Corrigendum: Effects of Xiao Chengqi formula on slow transit constipation by assessing gut microbiota and metabolomics analysis in vitro and in vivo.

[This corrects the article DOI: 10.3389/fphar.2022.864598.].

Piperine as a Potential Nutraceutical Agent for Managing Diabetes and Its Complications: A Literature Review.

The global prevalence of diabetes and its related complications has increased drastically and is currently a worldwide health challenge. There is still an urgent need for safe and effective natural products and supplements as alternative and/or adjunctive therapeutic interventions. Nowadays, people pay more and more attention to the nutritional and medicinal value of food ingredients. As one of the most widely employed spices in cooking, pepper also has novel medicinal values attributed to its main component, piperine (Pip). Pip is an amide alkaloid with pleiotropic properties such as anti-inflammatory, antioxidant, anti-cancer, and other related activities. Recently, Pip has received increasing scientific attention due to its antidiabetic and related complication properties. However, the values of existing studies are limited due to being scattered and unsystematic. The present study reviewed the therapeutic potential and possible mechanisms of Pip in diabetes and related complications, with the aim of providing promising candidates for the development of novel and effective alternative and/or adjunctive nutraceutical agents for the management of diabetes.

Praeruptorin C alleviates cognitive impairment in type 2 diabetic mice through restoring PI3K/AKT/GSK3ß pathway.

Diabetic encephalopathy is a common consequence of diabetes mellitus that causes cognitive dysfunction and neuropsychiatric disorders. Praeruptorin C (Pra-C) from the traditional Chinese medicinal herb Peucedanum praeruptorum Dunn. is a potential antioxidant and neuroprotective agent. This study was conducted to investigate the molecular mechanisms underlying the effect of Pra-C on diabetic cognitive impairment. A novel object recognition test and the Morris water maze test were performed to assess the behavioral performance of mice. Electrophysiological recordings were made to monitor synaptic plasticity in the hippocampus. A protein-protein interaction network of putative Pra-C targets was constructed, and molecular docking simulations were performed to predict the potential mechanisms of the action of Pra-C. Protein expression levels were detected by western blotting. Pra-C administration significantly lowered body weight and fasting blood glucose levels and alleviated learning and memory deficits in type 2 diabetic mice. Network pharmacology and molecular docking results suggested that Pra-C affects the PI3K/AKT/GSK3ß signaling pathway. Western blot analysis confirmed significant increases in phosphorylated PI3K, AKT, and GSK3ß levels in vivo and in vitro upon Pra-C administration. Pra-C alleviated cognitive impairment in type 2 diabetic mice by activating PI3K/AKT/GSK3ß pathway.

Yueju volatile oil plays an integral role in the antidepressant effect by up-regulating ERK/AKT-mediated GLT-1 expression to clear glutamate.

Phytochemical investigation of the volatile oil of Yueju (YJVO) and its constituent herbs induced the detection of 52 compounds in YJVO, mainly monoterpenes and sesquiterpenes as well as a small amount of aromatic and aliphatic compounds. 5 of these compounds were found only in the YJVO instead of the volatile oil of its constituent herbs. The anti-depressant effect of YJVO was proved by behavioral tests in chronic unpredictable mild stress (CUMS) mice. An acute oral toxicity evaluation determined the LD50 of YJVO was 5.780 mL/kg. Doppler ultrasound and laser speckle imaging have detected that the YJVO could improve depression-related cerebral blood flow. In addition, related neurotransmitters and proteins were analyzed through targeted metabolomics and immunofluorescence. The potential antidepressant mechanisms of YJVO related to significantly decreasing Glu in CUMS mice by up-regulating the ERK/AKT-mediated expression of GLT-1.

Gas-Mediated Tumor Energy Remodeling for Sensitizing Mild Photothermal Therapy.

The metabolic reprogramming of tumors requires high levels of adenosine triphosphate (ATP) to maintain therapeutic resistance, posing a major challenge for photothermal therapy (PTT). Although raising the temperature helps in tumor ablation, it frequently leads to severe side effects. Therefore, improving the therapeutic response and promoting healing are critical considerations in the development of PTT. Here, we proposed a gas-mediated energy remodeling strategy to improve mild PTT efficacy while minimizing side effects. In the proof-of-concept study, a Food and Drug Administration (FDA)-approved drug-based hydrogen sulfide (H2 S) donor was developed to provide a sustained supply of H2 S to tumor sites, serving as an adjuvant to PTT. This approach proved to be highly effective in disrupting the mitochondrial respiratory chain, inhibiting ATP generation, and reducing the overexpression of heat shock protein 90 (HSP90), which ultimately amplified the therapeutic outcome. With the ability to reverse tumor thermotolerance, this strategy delivered a greatly potent antitumor response, achieving complete tumor ablation in a single treatment while minimizing harm to healthy tissues. Thus, it holds great promise to be a universal solution for overcoming the limitations of PTT and may serve as a valuable paradigm for the future clinical translation of photothermal nanoagents.

Pulsatilla chinensis saponins ameliorated murine depression by inhibiting intestinal inflammation mediated IDO1 overexpression and rebalancing tryptophan metabolism.

BACKGROUND: Current antidepressant therapy remains unsatisfactory due to the complex pathogenesis. Emerging evidence suggested that depression is associated with inflammatory bowel disease (IBD), intestinal inflammation is an increasingly accepted factor that influences depression, but the mechanism is unclear. PURPOSE: In the current study, we determined whether Pulsatilla chinensis saponins (PRS), a phytomedicine from Pulsatilla chinensis (Bunge) Regel with excellent anti-IBD effect, could improve the depression. Furthermore, we investigated the mechanisms to explore the relationship between IBD and depression and provide new source for the urgent development of antidepressants from phytomedicine. METHODS: The antidepressant activity of PRS was accessed by behavioral test and multichannel technology in depression mice induced by Chronic Unpredictable Mild Stress (CUMS). 16S rDNA-based microbiota and RNA-seq in colon was used to explore potential intestinal metabolism affected by PRS. To illustrate the underlying mechanisms of anti-depression effect of PRS, targeted metabolomics, ELISA assay, immunofluorescence staining, Western Blot, and qPCR were carried out. RESULTS: The results clarified that CUMS induced depression with tryptophan (Trp) metabolism and intestinal inflammation. PRS effectively suppressed the depression and acted as a regulator of Trp/kynurenine (Kyn) metabolic and intestinal inflammation confirmed by analysis of microflora and colon RNA. Meanwhile PRS reduced interferon gamma (IFN-γ), inhibited JAK1-STAT1 phosphorylation, decreased IDO1 levels to protect against the overactivity of Trp/kyn path, suggesting that IFN-γ activated IDO1 probably a significant target for PRS to exert anti-depression effects. To further confirm the mechanism, this research expressed that PRS improved IDO1 activity and depressive behavior in mice with IFN-γ-induced depression. Furthermore, the therapeutic effect of 1-methyl-tryptophan (1-MT) well known as an IDO1 inhibitor in depression and clinically used anti-UC drug Mesalazine (MS) was demonstrated to confirm the potential mechanism. CONCLUSION: The study is the first to reveal the antidepressant effect of PRS and further demonstrate its potential therapeutic targets. In addition, it also clarifies that the Trp/kyn pathway is the crosstalk between IBD and depression and provides new choice for depression treatment. And it also provides an important basis for the follow-up development and exploration of anti-intestinal antidepressants.

[Research and application of model fruit fly in prevention and treatment of neuropsychiatric disorders by traditional Chinese medicine and natural compounds: a review].

As an important model animal, fruit fly is characterized by outstanding genetic characteristics, relatively perfect nervous system, rapid reproduction, and low cost. Thus, it has been applied in the research on neuropsychiatric disorders in recent years, showing great potential in life science. The incidence of neuropsychiatric disorders has been on the rise, and the disorders have high disability rate and low case fatality rate. The global drug demand for such diseases is second only to cardiovascular and cerebrovascular diseases. At the moment, the demand of the drugs for the diseases have been rising, and it is an urgent task to develop related drugs. However, the research and development of the drugs are time-intensive and have a high failure rate. A suitable animal model can help shorten the time for drug screening and development, thereby reducing the cost and failure rate. This study reviews the application of fruit flies in several common neuropsychiatric disorders, which is expected to provide new ideas for the research and application of the model animals in traditional Chinese medicine.

Pulsatilla chinensis saponins improve SCFAs regulating GPR43-NLRP3 signaling pathway in the treatment of ulcerative colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Pulsatilla decoction has been extensively used to treat ulcerative colitis (UC) in recent years. Pulsatilla chinensis saponin (PRS), the active ingredient of its monarch medicine Pulsatilla chinensis (Bunge) Regel, plays a crucial role in the treatment of UC, but its specific mechanism of action has not been fully elucidated. AIM OF THE STUDY: This study aims to investigate the protective effect and possible mechanism of PRS on DSS-induced ulcerative colitis in rats. MATERIALS AND METHODS: In this study, the DSS-induced colitis model was used to explore the metabolism and absorption of PRS under UC, detect the content of short-chain fatty acids (SCFAs) in colon tissue, the expression of receptor G Protein-Coupled Receptor 43 (GPR43) protein and inflammasome NLRP3, and observe the expression level of IL-1ß, IL-6 and TNF-α in colon tissue. The protective effect of the PRS was also observed. RESULTS: It was found that in the UC group, the absorption rate and extent of drugs increased, and the elimination was accelerated. Compared with the control group, PRS increased the content of short-chain fatty acids (SCFAs) in colon tissue, promoted the expression of SCFAs receptor GPR43 protein, inhibited the activation of the NLRP3 inflammasome, and decreased the content of IL-1ß, IL-6 and TNF-α. PRS protects the colon in DSS-induced inflammatory bowel disease by increasing the content of SCFAs, promoting the expression of GPR43 protein, inhibiting the activation of the NLRP3 inflammasome, and reversing the increase in IL-1ß, IL-6 and TNF-α levels. CONCLUSIONS: PRS can increase the content of colonic SCFAs, activate the GPR43-NLRP3 signaling pathway, and reduce the levels of pro-inflammatory cytokines, thereby improving the symptoms of DSS-induced colitis.

Targeting of non-apoptotic cancer cell death mechanisms by quercetin: Implications in cancer therapy.

The ultimate goal of cancer treatment is to kill cancer cells, based on the use of various therapeutic agents, such as chemotherapy, radiotherapy, or targeted therapy drugs. Most drugs exert their therapeutic effects on cancer by targeting apoptosis. However, alterations in apoptosis-related molecules and thus assisting cells to evade death, eventually lead to tumor cell resistance to therapeutic drugs. The increased incidence of non-apoptotic cell death modes such as induced autophagy, mitotic catastrophe, senescence, and necrosis is beneficial to overcoming multidrug resistance mediated by apoptosis resistance in tumor cells. Therefore, investigating the function and mechanism of drug-induced non-apoptotic cell death modes has positive implications for the development of new anti-cancer drugs and therapeutic strategies. Phytochemicals show strong potential as an alternative or complementary medicine for alleviating various types of cancer. Quercetin is a flavonoid compound widely found in the daily diet that demonstrates a significant role in inhibiting numerous human cancers. In addition to direct pro-tumor cell apoptosis, both in vivo and in vitro experiments have shown that quercetin exerts anti-tumor properties by triggering diverse non-apoptotic cell death modes. This review summarized the current status of research on the molecular mechanisms and targets through which quercetin-mediated non-apoptotic mode of cancer cell death, including autophagic cell death, senescence, mitotic catastrophe, ferroptosis, necroptosis, etc.

Exploring the mechanism of Tengli Kangliu Decoction in the prevention and treatment of colorectal cancer precancerous based on network pharmacology.

OBJECTIVE: This study aimed to predict the targets and signaling pathways affected by Tengli Kangliu Decoction (TKD) in the treatment of colorectal cancer (CRC) precursor lesions and to determine TKDs mechanism of action based on previous experimental results using network pharmacology techniques and methods. METHODS: Using the traditional Chinese medicine systems pharmacology database (TCMSP) and UniProt database, the active ingredients and potential targets of TKD were identified. Human colorectal adenoma (CRA) targets were analyzed using the GeneCards database, the Online mendelian inheritance in man (OMIM) database, and the NCBI database. The common targets of drug-disease interactions were input into the String database to construct a protein-protein interaction (PPI) network. These data were then used to construct the network diagram. Gene ontology (GO) function analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed on the target genes. Finally, the component-disease-pathway-target network file was imported into Cytoscape 3.8.0 and used to construct the pathway network diagram. RESULTS: Compounds with a drug-likeness (DL) score ≥ 0.18 and an oral bioavailability (OB) ≥ 30% were selected as the active constituents of TKD. Two hundred eighty eight chemical constituents were screened and 305 chemical drug targets were predicted. After further screening, 1942 disease-related targets, which are hypothesized to be the main chemical components of TKD, were obtained. When comparing the targets of action and CRA treatment targets, 172 common targets were identified. Using GO enrichment analysis of common targets of drug diseases, 2550 biological processes (BP) were predicted, 164 items of which were related to molecular functioning (MF), and 67 items related to cell composition. KEGG pathway analysis was performed on the common targets of drug diseases, and a total of 178 signaling pathways were enriched. CONCLUSION: Using network pharmacology research, this study reports on the synergistic effect of the multiple components of TKD on the multi-target, and multiple pathways of colorectal precancerous lesions. These findings lay a theoretical foundation for further colorectal precancerous lesions research.

Risk Assessment of (Herbal) Teas Containing Pyrrolizidine Alkaloids (PAs) Based on Margin of Exposure Approach and Relative Potency (REP) Factors.

Pyrrolizidine alkaloids (PAs) present distinct toxicity potencies depending on their metabolites and in vivo toxicokinetics. To represent the potency differences of various PAs, the interim relative potency (REP) factors have been derived. However, little is known about the risk assessment for (herbal) teas when taking REP factors into account. In this study, a set of 68 individual 1,2-unsaturated PA in 21 types of (herbal) teas was analyzed using LC-MS/MS. The REP factors for these PAs were applied on the PA levels. The margin of exposure (MOE) approach was employed to assess the risks of the exposure to PAs due to consumption of (herbal) teas. The results show that the total PA levels ranged from 13.4 to 286,682.2 µg/kg d.m., which were decreased by REP correction in most of the teas. The MOE values for tephroseris, borage and lemon balm (melissa) tea based on REP-corrected PA levels were below 10,000, assuming daily consumption of one cup of tea during a lifetime, indicating that consuming these teas may raise a concern. Our study also indicates a priority for risk management for tephroseris tea, as having nephrosis tea for more than 11.2 weeks during a 75-year lifetime would result in an MOE of 10,000.

[Network Meta-analysis of traditional Chinese medicine injections against anthracycline-induced cardiac injury].

This study aimed to systematically evaluate the effect of traditional Chinese medicine(TCM) injections on anthracycline-induced cardiac injury. The Cochrane Library, PubMed, EMbase, CNKI, and other databases were electronically retrieved to gather randomized controlled trials(RCTs) of TCM injections against anthracycline-induced cardiac injury from their inception to September 2021. After two research fellows independently screened the literature and extracted the data, the risk of bias of included RCTs was assessed and network Meta-analysis was performed by R 4.1.0 and Stata 15.1. A total of 50 RCTs were included, involving eight TCM injections. Network Meta-analysis showed that:(1)the combination of anthracyclines with Huachansu Injection might be the optimal treatment to reduce the abnormal electrocardiogram.(2)The combination with Shenfu Injection might be the optimum treatment to ameliorate the left ventricular ejection fraction(LVEF) decrease.(3)The combination with Shenqi Fuzheng Injection might reduce the incidence of cardiotoxicity most satisfactorily.(4)The combination with Xinmailong Injection might improve the elevated cardiac troponin I(cTnI) optimally.(5)The combination with Shenmai Injection might be optimal to control the rise of creatine kinase MB isoenzyme(CK-MB).(6)The combination with Kushen Injection might be the regimen with the lowest gastrointestinal reactions. TCM injections had desirable effect on anthracycline-induced cardiac injury, with low incidence of adverse reactions, and each TCM injection had its own unique advantages. Due to the limitations in quality and methodological conduct of the included studies, more high-level RCTs are needed to validate the conclusions.

Hesperetin, a Promising Treatment Option for Diabetes and Related Complications: A Literature Review.

The morbidity and mortality of diabetes have increased dramatically in recent decades. Novel strategies for treating diabetes and its complications with minimal side effects are in urgent need. New monomeric molecules extracted from herbal medicine, which is a form of alternative medicine, are being sought as drug candidates for the treatment of diabetes and its complications. Hesperetin (Hst), a citrus flavonoid, is of increasing interest in scientific studies recently due to its properties in combating diabetes and its complications, whereas existing studies are scattered and unsystematic. Here, we summarized the literature studies over the last 10 years to review the potential therapeutic role of Hst in the prevention and mitigation of diabetes and its complications, intending to provide promising strategies for the clinical management of diabetes and its complications.

The Low-density Lipoprotein Receptor-related Protein 6 Pathway in the Treatment of Intestinal Barrier Dysfunction Induced by Hypoxia and Intestinal Microbiota through the Wnt/ß-catenin Pathway.

Our study is to explore the key molecular of Low-density lipoprotein receptor-related protein 6 (LRP6) and the related Wnt/ß-catenin pathway regulated by LRP6 during the intestinal barrier dysfunction. Colorectal protein profile analysis showed that LRP6 expression was decreased in dextran sulfate sodium (DSS)-induced colitis mice, and mice received fecal bacteria transplantation from stroke patients. Mice with intestinal hypoxia and intestinal epithelial cells cultured in hypoxia showed decreased expression of LRP6. Overexpression of LPR6 or its N-terminus rescued the Wnt/ß-catenin signaling pathway which was inhibited by hypoxia and endoplasmic reticulum stress. In mice overexpressing of LRP6, the expression of ß-catenin and DKK1 increased, Bcl2 decreased, and Bax increased. Mice with LRP6 knockout showed an opposite trend, and the expression of Claudin2, Occludin and ZO-1 decreased. Two drugs, curcumin and auranofin could alleviate intestinal barrier damage in DSS-induced colitis mice by targeting LRP-6. Therefore, gut microbiota dysbiosis and hypoxia can inhibit the LRP6 and Wnt/ß-catenin pathway, and drugs targeting LRP6 can protect the intestinal barrier.

Effects of Xiao Chengqi Formula on Slow Transit Constipation by Assessing Gut Microbiota and Metabolomics Analysis in vitro and in vivo.

The Xiao Chengqi (XCQ) formula is a newly constituted traditional Chinese medicine prescription in the treatment of intestinal motility deficiency and is effective in patients with slow transit constipation (STC). XCQ formula was reconstructed based on a "Chengqi" decoction. Astragali Radix, Angelicae Sinensis Radix, and cooked ground Salviae Miltiorrhizae Radix et Rhizoma were added to the prescription to enhance. An STC rat model was constructed and treated with the formula to understand the detailed mechanism by which XCQ promotes intestinal peristalsis. The effects of the XCQ formula on intestinal microflora and metabolic levels and the possible molecular mechanism of its regulation were explored using 16S rDNA sequencing, metabolomics sequencing, and tissue RNA sequencing. The results showed a significant decrease in the abundance of Roseburia spp. in the feces of STC rats, a significant decrease in the content of butyl aminobenzene (BAB) in feces, and an increase in the number of interstitial cells of Cajal (ICC) in the colon of STC rats. Furthermore, in vitro and in vivo experiments revealed that BAB could activate IL-21R on the ICC surface, upregulate the phosphorylation of the downstream molecules STAT3 and ERK, and inhibit loperamide-induced ICC apoptosis. Therefore, the XCQ formula can improve the defecation status of patients with STC by protecting ICC activity, promoting the colonization of Roseburia spp. to promote peristalsis, and increasing the BAB content after metabolism.

Study on the mechanism of reducing biofilm toxicity and increasing antioxidant activity in vinegar processing phytomedicines containing pentacyclic triterpenoid saponins.

ETHNOPHARMACOLOGICAL RELEVANCE: Pentacyclic triterpenoid saponin (PTS) is a kind of particular chemicals with various pharmacological activities, as well as surface activity, mucosal irritation and hemolysis. PTS is closely related to the exertion of efficacy or adverse reactions in plant medicines rich in this component. For the better clinical application of natural resources, how to reduce toxicity and enhance curative efficacy is an important problem which needs to be solved at present. Till now, there has been few studies directly investigating the problem. AIM OF STUDY: Through comparison study of Radix Bupleuri (Chai hu) and Pulsatilla chinensis (Bai tou weng), which are typical traditional Chinese medicines containing PTS, explore the potential change rule of material basis and the mechanism of detoxification and synergistic effect of vinegar processing. MATERIALS AND METHODS: Composition change rule after vinegar processing was applied by UPLC-QTOF-MS/MS coupled with principal component analysis (PCA). Based on our previous research, this paper expounded the action mechanism from the perspective of reducing biofilm toxicity and increasing antioxidant activity. Direct toxicity reducing information was obtained at the cellular level including cellular morphology, MTT assays, western blots and RT-PCR in L02 cells with overload sphingomyelin (SM). The synergistic effect was investigated through histological examinations, mesenteric hemorheology, ELISA, flow cytometry and confocal microscopy. RESULTS: It was found that the structure of PTS take place a series of chemical reactions in the process of vinegar processing which enabled the more toxic components transformed into less toxic components and components with clear efficacy, so as to achieve the purpose of detoxification and synergistic effect. The results indicated that the mechanism of detoxification in vinegar processing was that vinegar processing could act on SM, cause less balance disturbance to sphingomyelin/ceramide (SM/Cer), inhibit apoptosis and then alleviate toxicity. In addition, the pharmacodynamic results showed that the vinegar processing could have an obvious synergistic effect through anti-oxidant stress. CONCLUSIONS: By changing the structures of the PTS, the SM/Cer disrupt was reduced and the antioxidant activity was enhanced, so as to decrease toxicity and increase efficiency in vinegar processing phytomedicines containing PTS.

Raw and Wine Processed Schisandra chinensis Regulate NREM-Sleep and Alleviate Cardiovascular Dysfunction Associated with Insomnia by Modulating HPA Axis.

Clinical studies have shown that insomnia and anxiety are usually accompanied by cardiovascular dysfunction. In traditional Chinese medicine, Schisandra chinensis (SC) and wine processed Schisandra chinensis (WSC) are mainly used for the treatment of dysphoria, palpitation and insomnia. However, little attention was paid to its mechanism. In this study, we monitored the effect of SC and WSC on the nervous system and cardiovascular system of free-moving rats in the real-time. Our results show that SC and WSC can alleviate cardiovascular dysfunction while promoting sleep, and we further explored their potential mechanisms. HPLC-QTOF-MS was used for the quality control of chemical components in SC and WSC. Data sciences international (DSI) physiological telemetry system was applied to collect the electroencephalogram (EEG), electrocardiogram (ECG) and other parameters of free-moving rats to understand the effects of long-term intake of SC and WSC on rats. The content of Cortisol (CORT), neurotransmitters and amino acids in rat pituitary and hypothalamus were analyzed by UPLC-MS to determine the activity of HPA axis. The expression of melatonin receptor MT1 was analyzed by immunofluorescence technique. Our results suggested that SC and WSC may play the role of promoting sleep by increasing the expression level of melatonin receptor MT1 in hypothalamus, and modulate the activity of HPA axis by regulating the levels of the related neurotransmitters and amino acid, so as to improve the abnormal cardiovascular system of rats. This study may provide theoretical support for explicating the advantages of SC and other phytomedicines in the treatment of insomnia.

Aroma effects of key volatile compounds in Keemun black tea at different grades: HS-SPME-GC-MS, sensory evaluation, and chemometrics.

The present study aimed to explore the relationship between the grade and the characteristic aroma in Keemun black tea (KBT). Headspace solid-phase microextraction (HS-SPME), gas chromatography-mass spectrometry (GC-MS), sensory evaluation, and chemometrics were employed to determine the changes in the flavor evolution of KBT at grade. The results showed that a total of 110 volatile components were identified. Linalool and linalool oxide were dominant. The orthogonal partial least squares discriminant analysis (OPLS-DA) combined with relative odor activity value (rOAV > 0.1) revealed that 11 volatile components were the key volatile compounds of KBT, such as benzeneacetaldehyde (rOAV: 3.43-5.96) and methyl salicylate (rOAV: 2.15 - 2.50). Furthermore, the partial least squares (PLS) model indicated that geraniol, linalool, and methyl salicylate benefited from the reservation of floral flavor of Keemun aroma characteristic of KBT. The findings presented in this thesis add to our understanding of KBT at different grades.

Study on the new anti-atherosclerosis activity of different Herba patriniae through down-regulating lysophosphatidylcholine of the glycerophospholipid metabolism pathway.

BACKGROUND: Atherosclerosis (AS) is a multifactor cardiovascular disease characterized by chronic inflammation. The safety of long-term medication is the focus of clinical treatment selection and application. It is urgent to develop more high-efficiency and low side effects drugs to treat AS. Therefore, the screening of anti-AS drugs with high efficiency and low toxicity from phytomedicine has attracted more and more attention. PURPOSE: The aim of this study was to explore the new pharmacological effect of Herba patriniae against AS, to find the best origin and extraction part of Herba patriniae, furthermore, to reveal its potential action mechanism. METHODS: Apolipoprotein E gene-knockout (ApoE-/-) mice were orally administered with different extracts of Patrinia villosa Juss (PVJ) and Patrinia scabiosaefolia Fisch (PSF). Their anti-AS effect was comprehensively evaluated by small animal ultrasound, HE staining, Oil-Red O staining, platelet aggregation rate and blood lipid level. Lipid metabolomics and network pharmacology were used to study the mechanism of drug action. Finally, the expression of related proteins were detected by western blots and immunofluorescence. RESULTS: PVJ EtOAc extract and PSF EtOAc extract could significantly reduce vascular plaque, liver inflammation, platelet aggregation and blood lipid levels in AS model. By comparison, the effect of PVJEE was better than that of PSFEE. Furthermore, the results of differential metabolites indicated that PVJEE may inhibit the apoptosis of vascular endothelial cells, proliferation and migration of smooth muscle cells by reversing lysophosphatidylcholine (LPC) in the glycerophospholipid metabolic pathway, so as to play an anti-AS role. This result was double verified by KEGG based metabolic pathway enrichment analysis and related protein expression study. CONCLUSION: By changing glycerophospholipid metabolism pathway, Herba patriniae can significantly regulate lipid metabolism and inflammatory level, showing the development potential of anti-AS, which provides new candidate drugs and good prospects for the safe treatment of AS. In addition, through comparison, this study also confirmed that PVJEE was the best origin and extraction part of anti-AS.

Screening for potential quality markers of Callerya nitida var. hirsutissima. Z.Wei based on components profile, pharmacokinetics, and anti-inflammatory study.

Callerya nitida var. hirsutissima. Z.Wei is a classical, traditional Chinese herbal medicine mostly used to treat rheumatoid arthritis. Recent reports suggest that inconsistent and poor-quality control levels have primarily affected the therapeutic efficacy. Therefore, the aim of the current study was to investigate the active chemical ingredients, stability of components in blood, pharmacokinetics, and pharmacodynamics to specify the potential markers for quality control and quality evaluation of Callerya nitida. The active components in vitro and in vivo were obtained by ultra-high-performance liquid chromatography-mass spectrometry. Moreover, the changes of the bioactive components in the blood were monitored over time (0-24 h) in order to identify stable active components. On this basis, the pharmacokinetic characteristics of these ingredients combined with the anti-inflammatory activity were determined to screen out the potential markers for ensuring the quality control of Callerya nitida. The identified four components, such as calycosin, daidzein, formononetin, and 5-hydroxymethylfurfural, have the characteristics of intrinsic components, clearly defined structures, high exposure values, and in vivo stability, which are important for the therapeutic activity of pharmacologically active materials. Therefore, they can be used as potential markers to control the quality levels of Callerya nitida.