Comparative pharmacokinetic study on phenolic acids and flavonoids in normal and microcirculation dysfunction rats plasma by UPLC-TQ/MS/MS after oral administration of Salvia miltiorrhiza stem-leaf extracts.

According to the Standard of Chinese Medicinal Materials of Shaanxi Province (2015 edition), Salvia miltiorrhiza caulis et folium is the dried stems and leaves of Salvia miltiorrhiza, which could activate blood and dispell blood stasis, clear the mind and remove annoyance. In this study, the dynamic absorption changes of phenolic acids (FS) and phenolic acids-flavonoids (FT) in rats after oral administration were studied by UPLC-TQ/MS/MS, to elucidate the pharmacokinetics of seven major bioactive components of the stem-leaf of Salvia miltiorrhiza in vivo. The results showed that the pharmacokinetic parameters of FS and FT were significantly different in normal rats and model rats. Compared with the control group, after injecting 10 % polymer dextran 500 into the tail vein to establish a model of microcirculation disturbance, the Cmax of caffeic acid decreased. The Cmax of rosmarinic acid and lithospermic acid increased. Danshensu showed a decrease in CLz/F, accompanied by an increase in both AUC0-t and AUC0-∞. The AUC0-t of lithospermic acid was also increased. These results indicated that microcirculation disturbance could decrease the absorption of caffeic acid while increasing the absorption of danshensu, rosmarinic acid and lithospermic acid. After oral administration of FT, the Cmax of danshensu and the AUC0-t of caffeic acid were increased significantly, suggesting that the presence of flavonoids may promote the absorption and exposure of phenolic acids in vivo. This study provides a reference for the elucidation of the in vivo substances and the mechanisms of action of FS and FT from the stem-leaf of Salvia miltiorrhiza.

Comparative Analysis of Pharmacokinetics and Metabolites of Three Main Terpenoids before and after Compatibility of Frankincense and Myrrh in Rats by UHPLC-MS.

BACKGROUND: 3-acetyl-11-keto-beta-boswellic acid (AKBA) and 11-keto-boswellic acid (KBA) are the main active components of frankincense as pentacyclic triterpenoids, which are designated by the European Pharmacopoeia 8.0 as the quality standard for the evaluation of Indian frankincense, 2-methoxy-8,12-epoxygermacra- 1(10),7,11-trien-6-one (MCS134) is a non-volatile sesquiterpene compound in myrrh. OBJECTIVE: In this paper, the absorption pharmacokinetics and metabolites of AKBA, KBA and MCS134 after frankincense, myrrh and their compatibility were analyzed, elaborated their absorption and metabolism mechanism and provided the ideas for the research on the bioactive components of frankincense and myrrh compatibility in vivo. METHODS: The area under the blood concentration time curve (AUC), half-life (t_1/2) and drug clearance (CL) of AKBA, KBA and MCS134 in rats were analyzed by LC-TQ / MS. The metabolites of AKBA, KBA and MCS134 in rats were analyzed by ultra-high pressure liquid chromatography with a linear ion trap-high resolution Orbitrap mass spectrometry system (UHPLC-LTQ-Orbitrap-MS). RESULTS: The results showed that AKBA, KBA and MCS134 reached the maximum plasma concentration at about 2 h, 2 h and 15 min, respectively. AUC_0-t and t_1/2 of the three components increased in varying degrees after compatibility, and the clearance/ bioavailability (CL/F) decreased. AKBA, KBA and MCS134 were metabolized in phase I and phase II in rats, and there represented differences before and after compatibility. CONCLUSION: After the compatibility of frankincense and myrrh, the absorption of effective components was improved to some extent, and there were some differences in the metabolites in rats. The results provide ideas for elucidating the in vivo effect mechanism of frankincense and myrrh.

[Preparation of Huoluo Xiaoling gel plaster and its transdermal penetration in vitro].

Huoluo Xiaoling Dan is a classical prescription commonly used for blood circulation and pain relief in clinic with obvious effects. To make it directly treat lesion and improve the effect, this research optimized the preparation process of Huoluo Xiaoling gel paste and further evaluated its in vitro transdermal absorption performance, so as to provide a scientific basis for its development and utilization. Using primary viscosity, holding viscosity, and sensory score as evaluation indexes, the matrix amount of gel paste was determined by the single factor test and Box-Behnken response surface method. The ultra-performance liquid chromatography(UPLC) method was established to determine the content of eight active ingredients, including Danshensu, ferulic acid, salvianolic acid B, salvianolic acid A, ligustilide, tanshinone Ⅱ_A, 11-keto-ß-boswellic(KBA), and 3-acetyl-11-keto-ß-boswellic acid(AKBA). A mo-dified Franz diffusion cell method was used to evaluate and compare the absorption properties of the gel paste without volatile oil and with volatile oil microemulsion. The results showed that the optimal prescription for Huoluo Xiaoling gel paste matrix was NP700(1.35 g), glycerol(7.00 g), micropowder silica gel(1.25 g), sodium carboxymethyl cellulose(0.20 g), tartaric acid(0.06 g), and glyceryl aluminum(0.04 g). The mass fractions of eight active ingredients in the paste were successively 0.48, 0.014, 0.95, 0.39, 0.57, 0.055, 0.35, and 0.97 mg·g~(-1). The results of the in vitro transdermal absorption test showed that the addition of the volatile oil or the volatile oil microemulsion promoted the transdermal absorption of the active ingredients, and the law of drug penetration conformed to the zero equation or the Higuchi equation. The gel paste prepared by the optimal prescription has good appearance and adhesion, with no residue, and has the characteristics of skeletal slow-release preparation, which is easy to reduce the number of administration, la-ying a foundation for the development of new external dosage forms of Huoluo Xiaoling Dan.

[Combination characteristics of frankincense and myrrh and progress and prospect of their combination efficacy and mechanism].

Herbal pair is formed based on the experience summary of doctors' deep understanding and perception of the medicinal nature in long-term clinical practice. It gradually becomes the exquisite structural unit for preparing traditional Chinese medicine(TCM) prescriptions, and often plays a core bridge role in the prescription combination. Frankincense and myrrh are raw resin materials of incense abroad, which are subsequently included as Chinese medicinal herbs and endowed with rich medicinal connotation. With the functions of relaxing Zang-fu organs, activating blood and relieving pain, they have definite clinical efficacy. From the perspective of herbal description and clinical application, this study systematically analyzed the combination of frankincense and myrrh as well as their combination proportion, efficacy characterization, diseases and syndromes, effective components and action mechanism. On this basis, the focus of in-depth research of frankincense-myrrh and the application prospects were proposed, in order to further reveal the potential meditation law of this herbal pair, thus contributing to clinical practice and drug innovation of traditional Chinese medicine, and providing reference for understanding of TCM medicinal nature and research of herbal pairs.

Potential roles of gut microbiota and microbial metabolites in chronic inflammatory pain and the mechanisms of therapy drugs.

Observational findings achieved that gut microbes mediate human metabolic health and disease risk. The types of intestinal microorganisms depend on the intake of food and drugs and are also related to their metabolic level and genetic factors. Recent studies have shown that chronic inflammatory pain is closely related to intestinal microbial homeostasis. Compared with the normal intestinal flora, the composition of intestinal flora in patients with chronic inflammatory pain had significant changes in Actinomycetes, Firmicutes, Bacteroidetes, etc. At the same time, short-chain fatty acids and amino acids, the metabolites of intestinal microorganisms, can regulate neural signal molecules and signaling pathways, thus affecting the development trend of chronic inflammatory pain. Glucocorticoids and non-steroidal anti-inflammatory drugs in the treatment of chronic inflammatory pain, the main mechanism is to affect the secretion of inflammatory factors and the abundance of intestinal bacteria. This article reviews the relationship between intestinal microorganisms and their metabolites on chronic inflammatory pain and the possible mechanism.

Seven 365-Million-Year-Old Trilobites Moulting within a Nautiloid Conch.

A nautiloid conch containing many disarticulated exoskeletons of Omegops cornelius (Phacopidae, Trilobita) was found in the Upper Devonian Hongguleleng Formation of the northwestern margin of the Junggar Basin, NW China. The similar number of cephala, thoraces and pygidia, unbroken thoraces, explicit exuviae, and lack of other macrofossils in the conch, indicate that at least seven individual trilobites had moulted within the nautiloid living chamber, using the vacant chamber of a dead nautiloid as a communal place for ecdysis. This exuvial strategy manifests cryptic behaviour of trilobites, which may have resulted from the adaptive evolution induced by powerful predation pressure, unstable marine environments, and competition pressure of organisms occupying the same ecological niche in the Devonian period. The unusual presence of several trilobites moulting within a nautiloid conch is possibly associated with social behaviours in face of a serious crisis. New materials in this study open a window for understanding the survival strategy of marine benthic organisms, especially predator-prey interactions and the behavioural ecology of trilobites in the middle Palaeozoic.

Zoophycos macroevolution since 541 Ma.

Zoophycos is one of the most complex and enigmatic trace fossils recorded in marine strata from Cambrian to Quaternary worldwide, which is invaluable for the study of Phanerozoic development of organism-environment interactions. Here we address and demonstrate the macroevolution of Phanerozoic Zoophycos by assembling 448 points in constructing the Phanerozoic Zoophycos database based on 291 papers from 1821 to 2015 and 180 specimens from Cambrian to Palaeogene. The comprehensive dataset reveals, for the first time, five peaks and six depressions in Phanerozoic Zoophycos occurrence frequency. Secondly, the palaeogeographical distribution of Zoophycos is closely associated with the supercontinent Pangaea shifting, independent of the latitude. Our data also attest that the bathymetrical shift of Zoophycos from the littoral-neritic to bathyal environments is synchronized with the tiering shift from shallow to deep. By detailed comparison with body fossils, geochemical and palaeogeographical records, we conclude that the macroevolution of Phanerozoic Zoophycos is multi-affected by the global biodiversity expansion, benthic nutrient enhancement, and the biotic macroevolution of the Zoophycos-producers. The macroevolution of development evidenced by the morphological changes of Zoophycos and other trace fossils, may have great implications on the behavioural and physiological adaptation of ancient animals to the environments.