owned obvious antibacterial activities against Bacillus subtilis, Escherichia coli and Staphylococcus aureus with MICs of 8.0, 8.0 and 4.0 µg/mL, respectively.

Production of a new tetracyclic triterpene sulfate metabolite sambacide by solid-state cultivated Fusarium sambucinum B10.2 using potato as substrate.

The aim of this work is to explore integracide analogues from secondary metabolites of microorganisms. A new tetracyclic triterpene sulfate was produced by solid-state fermentation (SSF) with Fusarium sambucinum B10.2. The tetracyclic triterpene sulfate was identified as (3S,5R,10S,11S,12S,13R,17R,20R)-4,4-dimethylergosta-8,14,24-triene-3,11,12-triol-12-acetate, 3-sulfate on the basis of HRESIMS, NMR and electronic circular dichroism (ECD) spectra and named sambacide (1). The antibacterial and antifungal assays of sambacide (1) showed significant antibacterial activities against Staphylococcus aureus and Escherichia coli. The fermentation conditions including culture media, fermentation temperature and time, were optimized. And potato was selected as the fermentation substrate, 28°C was used as the fermentation temperature, and 20-days fermentation time was determined for F. sambucinum-SSF to produce sambacide (1) with a high yield of 19.04±0.82g/kg. This paper provides an efficient approach to produce the antibacterial and antifungal agent sambacide (1) in a very high yield.

[Study on somato-type distribution and its correlations with body mass index, blood lipids and hepato-enzymes in 1 163 patients with non-alcoholic fatty liver disease].

OBJECTIVE: To investigate the distribution of somato-types in Chinese medicine and its correlations with body mass index (BMI), blood lipids and hepato-enzymes in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: From January 2008 to December 2008, the somato-types of 1 163 NAFLD patients were categorized, and its correlations with BMI, blood lipids and hepato-enzymes were analyzed. RESULTS: Among the 1 163 patients, 401 were categorized as qi-deficiency type and 371 as phlegm-dampness type, accounting for 66.38%. Levels of BMI, blood lipids (TC, TG, LDL) and hepato-enzymes (ALT, AST, GGT) in patients of phlegm-dampness type were higher than those in patients of other types, the differences were statistically significant (P<0.05). CONCLUSIONS: Qi-deficiency type and phlegm-dampness type are the dominant pathogenetic somsto-types in patients with NAFLD; abnormal BMI, blood lipids and hepato-enzymes may present in those of phlegm-dampness type more frequently.