Multi-omics combined to explore the purging mechanism of Rhei Radix et Rhizoma and Magnoliae Officinalis Cortex.

Rhei Radix et Rhizoma and Magnoliae Officinalis Cortex have been used together to treat constipation in the clinical practices for more than 2000 years. Nonetheless, their compatibility mechanism is still unclear. In this study, the amelioration of Rhei Radix et Rhizoma combined with Magnoliae Officinalis Cortex on constipation was systematically and comprehensively evaluated. The results showed that their compatibility could markedly shorten gastrointestinal transport time, increase fecal water content and frequency of defecation, improve gastrointestinal hormone disorders and protect colon tissue of constipation rats compared with the single drug. Furthermore, according to 16S rRNA sequencing in conjunction with UPLC-Q-TOF/MS, the combination of two herbal medications could greatly raise the number of salutary bacteria (Lachnospiraceae, Romboutsia and Subdoligranulum) while decreasing the abundance of pathogenic bacteria (Erysipelatoclostridiaceae). And two herb drugs could markedly improve the disorder of fecal metabolic profiles. A total of 7 different metabolites associated with constipation were remarkably shifted by the compatibility of two herbs, which were mainly related to arachidonic acid metabolism, alpha-linolenic acid metabolism, unsaturated fatty acid biosynthesis and other metabolic ways. Thus, the regulation of intestinal microbiome and its metabolism could be a potential target for Rhei Radix et Rhizoma and Magnoliae Officinalis Cortex herb pair to treat constipation. Furthermore, the multi-omics approach utilized in this study, which integrated the microbiome and metabolome, had potential for investigating the mechanism of traditional Chinese medicines.

Salvia miltiorrhiza stem-leaf of total phenolic acid conversion products alleviate myocardial ischemia by regulating metabolic profiles, intestinal microbiota and metabolites.

Myocardial ischemia (MI) is a significant contributor to ischemic heart diseases like angina pectoris and myocardial infarction. Reactive oxygen species produced during MI can trigger lipid peroxidation, damaging cell structure and function. Salvia miltiorrhiza (SM) has been widely used clinically in the treatment of cardiovascular diseases. However, in the process of rooting, the aboveground parts of this plant are usually discarded by tons. To make better use of these plant resources, the phenolic acids extracted and purified from the aerial part of SM were studied and chemically transformed, and the potential protective effect and possible mechanism of salvianolic acids containing a higher content of salvianolic acid A on MI were obtained. The transformed products of SM stem-leaves total phenolic acids with 8.16 % salvianolic acid A showed a better protective effect on the isoproterenol (ISO)-induced acute MI injury rat model. It can improve ST segment changes and has good antioxidant, anti-inflammatory and anticoagulant effects. In addition, the dysbiosis of gut microbiota and the related metabolic levels of short chain fatty acids (SCFAs), phenylalanine and glycerophospholipids were improved. This was achieved by reducing the abundance of Bacteroides, Faecalibaculum, and L-phenylalanine levels. In addition, the abundance of probiotics in Butyricoccus, Roseburia, and norank_f_Eubacterium_coprostanoligenes_group, as well as the contents of propionic acid and isobutyric acid, LPCs and PCs were increased. In conclusion, total phenolic acids of SM stem-leaves showed protective effects against ISO-induced rats, especially the strongest effect after conversion, which is a new option for the prevention and treatment of MI.

Saiga antelope horn suppresses febrile seizures in rats by regulating neurotransmitters and the arachidonic acid pathway.

BACKGROUND: Saiga antelope horn (SAH) is a traditional Chinese medicine for treating febrile seizure (FS) with precise efficacy, but its mechanism of action and functional substances are still unclear. Given the need for further research on SAH, our group conducted studies to elucidate its mechanisms and active substances. METHODS: An FS rat pup model was constructed through intraperitoneal injection of LPS and hyperthermia induction. Behavioural indicators of seizures, hippocampal histopathological alterations, serum levels of inflammatory cytokines and hippocampal levels of neurotransmitters were observed and measured to investigate the effects of SAH on FS model rats. Hippocampal metabolomics and network pharmacology analyses were conducted to reveal the differential metabolites, key peptides and pathways involved in the suppression of FS by SAH. RESULTS: SAH suppressed FS, decreased the inflammatory response and regulated the Glu-GABA balance. Metabolomic analysis revealed 13 biomarkers of FS, of which SAH improved the levels of 8 differential metabolites. Combined with network pharmacology, a "biomarker-core target-key peptide" network was constructed. The peptides of SAH, such as YGQL and LTGGF, could exert therapeutic effects via the arachidonic acid pathway. Molecular docking and ELISA results indicated that functional peptides of SAH could bind to PTGS2 target, inhibiting the generation of AA and its metabolites in hippocampal samples. CONCLUSION: In summary, the functional peptides contained in SAH are the main material basis for the treatment of FS, potentially acting through neurotransmitter regulation and the arachidonic acid pathway.

Comprehensive reutilization of Glycyrrhiza uralensis residue by extrusion-biological pretreatment for coproduction of flavonoids, cellulase, and ethanol.

A continuous chemical-free green approach was investigated for the comprehensive reutilization of all components in herbal extraction residues (HERs), taking Glycyrrhiza uralensis residue (GUR) as an example. The GUR structural changes induced by mechanical extrusion which improve the specific surface area and enzyme accessibility of GUR. With 3 % pretreated GUR loading of high-tolerance Penicillium oxalicum G2. The reducing sugar yield of 11.45 g/L was achieved, along with an 81.06 % in situ enzymatic hydrolysis. Finally, 8.23 g/L bioethanol (0.40 g/g total sugar) was produced from GUR hydrolysates after 24 h fermentation of Pichia stipitis G32. The amount of functional medicinal ingredients extracted from GUR after hydrolysis (39.63 mg/g) was 37.69 % greater than that of un-pretreated GUR. In total, 1.49 g flavonoids, 294.36 U cellulase, and 14.13 g ethanol could be produced from 100 g GUR using this process, illustrating that this green and efficient process has the potential for industrial production.

Luteoloside mitigates premature age-related macular degeneration by suppressing p53-p21-Rb1 axis: Insights from transcriptomic analysis, serum metabolomics and gut microbiota analysis.

Transcriptomics of dry age-related macular degeneration (AMD) patients with premature aging revealed the upregulated pathways involved in glycerolipid metabolism, tyrosine metabolism, and pentose and glucuronate interconversion. To investigate natural strategies for modulating these implicated pathways, we examined the impact and underlying mechanism of luteoloside on premature AMD using a stress-induced premature senescence (SIPS)-associated AMD animal model in middle-aged mice that mimicked the dysregulated pathways observed in dry AMD patients with premature aging. Luteoloside supplementation resulted in a significant reduction in serum levels of the pro-inflammatory cytokine IL-1ß and lipofuscin, along with increased serum activity of the antioxidant enzyme superoxide dismutase (SOD) and elevated levels of pigment epithelium-derived factor (PEDF), and preserved retinal thickness and structure in AMD mice. Furthermore, luteoloside supplementation effectively reversed the abnormal serum levels of metabolites, particularly by reducing harmful lysophosphatidylcholine (LysoPC) and increasing beneficial 4-guanidinobutanoic acid. In addition to its impact on metabolites, luteoloside modulated the composition of gut microbiota, promoting the enrichment of beneficial bacterial populations, including Lactobacillus, while reducing the abundance of harmful bacterial populations, including Bacteroides. Overall, our findings highlight the potential of luteoloside supplementation in regulating the dysregulated intestinal microbiota and metabolites in premature AMD, thereby reducing ocular levels of senescence-associated secretory phenotype (SASP) factors through the suppression of the p53-p21-retinoblastoma protein 1 (Rb1) axis.

Comparative pharmacokinetics of multi-components in normal and stomach cold syndrome rats after oral administration of Zingiberis Rhizoma - Jujubae Fructus herb pair and its single herb extracts by UHPLC-MS/MS.

The Zingiberis Rhizoma - Jujubae Fructus herb pair (ZJHP) is a classic herb pair in traditional Chinese medicine. The herb pair shows the effect of dispelling cold, harmonizing the middle and improving gastrointestinal function, and is widely used for patients with stomach cold syndrome (SCS), stomachache and anemofrigid cold. The gingerols, shogaols, flavonoids and triterpenic acids are the important bioactive ingredients of ZJHP. However, few pharmacokinetic studies have been investigated in vivo for the above compounds. To comprehend the kinetics of active components and promote their curative application, a fast and sensitive ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS/MS) method was established for simultaneous determination of 12 analytes in normal and SCS rats in this study. The results showed that the pharmacokinetic parameters (Cmax, Tmax, t1/2z, MRT0-t, AUC0-t and AUC0-∞) in SCS model were significantly different from those in normal rats. In addition, the pharmacokinetics of rats given ZJHP were also varied from single herb oral administration, especially in model condition. These results indicated that the in vivo processes of the above analytes changed under pathological conditions and the compatibility of the herb pair could significantly influence the absorption of active components, which might provide an insight and further supports for the clinical application of ZJHP.

Modulation of gut microbiota on intestinal permeability: A novel strategy for treating gastrointestinal related diseases.

Accumulating evidence emphasizes the critical reciprocity between gut microbiota and intestinal barrier function in maintaining the gastrointestinal homeostasis. Given the fundamental role caused by intestinal permeability, which has been scrutinized as a measurable potential indicator of perturbed barrier function in clinical researches, it seems not surprising that recent decades have been marked by augmented efforts to determine the interaction between intestinal microbes and permeability of the individual. However, despite the significant progress in characterizing intestinal permeability and the commensal bacteria in the intestine, the mechanisms involved are still far from being thoroughly revealed. In the present review, based on multiomic methods, high-throughput sequencing and molecular biology techniques, the impacts of gut microbiota on intestinal permeability as well as their complex interaction networks are systematically summarized. Furthermore, the diseases related to intestinal permeability and main causes of changes in intestinal permeability are briefly introduced. The purpose of this review is to provide a novel prospection to elucidate the correlation between intestinal microbiota and permeability, and to explore a promising solution for diagnosis and treatment of gastrointestinal related diseases.

Comparative pharmacokinetic study on phenolic acids and flavonoids in normal and microcirculation dysfunction rats plasma by UPLC-TQ/MS/MS after oral administration of Salvia miltiorrhiza stem-leaf extracts.

According to the Standard of Chinese Medicinal Materials of Shaanxi Province (2015 edition), Salvia miltiorrhiza caulis et folium is the dried stems and leaves of Salvia miltiorrhiza, which could activate blood and dispell blood stasis, clear the mind and remove annoyance. In this study, the dynamic absorption changes of phenolic acids (FS) and phenolic acids-flavonoids (FT) in rats after oral administration were studied by UPLC-TQ/MS/MS, to elucidate the pharmacokinetics of seven major bioactive components of the stem-leaf of Salvia miltiorrhiza in vivo. The results showed that the pharmacokinetic parameters of FS and FT were significantly different in normal rats and model rats. Compared with the control group, after injecting 10 % polymer dextran 500 into the tail vein to establish a model of microcirculation disturbance, the Cmax of caffeic acid decreased. The Cmax of rosmarinic acid and lithospermic acid increased. Danshensu showed a decrease in CLz/F, accompanied by an increase in both AUC0-t and AUC0-∞. The AUC0-t of lithospermic acid was also increased. These results indicated that microcirculation disturbance could decrease the absorption of caffeic acid while increasing the absorption of danshensu, rosmarinic acid and lithospermic acid. After oral administration of FT, the Cmax of danshensu and the AUC0-t of caffeic acid were increased significantly, suggesting that the presence of flavonoids may promote the absorption and exposure of phenolic acids in vivo. This study provides a reference for the elucidation of the in vivo substances and the mechanisms of action of FS and FT from the stem-leaf of Salvia miltiorrhiza.

6-Gingerol ameliorates ulcerative colitis by inhibiting ferroptosis based on the integrative analysis of plasma metabolomics and network pharmacology.

6-Gingerol (6-G), an active ingredient of ginger with anti-inflammation and anti-oxidation properties, can treat ulcerative colitis (UC). However, its underlying mechanism is still unclear. In this study, the pharmacodynamic evaluation of 6-G for treating UC was performed, and the mechanism of 6-G in ameliorating UC was excavated by plasma metabolomics and network pharmacology analysis, which was further validated by experimental and molecular docking. The results showed that 6-G could notably reduce diarrhea, weight loss, colonic pathological damage, and inflammation in UC mice. Plasma metabolomic results indicated that 6-G could regulate 19 differential metabolites, and its metabolic pathways mainly involved linoleic acid metabolism and arachidonic acid metabolism, which were closely associated with ferroptosis. Moreover, 60 potential targets for 6-G intervention on ferroptosis in UC were identified by network pharmacology, and enrichment analysis revealed that 6-G suppressed ferroptosis by modulating lipid peroxidation. Besides, the integration of metabolomics and network pharmacology showed that the regulation of 6-G on ferroptosis focused on 3 key targets, including ALOX5, ALOX15, and PTGS2. Further investigation indicated that 6-G significantly inhibited ferroptosis by decreasing iron load and malondialdehyde (MDA), and enhanced antioxidant capacity by reducing the content of glutathione disulfide (GSSG) and increasing the levels of superoxide dismutase (SOD) and glutathione (GSH) in UC mice and RSL3-induced Caco-2 cells. Furthermore, molecular docking showed the high affinity of 6-G with the identified 3 key targets. Collectively, this study elucidated the potential of 6-G in ameliorating UC by inhibiting ferroptosis. The integrated strategy also provided a theoretical basis for 6-G in treating UC.

[Identification of horn-derived animal medicines based on detection of keratin-derived characteristic peptides].

Due to the highly stable structure of keratin, the extraction and dissolution steps of animal medicines rich in keratin are complex, which seriously restricts the detection efficiency and flux. Therefore, this study simplified the pre-treatment steps of horn samples and optimized the detection methods of characteristic peptides to improve the efficiency of identifying the specificity of horn-derived animal medicines. For detection of the characteristic peptides in horn-derived animal medicines treated with/without iodoace-tamide(IAA), the ion pair conditions of the characteristic peptides were optimized, and the retention time, intensity and other data of the specific peptides were compared between the samples treated with/without IAA. Two pre-treatment methods, direct enzymatic hydrolysis and total protein extraction followed by enzymatic hydrolysis, were used to prepare horn-derived animal medicine samples. The effects of different methods on the detection of specific peptides in the samples of Saiga antelope horn, water buffalo horn, goat horn, and yak horn were compared regarding the retention time of specific peptides and ion intensity. The results indicated that after direct enzymatic hydrolysis, the specific peptides in the samples without IAA treatment can be detected. Compared with the characteristic peptides in the samples treated with IAA, their retention time shifted back and the mass spectrometry response slightly decreased. The specific peptides of the samples without IAA treatment had good specificity and did not affect the specificity identification of horn-derived animal medicines. Overall, the process of direct enzymatic hydrolysis can be used to treat horn samples, omitting the steps of protein extraction and dithiothreitol and IAA treatment, significantly improving the pre-treatment efficiency without affecting the specificity identification of horn-derived animal medicines. This study provides ideas for quality research and standard improvement of horn-derived animal medicines.

[Development of green pesticides from traditional Chinese medicines based on artificial intelligence and compatibility of traditional Chinese medicines].

The food security of China as a big agricultural country is attracting increasing attention. With the progress in the traditional Chinese medicine industry, Chinese medicinal materials and their preparations have been gradually developed as agents for disease prevention and with antimicrobial and insecticidal functions in agriculture. Promoting pesticide innovation by interdisciplinary integration has become the trend in pesticide research globally. Considering the increasingly important roles of green pesticides from traditional Chinese medicines and artificial intelligence in pest target prediction, this paper proposed an innovative green control strategy in line with the concepts of ecological sustainable development and food security protection. CiteSpace was used for visual analysis of the publications. The results showed that artificial intelligence had been extensively applied in the pesticide field in recent years. This paper explores the application and development of biopesticides for the first time, with focus on the plant-derived pesticides. The thought of traditional Chinese medicine compatibility can be employed to creat a new promosing field: pesticides from traditional Chinese medicine. Moreover, artificial intelligence can be employed to build the formulation system of pesticides from traditional Chinese medicines and the target prediction system of diseases and pests. This study provides new ideas for the future development and market application of biopesticides, aiming to provide more healthy and safe agricultural products for human beings, promote the innovation and development of green pesticides in China, and protect the sustainable development of the environment and ecosystem. This may be the research hotspot and competition point for the green development of the pesticide industry chain in the future.

[Methods for research on structures and functions of traditional Chinese medicine proteins].

Traditional Chinese medicine proteins(TCMPs) not only have nutritional values and biological activities but also serve as key enzymes in the synthesis of pharmacodynamic components in traditional Chinese medicines. They play a role in the synthesis of pharmacodynamic components by regulating biosynthesis and selective synthesis pathways and controlling drug quality and stability. The recent years have witnessed great progress in the research on the structures and functions of proteins using various methods and technologies. However, the research on the structures and functions of TCMPs lags behind. Therefore, it is urgent to study the structures and functions of TCMPs using modern means to promote the discovery of innovative drugs based on TCMPs and clarify the synthesis pathways of pharmacodynamic components. This study introduces the latest techniques for studying protein structures and functions, including spectroscopy, mass spectrometry, nuclear magnetic resonance, X-ray crystal diffraction, microscopy, and structure prediction. Furthermore, this paper introduces the methods for protein functional studies, including liquid chromatography-mass spectrometry, co-immunoprecipitation, yeast two-hybrid, and pull-down assay. By systematically reviewing these techniques and methods, this paper provides technical references for the structural identification and functional studies of TCMPs, with the aim of promoting the in-depth exploration of the structures and functions of TCMPs.

The relationship between polysaccharide structure and its antioxidant activity needs to be systematically elucidated.

Polysaccharides have a wide range of applications due to their excellent antioxidant activity. However, the low purity and unclear structure of polysaccharides have led some researchers to be skeptical about the antioxidant activity of polysaccharides. The current reports on the structure-activity relationship of polysaccharides are sporadic, so there is an urgent need to systematically summarize the antioxidant effects of polysaccharides with clear structures and the relationships between the structures to provide a scientific basis for the development and application of polysaccharides. This paper will systematically elucidate the structure-activity relationship of antioxidant polysaccharides, including the molecular weight, monosaccharide composition, glycosidic linkage, degree of branching, advanced conformation and chemical modification. For the first time, the antioxidant activity of polysaccharides is related to their chemical structure through histogram and radar map, and further studies using principal component analysis and cluster analysis. We critically discussed how the source, chemical structure and chemically modified groups of polysaccharides significantly contribute to their antioxidant activity and summarized the current research status and shortcomings of the structure-activity relationship of antioxidant polysaccharides. This review provides a theoretical basis and new perspective for further research on the structure-activity relationship of antioxidant polysaccharides and the development of natural antioxidants.

Xianlian Jiedu Decoction alleviates colorectal cancer by regulating metabolic profiles, intestinal microbiota and metabolites.

BACKGROUND: Xianlian Jiedu Decoction (XLJDD) has been used for the treatment of colorectal cancer (CRC) for several decades because of the prominent efficacy of the prescription. Despite the clear clinical efficacy of XLJDD, the anti-CRC mechanism of action is still unclear. PURPOSE: The inhibitory effect and mechanism of XLJDD on CRC were investigated in the azoxymethane/dextran sulfate sodium (AOM/DSS)-induced mice. METHODS: The AOM/DSS-induced mice model was adopted to evaluate the efficacy after administering the different doses of XLJDD. The therapeutic effects of XLJDD in treating AOM/DSS-induced CRC were investigated through histopathology, immunofluorescence and ELISA analysis methods. In addition, metabolomics profile and 16S rRNA analysis were used to explore the effective mechanisms of XLJDD on CRC. RESULTS: The results stated that the XLJDD reduced the number of tumor growth on the inner wall of the colon and the colorectal weight/length ratio, and suppressed the disease activity index (DAI) score, meanwhile XLJDD also increased body weight, colorectal length, and overall survival rate. The treatment of XLJDD also exhibited the ability to lower the level of inflammatory cytokines in serum and reduce the expression levels of ß-catenin, COX-2, and iNOS protein in colorectal tissue. The findings suggested that XLJDD has anti-inflammatory properties and may provide relief for those suffering from inflammation-related conditions. Mechanistically, XLJDD improved gut microbiota dysbiosis and associated metabolic levels of short chain fatty acids (SCFAs), sphingolipid, and glycerophospholipid. This was achieved by reducing the abundance of Turicibacter, Clostridium_sensu_stricto_1, and the levels of sphinganine, LPCs, and PCs. Additionally, XLJDD increased the abundance of Enterorhabdus and Alistipes probiotics, as well as the content of butyric acid and isovaleric acid. CONCLUSION: The data presented in this article demonstrated that XLJDD can effectively inhibit the occurrence of colon inner wall tumors by reducing the level of inflammation and alleviating intestinal microbial flora imbalance and metabolic disorders. It provides a scientific basis for clinical prevention and treatment of CRC.

Mijiao formula regulates NAT10-mediated Runx2 mRNA ac4C modification to promote bone marrow mesenchymal stem cell osteogenic differentiation and improve osteoporosis in ovariectomized rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The Mijiao (MJ) formula, a traditional herbal remedy, incorporates antlers as its primary constituent. It can effectively treat osteoporosis (OP), anti-aging, enhance immune activity, and change depression-like behavior. In this study, we investigated that MJ formula is a comprehensive treatment strategy, and may provide a potential approach for the clinical treatment of postmenopausal osteoporosis. AIM OF THE STUDY: The purpose of this study was to determine whether MJ formula promoted osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and improved osteoporosis in ovariectomized rats by regulating the NAT10-mediated Runx2 mRNA ac4C modification. MATERIALS AND METHODS: Female Sprague-Dawley (SD) rats were used to investigate the potential therapeutic effect of MJ formula on OP by creating an ovariectomized (OVX) rat model. The expression of osteogenic differentiation related proteins in BMSCs was detected in vivo, indicating their role in promoting bone formation. In addition, the potential mechanism of its bone protective effect was explored via in vitro experiments. RESULTS: Our study showed that MJ formula significantly mitigated bone mass loss in the OVX rat model, highlighting its potential as an OP therapeutic agent. We found that the possible mechanism of action was the ability of this formulation to stabilize Runx2 mRNA through NAT10-mediated ac4C acetylation, which promoted osteogenic differentiation of BMSCs and contributed to the enhancement of bone formation. CONCLUSIONS: MJ formula can treat estrogen deficiency OP by stabilizing Runx2 mRNA, promoting osteogenic differentiation and protecting bone mass. Conceivably, MJ formulation could be a safe and promising strategy for the treatment of osteoporosis.

Mechanism and functional substances of Saiga antelope horn in treating hypertension with liver-yang hyperactivity syndrome explored using network pharmacology and metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Saiga antelope horn (SAH) is a traditional Chinese medicine for treating hypertension with liver-yang hyperactivity syndrome (Gan-Yang-Shang-Kang, GYSK), that has a long history of clinical application and precise efficacy, but its mechanism and functional substances are still unknown. Based on the demand for alternative research on the rare and endangered SAH, the group designed and carried out the following studies. AIM OF THE STUDY: The purpose of this research was to demonstrate the functional substances and mechanisms of SAH in the treatment of GYSK hypertension. MATERIALS AND METHODS: The GYSK-SHR model was constructed by administering a decoction of aconite to spontaneously hypertensive rats (SHRs). Blood pressure (BP), behavioural tests related to GYSK, and pathological changes in the kidneys, heart and aorta were measured to investigate the effects of SAH on GYSK-SHRs. Proteomic analysis was used to identify the keratins and peptides of SAH. Moreover, network pharmacology and plasma metabolomics studies were carried out to reveal the mechanisms by which functional peptides in SAH regulate GYSK-hypertension. RESULTS: SAH has a significant antihypertensive effect on GYSK hypertensive animals. It has also been proven to be effective in protecting the function and structural integrity of the kidneys, heart and aorta. Moreover, SAH improved the abnormalities of 31 plasma biomarkers in rats. By constructing a "biomarker-target-peptide" network, 10 functional peptides and two key targets were screened for antihypertensive effects of SAH. The results indicated that SAH may exert a therapeutic effect by re-establishing the imbalance of renin-angiotensin (RAS) system. CONCLUSIONS: Functional peptides from keratin contained in SAH are the main material basis for the treatment of GYSK-hypertension and exhibited the protective effect on the GYSK-SHR model through the RAS system.

[Comparison of in vivo pharmacokinetics of twelve constituents in Qihe Fenqing Yin in normal rats and diabetic rats].

This paper aims to study the pharmacokinetic differences of twelve effective constituents(succinic acid, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, protocatechuic aldehyde, caffeic acid, 5-O-ferulogeninic acid, p-coumaric acid, nuciferine, quercetin, oleanolic acid, and ursolic acid) in Qihe Fenqing Yin in normal and diabetic rats. The diabetic rat model was established by a high-fat diet combined with intraperitoneal injection of streptozocin. A UHPLC-QTRAP-MS/MS method was established for the simultaneous determination of 12 constituents in the plasma of normal rats and model rats after a single intragastric administration of Qihe Fenqing Yin. The results show that the established analytical method has a good linear relationship with the 12 components, and the specificity, accuracy, precision, and stability meet the requirements. The computational pharmacokinetic parameters are fitted by DAS 3.2.8 software, and the results show that the half-life time(t_(1/2)) of the other nine components in the model group was longer than that in the normal group except for caffeic acid, 5-O-ferulogeninic acid, and oleanolic acid. The area under curve(AUC_(0-t)) of cryptochlorogenic acid, p-coumaric acid, ursolic acid, and oleanolic acid increases compared with the normal group. Meanwhile, mean residence time(MRT) delays. The "double peaks" of quercetin and nuciferine in the normal group are not observed in the model group, suggesting that the pharmacokinetic parameters of the drugs in the disease state are significantly different.

Network pharmacology analysis and experimental verification of the antithrombotic active compounds of trichosanthis pericarpium (Gualoupi) in treating coronary heart disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Trichosanthis pericarpium (TP; Gualoupi, pericarps of Trichosanthes kirilowii Maxim) has been used in traditional Chinese medicine (TCM) to reduce heat, resolve phlegm, promote Qi, and clear chest congestion. It is also an essential herbal ingredient in the "Gualou Xiebai" formula first recorded by Zhang Zhongjing (from the Eastern Han Dynasty) in the famous TCM classic "Jin-Guì-Yào-Lüe" for treating chest impediments. According to its traditional description, Gualou Xiebai is indicated for symptoms of chest impediments, which correspond to coronary heart diseases (CHD). AIM OF THE STUDY: This study aimed to identify the antithrombotic compounds in Gualoupi for the treatment of CHD. MATERIALS AND METHODS: A CHD rat model was established with a combination of high-fat diet and isoproterenol hydrochloride (ISO) administration via subcutaneous multi-point injection in the back of the neck. This model was used to evaluate the antithrombotic effect of two mainstream cultivars of TP ("HaiShi GuaLou" and "WanLou") by analyzing the main components and their effects. Network pharmacology, molecular docking-based studies, and a zebrafish (Danio rerio) thrombosis model induced by phenylhydrazine was used to validate the antithrombosis components of TP. RESULTS: TP significantly reduced the body weight of the CHD rats, improved myocardial ischemia, and reduced collagen deposition and fibrosis around the infarcted tissue. It reduced thrombosis in a dose-dependent manner and significantly reduced inflammation and oxidative stress damage. Cynaroside, isoquercitrin, rutin, citrulline, and arginine were identified as candidate active TP compounds with antithrombotic effects. The key potential targets of TP in thrombosis treatment were initially identified by molecular docking-based analysis, which showed that the candidate active compounds have a strong binding affinity to the potential targets (protein kinase C alpha type [PKCα], protein kinase C beta type [PKCß], von Willebrand factor [vWF], and prostaglandin-endoperoxide synthase 1 [PTGS1], fibrinogen alpha [Fga], fibrinogen beta [Fgb], fibrinogen gamma [Fgg], coagulation factor II [F2], and coagulation factor VII [F7]). In addition, the candidate active compounds reduced thrombosis, improved oxidative stress damage, and down-regulated the expression of thrombosis-related genes (PKCα, PKCß, vWF, PTGS1, Fga, Fgb, Fgg, F2, and F7) in the zebrafish model. CONCLUSION: Cynaroside, isoquercitrin, rutin, citrulline, and arginine were identified as the active antithrombotic compounds of TP used to treat CHD. Mechanistically, the active compounds were found to be involved in oxidative stress injury, platelet activation pathway, and complement and coagulation cascade pathways.

Chemical constituents of the aerial parts of Mitracarpus hirtus (L.) DC (Rubiaceae).

A phytochemical investigation of the aerial parts of Mitracarpus hirtus afforded thirteen compounds, including a new naphthoquinone di-glycoside (1), three isopentenyl isoflavones (2-4), four flavonoids (5-8), three iridoid glycosides (9 - 11) and two coumarins (12 and 13). Their structures were elucidated based on extensive spectroscopic analyses, chemical methods, and the comparison with the literature. Among them, compound 1 possesses a 2-(3-methylnaphthalen-2-yl)acetic acid core with two glucosyl groups, compounds 2-4 are the first three representatives from the Rubiaceae family, and compounds 9-11 and 13 were isolated from Mitracarpus genus for the first time. Additionally, compounds 2-4 displayed potent antibacterial activities against Helicobacter pylori G27/HP159/JRES00015 (MIC = 4-16 µg/mL) , comparable to metronidazole. To date, wighteone (2) is the most active isoflavone with favourable predicted ADMET properties reported against H. pylori.

Insights into the molecular mechanisms, structure-activity relationships and application prospects of polysaccharides by regulating Nrf2-mediated antioxidant response.

The occurrence and development of many diseases are closely related to oxidative stress. In this context, accumulating evidence suggests that Nrf2, as the master switch of cellular antioxidant signaling, plays a central role in controlling the expression of antioxidant genes. The core molecular mechanism of polysaccharides treatment of oxidative stress-induced diseases is to activate Keap1/Nrf2/ARE signaling pathway, promote nuclear translocation of Nrf2, and up-regulate the expression of antioxidant enzymes. However, recent studies have shown that other signaling pathways in which polysaccharides exert antioxidant effects, such as PI3K/Akt/GSK3ß, JNK/Nrf2 and NF-κB, have complex crosstalk with Keap1/Nrf2/ARE, may have direct effects on the nuclear translocation of Nrf2. This suggests a new strategy for designing polysaccharides as modulators of Nrf2-dependent pathways to target the antioxidant response. Therefore, in this work, we investigate the crosstalk between Keap1/Nrf2/ARE and other antioxidant signaling pathways of polysaccharides by regulating Nrf2-mediated antioxidant response. For the first time, the structural-activity relationship of polysaccharides, including molecular weight, monosaccharide composition, and glycosidic linkage, is systematically elucidated using principal component analysis and cluster analysis. This review also summarizes the application of antioxidant polysaccharides in food, animal production, cosmetics and biomaterials. The paper has significant reference value for screening antioxidant polysaccharides targeting Nrf2.