Study on quality analysis of different species of Coptidis rhizome based on fingerprint-effect relationship.

INTRODUCTION: The quality evaluation of Coptidis rhizome (CR) is attributed to the origin and processing method, and this strategy of ignoring the bioactive components usually leads to biased quality analysis, which is difficult to indicate the clinical efficacy. OBJECTIVES: In order to evaluate the quality level of different species of CR, we collected 20 batches of CR and investigated the fingerprint-effect relationship. METHODS: High-performance liquid chromatography (HPLC) fingerprints of CR were established, and the fingerprint-effect relationship was explored using cluster analysis, principal component analysis, Pearson correlation analysis, grey relation analysis, and partial least squares regression. RESULTS: We have identified a total of 10 common peaks (1-10) with similarity scores above 0.96. The study on the relationship between spectra and potency further showed that the contents of peaks 8, 9, and 10 are potential key components. And based on a previous study, a method of one measurement and multiple evaluations of CR was established to achieve the goal of simplifying the analytical process and reducing costs. CONCLUSION: Through a combination of fingerprint analysis, antioxidant activity evaluation, fingerprint-efficacy relationship analysis, and simultaneous quantification of multiple components, a CR quality control index and method have been selected and established, which can also provide a more comprehensive quality evaluation for traditional Chinese medicine.

Comparison of the efficacy and safety between rivaroxaban and dabigatran in the treatment of acute portal vein thrombosis in cirrhosis.

BACKGROUND: New oral anticoagulants (NOACs) have been becoming prevalent in recent years and are increasingly used in the treatment of port vein thrombosis. The difference of the efficacy and safety between rivaroxaban and dabigatran remains unclear in the treatment of cirrhotic patients with acute portal vein thrombosis (PVT). METHODS: This retrospective study included all consecutive cirrhotic patients with acute portal vein thrombosis in our institute from January 2020 to December 2021. The patients received oral anticoagulation with rivaroxaban or dabigatran. The demographic, clinical, and imaging data of patients were collected. The diagnosis of acute PVT was confirmed by imaging examinations. The severity of liver cirrhosis was assessed using Child-Pugh score and Model for End-Stage Liver Disease (MELD) score. Outcomes included recanalization (complete, partial, and persistent occlusion), liver function, bleedings, and survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. The Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: A total of 94 patients were included, 52 patients (55%) received rivaroxaban and 42 (45%) with dabigatran. The complete and partial recanalization of PVT was observed in 41 patients. There was no significant difference in complete recanalization, partial recanalization, and persistent occlusion between the two groups. With multivariate analysis, D-dimer (HR 1.165, 95% CI 1.036-1.311, p = 0.011) was independent predictors of complete recanalization. The Child-Pugh score (p = 0.001) was significantly improved in both two groups after anticoagulation, respectively. However, there was no difference between the two groups. The probability of survival was 94%, 95% in the rivaroxaban and dabigatran groups (log-rank p = 0.830). Major bleedings were reported in 3 patients (6%) in rivaroxaban group and 1 patient (2%) in dabigatran group (p = 0.646). Six patients (12%) in rivaroxaban group experienced minor bleeding, and five (12%) from dabigatran group (p = 0.691). CONCLUSIONS: The efficacy and safety were comparable between rivaroxaban and dabigatran in the treatment of cirrhotic patients with acute portal vein thrombosis. And D-dimer can contribute to the prediction of PVT recanalization in cirrhotic patients.

C. acnes qPCR-Based Antibiotics Resistance Assay (ACQUIRE) Reveals Widespread Macrolide Resistance in Acne Patients and Can Eliminate Macrolide Misuse in Acne Treatment.

Background: Macrolides have been widely used to treat moderate-to-severe acne for more than 50 years. However, the prevalent antibiotic resistance of Propionibacterium acnes, along with the absence of clinically available resistance tests, has made macrolide misuse a frequent occurrence around the globe, with serious consequences. Objective: We developed Cutibacterium acnes quantitative PCR (qPCR)-based antibiotics resistance assay (ACQUIRE) to enable fast and accurate detection of C. acnes macrolide resistance in clinical settings, representing an opportunity to administer antibiotics more wisely and improve the quality of care. Methods: A cross-sectional observational study (n = 915) was conducted to probe into the macrolide resistance of C. acnes in patients with acne. Results: The high sensitivity of ACQUIRE enabled us to reveal a much higher C. acnes 23S recombinant DNA (rDNA) point mutation rate (52%) and thus a higher macrolide resistance (75.5%) compared to previous reports. Carriage of ermX gene was discovered on 472 (53%) subjects, which concurs with previous studies. Conclusion: The macrolide resistance of C. acnes is much higher than previously reported. Integrating ACQUIRE into acne treatment modalities may eliminate macrolide misuse and achieve better clinical improvements.

Characterization, antioxidant, and neuroprotective effects of anthocyanins from Nitraria tangutorum Bobr. fruit.

An anthocyanin-rich extract was obtained from Nitraria tangutorum Bobr. fruit, namely ANF, and its composition, antioxidant and neuroprotective effects were studied. Nine anthocyanins were identified from the ANF using UPLC-Triple-TOF/MS analysis, and cyanidin-3-[2''-(6'''-coumaroyl)-glucosyl]-glucoside (C3G) is the most abundant anthocyanin (87.06%). ANF exhibited high ferric reducing antioxidant power (FRAP) and ABTS radical scavenging activity. The online HPLC-DPPH screening revealed that C3G contributed the highest antioxidant capacity. ANF showed potential neuroprotective effects by relieving d-Galactose-induced memory deficits, reducing overexpression of receptor for advanced glycation end products (RAGE) and amyloid-beta42 (Aß42) in the hippocampus of rats. Besides, ANF could inhibit oxidative stress by reducing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) in the hippocampus, while elevating amounts of total superoxide dismutase (T-SOD) and glutathione (GSH) in the serum of rats. Thus, ANF has great potential in the development of food and health products related to antioxidant and neuroprotective effects.

Study on the action mechanism of Wuling Powder on treating osteoporosis based on network pharmacology.

Osteoporosis is a health problem to cause global concern. A lot of methods have been used to prevent and treat osteoporosis, but there is still a lack of effective treatment for osteoporosis owing to limited understanding of its mechanism. Therefore, the aim of this present study is to explore the underlying mechanism of Wuling Powder, a traditional Chinese medicine on treating osteoporosis. In this study, we firstly screened and identified the common targets between Wuling Powder and osteoporosis through the related databases, and then explored the relationships among these targets, Wuling Powder and osteoporosis by using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and network analyses. Subsequently, the molecular docking was performed by using systemsDock to evaluate the potential binding relationships between the active components of Wuling Powder and their related targets. The results showed that in total of 14 common targets including CREBBP, ADAM17, GOT1, GAPDH, USP8, ERBB2, EEF1A1, MTOR, RAC1, ETS1, DDX58, GCK, EGF and S100A8 were screened. EGF, ERBB2, MTOR and HIF-1 were the potential therapeutic targets for osteoporosis, and they were also the related targets for predicting active components in Wuling Powder. Taken together, we concluded that Wuling Powder might be used to treat osteoporosis through above these targets.

Anthocyanins from Lycium ruthenicum Murr. Ameliorated d-Galactose-Induced Memory Impairment, Oxidative Stress, and Neuroinflammation in Adult Rats.

Lycium ruthenicum Murr. (LR) is a perennial shrub commonly used as a nutritional food and medicine. Herein, we identified 12 anthocyanins from LR, with petunidin derivatives constituting approximately 97% of the total anthocyanin content. Furthermore, the potential mechanism of anthocyanins exerting neuroprotective effects in d-galactose (d-gal)-treated rats was explored. Behavioral results showed that anthocyanins relieved d-gal-induced memory disorder. Additionally, anthocyanins reduced receptor for advanced glycation end products (RAGE) and suppressed oxidative stress caused by d-gal. Anthocyanins suppressed microgliosis and astrocytosis and reduced the overexpression of nuclear factor kappa B (NF-κB), interleukin-1-ß (IL-1ß), cyclooxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α). Moreover, anthocyanins lowered C-jun N-terminal kinase ( p-JNK), caspase-3 levels, and the B-cell lymphoma 2-associated X protein/B-cell lymphoma 2 (Bax/Bcl-2) ratio. Thus, anthocyanins from LR attenuated memory disfunction, neuroinflammation, and neurodegeneration caused by d-gal, possibly through the RAGE/NF-κB/JNK pathway, representing a promising, safe candidate for prevention and therapy of neurodegenerative diseases.

A Large-Scale, Multi-Center Urine Biomarkers Identification of Coronary Heart Disease in TCM Syndrome Differentiation.

Coronary heart disease (CHD) threatens human health. The discovery and assessment of potential biometabolic markers for different syndrome types of CHD may contribute to decipher pathophysiological mechanisms and identify new targets for diagnosis and treatment. On the basis of UPLC-Q-TOF/MS metabolomics technology, urine samples of 1072 participants from nine centers, including normal control, phlegm and blood stasis (PBS) syndrome and Qi and Yin deficiency (QYD) syndrome, and other syndromes of CHD, were conducted to find biomarkers. Among them, the discovery set ( n = 125) and the test set ( n = 337) were used to identify and validate biomarkers, and the validation set ( n = 610) was used for the application and evaluation of the support vector machine (SVM) prediction model. We discovered 15 CHD-PBS syndrome biomarkers and 12 CHD-QYD syndrome biomarkers, and the receiver-operator characteristic (ROC) area-under-the-curve (AUC) values of them were 0.963 and 0.990. The established SVM model has a good diagnostic ability and can well distinguish the two syndromes of CHD with a high predicted accuracy >98.0%. The discovery of biomarkers and metabolic pathways in different syndrome types of CHD provides a basis for the diagnosis and evaluation of CHD, thereby improving the accurate diagnosis and precise treatment level of Chinese medicine.

Clinical metabolomics analysis of therapeutic mechanism of Tongmai Yangxin Pill on stable angina.

Tongmai Yangxin Pill (TMYX) is a traditional Chinese medicine for the treatment of angina and arrhythmia. Although its clinical application is extensive, and the curative effect is significant, little information is available on the molecular biological basis and therapeutic mechanism of TMYX for the treatment of stable angina. In this study, we analyzed serum samples of clinical patients collected from seven different clinical units in China after oral administration of TMYX using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS). Multiple statistical analysis including principal component analysis (PCA) and partial least square discrimination analysis (PLS-DA), were used to examine metabolite profile changes in serum samples. After TMYX treatment, 10 biomarkers were reversed to the normal conditions. The above biomarkers were mainly involved in energy metabolism, amino acid metabolism, oxidative stress and inflammation. These results suggested that TMYX exerted therapeutic effects by improving myocardial energy supply disorder and amino acid dysfunction, and attenuating oxidative stress and inflammation. The present study, as the first multicenter clinical study which reveals the molecular biological basis and therapeutic mechanism of TMYX on stable angina, can provide objective indicators for efficacy evaluation of TMYX on stable angina. And it also lays a foundation for the use of TMYX clinically.

Rapid qualitative and quantitative analyses of eighteen phenolic compounds from Lycium ruthenicum Murray by UPLC-Q-Orbitrap MS and their antioxidant activity.

Lycium ruthenicum Murray (LR) is a functional food, and it has long been used in traditional folk medicine. However, detailed qualitative and quantitative analyses related to its phenolic compounds remains scarce. This work reports, for the first time, the establishment of a rapid method for simultaneous identification and quantification of 25 phenolic compounds by UPLC-quadrupole-Orbitrap mass spectrometry (UPLC-Q-Orbitrap MS). This method was validated by LODs, LOQs, precision, repeatability, stability, mean recovery, recovery range and RSD. The confirmed method was applied to the analysis of phenolic compounds in LR. Finally, 18 phenolic compounds in LR were qualitatively and quantitatively analyzed. Among them, 11 constituents were detected for the first time, which included two flavonoids (catechin and naringenin) and seven phenolic acids (gallic acid, vanillic acid, 2,4-dihydroxybenzoic acid, veratronic acid, benzoic acid, ellagic acid and salicylic acid). Moreover, Phloretin and protocatechuate, belonging to the dihydrochalcone flavonoid and protocatechuic acid respectively, were also identified and quantified. The total phenolics content (20.17 ±â€¯2.82 mg/g) and the total anthocyanin content (147.43 ±â€¯1.81 mg/g) were determined. In addition, the antioxidant activities of the LR extract were evaluated through 2,2-azinobis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical scavenging activity, ferric reducing antioxidant power (FRAP) and total antioxidant activity (T-AOC) assays.

Research on the Relationships between Endogenous Biomarkers and Exogenous Toxic Substances of Acute Toxicity in Radix Aconiti.

Radix Aconiti, a classic traditional Chinese medicine (TCM), has been widely used throughout China for disease treatment due to its various pharmacological activities, such as anti-inflammatory, cardiotonic, and analgesic effects. However, improper use of Radix Aconiti often generated severe acute toxicity. Currently, research on the toxic substances of Radix Aconiti is not rare. In our previous study, acute toxic biomarkers of Radix Aconiti have been found. However, few studies were available to find the relationships between these endogenous biomarkers and exogenous toxic substances. Therefore, in this study, toxic substances of Radix Aconiti have been found using UPLC-Q-TOF-MS technology. Then, we used biochemical indicators as a bridge to find the relationships between biomarkers and toxic substances of Radix Aconiti through Pearson correlation analysis and canonical correlation analysis (CCA). Finally, the CCA results showed that LysoPC(22:5) is related to 14-acetyl-talatisamine, mesaconitine, talatisamine and deoxyaconitine in varying degrees; l-acetylcarnitine is negatively correlated with deoxyaconitine and demethyl-14-acetylkaracoline; shikimic acid has a good correlation with karacoline, demethyl-14-acetylkaracoline and deoxyaconitine; and valine is correlated with talatisamine and deoxyaconitine. Research on these relationships provides an innovative way to interpret the toxic mechanism of traditional Chinese medicine, and plays a positive role in the overall study of TCM toxicity.

A Novel Method for Evaluating the Cardiotoxicity of Traditional Chinese Medicine Compatibility by Using Support Vector Machine Model Combined with Metabonomics.

Traditional biochemical and histopathological tests have been used to evaluate the safety of traditional Chinese medicine (TCM) compatibility for a long time. But these methods lack high sensitivity and specificity. In the previous study, we have found ten biomarkers related to cardiotoxicity and established a support vector machine (SVM) prediction model. Results showed a good sensitivity and specificity. Therefore, in this study, we used SVM model combined with metabonomics UPLC/Q-TOF-MS technology to build a rapid and sensitivity and specificity method to predict the cardiotoxicity of TCM compatibility. This study firstly applied SVM model to the prediction of cardiotoxicity in TCM compatibility containing Aconiti Lateralis Radix Praeparata and further identified whether the cardiotoxicity increased after Aconiti Lateralis Radix Praeparata combined with other TCM. This study provides a new idea for studying the evaluation of the cardiotoxicity caused by compatibility of TCM.