ABSTRACT
Phlomis brevidentata H.W.Li Radix (PbR) is a rare traditional Tibetan medicine, and it is widely used in the Chinese Tibetan region for the treatment of pharyngitis, pneumonia, and so forth. Nevertheless, there is very little research on its modern pharmacy, and the active ingredients and mechanisms against these diseases remain unknown. In this study, we employed the qualitative analysis and pharmacokinetic based on LC-MS technology and network pharmacology to explore the active ingredients and mechanisms of PbR for treatment of pneumonia. Ultraperformance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC-Q-TOF/MS) methodology was applied to identify the chemical composition of PbR. Meanwhile, a UPLC-MS/MS method was developed to quantify three active constituents (sesamoside, shanzhiside methyl ester, and barlerin) in rat plasma for the pharmacokinetic analysis after oral administration of PbR. Finally, in order to clarify the anti-pneumonia mechanism of this rare Tibetan medicine, a comprehensive network pharmacology strategy was applied. As a result, a total of 23 compounds were identified in PbR, including 14 iridoid glycosides, 7 phenylethanoid glycosides, and 2 other kinds of compounds. Pharmacokinetic studies have shown that the three compounds exhibit extremely similar pharmacokinetic characteristics, possibly due to their highly analogous chemical structure. We speculate that the iridoid glycosides may be the main active component in PbR. Then, the three iridoid glycoside constituents absorbed into blood were subjected to network pharmacology analysis for treatment of pneumonia. Compound-target-disease, gene ontology bioanalysis, KEGG pathway, and other network pharmacology analysis methods were applied to reveal that five main targets of the three iridoid glycosides, namely, GAPDH, ALB, MAPK1, AKT1, and EGFR, were significant in the regulation of the above bioprocesses and pathways. These results provide a basis for elucidating the bioactive compounds and the pharmacological mechanisms of P. brevidentata H.W.Li radix under clinical applications.
ABSTRACT
<p><b>OBJECTIVE</b>To explore the protective effects of Tibetan medicine Zuo-Mu-A Decoction (, ZMAD) on the blood parameters and myocardium of high altitude polycythemia (HAPC) model rats.</p><p><b>METHODS</b>Forty male Wistar rats were randomly divided into 4 groups by a random number table, including the normal, model, Rhodiola rosea L. (RRL) and ZMAD groups (10 in each group). Every group was raised in Lhasa to create a HAPC model except the normal group. After modeling, rats in the RRL and the ZMAD groups were administered intragastrically with RRL (20 mL/kg) and ZMAD (7.5 mL/kg) once a day for 2 months, respectively; for the normal and the model groups, 5 mL of distilled water was administered intragastrically instead of decoction. Then routine blood and hematologic rheology parameters were taken, levels of erythropoietin and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were tested, and ultrastructural change in the left ventricular myocardium was observed using transmission electron microscopy.</p><p><b>RESULTS</b>Compared with the model group, ZMAD significantly reduced the red blood cell count, hemoglobin levels, whole blood viscosity at low/middle shear rates, plasma viscosity, erythrocyte electrophoretic time, erythropoietin and 8-OHdG levels, and also increased the erythrocyte deformation index (P<0.05). There was no difference in all results between the RRL and the ZMAD groups. The cardiac muscle fibers were well-protected, mitochondrial matrix swelled mildly and ultrastructure changes were less prominent in the ZMAD group compared with the model group.</p><p><b>CONCLUSION</b>ZMAD has significant protective effects on the blood parameters against HAPC, and also has the beneficial effect in protecting against myocardial injury.</p>
