Mineral crude drug mirabilite (Mangxiao) inhibits the occurrence of colorectal cancer by regulating the Lactobacillus-bile acid-intestinal farnesoid X receptor axis based on multiomics integration analysis.

Mineral crude drug has revolutionized the treatment landscape in precision oncology niche that leads to the improvement in therapeutic efficiency on various tumor subtypes. Mangxiao (MX), a mineral crude drug in traditional Chinese medicine, has been used for treating gastrointestinal diseases for thousands of years. However, the action mechanisms are still ambiguous. Here, we attempt to explore inhibitory roles and associated pharmacological mechanisms of MX upon colorectal cancer (CRC) in APCMin/+ male mice by integrating metabolomics, 16S rDNA sequencing analyses, and metagenomic-based microbiota analysis. We found that MX can significantly inhibit the occurrence of CRC through the regulation of the dysregulated gut microbe metabolism. Furthermore, the correlation analysis of metabolomes and 16S rDNA revealed that MX could restore the disorders of gut microbes by specifically enriching the abundance of Lactobacilli to improve bile acid metabolism, which further activated the farnesoid X receptor (FXR) in CRC mice, then the improvement of gut dysbiosis could inhibit the development of CRC. Collectively, our effort confirmed MX has the capacity to intervene the development of CRC and further discovered that it targets Lactobacillus-bile acid-intestinal FXR axis, which can be regarded as a candidate medicine for future drug discovery and development against CRC.

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.

Chinmedomics: a potent tool for the evaluation of traditional Chinese medicine efficacy and identification of its active components.

As an important part of medical science, Traditional Chinese Medicine (TCM) attracts much public attention due to its multi-target and multi-pathway characteristics in treating diseases. However, the limitations of traditional research methods pose a dilemma for the evaluation of clinical efficacy, the discovery of active ingredients and the elucidation of the mechanism of action. Therefore, innovative approaches that are in line with the characteristics of TCM theory and clinical practice are urgently needed. Chinmendomics, a newly emerging strategy for evaluating the efficacy of TCM, is proposed. This strategy combines systems biology, serum pharmacochemistry of TCM and bioinformatics to evaluate the efficacy of TCM with a holistic view by accurately identifying syndrome biomarkers and monitoring their complex metabolic processes intervened by TCM, and finding the agents associated with the metabolic course of pharmacodynamic biomarkers by constructing a bioinformatics-based correlation network model to further reveal the interaction between agents and pharmacodynamic targets. In this article, we review the recent progress of Chinmedomics to promote its application in the modernisation and internationalisation of TCM.

Evaluation of the key ingredient from the main production areas of Phellodendri Amurensis Cortex using ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry and ultra-high-performance liquid chromatography coupled to triple-quadrupole mass spectrometry.

Phellodendri Amurensis Cortex (PAC) is a medicinal herb that has been generally used to treat diarrhea and jaundice. In order to comprehensively evaluate the PAC in the main production areas quality, a qualitative and quantitative method with highly effective, sensitive, and reliable was developed. The chemical compositions of PAC were analyzed, and fingerprints were established by ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS). Then, the determination of berberine, canthin-6-one, dictamnine, γ-fagarine, and magnoflorine from PAC samples was simultaneously performed using UPLC-QQQ-MS. Furthermore, the chemical components of PAC from different regions were compared and analyzed by combining hierarchical cluster analysis, principal component analysis, and orthogonal partial least squares discriminant analysis. A total of 58 compounds were identified, including 36 alkaloids, four phenylpropanoids, seven terpenoids, four flavonoids and their glycosides, an organic acid compound, and six other components. The fingerprint results show that samples have good similarity. Meanwhile, the content of the five ingredients in different habitats is quite different. By multivariate statistical analysis, 18 batches of PAC could be divided into three categories, and 20 components were identified as differential markers of various origins. A comprehensive method of PAC quality evaluation and chemical composition difference analysis was established, which provided the scientific basis for quality evaluation and further pharmacological mechanism research.

Elucidation for the pharmacological effects and mechanism of Shen Bai formula in treating myocardial injury based on energy metabolism and serum metabolomic approaches.

ETHNOPHARMACOLOGICAL RELEVANCE: Shen Bai formula (SBF) is a proven effective traditional Chinese medicine for treating viral myocarditis (VMC) sequelae in clinic, and myocardial injury is the pathological basis of VMC sequelae. However, the pharmacological action and mechanism of SBF have not been systematically elucidated. AIM OF THE STUDY: In present research, the doxorubicin-induced myocardial injury rat model was used to evaluate the efficacy of SBF, and energy metabolism and metabolomics approaches were applied to elucidate the effects of SBF on myocardial injury. MATERIALS AND METHODS: Through energy metabolism measurement system and UPLC-Q-TOF-MS/MS oriented blood metabolomics, directly reflected the therapeutic effect of SBF at a macro level, and identified biomarkers of myocardial injury in microcosmic, revealing its metabolomic mechanism. RESULTS: Results showed that SBF significantly improved the electrocardiogram (ECG), heart rate (HR), extent of myocardial tissue lesion, and ratio of heart and spleen. In addition, the serum levels of AST, CK, LDH, α-HBDH, cTnI, BNP, and MDA decreased, whereas SOD and ATP activity and content increased. Moreover, SBF increased locomotor activity and basic daily metabolism in rats with myocardial injury, restoring their usual level of energy metabolism. A total of 45 potential metabolomic biomarkers were identified. Among them, 44 biomarkers were significantly recalled by SBF, including representative biomarkers arachidonic acid (AA), 12-HETE, prostaglandin J2 (PGJ2), 15-deoxy-Δ-12,14-PGJ2, 15-keto-PGE2, 15(S)-HPETE, 15(S)-HETE, 8,11,14-eicosatrienoic acid and 9(S)-HODE, which involved AA metabolism, biosynthesis of unsaturated fatty acids and linoleic acid metabolism. CONCLUSION: We successfully replicated a myocardial injury rat model with the intraperitoneal injection of doxorubicin, and elucidated the mechanism of SBF in treating myocardial injury. This key mechanism may be achieved by targeting action on COX, Alox, CYP, and 15-PGDH to increase or decrease the level of myocardial injury biomarker, and then emphatically interven in AA metabolism, biosynthesis of unsaturated fatty acids and linoleic acid metabolism, and participate in regulating purine metabolism, sphingolipid metabolism, primary bile acid biosynthesis, and steroid hormone synthesis.

Potential of alisols as cancer therapeutic agents: Investigating molecular mechanisms, pharmacokinetics and metabolism.

Albeit remarkable achievements in anti-cancer endeavors, the prevention and treatment of cancer remain unresolved challenges. Hence, there is an urgent need to explore new and efficacious natural compounds with potential anti-cancer therapeutic agents. One such group of compounds is alisols, tetracyclic triterpene alcohols extracted from alisma orientale. Alisols play a significant role in cancer therapy as they can suppress cancer cell proliferation and migration by regulating signaling pathways such as mTOR, Bax/Bcl-2, CHOP, caspase, NF-kB and IRE1. Pharmacokinetic studies showed that alisols can be absorbed entirely, rapidly, and evenly distributed in vivo. Moreover, alisols are low in toxicity and relatively safe to take. Remarkably, each alisol can be converted into many compounds with different pathways to their anti-cancer effects in the body. Thus, alisols are regarded as promising anti-cancer agents with minimal side effects and low drug resistance. This review will examine and discuss alisols' anti-cancer molecular mechanism, pharmacokinetics and metabolism. Based on a comprehensive analysis of nearly 20 years of research, we evaluate the therapeutic potential of alisols for various types of cancer and offer insights and strategies for developing new cancer treatments.

Mass spectrum oriented metabolomics for evaluating the efficacy and discovering the metabolic mechanism of Naoling Pian for insomnia.

Insomnia is an accompanying symptom of many diseases and is closely associated with neurodegenerative diseases. Naoling Pian (NLP) is a patented Chinese medicine mainly used to treat insomnia. To evaluate the sedative and hypnotic effects of NLP and its modulatory effects on biological metabolites and metabolic pathways, rats with p-chlorophenylalanine (PCPA)-induced insomnia were given different doses of NLP by oral gavage for seven days. Diazepam (DZP) served as a positive control. Behavior was measured using the open field test, and neurotransmitter levels in the brain tissue related to sleep were measured using ELISA. The metabolic profiles and biomarkers of PCPA-induced insomnia in rats before and after NLP administration were analyzed using UPLC-Q/TOF-MS combined with multivariate data analysis. The results showed that the levels of 5-hydroxytryptamine, gamma-aminobutyric acid, norepinephrine, and dopamine in the brain tissue were significantly recovered in the NLP treatment groups, demonstrating similar or even superior therapeutic effects compared to the DZP group. The behavior of the PCPA-model rats partially recovered to normal levels after seven days of treatment. Metabolomics identified 30 metabolites in the urine as potential biomarkers of insomnia, and NLP significantly altered 25 of these, involving 21 metabolic pathways. NLP has a remarkable effect on insomnia, the therapeutic effects of which may be largely due to the rectification of metabolic disturbances. This is the first study of the sedative and hypnotic effects of NLP from a metabolomic perspective.

In Vivo Metabolite Profiling of DMU-212 in ApcMin/+ Mice Using UHPLC-Q/Orbitrap/LTQ MS.

3,4,5,4'-Trans-tetramethoxystilbene (Synonyms: DMU-212) is a resveratrol analogue with stronger antiproliferative activity and more bioavailability. However, the metabolite characterization of this component remains insufficient. An efficient strategy was proposed for the comprehensive in vivo metabolite profiling of DMU-212 after oral administration in ApcMin/+ mice based on the effectiveness of the medicine. Ultra-high performance liquid chromatography-quadrupole/orbitrap/linear ion trap mass spectrometry (UHPLC-Q/Orbitrap/LTQ MS) in the AcquireXTM intelligent data acquisition mode, combining the exact mass and structural information, was established for the profiling and identification of the metabolites of DMU-212 in vivo, and the possible metabolic pathways were subsequently proposed after the oral dose of 240mg/kg for 3 weeks in the colorectal adenoma (CRA) spontaneous model ApcMin/+ mice. A total of 63 metabolites of DMU-212 were tentatively identified, including 48, 48, 34 and 28 metabolites in the ApcMin/+ mice's intestinal contents, liver, serum, and colorectal tissues, respectively. The metabolic pathways, including demethylation, oxidation, desaturation, methylation, acetylation, glucuronide and cysteine conjugation were involved in the metabolism. Additionally, further verification of the representative active metabolites was employed using molecular docking analysis. This study provides important information for the further investigation of the active constituents of DMU-212 and its action mechanisms for CRA prevention.

A Non-targeted Metabolomics Reveals Therapeutical Effect and Mechanism of Sanmiao Pill on Adjuvant-induced Arthritis Rats.

BACKGROUND AND OBJECTIVE: Rheumatoid arthritis (RA) is an increasingly serious disease worldwide that can damage the joints and bones of sufferers. Sanmiao Pill (SMP), a classical traditional Chinese medicine (TCM) prescription, has been used for effective treatments for RA in the clinic. To comprehensively illuminate the therapeutic mechanism of SMP in the treatment of RA, the effects of SMP on biomarkers and metabolic pathways in rats with adjuvant-induced arthritis (AIA) were examined. > Methods: Sprague Dawley rats were randomly divided into two control (CC, Control) groups, two model (MM, Model) groups, a methotrexate group (MTX, 7.6 mg/kg body weight per week), and two SMP groups (San-L, 28.7 mg/kg body weight per day and San-H, 57.4 mg/kg body weight per day). Rats' body weight, paw swelling, arthritis scores, biochemical parameters, histopathology, and so on were used to evaluate the success of the model and the therapeutic effects of SMP. The metabolic techniques were used to characterize the metabolic profile and biomarkers of the serum and urine samples of rats to reveal the metabolic changes that occurred after SMP treatment. > Results: After 21 days of treatment, SMP improved weight gain, reduced the severity of paw swelling, lowered the levels of biochemical indicators (CCP-Ab, IL-6, TNF-α, RF), decreased destruction of articular cartilage and bone erosion, and protected the affected joints.Additionally, 17 and 19 potential biomarkers associated with RA were identified in the serum and urine, respectively. SMP significantly reversed 14 potential biomarkers, such as arachidonic acid, lysoPC(20:4(5Z,8Z,11Z,14Z)), L-tryptophan, 9-cis-Retinoic acid, hippuric acid, pyridoxine, and pantothenic acid. These metabolites are associated with arachidonic acid metabolism, glycerophospholipid catabolism, tryptophan metabolism, phenylalanine metabolism, vitamin B6 metabolism, etc. > Conclusion: These results indicated that RA-related biomarkers reflected the metabolic profile of AIA rats. Meanwhile, SMP could effectively treat RA mainly by reducing inflammation and regulating abnormal lipid metabolic pathways and amino acid metabolisms. It showed that metabolomics could be used to analyze the metabolic profiles involved in RA and reveal the mechanism of SMP treatment of RA.>.

Parsing the Q-Markers of Baoyin Jian to Treat Abnormal Uterine Bleeding by High-Throughput Chinmedomics Strategy.

Abnormal uterine bleeding (AUB) is a common and frequently occurring disease in gynecology, seriously threatening women's health. Baoyin Jian (BYJ) is a classical prescription for treating AUB. However, the lack of quality control standards of BYJ for AUB have limited the development and applications of BYJ. This experiment aims to explore the mechanism of action and screen the quality markers (Q-markers) of BYJ against AUB through the Chinmedomics strategy to improve the quality standards of Chinese medicine and provide scientific basis for its further development. BYJ has hemostatic effects in rats, as well as the ability to regulate the coagulation system following incomplete medical abortion. According to the results of histopathology, biochemical indexes and urine metabolomics, a total of 32 biomarkers of ABU in rats were identified, 16 of which can be significantly regulated by BYJ. Using traditional Chinese medicine (TCM) serum pharmacochemistry technology, 59 effective components were detected in vivo, of which 13 were highly correlated with efficacy, and 9 components, namely catalpol, rehmannioside D, paeoniflorin, berberine, phellodendrine, baicalin, asperosaponinVI, liquiritin, and glycyrrhizic acid, were screened out as the Q-markers of BYJ based on the "Five Principles" of Q-markers. In sum, BYJ can effectively alleviate abnormal bleeding symptoms and metabolic abnormalities in AUB rats. The study shows that Chinmedomics is an effective tool for screening Q-markers and provides scientific support for the further development and clinical use of BYJ.

Quality marker discovery of Danggui Jianzhong decoction for treating primary dysmenorrhoea based on chinmedomics strategy.

BACKGROUND: Danggui Jianzhong Decoction (DGJZD) has been proven as an effective classical prescription for clinically treating primary dysmenorrhoea (PD). However, the industrialisation development and drug innovation of DGJZD remain limited due to its undefined effective constituents and quality markers (Q-markers). PURPOSE: Elucidating the Q-markers of DGJZD, which is related to clinical efficacy. METHODS: In accordance with chinmedomics strategy, we evaluated the therapeutic efficacy of DGJZD on the basis of the metabolomic profile and biomarker of a PD rat model to further identify the constituents of DGJZD in vivo that originated from the formula under the acting condition of DGJZD. The potential effective constituents and Q-markers were identified by mining the dynamic relation between the constituents in vivo and the biomarkers. RESULTS: Subsequently, 29 serum metabolites were characterized as biomarkers for PD, and DGJZD adjusted the levels of the primary biomarkers involved in arachidonic acid metabolism, glycerophospholipid metabolism, tryptophan metabolism as well as the synthesis of steroid hormones. Under the active condition of DGJZD, 20 prototype ingredients and 4 metabolites of DGJZD were found in vivo, five of which were mostly related with the efficacy of PD, namely, ferulic acid, zizyphusin, cinnamic acid, protocatechuic acid-3-glucoside, and azelaic acid. They were the potential pharmacodynamic constituents for treating PD, and they could be regarded as the Q-markers of DGJZD. CONCLUSION: Taken together, the Q-markers of DGJZD identified in this research are credible and assist in solving problems related to quality control and drug innovation, accelerating industrialisation development. Besides, the efficacy, mechanism and active ingredients of DGJZD for the treatment of PD were innovatively elucidated for the first time on the basis of the chinmedomics strategy for uncovering the Q-markers of drugs from the system perspective.

Therapeutic Effects of Alisma orientale and its Active Constituents on Cardiovascular Disease and Obesity.

The treatment of cardiovascular diseases and obesity, two diseases posing a major risk to human health, has been plagued by the scarcity of potent and effective medication with fewer side effects. To address this problem, numerous efforts, and some progress, have been made. Among possible treatments are some medicinal herbs; particularly promising is Alisma orientale (AO). In the last decade, an increasing amount of research has shown that AO has some desirable therapeutic effects on cardiovascular diseases and obesity. Because of its efficacy, natural origin, and minimal adverse effects, AO has aroused great attention. Based on this, this review provides an overview of the latest progress from the last decade regarding the pharmacological and therapeutic effects, molecular mechanisms, and related effective constituents of AO in the treatment of cardiovascular diseases and obesity. Results from the research currently available reveal that active constituents of AO, such as alisol B 23-acetate, alisol A 24-acetace, and alisol A, have been proven to be effective for treating cardiovascular diseases by modulating the lipid metabolism of macrophages, improving the biological behavior of vascular smooth muscle cells (VSMCs), and enhancing anti-inflammatory effects. Moreover, the active constituents of AO can also intervene in obesity by modulating abnormal glucose and lipid metabolism and fat decomposition of the body by activating the AMPK- and PPAR-related signaling pathways. In summation, based upon our research of available literature, this review reveals that AO and its active constituents have a great potential to be used as drugs for treating cardiovascular diseases and ameliorating obesity.

Fecal metabolomics analysis for deciphering the lipid-lowering effect of Qizhi capsule on high-fat feed induced hyperlipidemia.

ETHNOPHARMACOLOGICAL RELEVANCE: Qizhi capsule (QZC), a Chinese patent drug, has been utilized to treat hyperlipidemia. AIM OF STUDY: The present study aims to investigate the lipid-lowering effect of QZC, as well as the mechanism of action for treating hyperlipidemia. MATERIALS AND METHODS: High-fat diet (HFD) induced hyperlipidemia rats were administrated with different doses of QZC for 28 days, and atorvastatin calcium tablets was used as the positive control. Serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were used to evaluate the effectiveness of QZC treatment. The metabolic profiles of feces were analyzed by UPLC-MS-based metabolomics approach coupled with multivariate data analysis. RESULTS: The levels of serum TC, TG, LDL-C, and HDL-C were significantly reversed in QZC treatment groups, showing a similar or even better treatment effect compared with the atorvastatin calcium group. Thirty-two potential fecal biomarkers related to hyperlipidemia were identified. QZC could partially recover the disturbed metabolic pathways of alpha-linolenic acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and glycosylphosphatidylinositol (GPI)-anchor biosynthesis. Meanwhile, the signal pathways of regulation of lipid metabolism by peroxisome proliferator-activated receptor α (PPARα), PPARα activates gene expression, and transcriptional regulation of white adipocyte differentiation can be also regulated by QZC. CONCLUSION: The lipid-lowering effect of QZC was confirmed by both serum biochemistry and metabolomics analysis. The beneficial effects of QZC were mainly attributed to the correction of metabolic disorders and the maintenance of the dynamic balance of metabolites.

Ephedrae Herba: A Review of Its Phytochemistry, Pharmacology, Clinical Application, and Alkaloid Toxicity.

Ephedrae Herba (Ephedra), known as "MaHuang" in China, is the dried straw stem that is associated with the lung and urinary bladder meridians. At present, more than 60 species of Ephedra plants have been identified, which contain more than 100 compounds, including alkaloids, flavonoids, tannins, sugars, and organic phenolic acids. This herb has long been used to treat asthma, liver disease, skin disease, and other diseases, and has shown unique efficacy in the treatment of COVID-19 infection. Because alkaloids are the main components causing toxicity, the safety of Ephedra must be considered. However, the nonalkaloid components of Ephedra can be effectively used to replace ephedrine extracts to treat some diseases, and reasonable use can ensure the safety of Ephedra. We reviewed the phytochemistry, pharmacology, clinical application, and alkaloid toxicity of Ephedra, and describe prospects for its future development to facilitate the development of Ephedra.

Quantitative multicomponent analysis of a single marker-based simultaneous determination and quality assessment of nucleoside analogs from Qi Zhi capsules.

Qi Zhi capsule (QZC) is approved by the State Drug Administration of China. The QZC consists of nine crude drugs, including astragalus, leeches, ground beetles, curcuma zedoary, hawthorn, semen cassiae, rhizoma sparganii, polygonum multiflorum, and peach kernel, of which leeches and ground beetles are Traditional Chinese Medicine of animal origin. Nucleosides are animal substances with pharmacological effects that are easy to extract and quantify. Different nucleoside analogs in distinct animal-based formulations can be used to characterize animal-based medicines. However, the quality control of a single indicator does not reflect the overall quality of Chinese medicine. Here, we developed a method to simultaneously determine the nucleoside analogs uracil, xanthine, hypoxanthine, uridine, guanine, and uric acid in QZCs using high-performance liquid chromatography. Hypoxanthine was used as an internal reference to determine relative correction factors for the other five components. The six components were determined in ten different batches of QZCs. There was no significant difference between the quantitative multicomponent analysis of a single marker and the external standard method. The relative standard deviation of total nucleosides analogs of 10 batches of samples was 7%. This method can be applied to simultaneously determine multiple active components in QZCs and other nucleoside analog drugs, enabling multi-indicator quality control.

Combination of ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and network pharmacology to reveal the mechanism of Shengyu Decoction for treating anemia.

Anemia is a common clinical hematological disease with a high incidence, which seriously affects human health. Shengyu Decoction is often used in the treatment of anemia. However, the pharmacodynamic substance basis and therapeutic mechanism are still unclear, which hinders the comprehensive development and utilization of Shengyu Decoction. In this study, 143 compounds were identified in Shengyu Decoction using high-throughput ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, 24 of which were absorbed into the blood. Taking these blood-entering ingredients as the research object, we found through network pharmacology research that ferulic acid, calycosin, and astragaloside A can act on AKT1, MAPK1, and MAPK14, and play a role in treating anemia through PI3K-Akt signaling pathway and Pathways in anemia. Finally, it was demonstrated that the active compound could bind to the core target with good affinity by molecular docking. The research shows that Shengyu Decoction has multi-component, multi-target, and multi-channel effects in the treatment of anemia, which provides a basis for the development and clinical application of Shengyu Decoction.

Development and Validation of a UPLC-MS/MS Method for the Quantification of Components in the Ancient Classical Chinese Medicine Formula of Guyinjian.

Guyinjian (GYJ) is an ancient classic formula of traditional Chinese medicine used for the treatment of liver and kidney yin deficiency; it was derived from the book "Jing Yue Quan Shu" in the Ming Dynasty. Modern clinical observation experiments have shown that GYJ has a definite therapeutic effect on the treatment of gynecological diseases such as kidney deficiency type oligomenorrhea, climacteric syndrome, intermenstrual bleeding, pubertal metrorrhagia, etc. However, the lack of GYJ quality control studies has greatly limited the development of its wider clinical application. In this study, a validated UPLC-MS/MS method was developed successfully for the first time and used to quantify fourteen compounds in GYJ samples with good specificity, linearity (r = 0.9960-0.9999), precision (RSD% ≤ 3.18%), stability (RSD% ≤ 2.22%) and accuracy (recovery test within 88.64-107.43%, RSD% at 2.82-6.22%). Simultaneously, the determination results of 15 batches of GYJ samples were analyzed by multivariate statistical methods, and it was found that the compounds have a greater influence on batch-to-batch stability, mainly Rehmannioside D, Loganin, Morroniside, Ginsenoside Re, and 3',6-Disinapoylsucrose. The proposed new method has the advantages of high sensitivity, high selectivity, and rapid analysis, which provides a reference for the GYJ quality control study.

Evaluation of the pharmacological effects and exploration of the mechanism of traditional Chinese medicine preparation Ciwujia tablets in treating insomnia based on ethology, energy metabolism, and urine metabolomic approaches.

Ciwujia Tablets (CWT) are produced by concentrating and drying the extract solution of the dried rhizome of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim [Araliaceae; E. senticosus radix et rhizoma]. Besides, CWT is included in the 2020 edition of Chinese Pharmacopoeia and is widely used in the treatment of insomnia. It mainly contains eleutheroside B, eleutheroside E, isofraxidin, eleutheroside C, ciwujiatone, and chlorogenic acid, as well as other chemical components. Although the clinical efficacy of CWT in treating insomnia has been confirmed, its functions and pharmacological effects have not been systematically evaluated and its mechanism of action in the treatment of insomnia remains unclear. Therefore, in this study, behavioral, energy metabolism, and metabonomics methods were applied to systematically evaluate the effect of CWT on insomnia. Additionally, urine metabonomics based on UPLC-Q-TOF-MS/MS were utilized to identify potential endogenous biomarkers of insomnia, detect the various changes before and after CWT treatment, explore the metabolic pathway and potential target of CWT, and reveal its pharmacological mechanism. Results revealed that CWT increased inhibitory neurotransmitter (5-HT and GABA) content and reduced the content of excitatory neurotransmitters (DA and NE). Moreover, CWT enhanced autonomous behavioral activity, stabilized emotions, and promoted the return of daily basic metabolic indexes of insomniac rats to normal levels. The urine metabolomics experiment identified 28 potential endogenous biomarkers, such as allysine, 7,8-dihydroneopterin, 5-phosphonooxy-L-lysine, and N-acetylserotonin. After CWT treatment, the content of 22 biomarkers returned to normal levels. The representative markers included N-acetylserotonin, serotonin, N-methyltryptamine, and 6-hydroxymelatonin. Additionally, the metabolic pathways in rats were significantly reversed, such as tryptophan metabolism, folate biosynthesis, phenylalanine metabolism, and tyrosine metabolism. Ultimately, it is concluded that CWT regulated tryptophan metabolism, folate biosynthesis, phenylalanine metabolism, and other metabolic levels in the body. This drug has been confirmed to be effective in the treatment of insomnia by regulating the content of serotonin, 6-hydroxymelatonin, N-acetylserotonin, and N-methyltryptamine to a stable and normal level in tryptophan metabolism.

Exploring potential mechanism of ciwujia tablets for insomnia by UPLC-Q-TOF-MS/MS, network pharmacology, and experimental validation.

Insomnia, whether chronic or intermittent, is a common central nervous system disease. Ciwujia Tablet (CWT) is a well-known traditional Chinese medicine (TCM) made from the extract of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. This medication is commonly used for treating insomnia in China, but the lack of in-depth research focused on the chemical ingredients of CWT creates a gap in knowledge regarding its effective constituents against insomnia. Considering that the therapeutic material basis, targets, and pathways related to this drug have not been fully investigated by scholars in the field, the focus of this study is on identifying the chemical ingredients or structural characteristics of CWT by the UPLC-Q-TOF-MS/MS technique. Besides, concepts of network pharmacology were also used to investigate the targets and pathways of CWT. An insomnia rat model was established by intraperitoneal injection of p-chlorophenylalanine, and the results were verified through various experiments. A total of 46 ingredients were identified in CWT, such as eleutheroside B, eleutheroside E, isofraxidin, and chlorogenic acid. Among them, 17 ingredients with good solubility, favorable gastrointestinal absorption, and high bioavailability were selected for network pharmacological analysis. It was concluded that CWT participated in the regulation of neurotransmitter levels, modulation of ion transport, neurotransmitter receptor activity, synaptic transmission, dopaminergic transmission and other essential processes. Results from the animal experiments showed that CWT can increase the content of inhibitory neurotransmitters 5-HT and GABA in the brain, reduce the synthesis of excitatory escalating transmitters DA and NE, shorten the sleep latency and prolong the sleep duration of insomnia rats. Furthermore, CWT could significantly alleviate the symptoms of insomnia in model rats. Identifying the chemical ingredients of CWT in this experiment is of great significance for exploring its potential curative effects, which provides a solid basis for further understanding the therapeutic value of this medication.

Rapid identification of chemical components in Zhizi Baipi decoction by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry coupled with a novel informatics UNIFI platform.

Zhizi Baipi decoction is a classic traditional Chinese medicine formula for the treatment of jaundice and various liver diseases. The chemical components of Zhizi baipi decoction were not clear resulting of the paucity of relevant studies, which hindered the elucidation of the pharmacological mechanism, and the comprehensive development and utilization of Zhizi baipi decoction in clinical. In this study, ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry combined with the UNIFI natural product information analysis platform was used to rapidly analyze and identify the chemical components in Zhizi baipi decoction. A total of 122 chemical components, including 53 flavonoids, 16 alkaloids, 25 terpenoids, five phenylpropanoids, 14 organic acids, and seven others, were identified from Zhizi baipi decoction. These compounds may be the active components of Zhizi baipi decoction. The method established in this study can systematically, rapidly, and accurately resolve the chemical components in Zhizi baipi decoction, which lays the foundation for further establishment of the pharmacodynamic substance basis and quality control of Zhizi baipi decoction.