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The gastroprotective effects of polysaccharides had become a hot topic in the field of functional polysaccharides research. Three polysaccharides, namely HPS-80-1, HPS-80-2, and HPS-80-3 were purified by DEAE-52 column chromatography. The thermodynamic characteristics, scanning electron microscopy, and Congo red experimental results of the above polysaccharides were greatly distinctive. Then a mature GES-1 oxidative stress cell model induced by H2O2 was established to screen out subsequent research subjects. It turned out that HPS-80-1 had a desirable protective effect, which was confirmed by analyses of cell cycle & apoptosis, and oxidative stress-related factors in the cell culture media, and so on. Furthermore, Structural features demonstrated that the backbone of HPS-80-1 appeared to mainly consist of →4)-α-D-Glcp-(1→, →4,6)-β-L-Glcp-(1→, and →6)-α-D-Galp-(1→, with branches at O-1, O-4, and O-6 position consisting of →2,4)-β-D-Rhap-(1→, →1)-α-D-Galp-(4→, and →3,4)-α-D-Manp-(1→. It was speculated that the excellent gastric mucosal protective activity of HPS-80-1 may be due to the high amount of glucose in the backbone. In addition, it was also related to the anti-inflammatory activity and antioxidant bases such as (1 → 4)-Glcp and (1 → 6)-Galp in the structure of HPS-80-1. These findings provide a scientific basis for further utilization of polysaccharides from Radix Hedysari.

Objective To evaluate the quality of Arnebiae Radix (AR) and Dictamni Cortex (DC) and study the efficacy of herbal extracts of these two herbs on the treatment of allergic contact dermatitis (ACD). Methods Qualitative and quantitative analysis of effective components was performed using High Performance Thin Layer Chromatography (HPTLC), High Performance Liquid Chromatography (HPLC), and HPLC-Quadrupole Time of Flight-Mass Spectrometry (HPLC-QTOF-MS). In vitro allergic ACD 3D model was established by incubating 3D reconstructed human epidermis (RHE) with skin sensitizer, potassium dichromate. A total of 65 gene expression that were associated with ACD, which included 24 antioxidant responsive element (ARE) and 41 SENS-IS genes were quantified by qRT-PCR. More than or equal to 10 ARE genes and 18 SENN-IS genes were induced by 1.3-fold, demonstrating the successful establishment of in vitro ACD model. Oil extracts of AR and DC were applied on the in vitro ACD model to study the efficacy. Results Batch 3 of AR and batch 2 of DC showed presence of all active ingredients with the highest concentrations. Active ingredients of the herbs were extracted using a special oil and formulated into herbal oil extracts. The herbal oil extracts were able to down regulate the induced genes in the in-vitro ACD skin model, bringing the tissue back to homeostatic status. Conclusion The oil extracts showed the potent efficacy of using AR and DC in ACD treatment. The combination study will be done to optimize the formulation ratio which will be developed into a topical cream.

Although Polygoni Multiflori Radix (PMR) has been widely used as a tonic and an anti-aging remedy for centuries, the extensively reported hepatotoxicity and potential kidney toxicity hindered its safe use in clinical practice. To better understand its toxicokinetics, the current study was proposed, aiming to evaluate the biodistributions of the major PMR components including 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucopyranoside (TSG), emodin, emodin-8-O-β-D-glucopyranoside (EMG) and physcion as well as their corresponding glucuronides following bolus and multiple oral administrations of PMR to rats. Male Sprague-Dawley rats received a bolus dose or 21 days of oral administrations of PMR concentrated granules at 4.12 g/kg (equivalent to 20.6 g/kg raw material). Fifteen minutes after bolus dose or the last dose on day 21, rats were sacrificed and the blood, liver, and kidney were collected for the concentration determination of both parent form and glucuronides of TSG, emodin, EMG, and physcion by HPLC-MS/MS. Among all the tested analytes, TSG, EMG, EMG glucuronides in liver and TSG, EMG, as well as all the glucuronides of these analytes in the kidney demonstrated the most significant accumulation after multiple doses. Moreover, the levels of the parent analytes were all significantly higher in liver and kidney in comparison to their plasma levels. Strong tissue binding of all four analytes and accumulation of TSG, EMG, and EMG glucuronides in the liver and TSG, EMG, as well as the glucuronides of all four analytes in the kidney after multiple dosing of PMR were considered to be associated with its toxicity.

The dried root of Dipsacus asperoides is known as Radix Dipsaci extract(RDE). It's a kidney-toning herbal medication with a lengthy track record of safe usage in the treatment of bone fractures and joint disorders. The drug rosiglitazone (RSG) causes an imbalance in bone remodelling, which results in increased apoptotic death of osteogenic cells and decreased bone production. The goal of this study was to investigate the effects of RDE on RSGinduced bone loss in diabetic rats in a systematic way. Five groups of six Wistar albino rats were studied: control (vehicle therapy), Streptozotocin (diabetes) group, RDE group, Rosiglitazone, and Rosiglitazone +RDE group. Insulin, oxidative stress, and bone turnover markers in the blood were all detected using ELISA tests. When compared to diabetic control rats, RDE therapy significantly raised insulin and osteocalcin levels. RDE may be able to prevent diabetic osteoporosis by boosting osteogenesis and lowering oxidative stress in the bone.These findings support the use of RDE as a bone loss inhibiting in diabetics. Well-designed clinical trials are likely to yield further scientific evidence on its bone-protective effects and safety. Keywords: Radix Dipsaci, Diabetic osteoporosis, Rosiglitazone.

Objectives: This study aims to describe the utilization of herbal formulas from Wenrejingwei by using network analysis and understand the treatment of acute exogenous febrile diseases.Methods: We constructed a matrix of high-frequency herbal combinations (HCs) from Wenrejingwei and Shang Han Lun and cluster networks based on cohesive analysis. Network analysis was performed to compare the results.Results: The results of the high-frequency HC network in Wenrejingwei showed cohesive patterns in three categories corresponding to dampness-heat and warm-fever treatment. Compared to the Shang Han Lun network, the Wenrejingwei network indicated a careful approach in the use of pungent and warm herbs such as Guizhitang. Moreover, the combination of Scutellaria baicalensis and Coptis chinensis along with the use of herbs strengthening yin, such as Ginseng Radix and Liriopes Radix, provide evidence of a holistic approach in the treatment of exogenous febrile diseases by considering the balance of the human body damaged by heat.Conclusion: The results of this study could help select appropriate herbal formulas and treatment methods for treating Onbyeong and modern acute febrile infectious diseases.

A rapid, sensitive and convenient method based on ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) was developed and validated for the simultaneous quantification of calycosin-7-O-β-d-glucoside (CCSG), ononin, calycosin, (6aR,11aR)-9,10-dimethoxypterocarpan-3-O-β-d-glucopyanoside (DPPG), and 7,2′-dihydroxy-3′,4′-dimethoxyisoflavan-7-O-β-d-glucopyanoside (DIFG) in rat plasma after oral administration of the methanol extraction from Radix Astragali. Theophylline played the role of internal standard (IS). Preparation of plasma samples by liquid-liquid extraction method with ethyl acetate after precipitation of protein with methanol. The analytes were detected with a triple quadrupole tandem mass spectrometery (MS) in multiple reaction monitoring (MRM) mode and a positive ion electrospray ionization (ESI). The method was validated with the concentration ranges of 1.96–62.69 ng/mL for CCSG, 1.70–54.5 ng/mL for ononin, 1.85–59.06 ng/mL for calycosin, 2.14–137.24 ng/mL for DPPG and1.96–125.25 ng/mL for DIFG, respectively. The method had the lower limit of quantification (LLOQ) with 0.49, 0.21, 0.92, 1.07, and 0.98 ng/mL for CCSG, ononin, calycosin, DPPG and DIFG respectively, and the precision less than 10%. The RSD of the accuracy was in the range of −4.35–8.91%. The results may be helpful to provide more accurate references to clinical application of this herb.

Introduction Codonopsis Radix (CR) is an edible food and traditional Chinese herb medicine that is widely used in China and Southeast Asia. Saccharides, including fructo-oligosaccharides (FOS) and polysaccharides, are among the most important active substances in CR. However, a quality evaluation of CR based on oligosaccharides has not been conducted. Objective This study aimed to establish a high-performance liquid chromatography coupled with charged aerosol detector method (HPLC-CAD) for the quality evaluation of CR and processed products based on analysis of monosaccharides and oligosaccharides. Method A sensitive and rapid HPLC-CAD method for the simultaneous determination of two monosaccharides (D-fructose and D-glucose), sucrose, and FOS (GF2-GF6) was established to evaluate the quality of CR for the first time. In the present study, 65 batches of CR from three species of the genus Codonopsis were analysed using multivariate statistical techniques. Furthermore, the effects of cultivation management measures (plant growth retardants supply, harvesting time, and growth period) and primary process (drying methods) in the production areas on the target compounds were studied by analysing 34 batches of processed samples. Results Different varieties of CR resulted in considerably different saccharide contents. Cultivation management measures and processing method remarkably affected the quality of CR. Low concentration of plant growth retardants was recommended. The best harvest time is in October after 4 years of growth. Dryer-drying was suggested to meet the requirement for large-scale processing. Conclusion This method would provide an efficient analytical tool for monosaccharides and oligosaccharides of CR and contribute to the improvement of CR quality.

As a valuable medicine food homology plant, Codonopsis Radix has been widely used in China. This study aimed to analyze the content of nine potentially toxic elements in three Codonopsis Radix varieties and evaluate their health risks to the human body. In this study, a total of 147 samples were collected from five provinces in China. The content of nine potentially toxic elements (Al, Mn, Cu, Cr, Ni, As, Pb, Cd, and Hg) were determined by ICP-MS. Results showed that the average contents of Al, Mn, Cu, Cr, Ni, Pb, As, Cd, and Hg were 486.81, 30.30, 5.59, 1.38, 1.24, 0.40, 0.20, 0.16, and 0.11 mg/kg, respectively. The Codonopsis tangshen Oliv. samples from Hubei showed the highest contents of eight elements (Al, Mn, Cr, Ni, Pb, As, Cd, and Hg) among three varieties, and the highest Cu level was found in Codonopsis pilosula (Franch.) Nannf. samples from Shanxi. The content of toxic elements in three Codonopsis Radix varieties showed significant differences (p

Objective To retrieve the core drug of osteoarthritis in clinic using Data Mining, predict the drug molecular action target through the Network Pharmacology, identify the key nodes of the interaction by combining with the related targtes of osteoarthritis, explore the pharmacological mechanism of Traditional Chinese Medicine against osteoarthritis and other possible mechanisms of actions. Methods to retrieve the commonly used therapeutic formulations for osteoarthritis patients in clinical with PubMed, CNKI, VIP, CBM, WanFang Database and other databases, and screen out the core drugs through the Ancient and Modern Medical Case Cloud Platform and software Gephi, filter out the core drug molecules and targets combined with TCMSP database and the targets of osteoarthritis in Genecard and OMIM database, plunge those data into R project and Cytoscape to construct the intersection model of Drug molecule-osteoarthritis, establish PPI network and GO and conduct KEGG enrichment analysis with String database. Vina molecular docking was finally implemented to draw molecular docking diagram, and the results were analyzed after comprehensive analysis. Results The core drug pairs were identified as "Eucommiae Cortex - Achyranthis Bidentatae Radix" through correlation analysis, complex network analysis based on the coefficient. "Eucommiae Cortex - Achyranthis Bidentatae Radix" can intervene cell behavior through multiple pathways and regulate cell metabolism, cytokine synthesis, oxidative and cellular immunity with the help of topology analysis in String Database. Conclusions The core molecules of Quercetin and Kaempferol derived from "Eucommia bark - achyranthes" can change the spatial conformation of PTGSs by hydrogen bonding with PTGSs, the hydrophobic bonds and van der Waals forces generated by Baicalein, Wogonin and β-carotene, thereby changing the activity of PTGSs and affecting bone properties the process of osteoarthritis.

Approximate computing is an efficient approach for reducing computational costs. This method involves a trade-off between computational accuracy and the circuit’s power consumption, delay, and area. However, the accuracy requirements may differ for different applications. In some situations, precise results are required. Therefore, this paper proposes an accuracy-configurable radix-4 adder (ACRA), which uses the power gating technique to turn on or turn off the partial logic gates of an adder element dynamically to compute accurate or approximate results. When the ACRA operates in the approximate mode, the partial sum of one adder element is modified to reduce the error distance between the approximate and accurate results. A comparison of the ACRA with two state-of-the-art accuracy-configurable adders indicated that the ACRA achieved the best trade-off between the power–delay product and computational accuracy. In addition, in the image processing experiment conducted in this study, under half-approximate computation, the peak signal-to-noise ratio of the ACRA was less than 1 dB and its structural similarity index measure was maintained above 0.99. These results are superior to those obtained for other accuracy-configurable adders.

Radix Paeoniae Rubra (RPR) is a widely used herb medicine. To better understand the mechanism of RPR in the treatment of myocardial ischemia-reperfusion injury (MIRI), in this study, the network of protein–protein interaction of the RPR-MIRI targets was constructed and analyzed through network pharmacology and molecular docking. The enrichment analysis was performed and the network map was established, and the componenttarget network was then verified by molecular docking. In the result, there were 14 components and 52 targets related to MIRI. The results of Gene Ontology (GO) analysis displayed 182 biological processes, 44 cellular components, 56 molecular functions. 45 signal pathways were collected from Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, which were mainly related to Rap1, PI3 K-Akt signal pathway and so on. Molecular docking verified that the active components had lower binding energy with key targets, indicating that it had better binding activity. In conclusion, the treatment of RPR on MIRI is implemented through multi-component, multi-target and multi-pathway, which makes a provision for exploring the therapeutic mechanism of RPR and expanding its clinical application.

Herb pairs are the unique combinations of two relatively fixed herbs, intrinsically convey the basic idea of traditional Chinese medicine prescriptions. The compatibility of Radix ginseng and Schisandra chinensis has been used in traditional Chinese medicine for treating Alzheimer's disease for many years. However, there are few studies on Radix ginseng-Schisandra chinensis herb pair, and the underlying action mechanism is still unclear. In this study, the mechanism of Radix ginseng-Schisandra chinensis herb pair on Alzheimer's disease was investigated by using mass spectrometry-based urinary metabolomics method. 16 urinary endogenous metabolites were identified as potential biomarkers. Meanwhile, 10 biomarkers were quantified with tandem mass spectrometry. The study result showed that the brain pathologic symptoms of model rats were improved and the potential biomarkers were adjusted backwards significantly after the herb pair administration. The metabolic pathways linked to the herb pair-regulated endogenous biomarkers included phenylalanine and tyrosine metabolism, tryptophan metabolism, purine metabolism, and so on. The above metabolic pathways reflected that Radix ginseng-Schisandra chinensis herb pair mainly regulates abnormal energy metabolism, reduces inflammation and regulates gut microbiota and neurotransmitters in the treatment of Alzheimer's disease. This article is protected by copyright. All rights reserved.

Stemonae Radix (dried roots of Stemona japonica (Bl.) Miq., Stemona sessilifolia (Miq.) Miq., and Stemona tuberosa Lour.), a widely used traditional Chinese medicine (TCM), is also known as “Baibu” (Chinese: 百部). Stemonae Radix has a wide range of pharmacological effects, mainly used to treat respiratory diseases and as an insecticide. In this review, with the help of both published materials (such as ancient and modern books, monographs on medicinal plants, and the pharmacopoeia of different countries) and electronic databases (such as PubMed, Web of Science, and Google Scholar), we have summarized the up-to-date research progress in botany, traditional application, phytochemistry, pharmacology, toxicity, and quality control, and discussed the research prospects and development direction of Stemonae Radix and its origin plants. Up to now, more than 170 compounds were isolated and identified from the three official species of Stemonae Radix, mainly including Stemona alkaloids, Stemona stilbenoids and other components. This medicine has also exhibited pharmacological activities, including antitussive, antiviral, insecticidal, antitumor, antioxidant, and therapeutic effects on lung diseases. However, pharmacological reports most often attribute activities to various extracts, rather than specific compounds. This hampers the establishment of a connection between chemical constituents and pharmacological activities, resulting in a difficulty to identify the major active compounds. Therefore, in the future, it is necessary to design experiments to deeply understand the development and clinical use of Stemonae Radix.

The 14-membered cycloisodityrosine is the core structure of RA-series antitumor bicyclic peptides obtained from Rubia plants (Rubiaceae). In this study, an efficient method for the synthesis of cycloisodityrosines from commercially available l-tyrosine derivatives was developed. Using synthetic cycloisodityrosines and cycloisodityrosines with modified structures, several RA-VII analogues were designed and synthesized to explore structure–activity relationships of the cycloisodityrosine moiety of the RA-series peptides, and newly isolated natural peptides were synthesized to establish their structures. Graphic abstract

Polygoni Multiflori Radix Praeparata (PMRP) is used as Chinese herbal medicine with long history. However, reports about PMRP hepatotoxicity have increased recently, and producing area might be one reason. This article aims to figure out the relationship between producing area and hepatotoxic ingredients in PMRP. HPLC fingerprint for PMRP was established and the contents of gallic acid, trans-stilbene glycoside (TSG), emodin-8-O-β-D-glucoside (EG), emodin and physcion were determined. Clustering heatmap was implemented by TCMNPAS software，and principal component analysis was implemented by SPSS and SIMCA-P software. Hepatotoxic constituents’ contents of PMRP from separate producing area were different. PMRP from Guangxi had the highest content of gallic acid, TSG, EG, emodin and physcion, followed by Hubei, Guangdong, Guizhou, Yunnan. PMRP from Henan had the lowest contents of hepatotoxic components. Hepatotoxic components’ contents of PMRP in southern were higher than central China. This study carried out a preliminary qualitative and quantitative investigation on the PMRP from different producing places, which provided a basis for safe medication of PMRP.

Purpose: To determine the molecular mechanism involved in the anti-migraine effect of Asari Radix et Rhizoma (ARR) using network pharmacology. Methods: The compounds present in ARR were identified through information retrieval from literature and public databases, and were screened based on absorption, distribution, metabolism, excretion and toxicity. Target genes related to the selected compounds and migraine were identified or predicted from public databases. Hub genes in ARR against migraine were identified through analysis of interactions in overlapping genes between compounds and migraine target genes, based on STRING database. Gene enrichment analysis of overlapping genes was performed using Database for Annotation, Visualization and Integrated Discovery. Results: A total of 138 compounds were selected as potential bioactive compounds in ARR. Target genes related to the selected compounds (611 genes) and migraine (278 genes) were obtained, including 71 overlapping genes. The hub genes in the anti-migraine effect of ARR were BDNF, IL6, COMT, APP and TNF. Gene enrichment analysis showed the top 10 biological processes or pathways involved in the mechanism of anti-migraine action of ARR. The tissue source of the overlapping genes was not limited to the brain. The results from gene enrichment analysis revealed that the effect of ARR on migraine was holistic, which is characteristic of traditional Chinese medicines. Conclusion: Network pharmacology has been used to decipher the molecular mechanism involved in the action of ARR against migraine. The results provide a scientific basis for the clinical effect of ARR on migraine.

Background: Cancer cachexia is a complex disease secondary to cancer, and no specific therapy for it has been found. The Chinese herb Kushen (Radix Sophorae flavescentis) is the dried root of Sophora flavescens Aiton, which has been widely applied in treating digestive and urinary inflammatory diseases. Matrine, one of the main components of Radix Sophorae flavescentis, can alleviate cancer cachexia. Methods: Compounds from Radix Sophorae flavescentis were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The targets related to cancer cachexia were queried from the Therapeutic Target Database (http://db.idrblab.net), DisGeNET database (http://www.disgenet.org), and Search Tool for Interacting Chemicals database, related literature, and constructed cancer cachexia-protein network. Cancer cachexia-protein network was merged with compound-protein networks respectively using Cytoscape software as well as network topology data and key targets counting. Pathway enrichment analysis was conducted via the Database for Functional Annotation Bioinformatics Microarray Analysis. Protein crystal structures and compound structures were queried from RCSB and PubChem databases, respectively. Molecular docking was conducted using Discovery Studio software. Results: The anticancer cachexia compounds of Radix Sophorae flavescentis were screened as oxymatrine, matrine, and kurarinol, and targets such as BIRC2, TNF and STAT3 were found. The mechanisms of oxymatrine, matrine, and kurarinol have the characteristics of synergy and complementarity. Kurarinol has a mechanism similar to that of matrine, which includes the FoxO signaling pathway, insulin resistance and mTOR signaling pathway. TNF signaling pathway is a common signaling pathway of kurarinol, oxymatrine and matrine. Adipocytokine signaling pathway is the other common pathway of kurarinol and oxymatrine except for the TNF signaling pathway. Kurarinol can be successfully docked with CYCS, GPX2, BIRC7, etc., and kushenol C can be successfully docked with IKBKB and PIK3CD. Conclusion: Kurarinol, matrine, oxymatrine, and kushenol C may be the key compounds of Radix Sophorae flavescentis treating cancer cachexia. Additionally, TNF signaling pathway is the key pathway for the synergistic action of kurarinol, matrine and oxymatrine.

Qi-Yu-San-Long decoction (QYSLD) is a classic traditional Chinese medicine prescription consisting of ten types of herbal medicines, including Astragali Radix, Polygonati Odorati Rhizoma, Scolopendra, Pheretima, Solanum nigrum L., Hedyotis diffusa Willd., Coicis Semen, Euphorbia helioscopia L., Curcumae Rhizoma, and Fritillariae Cirrhosae Bulbus, combined in a ratio of 15∶5∶3∶3∶10∶10∶10∶3∶5∶3 by weight. QYSLD has been used to treat non-small cell lung cancer (NSCLC) for over 20 years in clinical practice, and its curative effect is considered credible. However, the chemical constituents of QYSLD have not been revealed because of their complexity, which has significantly hindered the systematic clarification of the efficacy of the materials and quality evaluation. In this study, a reliable strategy based on the data-independent acquisition (DIA) technology of ultra high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) combined with a targeted screening method was established to investigate the chemical components of QYSLD. A 2-μL aliquot from each vial was injected into a Waters ACQUITY UPLC BEH C18 column (100 mm×2.1 mm, 1.7 μm) to separate complex components. The temperature of the column was 35 ℃, and the flow rate was set at 0.2 mL/min. The mobile phase consisted of 0.1% formic acid aqueous solution and acetonitrile. Detection was conducted using an Xevo G2-XS QTOF-MS with a LockSpray capable-electrospray interface. The data for complex components in QYSLD were collected by full-information tandem mass spectrometry (MS E) in the positive and negative ion modes. In the MSE mode, data acquisition was performed using a mass spectrometer by rapidly switching from a low-collision-energy (CE) scan to a high-CE scan during a single LC run. Thus, accurate precursor and fragment ions were collected in a single run, which was helpful for the structural elucidation of multiple components in QYSLD. In addition, systematic information on isolated chemical compounds was collected and distinguished from the ten individual herbs in QYSLD using databases such as China Academic Journals Full-text database (CNKI), PubMed, Web of Science, Medline, and ChemSpider. Accordingly, a self-building library of QYSLD, including the component name, molecular formula, and structure of the components from the herbs, was established. Subsequently, the raw MSE data of the collected samples and the self-building chemical composition library were imported into a natural product post-processing screening (UNIFI) platform for targeted screening of the chemical components in QYSLD. The parameters for UNIFI platform were as follows: the retention time deviation was ±0.1 min; an error margin of no more than 5×10 -6 for the identified compounds was allowed; positive adducts, including [M+H]+and [M+Na]+, were selected; and negative adducts, including [M-H]- and [M+HCOO]-, were selected. The results showed that a total of 166 compounds were initially identified, including 22 saponins, 13 alkaloids, 27 flavonoids, 32 terpenes, 20 amino acids, 16 phenylpropanoids, 9 organic acids, 6 sterols, 6 anthraquinones, and 15 other components. Among them, sixteen components were confirmed unambiguously with the reference substances. To better understand the chemical contribution of individual herbs to the entire decoction, the attributes of each component were summarized. This study provides a foundation for exploring the pharmacodynamic substances of QYSLD.

The 2,3,5,4’-tetrahydroxy-stilbene-2-O-β-D-glucoside (THSG) is a main active ingredient of Polygoni Multiflori Radix (PMR). In this study, THSG was found to be a differential chemical composition b...

Scrophulariae Radix is one of the widely used traditional Chinese medicines. In this study, a high-performance liquid chromatography coupled with triple quadrupole-linear ion trap mass spectrometry method was established for the simultaneous determination of multiple bioactive constituents including four iridoid glycosides, two phenylpropanoid glycosides, six organic acids, 11 nucleosides and 16 amino acids in Scrophulariae Radix. The validated method was used to analyze nine Scrophulariae Radix samples processed by different processing methods. In addition, Grey relational analysis and DTOPSIS were used to evaluate the samples according to the content of 39 ayalytes. The results showed that the quality of Scrophulariae Radix processed by cutting into slices, sun drying and “sweating” methods were better. All the results proved that the developed method was available and could be used to evaluate the quality of Scrophulariae Radix.

For a formal language [Formula: see text], the problem of language enumeration asks to compute the length-lexicographically smallest word in [Formula: see text] larger than a given input [Formula: see text] (henceforth called the [Formula: see text]-successor of [Formula: see text]). We investigate this problem for regular languages from a computational complexity and state complexity perspective. We first show that if [Formula: see text] is recognized by a DFA with [Formula: see text] states, then [Formula: see text] states are (in general) necessary and sufficient for an unambiguous finite-state transducer to compute [Formula: see text]-successors. As a byproduct, we obtain that if [Formula: see text] is recognized by a DFA with [Formula: see text] states, then [Formula: see text] states are sufficient for a DFA to recognize the subset [Formula: see text] of [Formula: see text] composed of its lexicographically smallest words. We give a matching lower bound that holds even if [Formula: see text] is represented as an NFA. It has been known that [Formula: see text]-successors can be computed in polynomial time, even if the regular language is given as part of the input (assuming a suitable representation of the language, such as a DFA). In this paper, we refine this result in multiple directions. We show that if the regular language is given as part of the input and encoded as a DFA, the problem is in [Formula: see text]. If the regular language [Formula: see text] is fixed, we prove that the enumeration problem of the language is reducible to deciding membership to the Myhill-Nerode equivalence classes of [Formula: see text] under [Formula: see text]-uniform [Formula: see text] reductions. In particular, this implies that fixed star-free languages can be enumerated in [Formula: see text], arbitrary fixed regular languages can be enumerated in [Formula: see text] and that there exist regular languages for which the problem is [Formula: see text]-complete.

In this paper, a novel high performance structure has been demonstrated which can be widely used for circuit-level realization of radix-4 Booth scheme. The notable privilege of proposed scheme is its higher speed for generation of Partial Products (PPs) compared to the previous designs. The objective has been achieved by means of the modified truth table of Booth algorithm. Moreover, Pass-Transistor Logic (PTL) has been employed to reduce the middle stage capacitances which has considerably enhanced the operating frequency of the designed architecture. The thorough analysis over previously reported works has also been provided to help the authors for optimized implementation of the Booth circuitry. Simulation results for TSMC 0.18µm CMOS technology and 1.8V power supply using HSPICE indicate the correct operation of the proposed scheme. In addition, the best-reported works have been redesigned and simulated on the same conditions to provide a fair comparative environment with our designed scheme. The results demonstrate the superiority of our circuit over the selected structures.

Ligustici Radix (Chinese name: maoqianhu) consists of the dried roots of Ligusticum brachylobum Franch., which is mainly distributed in the Yunnan and Sichuan provinces. This herbal medicine has been primarily used for the treatment of cough in traditional Chinese medicine. Ligustici Radix is rich in coumarin derivatives. Interestingly, enantiomers and diastereomers are widely used for these coumarins, thus posing a great challenge for in-depth chemical profile characterization. In the present study, a new analytical platform, achiral-chiral liquid chromatography-tandem mass spectrometry (achiral-chiral LC-MS/MS) was configured to profile the chemical composition of Ligustici Radix. Because achiral and chiral columns were serially coupled, especially enantiomers, both chemically and enantiomerically selective separations could be accomplished simultaneously. The newly configured achiral-chiral LC-MS/MS platform did not require any electronic valve; hence, it could overcome the drawbacks of heart-cutting achiral-chiral two-dimensional LC, i. e., sophisticated instrumentation and limited reproducibility due to the use of electronic valve(s) and the undesired retention time shift across different analytical runs. Some available candidates for chemically selective or enantiomerically selective separation were assayed; then, Capcell core RP-C18 column that was packed with core-shell type particles, and AD-RH column embedding amylose coated particles were employed the achiral and the chiral columns, respectively. The narrow-bore core-shell RP-C18 column served as the front tool to achieve efficient chemoselective separation of coumarin analogs, and enantioselective enantiomers were obtained by using a wide-bore AD-RH chiral column. The predictive multiple reaction monitoring (predictive MRM) mode allowed for the sensitive detection of potential components, and an enhanced product ion (EPI) scan, which was a unique function of Qtrap-MS, was programmed to record the MS2 spectra for all captured signals and thus aid structural annotation. Online energy-resolved mass spectrometry (online ER-MS) was introduced to pursue the suitable collision energy for each compound; in particular, inferior collision energy instead of the optimal one was utilized to suppress the response of the primary components such as praeruptorin A, B and pteryxin. The criteria to judge enantiomers or not included identical quantitative and qualitative precursor-to-product ion transitions, identical quantitative versus qualitative responses, and longer retention times from achiral-chiral LC over single-column achiral LC. As a result, a total of sixty components were observed and structurally identified. In particular, enantiomerically selective separations were achieved for eight enantiomers, cis-khellactone (CKL), qianhucoumarin G (QC-G), pteryxin (Pte), praeruptorin A (PA), cis-3'-isovaleryl-4'-acetylkhellactone (IAK), praeruptorin B (PB), praeruptorin E (PE), and cis-3',4'-diisovalerylkhellactone (DIK). Notably, none of the enantiomers were present as racemates; instead, the proportion of one enantiomer in each pair was greater than the other. Achiral-chiral LC-predictive MRM is a feasible choice for the quantitative and qualitative analyses of Ligustici Radix as well as other herbal medicines characterized by enantiomers and diastereomers.

Anatomical variations of the root canal system of mandibular molars are common and often present challenges for endodontic treatment. In some cases, an additional root is located in the distolingual, radix entomolaris (RE), or more rarely in the buccal, radix paramolaris (RP). This case report illustrates rare nonsurgical retreatment of the complex root canal morphology of a RP and demonstrates the utility of cone-beam computed tomography (CBCT) and 3D printing in managing such a case. Underscored is the need for clinicians to understand the possible variations of root canal morphology of mandibular molars and the role CBCT imaging can play in addition to periapical radiographs in order to successfully treat a tooth with radix paramolaris.

Colloidal gold immunochromatographic assay (CGIA) is commonly used for the on-site detection of β-agonists that are sometimes used illegally as feed additives in swine diets. However, few studies have evaluated the causes of false-positive results that sometimes occur when applying CGIA in agricultural settings. In this study, we investigated if this false-positive phenomenon is related to the addition of certain traditional Chinese medicines (TCMs) to swine feed. We established and verified an extraction method for TCMs, and then applied CGIA to detect β-agonists in the extracts of 105 TCMs and in the urine of swine dosed with TCMs, respectively. Liquid chromatography-tandem mass spectrometry was used to validate the results of the urine samples tested positive for β-agonists using CGIA. The results were also verified using TCMs and colloidal gold test strips produced by different manufacturers. The extracts of Citri Reticulatae Pericarpium Viride, Citri Reticulatae Pericarpium, Magnoliae Officinalis Cortex, Chaenomelis Fructus, and Rhodiolae Crenulatae Radix Et Rhizoma were tested positive for β-agonists. Meanwhile, the addition of Citri Reticulatae Pericarpium Viride and Citri Reticulatae Pericarpium to swine feed resulted in false-positive results for β-agonists in swine urine. The results provide a new way to explain false-positive CGIA results and provide valuable information for livestock feeding programs.

Objective To establish an ultra-high performance liquid chromatography (UPLC) method for simultaneous determination of umbelliferonel, nodakenin, psoralen, xanthotoxin and bergapten contents in Peucedanum decursivum Radix. Methods The analysis was achieved on a Symmetry®C18 column (4.6 mm × 250 mm, 5 μm), with acetonitrile and water as the mobile phase in gradient elution mode. The column temperature was maintained at 30°C, with flow rate 1.0 mL·min−1. The injection volume of sample was 10 μL. The ultraviolet detection wavelength was set at the maximum absorption wavelength 325 nm for umbelliferonel and nodakenin, 259 nm for psoralen, xanthotoxin and bergapten, respectively. Results The five kinds of coumarins in Peucedanum decursivum Radix were separated well and the linear relation was obtained (R2 ≥ 0.9998). The average recoveries were 101.31, 105.27, 90.85, 106.42 and 90.19%, respectively, with Relative standard deviation (RSD) 3.07, 3.17, 1.62, 2.53 and 4.54%, respectively. Conclusions The established method was accurate and feasible, which could be used as the basis of quality control of Peucedanum decursivum Radix.

Inhibition of protein disulfide isomerase (PDI) has been attempted as a promising anti-cancer strategy. However, there is still no currently available PDI inhibitors approved for clinical use. Here, we isolated seven high yield alkaloids from Stephaniae tetrandrae Radix (STR), a medical herb frequently prescribed in anti-tumor condition, and identified two potent natural PDI inhibitors, dicentrine and dicentrinone. Among the seven alkaloids isolated, dicentrinone (1), dicentrine (2), tetrandrine (4), and fangchinoline (5) could significantly reduce cell viability in a dosage dependent manner detected by MTT assay in human hepatoma cells. To examine whether the candidate compounds are potent PDI inhibitors, we performed insulin turbidity assay and found dicentrine and dicentrinone, but not tetrandrine and fangchinoline, could effectively inhibit PDI activity, with IC50 of 56.70 μM and 43.95 μM respectively. Meanwhile, dicentrine and dicentrinone failed to further reduce the cell number index when co-treated with siRNA of PDI, suggesting the compounds behave as PDI inhibitors. Furthermore, dicentrinone and dicentrine have been successfully docked to the active pocket of PDI (PDB #3UEM) by molecular docking, suggesting the existence of physical interaction between compounds and PDI. Our results suggested that dicentrine and dicentrinone may be developed into safe PDI inhibitors.

Elliptic curve scalar multiplication $k$ . $P$ , where $k$ is a nonnegative constant and $P$ is a point on the elliptic curve, requires two distinct operations: addition (ADD) and doubling (DBL). To reduce the number of ADDs without increasing the number of DBLs, a recoding of $k$ with fewer nonzero digits is necessary. Based on Radix- $2^{w}$ arithmetic, we introduce a principled $w$ -bit windowing method where the properties of speed, memory, and security are described by exact analytic formulas as proof of superiority. Contrary to existing windowing algorithms, to minimize the number of ADDs the window size ( $w$ ) is guided by an optimum depending on the bit-length ( $l$ ) of the scalar k. The number of required precomputations is minimal regarding the value of $w$ . The proposed method recodes the binary string $k$ and evaluates the multiplication on-the-fly from right-to-left and left-to-right, likewise. Radix- $2^{w}$ method is very easy to be used and highly reconfigurable, allowing speed-memory and speed-security trade-offs to satisfy different crypto-system constraints. Furthermore, the method shows a high resilience to side-channel attacks based on power, timing, and statistical analysis. All Radix- $2^{w}$ properties are confronted to standard windowing methods’ through an in-depth analysis of the complexities. An overall comparison is made via NIST-recommended GF( $2^{l}$ ) finite fields.

Objectives Radix Bupleuri–Radix Paeoniae Alba (BP), a traditional Chinese medicine herb pair, has treated depression by coordinating the liver in Chinese classical medicine books and modern research. This study aims to verify the antidepressant effect of BP by behavioural examination, and reveal the underlying antidepressant mechanisms of BP. Methods The antidepressant effects in chronic unpredictable mild stress (CUMS) of BP were observed by behavioural indicators and 1H nuclear magnetic resonance (1H-NMR) and ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) metabonomics techniques combined with the related analysis platforms. Key findings BP could significantly improve the depressive behaviour of CUMS rats. Compared with the model group, body weight (P < 0.05), the number of crossing (P < 0.001) and rearing (P < 0.01) and sucrose preference rate (P < 0.01) were significantly enhanced, and the immobility time was shortened in the forced swimming test (P < 0.001) of the BP group. In metabonomics study, 35 depression-related metabolites were identified by 1H NMR and UHPLC-MS/MS metabonomics by comparing model and control groups. BP could significantly retrieve 17 depression-related metabolites. Thirteen depression-related metabolic pathways were found through Met-PA and BP could regulate seven metabolic pathways. Conclusions BP herb pair had significantly antidepressant effect, which provides a basis for further finding drug targets.

Radix Angelica sinensis (RAS) is a famous Chinese medicine with hematinic effects and has been applied for the treatment of blood deficiency syndrome for many years. Previous studies have indicated that RAS has beneficial effects in the treatment of hemolytic anemia. The hemolytic anemia/blood deficiency syndrome is a common syndrome that is often presented in most traditional Chinese medicine (TCM) clinics. Based on routine blood indicators, metabolomics analysis was conducted to investigate the mechanism of RAS in the treatment of hemolytic anemia. Multivariate and univariate statistical analysis were used to identify potential biomarkers in the serum. On administering RAS to the haemololitic anaemic rat, the levels of WBC, RBC, HGB, and PLT in AG tended to shift toward that of the control group. Additionally, all the 26 metabolites such as cholic acid, succinic acid and orotate which are regulated by blood deficiency appeared normal through the five metabolic pathways, such as linoleic acid metabolism, alanine, aspartic acid and glutamate metabolism, pyrimidine metabolism, arginine and proline metabolism. Thus, three metabolic pathways predicted by the network pharmacology were consistent with the metabolism pathway of Angelica sinensis: linoleic acid metabolism, arginine and proline metabolism, tryptophan metabolism. The integrated metabolomics and network pharmacology comprehensively improved the understanding of the physiological and metabolic state of an organism. The possible hematopoietic effects and underlying mechanism of action on hemolytic anemia rats after lavage with RAS water extracts, could potentially be elucidated by combining pharmacology with untargeted metabolomics. These pointed out the significance of metabolomics as a valuable tool for studying the essence of Chinese medicine’s syndrome theory and the mechanism of RAS under anti-blood deficiency syndrome.

This paper presents the implementation and design of Radix-8 booth Multiplier using 32-bit parallel prefix adders. High performance processors have a high demand in the industrial market. For achieving high performance and to enhance the computational speed multiplier plays a key role in performance of digital system. But the major drawback is it consumes more power , area and delay. To enhance the performance and decrease the area consumption and delay there are many algorithms and techniques. In this paper we designed a radix-8 Booth Multiplier using two parallel prefix adders and compared them for best optimized multiplier. The number of parital products generation can be reduced by n/3 by using radix-8 in the multiplier encoding. To further reduce the additions we have used booth recoding mechanism .We have implemented the design using Kogge stone adder and Brent kung adder. We observed that by using parallel prefix adders reduces the delay further more which results in significant increase in speed of the digital systems. The simulation results are carried out on XILINX VIVADO software.

Shrinkage is an important factor affecting the final quality of Radix Paeoniae Alba (RPA) slices during drying processes. In this study, drying experiments were carried out to determine the effect ...

Objective Astragalus Radix (AR, Huangqi in Chinese) has been widely used as a qi (energy) restoring herb that is thought to act through reinvigorating the spleen and lung. Aconite is used to rebalance the body temperature during illness and played an irreplaceable role in disease control since ancient times, but it is limited by its strong neuro and cardiotoxicity. Since the Song Dynasty (1227), the two herbs have been commonly used as herbal pairs including in the famous Qifu Decotion, from the “Wei's Family Prescription”. However, many ancient texts also record that they are not compatible using together, suggesting they can have negative outcomes when mixed. This study investigated whether Astragali Radix had either positive or negative effects on absorption of six different active alkaloids derived from aconite. Methods Single intestinal perfusion model was used to study the effects of Astragali Radix on aconite alkaloids absorption. Response of ABC transporters and distribution of three tight junction proteins on the surface of intestinal enothelium were assessed by Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Western blot and immunofluorescence microscopy, respectively. Results The results showed that aconite alkaloids absorption could be inhibited, and different concentrations of Astragali Radix considerably increased the expression levels of the ABC transporters and tight junction proteins with Astragali Radix treatment. Conclusion These results suggest that Astragali Radix can block absorption of aconite alkaloids through the upregulation expression of ATP-binding cassette transporters (ABC transporters) and tight junction proteins. It demonstrates that co-administration of Astragali Radix with other drugs might change the absorption profile of the second drug which is important to know in clinic therapy.

Three new bis-trinorcadalenes, bistrinorcadintermes A–C (1-3) along with seven known compounds, parvifloral D (4), parvifloral E (5), parvifloral C (6), hymexelsin (7), scopoletin (8), scopolin (9), and hibiscolactone A (10) were isolated from the aerial parts and radix of Decaschistia intermedia Craib. Their chemical structures were determined based on spectroscopic methods, including 1D, 2D NMR, MS, and experimental CD spectra. All compounds were evaluated for their α-glucosidase inhibitory effects. Compounds 1, 5, and 8 showed moderate α-glucosidase inhibitory activities with IC50 values of 45.6 ± 4.2, 43.7 ± 3.6, and 43.7 ± 3.6 μg/mL, respectively. Compounds 2-4 and 10 showed weak α-glucosidase inhibitory activities with IC50 values ranging from 87.5 ± 6.3 to 219.8 ± 4.9 μg/mL.

A 6-bit 2.3 GS/s single-channel sub-radix pipeline ADC using an incomplete settling concept is presented. A radix detector is proposed to detect stage gain in the background so that low gain and low bandwidth opamps can be utilized to conserve power. The raw ADC output codes can be reconstructed with the detected radix to retrieve its accuracy. The simulated results show that the prototype ADC in 40 nm CMOS process exhibits an SNDR of 34.3 dB at Nyquist input frequency with the conversion rate of 2.3 GS/s. It consumes 94 mW at 1 V supply and occupies an active chip area of 0.12 mm2.

Context Current medicine for Alzheimer's disease (AD) cannot effectively reverse or block nerve injury. Traditional Chinese Medicine practice and research imply Aconiti lateralis Radix Praeparata (Fuzi) may meet this goal. Objective Analysing the anti-AD effect of Fuzi and its potential molecular mechanism. Materials and methods AD model cells were treated with Fuzi in 0-300 mg/mL for 24 h in 37 °C. The cell viability (CV) and length of cell projections (LCP) for each group were observed, analysed, and standardised using control as a baseline (CVs and LCPs). The Fuzi and AD relevant genes were identified basing on databases, and the molecular mechanism of Fuzi anti-AD was predicted by network analysis. Results Experiment results showed that Fuzi in 0.4 mg/mL boosted LCP (LCPs = 1.2533, p ≤ 0.05), and in 1.6-100 mg/mL increased CV (CVs from 1.1673 to 1.3321, p ≤ 0.05). Bioinformatics analysis found 17 Fuzi target genes (relevant scores ≥ 20), showing strong AD relevant signals (RMS_p ≤ 0.05, related scores ≥ 5), enriched in the pathways regulating axon growth, synaptic plasticity, cell survival, proliferation, apoptosis, and death (p ≤ 0.05). Especially, GRIN1 and MAPK1 interacted with APP protein and located in the key point of the "Alzheimer's disease" pathway. Discussion and conclusions These results suggest that Fuzi may have therapeutic and prevention potential in AD, and GRIN1 and MAPK1 may be the core of the pathways of the Fuzi anti-AD process. Fuzi should be studied more extensively, especially for the prevention of AD.

Ovarian cancer (OC) has been identified to have the highest mortality rate among gynecological tumors. Most patients are diagnosed at an advanced stage because of its asymptomatic nature and a lack of effective early diagnostic methods. Advanced-stage cancer cells are prone to metastasis which reduces the efficacy of standard therapies. Thus, we evaluated the effect of different concentrations of radix tetrastigma hemsleyani flavone (RTHF) on SKOV3 OC cells. Our findings indicated a significant inhibition in cell proliferation, migration, and invasion. RTHF treatment resulted in a significant increase in p21 protein expression, whereas the expression of cyclin D1, MMP-2, and MMP-9 has reportedly decreased. In addition, the expression of miRNA-4458 expression increased significantly in a dose-dependent manner. Co-transfection of miRNA-4458 mimics into SKOV3 cells revealed that overexpressed miRNA-4458 can increase SKOV3 cell proliferation and p21 protein expression. Reduced cell migration and invasion were also observed along with decreased expression of cyclin D1, MMP-2, and MMP-9. Furthermore, inhibition of miRNA-4458 expression reversed the RTHF effect on SKOV3 cell proliferation, migration, invasion, and cyclin D1, MMP-2, and MMP-9 expression. These results indicate that RTHF reduces the proliferation, migration, and invasion of OC cells, and the underlying mechanism is associated with the upregulation of miRNA-4458 expression. These findings provide a new treatment strategy for advanced OC.

Our study for the first time, demonstrates that ES, AP, and their combinations significantly inhibits SARS-CoV-2 viral growth in Vero E6 cells in a dose-dependent manner. The antiviral activity of the combinations of ES and AP are greater than expected.

Radix Rhodomyrti is the dried root of Rhodomyrtus tomentosa (Aiton) Hassk., which is used as a herb in southeast Asian countries and regions. Its main active ingredients are phenols. To make efficient use of the active components in Radix Rhodomyrti, 2,2-diphenyl-1-picrylhydrazyl radical–ultra-high-performance liquid chromatography–photo diode array (DPPH–UPLC–PAD) analysis and UPLC–quadrupole time-of-flight tandem mass spectrometry (UPLC–QTOF-MS/MS) were applied to evaluate and identify the antioxidant phenolic components in Radix Rhodomyrti. Gallic acid and ellagic acid were identified as the major phenolic components in Radix Rhodomyrti. The levels of gallic acid and ellagic acid in Radix Rhodomyrti were 2.16 ± 0.27 mg/g and 0.17 ± 0.04 mg/g, respectively. Both compounds showed excellent free-radical scavenging activity in vitro. The known antioxidant capacity of ellagic acid is slightly higher than that of gallic acid, which is consistent with the results of the DPPH radical-scavenging assay. The results of this study indicate that the proposed method could be applied for rapid screening and identification of antioxidants from complex natural products.

Lung cancer with high mortality is regarded as a challenging global problem with unsatisfied curative effects. Clinically, the chemotherapy drugs are often faced with side-effects and tumor resistance. Radix Tetrastigma (RT) is a traditional Chinese herb and now regarded as a kind of functional food. In this study, A549-bearing nude mice control was adopted to evaluate the anti-tumor capacity of RT. Results demonstrated that RT showed excellent anti-tumor ability with no side-effect on mice compared to chemotherapy drug (5-Fu).Further studies proved that RT down-regulated the proliferation-related proteins (PCNA, Ki67) and vascular endothelial growth factor (VEGF). Additionally, RT up-regulated the ratio of Bax/Bcl-2, which caused the over-expression of Caspase-9, leading to the activation of downstream protein caspase-3, eventually resulting in apoptosis of A549 in solid tumor. These results together suggest that RT inhibits the non-small cell lung cancer (NSCLC) via Bax/Bcl2/Caspase-9/Caspase-3 pathway. Furthermore, the anti-A549 abilities of the main flavonoid components from RT were compared, and kaempferol-3-O-rutinoside would play a role in RT's outstanding anti-NSCLC ability.

Puerarin, a natural isoflavone extracted fromThis study was designed to investigate theMTT and neutral red phagocytosis assays were conducted to evaluate theResults showed that puerarin improves immunomodulatory activity by increasing cell proliferation, cell phagocytosis, and NO secretion in RAW264.7 macrophages and reduces the abnormal immunologic activity by decreasing cell phagocytosis and NO secretion in LPS-stimulated RAW264.7 macrophages. In addition, puerarin enhanced the immunologic activity of cyclophosphamide-induced immunosuppression mice by increasing the secretion of NO, IFN-γ, and IL-4, the serum half hemolysis value (HCPuerarin exhibited an upregulated immunomodulatory effect on RAW264.7 macrophages and immunosuppression mice. In addition, puerarin had a downregulated immunomodulatory effect on RAW264.7 macrophages. The results suggest that puerarin could be a promising immunomodulator to assist in the treatment of tumors.

Process quality control of the herbal medicines (HMs) still hits technical bottlenecks due to their complicated multi-step pretreating. Nuclear magnetic resonance (NMR) spectroscopy could serve as a powerful technique able to obtain comprehensive information of chemical compounds in the manufacturing process of HMs by a single analytical test. In this study, ethanol precipitation, a critical pretreating process of an especially widely used HM preparation, was conducted with different process variables, including ethanol-material ratio, apparent ethanol concentration and moisture concentration of the raw material, 40 lab-scale experiments of ethanol precipitation were orchestrated by a full factor design with additional central composite circumscribed experiments. Then, 16 metabolites were recognized as the most critical potential chemical markers in the process by 1H NMR spectra and orthogonal partial least squares-discriminant analysis (OPLS-DA). Finally, multiple linear regression (MLR) was applied to evaluate the impacts of process variables and their interaction on the chemical markers and explain the consistency variation of the process intermediates. The results promote the further understanding of ethanol precipitation process and open up possibilities to develop a more effective process quality control methodology of an HM, through providing a more in-depth and improved pharmaceutical process understanding and characterization.