[Prediction and analysis of Q-markers of Elephantopus scaber based on its UPLC fingerprint, content determination of components, and in vitro a nti-tumor activity].

This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 µm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 µL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 µmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.

Corrigendum to "Selection of quality markers of Jasminum amplexicaule based on its anti-diarrheal and anti-inflammatory activities: Effect-target affiliation-traceability-pharmacokinetics strategy" [Chinese Herbal Medicines 11 (2019) 379-386].

[This corrects the article DOI: 10.1016/j.chmed.2019.08.002.].

Metabolic Insight Into the Neuroprotective Effect of Tao-He-Cheng-Qi (THCQ) Decoction on ICH Rats Using Untargeted Metabolomics.

Tao-He-Cheng-Qi decoction (THCQ) is an effective traditional Chinese medicine used to treat intracerebral hemorrhage (ICH). This study was performed to investigate the possible neuroprotective effect of THCQ decoction on secondary brain damage in rats with intracerebral hemorrhage and to elucidate the potential mechanism based on a metabolomics approach. Sprague-Dawley (SD) rats were randomly divided into five groups: the sham group, collagenase-induced ICH model group, THCQ low-dose (THCQ-L)-treated group, THCQ moderate-dose (THCQ-M)-treated group and THCQ high-dose (THCQ-H)-treated group. Following 3 days of treatment, behavioral changes and histopathological lesions in the brain were estimated. Untargeted metabolomics analysis with multivariate statistics was performed by using ultrahigh-performance liquid chromatography-mass spectrometry (UPLC-Q-Exactive Orbitrap MS). THCQ treatment at two dosages (5.64 and 11.27 g/kg·d) remarkably improved behavior (p < 0.05), brain water content (BMC) and hemorheology (p < 0.05) and improved brain nerve tissue pathology and inflammatory infiltration in ICH rats. Moreover, a metabolomic analysis demonstrated that the serum metabolic profiles of ICH patients were significantly different between the sham group and the ICH-induced model group. Twenty-seven biomarkers were identified that potentially predict the clinical benefits of THCQ decoction. Of these, 4 biomarkers were found to be THCQ-H group-specific, while others were shared between two clusters. These metabolites are mainly involved in amino acid metabolism and glutamate-mediated cell excitotoxicity, lipid metabolism-mediated oxidative stress, and mitochondrial dysfunction caused by energy metabolism disorders. In addition, a correlation analysis showed that the behavioral scores, brain water content and hemorheology were correlated with levels of serum metabolites derived from amino acid and lipid metabolism. In conclusion, the results indicate that THCQ decoction significantly attenuates ICH-induced secondary brain injury, which could be mediated by improving metabolic disorders in cerebral hemorrhage rats.

Mechanism of YLTZ on glycolipid metabolism based on UPLC/TOF/MS metabolomics.

Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by dysfunction of glycolipid metabolism. YLTZ is used to treat hyperlipidemia, yet its hypolipidemic and hypoglycemic mechanism on T2DM are unknown. Thus, UPLC/TOF/MS was applied in this study to identify the potential bio-markers, and deduce the possible metabolic pathways. According to bio-indexes, the increased blood lipid levels, including TC, TG, LDL and FA, and the decreased HDL, the elevated glucose, reduced insulin level and impaired OGTT were observed in diabetic rat model. While YLTZ can decrease the lipid levels and glucose content, as well as increased insulin standards and improve OGTT. After data from UPLC/TOF/MS processed, 17 metabolites were obtained, including phospholipids (LPCs, PCs and PGP (18:1)), beta-oxidation production (HAA, VAG and CNE) and precursors (THA), bile acid (CA, CDCA and IDCA), hydrolysate of TG (MG (22:4)), glycometabolism (G6P), cholesterol-driven synthetics (ADO) and production of arachidonate acid (THETA). As a result, YLTZ was able to reduce LPCs, PCs, PGP (18:1), HAA, VAG, CNE, CA, ADO and THETA, as well as enhance MG (22:4) and G6P. After analyzing results, several metabolic pathways were deduced, which containing, cholesterol synthesis and elimination, FA beta-oxidation, TG hydrolysis, phospholipids synthesis, glycolysis, gluconeogenesis and inflammation. Consequently, YLTZ performed to prohibit the FA beta-oxidation, synthesis of cholesterol and phospholipids, gluconeogenesis and inflammation level, as well as promote TG hydrolysis, glycolysis and blood circulation. Hence, applying metabonomics in TCM research can uncover its pharmacological edges, elucidating comprehensively that YLTZ has capacity of hypolipidemic, hypoglycemic and promoting blood circulation, matching the effect of removing blood stasis, eliminating phlegm and dampness.

Effect of a derived herbal recipe from an ancient Chinese formula, Danggui Buxue Tang, on ovariectomized rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Astragali (root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao, RA), Radix Angelicae sinensis (root of Angelica sinensis (Oliv.) Diels, RAS) and Folium Epimedii (leaves of Epimedium brevicomum Maxim., FE) are three of the extensively applied herbal remedies among traditional Chinese medicines for gynecological disorders and osteoporosis. A derivative herbal recipe-RRF, composed of the three medicines with a weight ratio of 5:1:5, is derived from a famous Chinese herbal formula-Danggui Buxue Tang (DBT). RRF has shown noteworthy protective effect in ovariectomized rats, which might represent a promising candidate for the treatment of perimenopausal disorders. The aim of this study was to investigate the herbal recipe RRF for its efficacy on perimenopausal disorders and the underlying mechanisms via ovariectomy (OVX) models. MATERIALS AND METHODS: An experimental model of OVX female rats was applied. Vehicle (Sham and OVX group), RRF (564, 282 and 141 mg/kg/d) and conjugated equine estrogens (CEE, 0.1mg/kg/d, reference drug) were all administrated orally once daily for 16 weeks post operation. After the treatment, radioimmunoassay for estradiol (E(2)), lutenizing hormone (LH), follicle stimulating hormone (FSH) and ß-endorphin (ß--EP), neurotransmitter determination by high-performance liquid chromatography with electrochemical detector (HPLC-ECD) for norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT) and 5-HIAA (5-hydroxyindoleacetic acid), bone mineral density (BMD) assay as well as lipid peroxidation assessment, were carried out to probe into the effectiveness of RRF. RESULTS: (1) RRF treatment enhanced E(2) synthese while diminished the elevated serum FSH and LH levels; in terms of neurotransmitter, ß-EP syntheses rallied whereas the hypothalamic NE, DA and 5-HT release experienced varying mitigation in OVX female rats. (2) Repeated administration of RRF was able to attenuate osteoporosis by elevating the BMD levels of total body, and arrest the bone trabeculae degradation. (3) RRF exposure decreased serum levels of constituent MDA and increased endogenous SOD activity. CONCLUSIONS: Results of the current studies revealed that RRF was capable of acting at multiple targets which presumably underlay its potential protective effect in OVX rats mimicking symptoms as observed in perimenopausal women. Hence, RRF might represent a promising candidate in the treatment of perimenopausal disorders in midlife women.

[Effect of acupoint sticking of "Hua yutie" on VEGF expression in rats of focal cerebral ischemia].

OBJECTIVE: To explore the mechanism of acupoint sticking of "Hua yutie" in improving ischemic stroke. METHODS: Eighty rats were randomly divided into 5 groups, a model group, an acupoint sticking group, an acupuncture group, a Nimodipine group and a normal group. Middle cerebral artery occlusion (MCAO) was used for preparation of focal cerebral ischemic rat model. After modeling, any treatment was not given to the model group; for the acupoint sticking group, "Hua yutie" was applied at "Dazhui" (GV 14) ,"Qihai" (CV 6) and "Mingmen" (GV 4); for the acupuncture group, acupuncture was given at the same acupoints as those in the acupoint sticking group; the Nimodipine group received intragastric administration of Nimodipine. And the normal group did not receive any treatment. Their infarction volume, the cerebral water content, expression of vascular endothelial growth factor (VEGF) and the protein level were observed. RESULTS: The infarction volume coincided with the dominative scope of the middle cerebral artery of the electric coagulation. There were significant differences in the cerebral water content as the various treatment groups compared with that of the model group (all P<0.05). The VEGF positive cell number and the protein level around the infarction area in the acupoint sticking group were increased as compared with those in the model group (P<0.01), with no significant difference as compared with the Nimodipine group and the acupuncture group (all P>0.05). CONCLUSION: Acupoint sticking of "Hua yutie" alleviates the cerebral damage after ischemia possibly through enhancing the expression and protein level of VEGF.