Analytical strategies to identify multicomponent quality markers for commercial Hua-ju-hong using multidimensional chemical analysis.

Hua-ju-hong (HJH) is a Chinese medicinal material obtained from Citrus grandis 'Tomentosa' (CGT) and Citrus grandis (L.) Osbeck (CG) with various commercial specifications. It is known for relieving cough and dispelling phlegm. To reveal the quality marker for distinguishing the various HJH, 215 batches of commercial HJH were studied systematically using multidimensional chemical analysis. Ten major components were identified by high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry and quantified via high-performance liquid chromatography coupled with diode array detection. In this study, a rapid, efficient, and low-cost chromatographic method was established. Total coumarin-hemiterpene and total coumarin-monoterpene were first classified and analyzed in HJH. The result indicated that the main component, naringin, was not the quality marker for differentiating CGT from CG. For reflecting the unique medicinal and food value of HJH, coumarins should be the more potential quality markers. Flavonoids were the possible quality markers for distinguishing two growth stages of fruit-exocarp and young fruit. For the first time, two chemotypes of HJH were identified in CG. This study provides a convenient yet reliant chromatographic method and novel yet systematic strategies for overall quality control of commercial HJH.

Hypoglycemic Effects and Quality Marker Screening of Dendrobium nobile Lindl. at Different Growth Years.

(1) Background: The effect of Dendrobium nobile Lindl. (D. nobile) on hyperglycemic syndrome has only been recently known for several years. Materials of D. nobile were always collected from the plants cultivated in various growth ages. However, regarding the efficacy of D. nobile on hyperglycemic syndrome, it was still unknown as to which cultivation age would be selected. On the other hand, with the lack of quality markers, it is difficult to control the quality of D. nobile to treat hyperglycemic syndrome. (2) Methods: The effects of D. nobile cultivated at year 1 and year 3 were checked on alloxan-induced diabetic mice while their body weight, diet, water intake, and urinary output were monitored. Moreover, levels of glycosylated serum protein and insulin were measured using Elisa kits. The constituents of D. nobile were identified and analyzed by using UPLC-Q/trap. Quality markers were screened out by integrating the data from UPLC-Q/trap into a network pharmacology model. (3) Results: The D. nobile cultivated at both year 1 and year 3 showed a significant effect on hyperglycemic syndrome at the high dosage level; however, regarding the significant level, D. nobile from year 1 showed the better effect. In D. nobile, most of the metabolites were identified as alkaloids and sesquiterpene glycosides. Alkaloids, represented by dendrobine, were enriched in D. nobile from year 1, while sesquiterpene glycosides were enriched in D. nobile from year 3. Twenty one metabolites were differentially expressed between D. nobile from year 1 and year 3. The aforementioned 21 metabolites were enriched to 34 therapeutic targets directly related to diabetes. (4) Conclusions: Regarding the therapy for hyperglycemic syndrome, D. nobile cultivated at year 1 was more recommended than that at year 3. Alkaloids were recommended to be used as markers to control the quality of D. nobile for hyperglycemic syndrome treatment.

[Charcoal-frying process and quality markers of Sanguisorbae Radix based on hemostatic effect].

Studies have reported that the hemostatic effect of Sanguisorbae Radix(SR) is significantly enhanced after processing with charcoal. However, the standard components(tannins and gallic acid) specified in the Chinese Pharmacopeia decrease in charcoal-fried Sanguisorbae Radix(CSR), which is contrast to the enhancement of the hemostatic effect. Therefore, this study aimed to optimize the charcoal-frying process of SR based on its hemostatic efficacy and comprehensively analyze the components of SR and its processed products, thus exploring the material basis for the hemostatic effect. The results indicated that SR processed at 250 ℃ for 14 min(14-min CSR) not only complied with the description in the Chinese Pharmacopeia but also demonstrated improved blood-coagulating and blood-adsorbing effects compared with raw SR(P<0.05). Moroever, 14-min CSR reduced the bleeding time in the rat models of tail snipping, liver bleeding, and muscle injury, surpassing both raw and excessively fried SR(16 min processed) as well as tranexamic acid(P<0.05). Ellagitannin, ellagic acid, methyl gallate, pyrogallic acid, protocatechuic acid, Mg, Ca, Mn, Cu, and Zn contributed to the hemostatic effect of CSR over SR. Among these substances, ellagitannin, ellagic acid, Mg, and Ca had high content in the 14 min CSR, reaching(106.73±14.87),(34.86±4.43),(2.81±0.23), and(1.21±0.23) mg·g~(-1), respectively. Additionally, the color difference value(ΔE~*ab) of SR processed to different extents was correlated with the content of the aforementioned hemostatic substances. In summary, this study optimized the charcoal-frying process as 250 ℃ for 14 min for SR based on its hemostatic effect. Furthermore, ellagic acid and/or the powder chromaticity are proposed as indicators for the processing and quality control of CSR.

[Discrimination of anti-tumor and cardioprotective effect quality markers from Aidi Injection based on "spider web" mode].

Chinese medicinal preparations play an equally important role in reducing toxicity and treating tumors. Few studies discriminate the quality markers(Q-markers) conferring different therapeutic effects of traditional Chinese medicine preparations. Therefore, we take Aidi Injection(AD) as an example to comprehensively identify the Q-markers of anti-tumor and cardioprotective effects based on the "spider web" mode. Firstly, based on the principle of measurability, the chemical components in the prescription were qualitatively analyzed, and then the components with high content and capable to be measured were quantitatively analyzed as measurable evaluation indexes. Based on the principle of stability, the effects of light and temperature on the content of each component of AD were investigated as indicators of stability. Based on the principle of compatibility, the compounds were classified according to the law of compatibility of sovereign, minister, assistant, and guide medicinal materials in the prescription. Based on the principle of efficacy, the anti-tumor and antiangiogenic activities of the Q-markers were evaluated, and their synergistic effects with doxorubicin(DOX) in inhibiting tumorigenesis and angiogenesis and lowering cardiotoxicity were evaluated as the evaluation indexes of effectiveness. The seven-dimensional spider web of "compatibility-content-stability-antitumor activity-synergistic anti-tumor activity with DOX-antiangiogenic activity-synergistic anti-angiogenic activity with DOX" and the four-dimensional spider web of "compatibility-content-stability-protective effects against DOX-induced myocardial toxicity" were established, on the basis of which the Q-markers of anti-tumor and cardioprotective effects of AD were comprehensively analyzed. The results showed that 12 components were selected as the Q-markers of AD, among which cantharidin, ginsenoside Re, ginsenoside Rb_1, astragaloside Ⅱ, cryptochlorogenic acid, and ginsenoside Rg_2 were the anti-tumor Q-markers of AD. Ginsenoside Rd, isofraxidin, syringin, eleutheroside E, calycosin-7-O-ß-D-glucoside, and azelaic acid were the cardioprotective Q-markers of AD. Taking into account both the anti-tumor and cardioprotective effects, these Q-markers could cover the four herbs constituting the prescription. The findings provides a scientific basis for the quality control of AD and an effective method for identifying comprehensive and reasonable Q-markers for the two effects of Chinese medicinal preparations.

[Research progress in raw and processed Raphani Semen and prediction of quality markers].

Raphani Semen, with both edible and medicinal values, is a typical Chinese herbal medicine with different effects before and after processing. The raw helps ascending and the cooked helps descending. This paper comprehensively summarizes the differences in chemical constituents and pharmacological effects between raw and processed Raphani Semen that are reported in recent years. Based on the principle of quality markers(Q-markers) of traditional Chinese medicines, the chemical constituent sources, chemical constituent detection techniques, and correlation between bidirectional regulatory efficacy and chemical constituents are compared between raw and processed Raphani Semen. The results suggest that sulforaphene and glucoraphanin could be used as candidate Q-markers of raw and processed Raphani Semen, respectively. This review is expected to provide a reference for further research on the processing, new drug development, and improvement of safety and effectiveness of Raphani Semen in clinical application.

[Prediction of quality markers and medicinal value of sea buckthorn leaves based on network pharmacology, content determination, and activity evaluation].

The leaves of sea buckthorn(Hippophae rhamnoides), considered as common food raw materials, have records of medicinal use and diverse pharmacological activities, showing a potential medicinal value. However, the active substances in the sea buckthorn leaves and their mechanisms of action remain unclear. In addition, due to the extensive source and large variety variations, the quality evaluation criteria of sea buckthorn leaves remain to be developed. To solve the problems, this study predicted the main active components, core targets, key pathways, and potential pharmacological effects of sea buckthorn leaves by network pharmacology and molecular docking. Furthermore, ultra-performance liquid chromatography with diode-array detection(UPLC-DAD) was employed to determine the content of active components and establish the chemical fingerprint, on the basis of which the quality markers of sea buckthorn leaves were predicted and then verified by the enzyme activity inhibition method. The results indicated that sea buckthorn leaves had potential therapeutic effects on a variety of digestive tract diseases, metabolic diseases, tumors, and autoimmune diseases, which were consistent with the ancient records and the results of modern pharmacological studies. The core targets of sea buckthorn leaves included PTPN11, AKT1, PIK3R1, ESR1, and SRC, which were mainly involved in the PI3K-AKT, MAPK, and HIF-1 signaling pathways. In conclusion, the active components of sea buckthorn leaves are associated with the rich flavonoids and tannins, among which quercitrin, narcissoside, and ellagic acid can be used as the quality markers of sea buckthorn leaves. The findings provide a reference for the quality control and further development and utilization of sea buckthorn leaves as medicinal materials.

[Identification of Q-markers for Schisandrae Sphenantherae Fructus in treating drug-induced liver injury based on network pharmacology, fingerprint and quantitative analysis].

This study aims to establish the ultra-performance liquid chromatography(UPLC) fingerprint and multi-indicator quantitative analysis method for Schisandrae Sphenantherae Fructus(SSF) and to screen out the potential quality markers(Q-markers) of hepatoprotection based on network pharmacology. The similarity analysis was performed using the Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System, which showed that the similarity of the fingerprints of 15 samples from different regions ranged from 0.981 to 0.998. Eighteen common components were identified, from which 3 differential components were selected by cluster analysis and principal component analysis. The "component-target-pathway" network was built to predict the core components related to the hepatoprotective effects. Fourteen core components were screened by network pharmacology. They acted on the targets such as AKT1, CCND1, CYP1A1, CYP3A4, MAPK1, MAPK3, NOS2, NQO1, and PTGS2 to regulate the signaling pathways of lipid metabolism and atherosclerosis, hepatitis B, interleukin-17, and tumor necrosis factor. Considering the chemical measurability, characteristics, and validity, schisantherin A, anwulignan, and schisandrin A were identified as the Q-markers. The content of schisantherin A, anwulignan, and schisandrin A in the test samples were 0.20%-0.57%, 0.13%-0.33%, and 0.42%-0.70%, respectively. Combining the fingerprint, network pharmacology, and content determination, this study predicted that schisantherin A, anwulignan, and schisandrin A were the Q-markers for the hepatoprotective effect of SSF. The results can provide reference for improving the quality evaluation standard and exploring the hepatoprotective mechanism of SSF.

[Screening of quality markers and activity verification of Glycyrrhizae Radix et Rhizoma based on small molecule compound-protein interaction].

In order to solve the problem of weak correlation between quality control components and efficacy of Glycyrrhizae Radix et Rhizoma, this study detected the interaction between small molecular chemical components of Glycyrrhizae Radix et Rhizoma and total proteins of various organs of mice by fluorescence quenching method to screen potential active components. The 27 chemical components in Glycyrrhizae Radix et Rhizoma were detected by HPLC and their deletion rates in 34 batches of Glycyrrhizae Radix et Rhizoma were calculated. Combined with the principle of component effectiveness and measurability, the potential quality markers(Q-markers) of Glycyrrhizae Radix et Rhizoma were screened. RAW264.7 macrophage injury model was induced by microplastics. The cell viability and nitric oxide content were detected by CCK-8 and Griess methods. The levels of inflammatory factors(TNF-α, IL-1ß, IL-6, CRP) and oxidative stress markers(SOD, MDA, GSH) were detected by the ELISA method to verify the activity of Q-markers. It was found that the interaction strength between different chemical components and organ proteins in Glycyrrhizae Radix et Rhizoma was different, reflecting different organ selectivity and 18 active components were screened out. Combined with the signal-to-noise ratio of the HPLC chromatographic peaks and between-run stability of the components, seven chemical components such as liquiritin apioside, liquiritin, isoliquiritin apioside, isoliquiritin, liquiritigenin, isoliquiritigenin and ammonium glycyrrhizinate were finally screened as potential Q-markers of Glycyrrhizae Radix et Rhizoma. In vitro experiments showed that Q-markers of Glycyrrhizae Radix et Rhizoma could dose-dependently alleviate RAW264.7 cell damage induced by microplastics, inhibit the secretion of inflammatory factors, and reduce oxidative stress. Under the same total dose, the combination of various chemical components could synergistically enhance anti-inflammatory and antioxidant effects compared with the single use. This study identified Q-markers related to the anti-inflammatory and antioxidant effects of Glycyrrhizae Radix et Rhizoma, which can provide a reference for improving the quality control standards of Glycyrrhizae Radix et Rhizoma.

[Research progress on Huangqi Guizhi Wuwu Decoction and predictive analysis of quality markers].

Huangqi Guizhi Wuwu Decoction is a classic prescription in traditional Chinese medicine(TCM) and is known for its effects of tonifying Qi, warming the meridians, and promoting blood circulation to alleviate obstruction. It is primarily used to treat conditions characterized by Qi stagnation, Yang deficiency, and obstruction, and it exhibits pharmacological effects such as immune regulation, anti-inflammation, analgesia, protection of the cardiovascular and cerebrovascular systems, itch relief, reduction of frostbite symptoms, antioxidative stress, promotion of cell apoptosis, and kidney protection. In modern clinical practice, it is commonly used to treat acute myocardial infarction, sequelae of cerebral infarction, cervical spondylosis, frozen shoulder, lower limb arteriosclerosis, lower limb vascular disorders, peripheral neuropathy in diabetes, and lupus nephritis. Recent research has focused on the chemical components, pharmacological effects, and clinical applications of Huangqi Guizhi Wuwu Decoction. Based on the "five principles" of quality markers(Q-markers) in TCM, this study predicted and analyzed the Q-markers of Huangqi Guizhi Wuwu Decoction. It suggested that astragaloside Ⅳ, formononetin, kaempferol, quercetin, cinnamic acid, cinnamaldehyde, 6-gingerol, paeoniflorin, albiflorin, and gallic acid could serve as Q-markers for Huangqi Guizhi Wuwu Decoction. The findings of this study can provide references for quality control of Huangqi Guizhi Wuwu Decoction and the development of new Chinese medicinal formulations.

[Identification of quality markers of Gei Herba based on analytic hierarchy process-entropy weight method and network pharmacology].

Analytic hierarchy process(AHP)-entropy weight method(EWM) and network pharmacology were employed to identify the potential quality markers(Q-markers) of Gei Herba. According to the new concept of Q-markers in traditional Chinese medicine(TCM), the AHP-EWM was applied to quantitatively identify the Q-markers of Gei Herba. The AHP was used for the weight analysis of primary indicators(factor layer), and the EWM for the analysis of literature and experimental data of secondary indicators(control layer). In addition, network pharmacology was employed to build the "component-target-disease-efficacy" network for Gei Herba, and the components showing strong associations with the Qi-replenishing, spleen-invigorating, blood-tonifying, Yin-nourishing, lung-moistening, and phlegm-resolving effects of Gei Herba were screened out. According to the results of AHP-EWM and network pharmacology, four components, i.e., ellagic acid, gallic acid, gemin G, and gemin C, were finally identified as potential Q-markers of Gei Herba. In this study, the AHP-EWM and network pharmacology were employed to screen the Q-markers of Gei Herba, which provided ideas for the quantitative evaluation and identification of Q-markers of TCM.

[Prediction analysis of quality markers and resource evaluation of Artemisiae Argyi Folium based on chemical composition and network pharmacology].

This study is based on ultra-high-performance liquid chromatography(UPLC), gas chromatography-mass spectrometry(GC-MS), and network pharmacology methods to analyze and predict potential quality markers(Q-markers) of Artemisiae Argyi Folium. First, UPLC and GC-MS techniques were used to analyze the content of 12 non-volatile components and 8 volatile components in the leaves of 33 Artemisia argyi germplasm resources as candidate Q-markers. Subsequently, network pharmacology was employed to construct a "component-target-pathway-efficacy" network to screen out core Q-markers, and the biological activity of the markers was validated using molecular docking. Finally, cluster analysis and principal component analysis were performed on the content of Q-markers in the 33 A. argyi germplasm resources. The results showed that 18 candidate components, 60 targets, and 185 relationships were identified, which were associated with 72 pathways related to the treatment of 11 diseases and exhibited 5 other effects. Based on the combination of freedom and component specificity, six components, including eupatilin, cineole, ß-caryophyllene, dinatin, jaceosidin, and caryophyllene oxide were selected as potential Q-markers for Artemisiae Argyi Folium. According to the content of these six markers, cluster analysis divided the 33 A. argyi germplasm resources into three groups, and principal component analysis identified S14 as having the highest overall quality. This study provides a reference for exploring Q-markers of Artemisiae Argyi Folium, establishing a quality evaluation system, further studying its pharmacological mechanisms, and breeding new varieties.

[Research progress in chemical constituents, pharmacological effects, and clinical application of Curcuma wenyujin and prediction of its quality markers].

Curcuma wenyujin, as one of the eight Daodi-herbs in Zhejiang province, is widely used. It has the effects of eliminating stasis and dissipating mass, moving Qi and activating blood, and clearing heart and relieving depression. Modern studies have shown that it has anti-tumor, anti-inflammatory, anti-oxidation, anti-thrombus and liver-protecting effects and mainly contains sesquiterpenoids, monoterpenoids, diterpenoids, and curcumins. This paper reviews the research progress in the chemical constituents and pharmacological effects of C. wenyujin in the last decade, discusses the modern clinical applications combined with the traditional efficacy, and predicts its quality markers(Q-markers) from plant consanguinity, medicinal properties, efficacy, processing and measurability of chemical components based on the theory of Q-markers, so as to provide a reference for the establishment of a scientific quality evaluation system and the research and application of this herb in the future.

Screening and evaluation of quality markers of Radix Cudramiae for liver disease based on an integrated strategy of in vivo pharmacokinetics and in vitro HPLC fingerprint.

Radix Cudramiae, the dried root of Cudrania cochinchinensis (Lour.) Kudo et Masam., is a valuable ethnomedicine with outstanding antihepatitis activity. However, the lack of reports on quality markers (Q-markers) hindered its quality evaluation and standardization, as a result restricted its clinical application. This paper aimed to discover the Q-markers of Radix Cudramiae with a comprehensive strategy based on in vivo pharmacokinetics and in vitro HPLC fingerprint. A rapid and sensitive ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) analytical method was firstly developed and validated for simultaneous determination of six potential active ingredients (eriodictyol, dihydrokaempferol, dihydromorin, kaempferol, naringenin and morin) of Radix Cudramiae in rat plasma and tissues, which was successfully applied to the holistic comparison of pharmacokinetics and tissue distribution between normal and acute liver injury rats. On the other hand, a representative HPLC fingerprint of Radix Cudramiae was also established to elucidate the chemical profile for overall quality evaluation. Dihydrokaempferol-7-O-ß-D-glucoside (the naturally existed chemical formation of dihydrokaempferol) and kaempferol screened out with high exposure levels in vivo and high resolution in HPLC fingerprint were finally selected as Q-markers of Radix Cudramiae. To the best of our knowledge, it was the first time for people to discover in vivo properties and pharmacokinetic parameters of components in Radix Cudramiae, as well as the first report on its representative HPLC fingerprint. Also, the integrated strategy could offer an effective way for TCMs Q-markers screening.

Establishment of a multi-strategy platform for quality control and quality markers screen of Mailuoshutong pill.

Thromboangiitis obliterans (TAO) is a non-atherosclerotic segmental inflammatory occlusive disease with a high recurrence rate, high disability rate, difficulty to cure, and poor prognosis. It has been clinically proven that Mailuoshutong pill (MLSTP) is an effective traditional Chinese medicine for treating TAO. As MLSTP contains hundreds of chemical components, the quality control of which is a challenge in the development of reliable quality evaluation metrics. This study aimed to evaluate the quality uniformity of MLSTP by establishing a multi-strategy platform. In the present study, the key targets and signaling pathways of MLSTP treating TAO were predicted by network pharmacology. It was further shown by in vivo validation experiments that MLSTP exerted therapeutic effects on TAO by modulating the PI3K-AKT signaling pathway, VEGF signaling pathway, and HIF-1 signaling pathway. In addition, UPLC fingerprints of MLSTP were established and screened for potential Q-markers of MLSTP in combination with network pharmacology results. Six components, including chlorogenic acid, liquiritin, paeoniflorin, calycosin-7-glucoside, berberine, and formononetin, were selected as potential quality markers (Q-markers) in MLSTP. Finally, the quantitative analysis of multi-components by single marker (QAMS) method was established to quantitatively analyze the six potential Q-markers, and the results were consistent with those obtained by the external standard method (ESM). Taken together, the multi-strategy platform established in this study would be conducive to the Q-markers screening and quality control of MLSTP, improving the quality standard of MLSTP and providing favorable assurance for the clinical management of TAO.

Quality markers of Guchang Zhixie pills based on multicomponent qualitative and quantitative analysis combined with network pharmacology and chemometric analysis.

Traditional Chinese medicine Guchang Zhixie pills(GCZX) is one of the famous varieties of "Qin medicine" that has been extensively applied to treating irritable bowel syndrome(IBS). However, despite the acknowledged clinical advantages of GCZX there are significant constraints on its quality control and evaluation. The present study utilized UHPLC-Q-Exactive-Orbitrap-MS to analyze the chemical composition of GCZX. Additionally, network pharmacology approaches were utilized to explore the underlying mechanism by which blood components exert therapeutic effects in the treatment of IBS. Furthermore, the GCZX samples were evaluated for their quality on the basis of the qualitative results obtained from 25 batches of GCZX samples using fingerprinting; subsequently, multivariate statistical analysis methods were employed for further analysis. The results indicated the presence of 198 individual components. Among them, 17 prototype compounds were detected in the serum of rats that were administered with GCZX. The potential therapeutic mechanism of GCZX in the treatment of IBS may be associated with the modulation of the neurological system, the immunological system, and the inflammatory response. Moreover, a total of seven prominent peaks were identified after fingerprint analysis. The range of fingerprint similarity among the 25 batches of samples varied from 0.843 to 1.000. The application of chemometrics analysis successfully facilitated the categorical classification of 25 batches of GCZX into three distinct groups. Seven components hold significant importance and should be duly considered during the quality control process of GCZX. The present study can establish the Q-Markers of GCZX for IBS, thereby providing a foundation for investigating the theoretical underpinnings and elucidating the mechanisms underlying the therapeutic effects of GCZX in the treatment of IBS.

Herbal textual research of Belamcanda chinensis (L.) redouté and screening of quality-markers based on 'pharmacodynamics-substance'.

ETHNOPHARMACOLOGICAL RELEVANCE: Belamcanda chinensis (L.) Redouté is widely distributed in East Asia, such as China, Russia and North Korea. Belamcandae Rhizoma is the sun-dried rhizome of B. chinensis and has a long history of traditional medicinal use. It was first recorded in the Shennong's Herbal Classic, and has the effects of clearing heat and detoxifying, eliminating phlegm and benefiting the pharynx. AIM OF THE STUDY: To systematically study the source of Belamcandae Rhizoma, summarize the evolution of its medicinal properties, efficacy and the application history of its prescriptions, summarize its biological activity, phytochemistry, synthetic metabolic pathway and toxicology, and screen the Quality-Markers of Belamcandae Rhizoma according to the screening principle of traditional Chinese medicine Quality-Markers. MATERIALS AND METHODS: All information available on Belamcandae Rhizoma was collected using electronic search engines, such as Pubmed, Web of Science, CNKI, WFO (www.worldfloraonline.org), MPNS (https://mpsn.kew.org), Changchun University of Traditional Chinese Medicine Library collections, Chinese Medical Classics. RESULTS: The source of Belamcandae Rhizoma is B. chinensis of Iridaceae. It has a long history of application in China. It has the effects of clearing heat and detoxifying, eliminating phlegm and promoting pharynx. Modern pharmacological studies have shown that it has anti-inflammatory, anti-oxidation, anti-tumor and other physiological activities, and is safe and non-toxic at normal application doses. At present, tectoridin, iridin, tectorigenin, irigenin and irisflorentin are identified as the Quality-Markers of Belamcandae Rhizoma. CONCLUSIONS: As a traditional Chinese medicine, Belamcandae Rhizoma has a long history of application, and multifaceted studies have demonstrated that Belamcandae Rhizoma is a promising Chinese medicine with good application prospects. By reviewing and identifying the Quality-Markers of Belamcandae Rhizoma, this study can help to establish the evaluation procedure of it on the one hand, and identify the shortcomings research on the other hand. Currently, there are few studies on the anabolism and toxicology of it, and future studies may focus on its in vivo processes, toxicology and adverse effects.

Chinmedomics strategy for elucidating the effects and effective constituents of Danggui Buxue Decoction in treating blood deficiency syndrome.

Introduction: Danggui Buxue Decoction (DBD) is a clinically proven, effective, classical traditional Chinese medicine (TCM) formula for treating blood deficiency syndrome (BDS). However, its effects and effective constituents in the treatment of BDS remain unclear, limiting precise clinical therapy and quality control. This study aimed to accurately evaluate the effects of DBD and identify its effective constituents and quality markers. Methods: BDS was induced in rats by a combined injection of acetylphenylhydrazine and cyclophosphamide, and the efficacy of DBD against BDS was evaluated based on body weight, body temperature, energy metabolism, general status, visceral indices, histopathology, biochemical markers, and metabolomics. The effects of DBD on urinary and serum biomarkers of BDS were investigated, and the associated metabolic pathways were analyzed via metabolomics. Guided by Chinmedomics, the effective constituents and quality markers of DBD were identified by analyzing the dynamic links between metabolic biomarkers and effective constituents in vivo. Results: DBD improved energy metabolism, restored peripheral blood and serum biochemical indices, and meliorated tissue damage in rats with BDS. Correlation analyses between biochemical indices and biomarkers showed that 15(S)-HPETE, LTB4, and taurine were core biomakers and that arachidonic acid, taurine, and hypotaurine metabolism were core metabolic pathways regulated by DBD. Calycosin-7-glucoside, coumarin, ferulic acid sulfate, cycloastragenol, (Z)-ligustilide + O, astragaloside IV, acetylastragaloside I, and linoleic acid were identified as effective constituents improving the hematopoietic function of the rats in the BDS model. Additionally, calycosin-7-glucoside, ferulic acid, ligustilide, and astragaloside IV were identified as quality markers of DBD. Conclusion: The hematopoietic function of DBD was confirmed through analysis of energy metabolism, biochemical markers, histopathology, and metabolomics. Moreover, by elucidating effective constituents of DBD in BDS treatment, quality markers were confirmed using a Chinmedomics strategy. These results strengthen the quality management of DBD and will facilitate drug innovation.

Artificial aging conditions for Artemisia argyi leaves based on quality-inflammation-quality marker transformation.

BACKGROUND: Appropriate conditions for storage of Artemisia argyi leaves reduce irritation during treatment and increase the active ingredient content. Naturally aged A. argyi leaves (≥1 year) are optimal for moxibustion; however, this process is time-consuming and costly. A comprehensive understanding of the conditions for artificial aging of A. argyi leaves and the mechanism of quality-marker conversion are required to guarantee A. argyi quality and moxibustion efficacy. OBJECTIVE: To identify the optimal conditions for artificial aging of A. argyi leaves and clarify the mechanism of quality-marker conversion. METHOD: Gas chromatography (GC), high-performance liquid chromatography (HPLC), colorimeter (CD), and near-infrared spectroscopy (NIRS) were used to determine the chemical composition of A. argyi leaves before and after artificial and natural (1 year) aging and to determine the optimal artificial aging conditions. The effects of both artificially and naturally aged A. argyi leaves were then evaluated in a mouse model of ulcerative colitis (UC). The main chemical components of aged A. argyi leaves were then analyzed to determine quality-markers and the transformation mechanism. RESULTS: Comprehensive analysis of volatile and non-volatile components, color values, and characteristic near-infrared spectra revealed that the quality of artificially aged A. argyi leaves was similar to that of naturally aged A. argyi leaves. In the mouse model, artificially and naturally aged A. argyi leaves not only improved the symptoms of UC with the same therapeutic effects, but also safeguarded the barrier of the colonic mucosa and prevented the release of colitis-related substances. In addition, the content of caffeic acid converted from L-phenylalanine in A. argyi leaves increased during the aging process. CONCLUSION: Conditions for artificial aging of A. argyi leaves were identified for the first time, and the equivalent efficacy of artificially aged A. argyi leaves and naturally aged A. argyi leaves for improving UC was confirmed. This method for artificial aging of A. argyi leaves not only reduces the time and cost associated with this process, but also provides technical support to ensure the quality and stability of artificially aged A. argyi leaves. In addition, caffeic acid was identified as a potential quality-marker for establishing standards and specifications for aging A. argyi leaves for the first time, and its possible transformation mechanism was preliminarily elucidated.

Overlooked poor-quality patient samples in sequencing data impair reproducibility of published clinically relevant datasets.

BACKGROUND: Reproducibility is a major concern in biomedical studies, and existing publication guidelines do not solve the problem. Batch effects and quality imbalances between groups of biological samples are major factors hampering reproducibility. Yet, the latter is rarely considered in the scientific literature. RESULTS: Our analysis uses 40 clinically relevant RNA-seq datasets to quantify the impact of quality imbalance between groups of samples on the reproducibility of gene expression studies. High-quality imbalance is frequent (14 datasets; 35%), and hundreds of quality markers are present in more than 50% of the datasets. Enrichment analysis suggests common stress-driven effects among the low-quality samples and highlights a complementary role of transcription factors and miRNAs to regulate stress response. Preliminary ChIP-seq results show similar trends. Quality imbalance has an impact on the number of differential genes derived by comparing control to disease samples (the higher the imbalance, the higher the number of genes), on the proportion of quality markers in top differential genes (the higher the imbalance, the higher the proportion; up to 22%) and on the proportion of known disease genes in top differential genes (the higher the imbalance, the lower the proportion). We show that removing outliers based on their quality score improves the resulting downstream analysis. CONCLUSIONS: Thanks to a stringent selection of well-designed datasets, we demonstrate that quality imbalance between groups of samples can significantly reduce the relevance of differential genes, consequently reducing reproducibility between studies. Appropriate experimental design and analysis methods can substantially reduce the problem.

Discovery of quality markers of Phyllanthus emblica by integrating chromatographic fingerprint, serum pharmacochemistry and network pharmacology.

Phyllanthus emblica (P. emblica) is a vital medicinal plant with both medical and edible values. In the quality standard of P. emblica listed by the Chinese Pharmacopoeia, gallic acid is used as the index component for the content determination. However, a large number of tannin components can be decomposed into gallic acid during its refluxing extraction process, thus affecting the accuracy and specificity of the content determination. Thus, the index component used for the quality control needs to be further determined. In this study, the quality markers of P. emblica was specified by integrating chromatographic fingerprint, serum pharmacochemistry and network pharmacology. The chromatographic fingerprint of 18 batches of P. emblica samples were established by ultra-high-performance liquid chromatography (UPLC), and 8 differential components causing quality fluctuation were identified by chemometric analysis and UPLC-Q-TOF/MS analysis. Afterwards, 14 prototype migration components absorbed into the blood after gavage administration to rats were identified by UPLC-Q-TOF/MS analysis. Subsequently, a network pharmacology approach was used to construct the component-target-disease-pathway network, resulting in the identification of 22 components responsible for efficacy of P. emblica. Finally, by integrating the above results, ellagic acid was screened out as one of the Q-markers and could be employed as a quantitative component of P. emblica to improve the quality standard. The strategy is also informative for discovering Q-markers of other TCMs.