Natural resourced polysaccharides: Preparation, purification, structural elucidation, structure-activity relationships and regulating intestinal flora, a system review.

Natural resourced polysaccharides (NRPs), as metabolites synthesized during activity of organisms, widely present in animal cell membranes or plant and microbial cell walls. NRPs have garnered extensive attention in the fields of medicine, foods, and farming owing to their distinct bioactivities and structural diversity. Despite the burgeoning growth in NRPs research, the available literature focuses primarily on a review of specific polysaccharides, necessitating an urgent need for a comprehensive summary of NRPs to offer readers a whole landscape of current advancements in NRPs research. Based on this, this article comprehensively reviews the latest research progress regarding preparation, purification, structure elucidation, structure-activity relationships and regulation of intestinal flora of NRPs in electronic databases, such as PubMed, Wiley, ScienceDirect and Web of Science from last 5 years. This review analyzes the effects of various extraction techniques on NRPs and also delves into the intrinsic correlation between the biological activity and structure of NRPs, highlighting that chemical modification can enhance their structural diversity and confer novel or improved biological functions. Moreover, this article extensively explores the application of NRP in promoting intestinal microecology balance, underscoring its significant potential as a probiotic initiator. This review lays a solid theoretical foundation for the future research and development of NRPs.

Integrated metabolomics and lipidomics investigation of the mechanism of Danggui Sini Decoction on improving lipid homeostasis in primary dysmenorrhea.

BACKGROUND: Danggui Sini Decoction (DGSND) is a classic prescription for treating primary dysmenorrhea (PD), while, the ameliorating effects of DGSND on PD and its mechanisms are not yet fully understood. PURPOSE: The present study is devoted to investigate the protective effect of DGSND against PD and the possible mechanism from the perspective of metabolomics as well as lipidomics. METHODS: DGSND was characterized by UPLC-Q-TOF/MS. The PD rat model was induced by estradiol benzoate and oxytocin, and traditional pharmacology, including writhing times, latency time, biochemical index, organ index, and histopathology were performed to evaluated the efficacy of DGSND on PD. Urine metabolomics strategy combined with functional analysis was adopted to delineate the therapeutic effect of DGSND on PD rats and anchor the crucial pathway, and lipidomics analysis was further performed with the uterine tissue as the research object to elucidate the protective mechanism of DGSND from the perspective of lipid homeostasis. Finally, western blot analysis was used to validate the expression of key metabolic enzymes in lipid metabolism. RESULTS: DGSND was effective in ameliorating writhing times, latency time, the value of prostaglandin F2α (PGF2α)/PGE2, uterus index, and morphological changes of PD rats. Metabolic signature of PD rats was primarily characterized by the disturbance of steroid hormone metabolism, amino acid metabolism, and lipid metabolism. Functional analysis revealed the urine biomarkers of PD were most related with lipid abnormality. Further lipidomics analysis indicated DGSND exerted anti-PD effects by remodeling lipid homeostasis, which might be due to the significant correlations between different kinds of lipids, especially the extremely high correlation of phosphatidylethanolamine, phosphatidylcholine, and fatty acids. Moreover, the key metabolic enzymes expression of CK, PLA2, LPCAT3, COX-2, and 5-LOX can be greatly downregulated by DGSND. CONCLUSION: Our findings demonstrated a novel protective mechanism of DGSND against PD by regulating lipid homeostasis.

Huangqi Guizhi Wuwu Decoction Improves Inflammatory Factor Levels in Chemotherapy-induced Peripheral Neuropathy by Regulating the Arachidonic Acid Metabolic Pathway.

BACKGROUND: Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a common complication that arises from the use of anticancer drugs. Huangqi Guizhi Wuwu Decoction (HGWWD) is an effective classic prescription for treating CIPN however, the mechanism of the activity is not entirely understood. OBJECTIVE: This study aimed to investigate the remedial effects and mechanisms of HGWWD on CIPN. METHODS: Changes in behavioral biochemical histopathological and biomarker indices were used to evaluate the efficacy of HGWWD treatment. Ultra-high-performance liquid chromatography/mass spectrometry combined with the pattern recognition method was used to screen biomarkers and metabolic pathways related to CIPN. The results of pathway analyses were verified by protein blotting experiments. RESULTS: A total of 29 potential biomarkers were identified and 13 metabolic pathways were found to be involved in CIPN. In addition HGWWD reversed the levels of 19 biomarkers. Prostaglandin H2 and 17α 21-dihydroxypregnenolone were targeted as core biomarkers. CONCLUSION: This study provides scientific evidence to support the finding that HGWWD mainly inhibits the inflammatory response during CIPN by regulating arachidonic acid metabolism.

Diabetes cardiomyopathy: targeted regulation of mitochondrial dysfunction and therapeutic potential of plant secondary metabolites.

Diabetic cardiomyopathy (DCM) is a specific heart condition in diabetic patients, which is a major cause of heart failure and significantly affects quality of life. DCM is manifested as abnormal cardiac structure and function in the absence of ischaemic or hypertensive heart disease in individuals with diabetes. Although the development of DCM involves multiple pathological mechanisms, mitochondrial dysfunction is considered to play a crucial role. The regulatory mechanisms of mitochondrial dysfunction mainly include mitochondrial dynamics, oxidative stress, calcium handling, uncoupling, biogenesis, mitophagy, and insulin signaling. Targeting mitochondrial function in the treatment of DCM has attracted increasing attention. Studies have shown that plant secondary metabolites contribute to improving mitochondrial function and alleviating the development of DCM. This review outlines the role of mitochondrial dysfunction in the pathogenesis of DCM and discusses the regulatory mechanism for mitochondrial dysfunction. In addition, it also summarizes treatment strategies based on plant secondary metabolites. These strategies targeting the treatment of mitochondrial dysfunction may help prevent and treat DCM.

Efficacy and mechanism of the Ermiao San series of formulas for rheumatoid arthritis based on Chinmedomics strategy.

BACKGROUND: The Ermiao San Series of Formulas (ESSF) refers to Ermiao San (TS), Sanmiao Wan (TW), and Simiao Wan (FW), which are widely used traditional Chinese medicine (TCM) formulas for treating rheumatoid arthritis (RA). However, the therapeutic advantages and underlying mechanisms of ESSF treatment are unclear, especially regarding the improper selection of these three formulas when treating RA. PURPOSE: To explore the efficacy and mechanisms of ESSF treatment for RA. METHODS: Complete Freund's adjuvant was used to induce RA in rats. Chinmedomics strategy, which included metabolomics, serum pharmacochemistry of TCM, molecular docking, western blotting and qPCR, was applied to reveal the therapeutic advantages, pathways, and targets of ESSF. RESULTS: In the early stages of treatment, TS quickly reduced joint swelling and the arthritis score index and regulated pathways such as arachidonic acid metabolism and purine metabolism. TW increases the regulation of tryptophan metabolism and pyrimidine metabolism pathways, promoting the recovery of the thymus and spleen. FW increases the regulation of linoleic acid metabolism and has the greatest effect on immune organ and bone recovery. In addition, 54, 67, and 86 bioactive compounds were detected in the serum from TS, TW, and FW, respectively. Berberine, phellodendrine, atractylolide III, limonin, 25R-inokosterone, coixol, and stigmasterol were found to act on the key enzymes COX-2, mPGES-1, ALOX5, and XDH in arachidonic acid metabolism and purine metabolism pathways. Western blot and qPCR results showed that ESSF can reduce the activity of these targets, thereby inhibiting the expression of the inflammatory factors IL-1ß, IL-6, IL-17, and TNF-α; the tissue injury factors MMP-3 and CRP; and the rheumatoid factors CCP Ab and RF, thereby achieving anti-RA efficacy. CONCLUSION: ESSF has a good therapeutic effect on RA. TS focus on rapid swelling reduction in the early stages of RA, TW focus on the recovery of immune organ function, and FW can be used for bone recovery in the later stage of RA treatment. The key mechanism of treating RA is that ESSF reduces the activity of COX-2, mPGES-1, ALOX5, and XDH. These findings provide valuable guidance for targeted therapy for RA and for the clinical application of ESSF.

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.

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: 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.

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.

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.>.

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.