[Mechanism of Cordyceps militaris against non-small cell lung cancer: based on serum metabolomics].

This study investigated the potential mechanism of Cordyceps militaris(CM) against non-small cell lung cancer(NSCLC) based on serum untargeted metabolomics. Specifically, Balb/c nude mice were used to generate the human lung cancer A549 xenograft mouse model. The tumor volume, tumor weight, and tumor inhibition rate in mice in the model, cisplatin, Cordyceps(low-, medium-, and high-dose), and CM(low-, medium-, and high-dose) groups were compared to evaluate the influence of CM on lung cancer. Gas chromatography-mass spectrometry(GC-MS) was used for the analysis of mouse serum, SIMCA 13.0 for the compa-rison of metabolic profiles, and MetaboAnalyst 5.0 for the analysis of metabolic pathways. According to the pharmacodynamic data, the tumor volume and tumor weight of mice in high-dose CM group and cisplatin group decreased as compared with those in the model group(P<0.05 or P<0.01). The results of serum metabolomics showed that the metabolic profiles of the model group were significantly different from those of the high-dose CM group, and the content of endogenous metabolites was adjusted to different degrees. A total of 42 differential metabolites and 7 differential metabolic pathways were identified. In conclusion, CM could significantly inhibit the tumor growth of lung cancer xenograft mice. The mechanism is the likelihood that it influences the aminoacyl-tRNA biosynthesis, the metabolism of D-glutamine and D-glutamate, metabolism of alanine, aspartate, and glutamate, metabolism of glyoxylate and dicarboxylic acid, biosynthesis of phenylalanine, tyrosine, and tryptophan, arginine biosynthesis as well as nitrogen metabolism. This study elucidated the underlying mechanism of CM against NSCLC from the point of metabolites. The results would lay a foundation for the anticancer research and clinical application of CM.

A target lipidomics approach to investigate the acute inflammatory irritation induced by indolealkylamines from Chansu water fraction in rats.

Chansu has demonstrated adverse reactions in clinical settings, which is associated with its toxicity and limits its clinical applications. But there are methodological limitations for drug safety evaluation. In the current study, ultra-high performance liquid chromatography, lipidomic profiling, and molecular docking were used to systemically assess Chansu-induced acute inflammatory irritation and further identify the underlying drug targets. Compared with the EtOAc extract, Chansu water fraction containing indolealkylamines caused acute inflammatory irritation in rats, including acute pain (spontaneous raising foot reaction), and inflammation (paw edema). At the molecular level, lipids analysis revealed significantly higher levels of pro-inflammatory mediators of the COX and LOX pathways. However, anti-inflammatory mediators from the CYP 450, ALA, and DHA pathways markedly decreased after exposure to Chansu water fraction. Moreover, four indolealkylamines from Chansu showed a high theoretical affinity to a known irritation target, 5-HT2AR. These results suggest that Chansu-induced inflammatory irritation is related to the distinct dysregulation of inflammatory lipids, and peripheral 5-HT2AR is a potential target for irritation therapy. The strategy used in this study can be a crucial approach in the safety evaluation of natural medicinal substances.

[Structural Chinese medicine: new research field on pharmacodynamic substance basis of traditional Chinese medicine].

The research on the pharmacodynamic substance basis of traditional Chinese medicine(TCM) is a key scientific issue for the inheritance and development of TCM. At present, a large number of remarkable achievements have been made in the field of chemical components in Chinese medicine, however, another important aspect, namely the physical structure and mode of action of the multi-component assembly of TCM, has not been clearly understood and deeply studied. From the bottleneck of restricting material ba-sic research, we objectively analyzed the common cause of the existing problems. Based on the new discoveries and advances of active substances from TCM emerging in recent years, we extracted and summarized the concept of structural Chinese medicine, elaborated the basic ideas, main features and research modes, hoping to provide theoretical and practical references for the study on the pharmacodynamic substance basis and other research fields of TCM.

[Quality evaluation of fried Glycyrrhizae Radix et Rhizoma pieces by HPLC fingerprint and multicomponent quantitative analysis].

To establish the HPLC fingerprint and multi-component determination method of fried Glycyrrhizae Radix et Rhizoma pieces. HPLC analysis was performed on Thermo Acclaim ~(TM)120 C_(18) column(4.6 mm×250 mm, 5 µm). Acetonitrile-0.1% phosphoric acid aqueous solution was taken as the mobile phase for gradient elution. The flow rate was 1 mL·min~(-1),the column temperature was maintained at 30 ℃, and the detection wavelength was 237 nm and 360 nm. The similarity of 15 batches of fried Glycyrrhizae Radix et Rhizoma pieces was higher than 0.849, and 17 common peaks were identified. Liquiritin, isoliquiritin apioside, isoliquiritin, liquiritigenin, isoliquiritigenin and glycyrrhizic acid were identified; among them, the mass fractions of Liquiritin, isoliquiritin apioside, isoliquiritin, liquiritigenin, glycyrrhizic acid were were 0.519%-3.058%, 0.227%-0.389%, 0.070%-0.439%, 0.038%-0.173%, 1.381%-4.252%, respectively. According to the cluster analysis, the 15 batches of decoction pieces were classified into three categories; principal component analysis screened out four principal components, with the cumulative variance contribution rate of 86.630%, indicating that the principal components contained most information of original data. Partial least squares discriminant ana-lysis marked 6 differential components in the decoction pieces. The established fingerprint and multicomponent determination are stable and reliable, and can provide a reference for the quality control of Radix Glycyrrhizae Radix et Rhizomae and fried Glycyrrhizae Radix et Rhizoma pieces.

Challenges and strategies in progress of drug delivery system for traditional Chinese medicine Salviae Miltiorrhizae Radix et Rhizoma (Danshen).

Traditional Chinese medicines (TCMs), with a history of thousands of years, are widely used clinically with effective treatment. However, the drug delivery systems (DDSs) for TCMs remains major challenges due to the characteristics of multi-components including alkaloids, flavones, anthraquinones, glycosides, proteins, volatile oils and other types. Therefore, the novel preparations and technology of modern pharmaceutics is introduced to improve TCM therapeutic effects due to instability and low bioavailability of active ingredients. Salviae Miltiorrhizae Radix et Rhizoma, the radix and rhizomes of Salvia miltiorrhiza Bunge (Danshen in Chinese), is a well known Chinese herbal medicine for protecting the cardiovascular system, with active ingredients mainly including lipophilic tanshinones and hydrophilic salvianolic acids. In this review, this drug is taken as an example to present challenges and strategies in progress of DDSs for TCMs. This review would also summary the characteristics of active ingredients in it including physicochemical properties and pharmacological effects. The purpose of this review is to provide inspirations and ideas for the DDSs designed from TCMs by summarizing the advances on DDSs for both single- and multi-component from Danshen.

Pudilan xiaoyan oral liquid alleviates LPS-induced respiratory injury through decreasing nitroxidative stress and blocking TLR4 activation along with NF-ΚB phosphorylation in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Pudilan xiaoyan oral liquid (PDL), collected in Chinese Pharmacopoeia, has been used clinically for treating inflammatory diseases such as upper respiratory tract infection diseases. However, its potential anti-inflammation and the mechanism are still unclear. MATERIALS AND METHODS: lipopolysaccharide (LPS) was used to induce respiratory inflammation of mice by intratracheal administration. UPLC/MS was performed for components analysis of PDL. Enzyme-linked immune sorbent assay (ELISA) was conducted for determining interleukin-6(IL-6), interleukin-1ß(IL-1ß) and tumor necrosis factor-α(TNF-α) in serum and supernatant of tracheal tissue while Nitric oxide assay kit for nitric oxide (NO) content. Hematoxylin-Eosin (HE) staining was applied to evaluate pathological lesions. Western blotting analysis (WB) and Immunohistochemistry(IHC) were employed for the determination of Toll-like receptors 4(TLR4), TNF-α, IL-6, inducible nitric oxide synthase(iNOS) and nuclear factor-kappa B p65 (NF-κB p65) protein expressions. RESULTS: Seven major compounds of PDL were analyzed simultaneously. The treatment of PDL could attenuate LPS-induced histopathological damage of tracheal tissues, followed by reducing pro-inflammation mediators including TNF-α and IL-6 in serum and supernatant of tracheal tissue. LPS-induced nitroxidative stress including NO content and iNOS expression was inhibited significantly by PDL. Furthermore, PDL also down-regulated NF-kB p65 phosphorylation and TLR4 expressions. CONCLUSION: The results indicated that the PDL had a protective effect on LPS-induced respiratory inflammation injury in mice. Our findings for the first time provide experimental evidence for the application of PDL on respiratory inflammation injury in clinical practice.

Components of Goutengsan in Rat Plasma by Microdialysis Sampling and Its Protection on Aß1-42-Induced PC12 Cells Injury.

Goutengsan, a Chinese herbal formula, potential protection on Alzheimer's disease (AD) has been less reported. In current study, we investigated the protection of Goutengsan on Aß1-42-induced pheochromocytoma-derived cells (PC12). Furthermore, the components from Goutengsan in rat plasma were identified by microdialysis (MD) for in vivo sampling. Meanwhile, the protection of components identified was also verified. At last, we found that Goutengsan has a potential protective effect on Aß1-42-induced PC12 cells via reducing cells damage and increasing cells vitality as well as six components (pachymic acid, liquiritin, rhynchophylline, isorhynchophylline, corynoxeine, and isocorynoxeine) which may be effective components. This study helps to understand the treatment of Goutengsan for AD and would facilitate the clinical and further studies for this formula.

Application of Traditional Chinese Medical Herbs in Prevention and Treatment of Respiratory Syncytial Virus.

Respiratory syncytial virus (RSV) is a common viral pathogen of the lower respiratory tract, which, in the absence of effective management, causes millions of cases of severe illness per year. Many of these infections develop into fatal pneumonia. In a review of English and Chinese medical literature, recent traditional Chinese medical herb- (TCMH-) based progress in the area of prevention and treatment was identified, and the potential anti-RSV compounds, herbs, and formulas were explored. Traditional Chinese medical herbs have a positive effect on inhibiting viral attachment, inhibiting viral internalization, syncytial formation, alleviation of airway inflammation, and stimulation of interferon secretion and immune system; however, the anti-RSV mechanisms of TCMHs are complicated, which should be further investigated.

A metabolomics approach to studying the effects of Jinxin oral liquid on RSV-infected mice using UPLC/LTQ-Orbitrap mass spectrometry.

ETHNOPHARMACOLOGICAL RELEVANCE: Jinxin oral liquid (JOL) is a traditional Chinese medicine (TCM) formula modified from ma-xing-shi-gan-tang, an ancient formula widely used in the treatment of respiratory diseases such as bronchitis, pneumonia, and asthma. In our previous studies, JOL was shown to safely and effectively treat viral pneumonia, especially that involving respiratory syncytial virus (RSV). AIM OF THE STUDY: To investigate the mechanism of the effect of JOL in RSV infected mice, using a metabolomics approach based on ultra-performance liquid chromatography coupled with linear ion trap quadrupole-Orbitrap mass spectrometry (UPLC/LTQ-Orbitrap-MS). MATERIALS AND METHODS: BALB/c mice were divided into four groups, the control group (saline inoculation/no treatment), RSV group (RSV inoculation/saline treatment), RSV+JOL group (RSV inoculation/JOL treatment), and RSV+Riba group (RSV inoculation/ribavirin treatment). Plasma and lung tissue samples were collected 7 days after the inoculation/treatment protocols, and UPLC/LTQ-Orbitrap-MS method based on metabolomics was developed. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were utilized to identify biomarkers potentially associated with the anti-RSV activity of JOL. RESULTS: JOL was associated with reduced inflammatory responses in RSV-infected lung tissue. The combination of PCA and OPLS-DA revealed deviations in 11 biomarkers in plasma, and 16 biomarkers in lung tissue induced by RSV that were corrected with JOL treatment. These biomarkers were primarily components of metabolic pathways involving glycerophosphocholines, sphingolipids, and glycerolipids. JOL was able to restore the abnormal levels of these biomarkers detected in the plasma and lung tissue of RSV-infected mice to approximately normal levels. CONCLUSIONS: This study suggested that JOL can treat RSV pneumonia effectively, partially by ameliorating the associated disturbances to lipid metabolism. The results provided insight into the anti-RSV mechanism of JOL, and also demonstrated that metabolomics is a valuable tool for investigating the efficacy of TCM treatment for RSV pneumonia, and the associated biomarkers involved.

Effects of Gancao on pharmacokinetic profiles of platycodin D and deapio-platycodin D in Jiegeng.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiegeng (Radix Platycodi), the dried root of Platycodon grandiflorum A. DC (Campanulaceae), has been used to treat cough, sore throat, bronchitis, and bronchial asthma for thousands of years. It is commonly prescribed with Gancao (Radix et Rhizoma Glycyrrhizae) as a herbal combination in traditional Chinese medicine (TCM) to produce synergistic effects. AIM OF THE STUDY: To elucidate the herbaceous compatibility of Jiegeng and Gancao, we investigated the comparative pharmacokinetics, intestinal absorption, and microbial metabolism of platycodin D (PD) and deapio-platycodin D (DPD), the platycodins contained in Jiegeng. MATERIALS AND METHODS: In the comparative pharmacokinetic study, the concentrations of PD and DPD in Jiegeng extract (JE) and the Jiegeng-Gancao herb pair (JGHP) were determined in rat plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, the main pharmacokinetic parameters were calculated using data analysis software (DAS). Furthermore, in vitro studies using Caco-2 cells and fecal lysates were performed to contradistinguish the intestinal absorption and microbial metabolism of PD and DPD in JE from those in JGHP. RESULTS: The peak concentration (Cmax) and area under the plasma concentration curve (AUC) of PD in rats orally administrated JGHP significantly increased compared to that in rats treated with JE. In addition, the time to reach peak concentration (Tmax) and half-life (t1/2) of PD and DPD in combination with JGHP were all prolonged compared with those of JE. There was no significant difference in the absorption of PD between JE and JGHP in Caco-2 cells. However, the hydrolysis of both PD and DPD in JGHP were weaker than that in JE after a 2-h incubation in fecal lysate which might be responsible for the different pharmacokinetic profiles of the platycodins in JE and JGHP. CONCLUSION: In this study, we discovered that Gancao might influence the pharmacokinetic profiles of PD and DPD in Jiegeng. Furthermore, the difference in profiles may be attributable to the inequable microbial metabolism rather than intestinal absorption of the platycodins in JE and JGHP. The results of this study elucidated the pharmacokinetic compatibility and rationale for the use of JGHP.