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Diabetic kidney disease (DKD) is a common diabetic complication. Salvia miltiorrhiza has significant therapeutic effects on diabetes complications, although the mechanism remains unclear. Here, biochemical indicators and pathological changes were used to screen out the optimal Salvia miltiorrhiza multi-bioactive compounds combination. Metabolomics, transcriptomics and proteomics were used to explore the pathogenesis of DKD. RT-PCR and parallel reaction monitoring targeted quantitative proteome analysis were utilized to investigate treatment mechanisms of the optimal Salvia miltiorrhiza multi-bioactive compounds combination. The db/db mice showed biochemical abnormalities and renal lesions. The possible metabolic pathways were steroid hormone biosynthesis and sphingolipid metabolism. The 727 differential genes found in transcriptomics were associated with biochemical indicators via gene network to finally screen 11 differential genes, which were mainly key genes of TGF-β/Smad and PI3K/Akt/FoxO signaling pathways. Salvia miltiorrhiza multi-bioactive compounds combination could significantly regulate the Egr1, Pik3r3 and Col1a1 genes. 11 differentially expressed proteins involved in the two pathways were selected, of which 9 were significantly altered in db/db mice compared to db/m mice. Salvia miltiorrhiza multi-bioactive compounds combination could callback Q9DBM2, S4R1W1, Q91Y97, P47738, A8DUK4, and A2ARV4. In summary, Salvia miltiorrhiza multi-bioactive compounds combination may ameliorate kidney injury in diabetes through regulation of TGF-β/Smad and PI3K/Akt/FoxO signaling pathways.

Background: The frankincense and myrrh can be used in traditional Chinese medicine (TCM) clinic with the treatment of stroke, while its mechanism is still unclear. The aim of this study was to investigate the effects of boswellic acid (BA) and myrrh sesquiterpene (MS) compositions on ischemic stroke in rats. Methods: The ischemic stroke rat model induced by ischemia-reperfusion (I/R) after transient middle cerebral artery occlusion (MCAO) was adopted and treated with boswellic acid and myrrh sesquiterpenes with proportions compatibility (BA-MS) of 10:1, 5:1 and 20:1. Biochemical indexes, histopathological analysis, metabolomics analysis of plasma and urine, as well as 16S rDNA sequencing of gut microbiota and short chain fatty acids were investigated. Results: BA and MS could obviously significantly ameliorated neurological deficits scores, reduced cerebral infarction area in I/R, and improve the damage of brains and lungs of MCAO rats. Additionally, it could significantly reduce the expression of neuroinflammatory factors (IL-1β, nNOS, BDNF, NGF) and angiogenic growth factors (ET-1, PAI-1, PDGF, VEGF, VWF), and significantly increase the expression of nerve indicators (TDP-43, NeuN) and angiogenic growth factors (Ang Ⅱ, TGF-β1, bFGF). After the administration of BA-MS, the metabolites of ischemic stroke in plasma and urine of ischemic stroke of rats were reversed, mainly correlated with the metabolic pathway of linoleic acid metabolism (impact value =1), and the gut microbiota and SCFAs metabolism of cecal contents were also improved. Conclusions: BA-MS can improve brain injury of MCAO rats via Ang/Tie and TLR4 signaling pathway, improve metabolism disorder by regulating linoleic acid metabolism pathway, and ameliorate gut microbes and their metabolic disorders.

Ethnopharmacological relevance Kai-Xin-San, an ancient formula composed of Ginseng Radix et Rhizoma, Polygalae Radix, Acori Tatarinowii Rhizoma and Poria, was frequently applied for major depression disorders for thousands of years. However, its molecular mechanism has not clearly been investigated. Aim of the study We aimed to reveal the action mechanism of KXS on anti-depression on inducing neuronal differentiation on PC12 cells. Materials and methods A chemically standardized water extract of KXS was applied onto cultured PC12 cells in determining its effect on neurotransmitter regulation enzymes and neurite outgrowth. Results Single KXS treatment showed obvious changes in the expression of neurofilament and neurotransmitter regulation enzymes, which in parallel to treatment of nerve growth factor (NGF). Although KXS by itself did not show significant inductive effect on neurite outgrowth of PC12 cells, KXS could potentiate the NGF induced neurite outgrowth. Among the three ratios, K-652 showed the most powerful effect and cAMP-dependent pathway might play the major role. Conclusions KXS might exert the anti-depressant-like action of be inducing neuronal differentiation, which supported the clinically usage of this decoction.

To investigate the metabolic routes and metabolites of myricitrin, an important active ingredient of traditional herbal medicine, yielded by the isolated human intestinal bacteria, which have not been reported previously.Fresh human fecal samples were collected from a healthy female volunteer and about 100 different bacterial colonies were isolated. Ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry technique combined with Metabolynx™ software was used for analysis of the metabolic profile of myricitrin by the isolated human intestinal bacteria.One hundred different bacterial colonies, which developed on plates, were picked up, and four of them were further identified by using the technique of 16S rRNA gene sequencing due to their relatively strong metabolic capacity toward myricitrin. Most of them belong to Escherichia. Parent compound and three metabolites (quercetin-3-O-rhamnoside, myricetin and quercetin) were detected in the isolated bacterial samples compared with blank samples. The metabolic pathways of myricitrin included deglycosylation and dehydroxylation.These metabolites suggested that myricitrin was first dehydroxylated to quercetin-3-O-rhamnoside and subsequently deglycosylated to quercetin. Additionally, myricitrin could also be deglycosylated to the aglycon myricetin. Moreover, those metabolites might influence the biological effect of myricitrin in vivo, which led to affect the clinical effects of the medicinal plants and traditional herb medicines.

This paper proposes three kinds of action patterns of traditional Chinese medicine (TCM) incompatibility based on the theories of Seven Ways of Compatibility and Drug Interaction. These are toxification and potential toxicity action pattern embodied in the characteristic of antagonism, efficiency reduction, and decrease in effect—patterns reflected by the characteristics of mutual inhibition/restraint and toxic-effect multiple action patterns embodying the complex characteristics of antagonism and mutual inhibition/restraint. In addition, we put forward eight possible mechanisms of TCM incompatibility. They are potential toxicity by promoting the release of toxic substances, potential toxicity by producing new toxic components, potential toxicity because of increased toxic components resulting from mutual transformation of chemical constituents, efficiency reduction through inhibiting the dissolving of active components, efficiency reduction through inactivating the active components, toxification that results from toxic metabolites generated in vivo based on drug interaction, adverse effects caused by affecting the physiological disposition of incompatibility combinations, and adverse effects caused by regulating and controlling the drug metabolic enzymes. Furthermore, the authors discussed the correlations between the different action patterns and mechanisms and relationships of the seven ways of compatibility. These opinions would provide references for understanding and researching the essences of TCM incompatibility.