Patent Medicine Research Articles

Multi-target mechanism of Naoshuantong capsule for treatment of Ischemic stroke based on network pharmacology and molecular docking.

Naoshuantong capsule (NST capsule) is a classic Chinese patent medicine, which can treat ischemic stroke (IS) and has good clinical efficacy. However, its pharmacological mechanism remains to be further explored in the treatment of IS. The bio-active components and potential targets of NST Capsules were obtained by ETCM and TCMSP databases. In addition, the related targets of IS were collected by Genecard, OMIM, DrugBank, TTD and DisGeNET databases. NST-IS common target was obtained by Venn platform. PPI network of NST-IS common target and the composition - target network diagram of NST Capsule were constructed by Cytoscape3.8.1. Finally, AutoDock was used for molecular docking. 265 targets were predicted from 32 active compounds in NST Capsule, 109 common targets were identified between NST Capsule and IS. The top 10 key targets of PPI network were ALB, TNF, TP53, VEGFA, CASP3, MYC, etc. Enrichment analysis showed that NST capsules treated IS mainly through lipid and atherosclerosis, fluid shear stress and atherosclerosis signaling pathways. Through the methods of network pharmacology and molecular docking, this study clarified that NST capsules play a role in the treatment of IS, which is multi-target, multi-channel and multi-component regulation. This study further explored the pharmacological mechanism of NST capsule in the treatment of IS, which can provide some references for the subsequent research in the pharmacological mechanism of NST capsule.

Cucurbitacin B suppresses hepatocellular carcinoma progression through inducing DNA damage-dependent cell cycle arrest

BackgroundThe mortality rate of liver cancer ranks third in the world, and hepatocellular carcinoma (HCC) is a malignant tumor of the digestive tract. Cucurbitacin B (CuB), a natural compound extracted from Cucurbitaceae spp., is the main active component of Chinese patent medicine the Cucurbitacin Tablet, which has been widely used in the treatment of various malignant tumors in clinics, especially HCC. PurposeThis study explored the role and mechanism of CuB in the suppression of liver cancer progression. MethodsCell Counting Kit-8 (CCK-8) and colony formation assays were used to detect the inhibitory function of CuB in Huh7, Hep3B, and Hepa1/6 hepatoma cells. Calcein-AM/propidium iodide (PI) staining and lactate dehydrogenase (LDH) measurement assays were performed to determine cell death. Mitochondrial membrane potential (Δψm) was measured, and flow cytometry was performed to evaluate cell apoptosis and cell cycle. Several techniques, such as proteomics, Western blotting (WB), and ribonucleic acid (RNA) interference, were utilized to explore the potential mechanism. The animal experiment was performed to verify the results of in vitro experiments. ResultsCuB significantly inhibited the growth of Huh7, Hep3B, and Hepa1/6 cells and triggered the cell cycle arrest in G2/M phage without leading to cell death, especially apoptosis. Knockdown of insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), a target of CuB, did not reverse CuB elicited cell cycle arrest. CuB enhanced phosphorylated ataxia telangiectasia mutated (p-ATM) and phosphorylated H2A histone family member X (γ-H2AX) levels. Moreover, CuB increased p53 and p21 levels and decreased cyclin-dependent kinase 1 (CDK1) expression, accompanied by improving phosphorylated checkpoint kinase 1 (p-CHK1) level and suppressing cell division cycle 25C (CDC25C) protein level. Interestingly, these phenomena were partly abolished by a deoxyribonucleic acid (DNA) protector methylproamine (MPA). Animal studies showed that CuB also significantly suppressed tumor growth in BALB/c mice bearing Hepa1/6 cells. In tumor tissues, CuB reduced the expression levels of proliferating cell nuclear antigen (PCNA) and γ-H2AX but did not change the terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL) level. ConclusionThis study demonstrated for the first time that CuB could effectively impede HCC progression by inducing DNA damage-dependent cell cycle arrest without directly triggering cell death, such as necrosis and apoptosis. The effect was achieved through ataxia telangiectasia mutated (ATM)-dependent p53-p21-CDK1 and checkpoint kinase 1 (CHK1)-CDC25C signaling pathways. These findings indicate that CuB may be used as an anti-HCC drug, when the current findings are confirmed by independent studies and after many more clinical phase 1, 2, 3, and 4 testings have been done.

Corrosion inhibition of extracts from the expired traditional Chinese patent medicines for Q235 carbon steel in hydrochloric acid

During the COVID-19 epidemic, traditional Chinese patent medicine played a significant role in treatment and prevention. However, excessive production of medicines will face serious disposal problems once they are expired, and how to achieve safe and efficient utilization of resources becomes another challenge. In this study, the diverse organic components of traditional Chinese patent medicine-YanReQing Granules (YGE) have been extracted and enriched using a low-temperature extraction method, and the main compositions have been analyzed by liquid chromatography-mass spectrometry (LC-MS). The inhibition performance of YGE for Q235 steel in 0.1 mol L−1 HCl solution was evaluated by various methods. The results indicated that the corrosion rate of metal decreased significantly with the addition of YGE, and the corrosion potential shifted positively as the increase of cathodic and anodic Tafel slopes, indicating that the YGE belongs to a mixed type of corrosion inhibitor with the simultaneously inhibition on cathode and anode. The inhibition efficiency of YGE increased gradually with the more additive amounts, and exceeded 99% calculated by the fitting current density in polarization curves. The active ingredients in YGE are mainly composed of hydroxyl and carbon-based aromatic hydrocarbons, which are easily protonated in hydrochloric acid solution and carry a positive charge, and then adsorb at the metal interface electrostatically to form a shielding layer. Moreover, the theoretical calculations have confirmed that the chemical adsorption can be achieved between the polar atoms and metal to enhance the protective layer ultimately.

Network Meta-analysis of efficacy of seven Chinese patent medicines in treatment of inflammatory response in chronic glomerulonephritis

This study aimed to evaluate the efficacy and safety of various Chinese patent medicines in the treatment of inflammatory response in chronic glomerulonephritis(CGN) based on network Meta-analysis. Randomized controlled trial(RCT) of oral Chinese patent medicines for improving inflammatory response in patients with CGN was retrieved from databases such as CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science from database inception to March 2023. All investigators independently screened the literature, extracted data, and evaluated the quality. Stata 16.0 and RevMan 5.4.1 software were used to analyze the data of the literature that met the quality standards. Finally, 71 RCTs were included, involving 7 Chinese patent medicines. The total sample size was 6 880 cases, including 3 441 cases in the test group and 3 439 cases in the control group. The network Meta-analysis showed that(1) in terms of reducing TNF-α, the top 3 optimal interventions according to the surface under the cumulative ranking curve(SUCRA) were Shenyanshu Capsules/Granules/Tablets+conventional western medicine, Huangkui Capsules+conventional western medicine, and Bailing Capsules+conventional western medicine.(2) In terms of reducing hs-CRP, the top 3 optimal interventions according to SUCRA were Yishen Huashi Granules+conventional western medicine, Huangkui Capsules+conventional wes-tern medicine, and Bailing Capsules+conventional western medicine.(3) In terms of reducing IL-6, the top 3 optimal interventions according to SUCRA were Yishen Huashi Granules+conventional western medicine, Bailing Capsules+conventional western medicine, and Shenyan Kangfu Tablets+conventional western medicine.(4) In terms of reducing 24hUTP, the top 3 optimal interventions according to SUCRA were Shenyan Kangfu Tablets+conventional western medicine, Bailing Capsules+conventional western medicine, and Huangkui Capsules+conventional western medicine.(5) In terms of reducing Scr, the top 3 optimal interventions according to SUCRA were Bailing Capsules+conventional western medicine, Shenyanshu Capsules/Granules/Tablets+conventional western medicine, and Yishen Huashi Granules+conventional western medicine.(6) In terms of reducing BUN, the top 3 optimal interventions according to SUCRA were Yishen Huashi Granules+conventional western medicine, Shenyanshu Capsules/Granules/Tablets+conventional western medicine, and Bailing Capsules+conventional western medicine.(7) In terms of improving the clinical total effective rate, the top 3 optimal interventions according to SUCRA were Huangkui Capsules+conventional western medicine, Kunxian Capsules+conventional western medicine, and Yishen Huashi Granules+conventional western medicine. The results showed that the combination of conventional western medicine and Chinese patent medicine could reduce the expression of serum inflammatory factors TNF-α, hs-CRP, and IL-6 and inhibit the inflammatory response. The combination of conventional western medicine and Chinese patent medicine was superior to conventional western medicine alone in reducing Scr, BUN, and 24hUTP, and improving the clinical total effective rate of treatment. Due to the limitation of the quantity and quality of literature included, the above conclusions need to be validated by more high-quality studies.

Pharmacokinetic and pharmacodynamic drug-drug interaction of Nomilin with atorvastatin in hyperlipidemic mice

Atorvastatin (Atv) is widely used to lower cholesterol levels and treat hyperlipidemia in clinical application. Nomilin (Nom) is a kind of limonoids, which is found and isolated from the citrus herbs of Rutaceae family, which are widely used as patent medicines, functional foods, and nutritional supplements in many countries. In previous studies, Nom has the effect of anti-obesity and curing other metabolic diseases. Nevertheless, in recent years, the drug-drug interaction (DDI) caused by the administration of drugs with synergistic effects have raised worldwide concerns. To investigate the DDI of Nom and Atv in vivo, the pharmacokinetic studies were performed with using C57BL/6 mice. The plasma concentrations of Nom and Atv were measured after oral administration of different drug combinations by a simple and sensitive UHPLC-MS/MS method. The experimental mice were randomly divided into five groups, including control group, model group, administered Nom individually group, administered Atv individually group and co-administered of Nom and Atv group. The lipid levels including total cholesterol (TC), triglycerides (TG), high density lipoproteins-cholesterol (HDL-C), low density lipoproteins-cholesterol (LDL-C) were measured for pharmacodynamic study. The hepatic microsomal Cytochrome P450 (CYP1A2, CYP2E1 and CYP3A11) activities were probed using cocktail assay. The gene and protein expressions of CYP3A11 were detected via qPCR and Western blot method. The results shown that the area under the plasma concentration-time curve (AUC) of Atv in administered Atv individually group was 69.30 ± 15.45 ng/mL × h, while that of combined Nom with Atv group was 42.37 ± 10.15 ng/mL × h (p＜0.05). The degree of reduction in lipid levels of mice treated with co-administration of Atv and Nom was less than that of mice treated with Atv alone. In addition, Nom could cause an increased hepatic microsomal CYP3A11 activity significantly, and induce the gene levels and protein expressions of CYP3A11 elevated in mice livers. In conclusion, Nom could up-regulate CYP3A11 activity, thereby impacting on the pharmacokinetic profile and pharmacodynamic effect of Atv. The findings provide more insight for the use risk of these two drugs to treat hyperlipidemia diseases.

Regulatory Guidelines and Production Planning Strategies for Biosimilars in the USA

At present, biosimilar projects are ruling the pharma market. This article aims to show that project management is crucialin developing biosimilars. Bad project management will give a bad reputation to the organization, project cost overruns, projectschedule delays, demotivation of the project team, sustainability risk to the organization, and more over huge loss. It is the main reasonmost companies are spending more on the training of employees, particularly on project management. Biosimilars are biologicalproducts that are highly similar to a reference product despite modest changes in therapeutically inactive components. Biosimilarshave no clinically significant changes in product safety, purity, or potency compared to the reference product. With the imminentpatent expiration of certain important high-cost biologics, biosimilar manufacture is becoming increasingly profitable for firms.However, the introduction of biosimilars necessitates the adoption of critical new rules. Because of the inherent differences involvedwith the production methods used by different companies and even different sites within the same company, the existing standardsthat regulate the approval pathways for generic pharmaceuticals are insufficient for biosimilars. Biosimilars are similar to but notidentical to the original. Due to the exclusive nature of the manufacturing line and the techniques employed by these competitors,basic variances in methodology may exist between competing organizations. Even modest variations in the manufacturing process canresult in micro heterogeneity, characterized by minor differences in molecular structure, stability, production cell line behavior, growthconditions, vectors, and purification methods. For these reasons, developing biosimilars takes a lot of work.1 CBER regulatesbiosimilars in the US Market. The reference Medicine's Patent status and market potential should be considered when developingbiosimilars. The main objective of this article is to show that the project management strategies and regulatory approval process areequally important to enter biosimilars into the market. Concerning quality in the project management of biosimilar products, budget,deadlines, and scopes are major constraints. A Gantt chart has been enacted to represent a graphical illustration of a schedule. Ganttchart helps to plan, coordinate, and track specific tasks in a project.

Syndrome of liver depression and spleen deficiency is a primary TCM syndrome of response to entecavir + FuZheng HuaYu in patients with HBV-related liver fibrosis

ObjectiveAlthough clinical studies have found that Chinese patent medicine FuZheng HuaYu tablet/capsule can promote the reversal of HBV-related liver fibrosis, not all sufferers have histopathological responses. This study aims to explore the correlation between traditional Chinese medicine (TCM) syndromes and response to entecavir + FuZheng HuaYu (ETV + FZHY) in patients with HBV-related liver fibrosis. MethodsThis a multi-center cross-sectional study. According to the different treatment strategies that sufferers have ever received, a total of 437 cases were included and divided into ETV + FZHY group and ETV + placebo group. And based on the relevant efficacy determination criteria, the two groups were subdivided into efficacy responders and non-responders. Then, TCM clinical questionnaire information of these patients were collected for subsequent analysis to acquire relevant syndrome elements and TCM syndromes. ResultsNo matter what group was, the first three frequency of TCM pathological position in efficacy responders were as follows: Liver > Spleen > Stomach (TCM concepts). As for the ETV + FZHY group, the first three frequency of pathological nature was ranked as Qi deficiency > Dampness > Heat. Compared with the non-responders, the frequency of Spleen, Stomach, Qi deficiency, Heat, and Qi movement stagnation was significantly increased in the efficacy responders (P < 0.05). In terms of TCM syndromes, the frequency increase of Syndrome of liver depression and spleen deficiency (LDSD), in the efficacy responders, changed more obviously than the non-responders (Chi2 = 6.32, P = 0.0006). ConclusionsTCM syndrome elements of Spleen, Stomach, Qi deficiency, Heat, and Qi movement stagnation were closely associated with efficacy responders with HBV-related liver fibrosis in the ETV + FZHY group. Moreover, LDSD was a primary TCM syndrome in these responders.

Clinical comprehensive evaluation of Ruyi Zhenbao Pills in treatment of osteoarthritis

This study evaluated the clinical effectiveness of Ruyi Zhenbao Pills in the treatment of osteoarthritis, aiming to clarify its clinical advantages and promote rational drug use and related policy transformation. Following the relevant standards in Guidelines for the Comprehensive Evaluation of Drugs in Clinical Practice and Technical Specifications for the Clinical Comprehensive Evaluation of Chinese Patent Medicine, comprehensive research and related data on Ruyi Zhenbao Pills in the treatment of osteoarthritis were collected in the dimensions of safety, effectiveness, economy, innovation, suitability, accessibility, and traditional Chinese medicine(TCM) cha-racteristics(referred to as the &quot;6+1&quot; dimensions). Through evidence-based medicine, questionnaire surveys, health technology assessment, pharmacoeconomic evaluation, and other methods, a multi-criteria decision analysis(MCDA) model and CSC v2.0 software were used to comprehensively evaluate the clinical value of Ruyi Zhenbao Pills. Spontaneous reporting system data on adverse reactions and literature data indicate that the adverse reactions of Ruyi Zhenbao Pills are mostly general adverse reactions, with no reports of se-rious adverse reactions. The known risks are small, and its safety is rated as class A. It has been shown to effectively relieve joint pain and restore joint function in the treatment of osteoarthritis. However, more high-quality, large-sample randomized controlled trials are needed to further validate its effectiveness, which is rated as class B. There is evidence supporting its economic viability, and its economic is rated as class B. It demonstrates good clinical innovation, innovative enterprise service system, and industrial innovation, and innovation is rated as class A. Medical professionals and patients have a favorable perception of the suitability of Ruyi Zhenbao Pills, and further improvement can be made in terms of convenience of administration and promotion to facilitate rational drug use by healthcare professionals and patients. Suitability is rated as class B. The drug has a favorable price level, availability, and affordability, and accessibility is rated as class A. Ruyi Zhenbao Pills are a classic Tibetan medicinal prescription with excellent TCM theoretical characteristics. However, further research is needed on its use in human studies. TCM characteristics are rated as class B. Based on the evaluation results of the &quot;6+1&quot; dimensions, the comprehensive clinical evaluation is rated as grade B. Ruyi Zhenbao Pills have good clinical value in the treatment of osteoarthritis, and it is recommended to undergo the necessary procedures for conditional transformation into a policy for the management of essential clinical drugs.

Exercise performance reduction and preventive measures in highland sports.

The plateau is a special environment with low pressure, low oxygen, low temperature, and high ultraviolet radiation. The exercise performance of people on the plateau is generally reduced, which seriously affects the life and health of people living in the plateau and entering the plateau. In recent years, the prevention and treatment of injury caused by high altitude hypoxia has attracted wide attention. It has shown that the higher the altitude with the longer the duration of exercise, the faster the stationing, the greater the impact on people's sports performance. Rapid entry into the plateau and long-term stay in the plateau have an impact on people's explosive power, endurance and fine operation. Advances in medical technology enable various prevention methods to be used to acclimate to high altitude environments. However, in vitro intervention methods are costly, easy to rebound and possess limited effects. Therefore, drug prevention and treatment is obviously a more economical choice. Chemical drugs increase the efficiency of high altitude exercise by improving the ischemic and hypoxic symptoms of the heart and brain, increasing lung ventilation and arterial oxygenation capacity, and accelerating the elimination of adverse product accumulation after exercise. Single Chinese medicine, Chinese patent medicine, and compound preparations can improve exercise performance by promoting body metabolism, improving muscle endurance, enhancing immunity, and other mechanisms. Traditional Chinese medicine has unique advantage and application prospect in improving plateau sports performance damage.

Study on arsenic speciation, bioaccessibility, and gut microbiota in realgar-containing medicines by DGT technique and artificial gastrointestinal extraction (PBET) combine with simulated human intestinal microbial ecosystem (SHIME)

It is well-known that several Chinese patent medicines use realgar as a specific component. People are more aware of the health dangers associated with realgar since it includes arsenic. Previous research overstated the arsenic toxicity of realgar-containing Chinese prescription medications because little thought was given to the influence of arsenic bioaccessibility by gut microbiota. In light of this, this study examined the total content, bioaccessibility and speciation of targeted medications while also examining intestinal epithelial transit utilizing the diffusive gradients in thin-films (DGT). All samples contained arsenic, and the bioaccessibilities of the colon, intestine and gastric regions ranged from 0.19% to 1.73%, 0.25–1.88% and 0.21–1.70% respectively. The range of DGT-bioaccessibility is 0.01–0.0018%. Three steps of analysis were conducted on inorganic As(III) and As(V). In health risk assessment, the ADDs and HQs of DGT-bioaccessibility were below the threshold levels when compared to computing average daily intake dose (ADD) and hazard quotient (HQ) by bioaccessibility of gastric, intestinal and colon. Additionally, Proteobacteria and Firmicutes were discovered to be the two predominant kinds of gut microbes in this study. Under arsenic exposure, the abundance of Christensenellaceae, Desulfovibrionaceae and Akkermansiaceae increased, but the quantity of Rikenellaceae decreased. These findings revealed that alterations in gut microbiota had an impact on host metabolism.

Analysis of medication rules and application characteristics of Chinese patent medicine containing borneol based on data mining

BackgroundIn this study, the regularity of drug containing borneol proprietary Chinese medicine was mined, to provide reference for the clinical application and new drug research and development of borneol. MethodsThe database of proprietary Chinese medicines on Pharmaceutical Intelligence Network was searched for internal and external prescriptions that contained borneols and the diseases they treat. Microsoft Office Excel 2019 and SPSS Modeler 18.0 were used to analyze the properties, flavors, meridians tropisms and association rule analysis of the medicines, and Origin 21.0 software was used to draw the association rules diagram. ResultsAmong them, 528 prescriptions of internal Chinese patent medicine containing borneol and 387 prescriptions of external Chinese patent medicine were included. The diseases treated by internal prescription were mainly neurological diseases and heart diseases, among which Chinese medicines with higher frequency of compatibility with borneol were bezoar, licorice, cinnabar, musk and scutellaria. The diseases treated by external prescription were mainly physical disabilities, paralysis diseases, sore and ulcer diseases and so on. Among them, menthol, camphor, frankincense, angelica, and carthami flos and so on are the most frequently combined with borneol. ConclusionThe prescription of Chinese patent medicine containing borneol is composed of cold or warm, pungent or bitter Chinese medicine. Internal prescription primarily targets the meridians of the heart, liver, and lungs, and is often combined with sedative, antipyretic and detoxicating drugs to treat stroke, infantile convulsion and angina pectoris. External prescription mainly acts on liver, heart and spleen meridian, and is often combined with drugs for clearing heat, promoting blood circulation and removing blood stasis to treat rheumatic arthralgia syndrome and sore and ulcer diseases.

Chinese guidelines for the treatment of chronic pain disorders with non-opioid analgesics

Non-opioid analgesics are one of the important clinical treatment drugs for chronic pain disorders, which mainly include non-steroidal anti-inflammatory analgesics, ion channel drugs, antidepressants, glucocorticoids, neurotrophic drugs, muscle relaxants, α2 adrenergic receptor agonists, bone metabolism regulating drugs, N-methyl-D-aspartate receptor antagonists and traditional Chinese patent medicines. The guidelines for the treatment of chronic pain disorders based on international classification of diseases (ICD)-11 with non-opioid analgesics have not been reported. This guideline was formulated under the leadership of expert group on Pain Disease Diagnosis and Treatment Special Ability Training Project of National Health Commission Capacity Building and Continuing Education Center (hereinafter referred to as the expert group). The expert group systematically searches and evaluates the effectiveness evidence related to the indications, contraindications, precautions, and other issues of non-opioid analgesics treatment for the seven major categories of chronic pain diseases in ICD-11. It also recommends non-opioid analgesic drug treatment for special chronic pain patients such as the elderly, women and children, as well as patients with liver and kidney dysfunction. This guide aims to provide reference for the application of non-opioid analgesics in the treatment of chronic pain disorders in different disciplines.

Traditional Chinese Medicine Compound (Tongxinluo) and Clinical Outcomes of Patients With Acute Myocardial Infarction

Tongxinluo, a traditional Chinese medicine compound, has shown promise in in vitro, animal, and small human studies for myocardial infarction, but has not been rigorously evaluated in large randomized clinical trials. To investigate whether Tongxinluo could improve clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Randomized, double-blind, placebo-controlled clinical trial was conducted among patients with STEMI within 24 hours of symptom onset from 124 hospitals in China. Patients were enrolled from May 2019 to December 2020; the last date of follow-up was December 15, 2021. Patients were randomized 1:1 to receive either Tongxinluo or placebo orally for 12 months (a loading dose of 2.08 g after randomization, followed by the maintenance dose of 1.04 g, 3 times a day), in addition to STEMI guideline-directed treatments. The primary end point was 30-day major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiac death, myocardial reinfarction, emergent coronary revascularization, and stroke. Follow-up for MACCEs occurred every 3 months to 1 year. Among 3797 patients who were randomized, 3777 (Tongxinluo: 1889 and placebo: 1888; mean age, 61 years; 76.9% male) were included in the primary analysis. Thirty-day MACCEs occurred in 64 patients (3.4%) in the Tongxinluo group vs 99 patients (5.2%) in the control group (relative risk [RR], 0.64 [95% CI, 0.47 to 0.88]; risk difference [RD], -1.8% [95% CI, -3.2% to -0.6%]). Individual components of 30-day MACCEs, including cardiac death (56 [3.0%] vs 80 [4.2%]; RR, 0.70 [95% CI, 0.50 to 0.99]; RD, -1.2% [95% CI, -2.5% to -0.1%]), were also significantly lower in the Tongxinluo group than the placebo group. By 1 year, the Tongxinluo group continued to have lower rates of MACCEs (100 [5.3%] vs 157 [8.3%]; HR, 0.64 [95% CI, 0.49 to 0.82]; RD, -3.0% [95% CI, -4.6% to -1.4%]) and cardiac death (85 [4.5%] vs 116 [6.1%]; HR, 0.73 [95% CI, 0.55 to 0.97]; RD, -1.6% [95% CI, -3.1% to -0.2%]). There were no significant differences in other secondary end points including 30-day stroke; major bleeding at 30 days and 1 year; 1-year all-cause mortality; and in-stent thrombosis (<24 hours; 1-30 days; 1-12 months). More adverse drug reactions occurred in the Tongxinluo group than the placebo group (40 [2.1%] vs 21 [1.1%]; P = .02), mainly driven by gastrointestinal symptoms. In patients with STEMI, the Chinese patent medicine Tongxinluo, as an adjunctive therapy in addition to STEMI guideline-directed treatments, significantly improved both 30-day and 1-year clinical outcomes. Further research is needed to determine the mechanism of action of Tongxinluo in STEMI. ClinicalTrials.gov Identifier: NCT03792035.

Bavachin combined with epimedin B induce idiosyncratic liver injury under immunological stress conditions

Reports on Chinese patent medicines preparations containing Epimedii Folium (EF) and Psoraleae Fructus (PF) resulting in idiosyncratic drug-induced liver injury (IDILI) have received widespread attention. Previous studies have shown that bavachin and epimedin B—two active ingredients derived from both EF and PF—are potential components associated with IDILI, but the underlying mechanism remains unclear. We evaluated bavachin and epimedin B-induced IDILI under TNF-α-mediated immunological stress conditions and generated liver lipid metabolism profiles using lipidomics and multivariate statistical analysis. We next applied transcriptomics to identify the differential gene expression on the transcription level. Our results showed that co-exposure to bavachin, epimedin B under immunological stress conditions resulted in obvious liver injury. The differential metabolites screened in our study were closely related to the immune homeostasis of the liver. Sixteen differentially expressed genes were found, Zc3h6 and R3hdml were upregulated, while Sumo2, Cd74, Banp, Oas3, Oas2, Gbp8, Slfn8, Gbp2b, Serpina3g, Zbtb40, H2-Ab1, Osgin1, Tgtp1 and Hspa1b were all downregulated. These differentially expressed genes were associated with biological processes concerning metabolic process and immune system process. Further integrative analysis indicated that bavachin combined with epimedin B affected genes that were not only related to immune system processes, but also to lipid metabolism. Ultimately, this led to an imbalance in the immune microenvironment in the liver and may have contributed to the observed liver injury.

Comparative efficacy and safety of Chinese patent medicines of acute ischemic stroke: A network meta-analysis.

Acute ischemic stroke (AIS) is characterized by high morbidity, disability, mortality, recurrence, and economic burden. Clinical trials have demonstrated that the clinical efficacy of combining oral Chinese patent medicines (CPMs) with chemical drugs (CDs) is better than that of CDs alone. In this study, we performed a network meta-analysis (NMA) of RCTs to assess the efficacy of different CPMs in combination with CDs in the treatment of AIS. Search 6 databases from the beginning to January 10, 2023. The Cochrane Risk of Bias tool assessed the methodological quality of the included studies. The NMA was then performed using the STATA 13.0 program. The surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the studied treatments, and cluster analysis was used to compare the effects of CPMs between 2 different outcomes. A total of 94 eligible RCTs, involving 9581 participants, were included in this analysis. Nine CPMs, including Nao-mai-li granule (NML), Nao-mai-tai granule (NMT), Qi-long granule (QL), Long-sheng-zhi capsule (LSZ), Nao-xin-tong capsule (NXT), Nao-xue-shu oral liquid (NXS), Tong-xin-luo capsule (TXL), Xiao-shuan-chang-rong capsule (XSCR), and Xue-shuan-xin-mai-ning capsule (XSXMN) were included. Regarding the clinical effective rate, all types of CPMs + CDs treatments were significantly better than CDs treatments alone, with significant differences among the 9 selected CPMs. Compared with CDs, results showed that NXS + CDs performed best in improving clinical effective rate [OR = 4.73; 95% CI: 1.26-17.78; (SUCRA: 76.1%)]. TXL + CDs showed the most effective effect in alleviating National Institutes of Health Stroke Scale (NIHSS) [MD = -3.84; 95% CI: -5.23, -2.45; (SUCRA: 81.6%)]; NXT + CDs were most effective in improving Barthel index [MD = 13.05; 95% CI: 3.98-22.12; (SUCRA: 63.5%)]. Combined with other outcome indicators and the results of cluster analysis, NXS + CDs may assist in the potential optimal treatment regimen for AIS. In conclusion, CPMs were found to be beneficial as adjuvant therapy in patients with AIS. Taking into account the clinical effective rate and other outcomes, NXS + CDs may be the most effective option to improve the condition of AIS patients.

Identification and quantitation of NF-κB inhibitory components in weichang'an pill based on UHPLC-QE-MS and spectrum-effect relationship

Weichang'an pill (WCAP) is a traditional Chinese patent medicine, which is clinically used for the treatment of bowel syndrome and functional dyspepsia such as diarrhea, abdominal distension, and enteritis. So far, quality control studies of WCAP have mainly focused on the determination of chemical composition content, which has little relevance to biological activity and clinical effects. With the aim of identifying the multi-index ingredients with NF-κB inhibitory activities related to WCAP clinical effect, this present work described the chemical profile of WCAP by UHPLC-QE-MS, established the correlated relationship between chromatographic fingerprints and the NF-κB inhibitory activities based on multivariate statistical analysis, including hierarchical clustering analysis (HCA), Pearson correlation analysis, and Partial least squares regression analysis (PLSR). The spectrum-effect relationship analysis indicated 10 compounds, which were ferulic acid, naringin, narirutin, hesperidin, neohesperidin, aloe emodin, emodin, honokiol, magnolol, and physcion, might be the potential NF-κB inhibitory constituents in the pill. The NF-κB inhibitory effects of the ten compounds were verified by in vitro dual luciferase reporting detection system. Considering that the detection index should be representative of more medicinal materials, a rapid and efficient UPLC-DAD method was eventually developed to determine the content of the 13 components. Our findings will provide data support for WCAP quality control and advance the understanding of the quality assessment of traditional Chinese patent medicines.

Simultaneous determination of multiple components in Fuke Yangrong pill by HPLC

AbstractFuke Yangrong pill, a traditional Chinese patent medicine, with the functions of nourishing qi and blood, soothing liver and relieving depression, regulating menstruation and removing blood stasis, is composed of 16 Chinese medicinal herbs. For quality control purpose, an HPLC method was established for simultaneous quantification of paeoniflorin, hesperidin and ligustilide in Fuke Yangrong pill. With acetonitrile-0.1% formic acid as mobile phase, gradient elution was carried out using Agilent ZORBAX Eclipse Plus C18 column (250 mm × 4.6 mm, 5.0 μm) at 1.0 mL min−1. Detection wavelength was set at 230 nm for paeoniflorin, 280 nm for hesperidin and ligustilide. The temperature was 30 °C. There was a good linearity between the peak area and the concentration of each component to be measured within their linear range (r ≥ 0.9994). The average recoveries were between 98.6% and 102.6% with RSDs no more than 2.93%. This method was validated to be accurate and convenient, which is suitable for the quality control of Fuke Yangrong pill.

Efficacy and safety of Chinese patent medicine compound preparation combined with routine treatment in vitiligo: A Bayesian network meta-analysis.

Treating vitiligo in clinical practice is challenging. Furthermore, oral drugs used in Western medicine have considerable side effects and are unsuitable for long-term treatment. In contrast, Chinese patent medicines (CPMs) are more suitable for long-term oral vitiligo treatment, but medical evidence of their efficacy and safety is lacking. Therefore, in this study, the efficacy and safety of CPMs were evaluated and ranked using a Bayesian network meta-analysis. Seven Chinese and English databases were searched for all relevant articles published up to February 2023. The Bayesian network meta-analysis method was used to analyze the extracted data to evaluate efficacy and safety. Six common CPMs for treating vitiligo were selected in our study, and 48 targeted articles and 4446 patients were included. This study showed that Qubai Babuqi tablets (QT) were the most effective for short-term treatment of vitiligo, and that vitiligo capsules or pills (VCP) were the most effective for long-term treatment, together with compound Quchong Banjiuju pills (QP). In terms of surface area under the cumulative ranking curve (SUCRA) values, the order of efficacy of each treatment was as follows: QT (92.18%) > Taohong Qingxue pills (TP) (63.81%) > VCP (55.53%) > QP (50.72%) > Bailing tablets or capsules (BTC) (49.01%) > Baishi pills (BP) (35.69%)>routine therapy (RT) (3.1%) in terms of total effective rate and QT (92.05%) > VCP (71.50%) > QP (66.60%) > TP (42.95%) > BTC (39.66%) > BP (36.60%)>RT (0.6%) in terms of improvement rate. In addition, the safety of the 6 CPMs did not significantly differ in terms of adverse effects. The SUCRA values indicated that QT performed slightly worse than other drugs. In treating vitiligo, QT is most effective but only suitable for short-term administration owing to its poor safety. VCP and QP could be used as first-choice long-term medications. TP may positively affect repigmentation in patients with limited lesion areas.

Total Glucosides of White Paeony Capsule ameliorates Parkinson's disease-like behavior in MPTP-induced mice model by regulating LRRK2/alpha-synuclein signaling

Ethnopharmacological relevanceThe Total Glucosides of White Paeony Capsule (TGPC), one of the traditional Chinese patent medicines, has been used for the treatment of autoimmune diseases such as rheumatoid arthritis (RA) in clinical practice. Besides, the components of TGPC are extracted from Radix Paeoniae Alba (RPA) and have displayed neuroprotective properties. Aim of the studyThe present study was designed to evaluate the anti-PD-like effects of TGPC on a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced mice model and explore its potential molecular mechanisms. Materials and methodsBehavioral tests, hematoxylin and eosin (HE) staining, Nissl staining, immunohistochemistry (IHC), western blotting (WB) and Enzyme-Linked Immunosorbent Assay (ELISA) were performed in this study. ResultsIt was observed that TGPC treatment (150, 300 mg/kg) significantly reversed MPTPinduced PD-like behaviors, such as reduced locomotive activity in the open field test, prolonged time to turn downward on the ball (T-turn) and to climb down the whole pole (T-descend) in the pole test, decreased movement scores in the traction test and extended the latency to fall in the hanging wire test. In addition, TGPC improved neurodegeneration, inhibited the excessive activation of microglia and suppressed the overproduction of proinflammatory cytokines induced by MPTP, partially by restoring leucine-rich repeat kinase 2 (LRRK2) activity and inhibiting alpha-synuclein (α-syn) mediated neuroinflammation signaling. ConclusionTaken together, TGPC exhibited neuroprotective effects on MPTP-induced mice model of PD, which was associated with the prevention of neuroinflammation and neurodegeneration modulated by LRRK2/α-syn pathway.

Systematic Characterization of the Chemical Components and Absorbed Prototypes in Sanqi Xueshangning Capsules Using UPLC-Q-TOF-MS with SCIEX OS Software

Background Sanqi Xueshangning Capsules (SXC) is a famous Chinese patent medicine with a good curative effect on various gynecological pain diseases in China. However, its chemical composition and potential active ingredients were clearly unrevealed, which hindered the elaboration of its material basis functional mechanism and clinical application. Materials and Methods In the study, we developed an integrative ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) method coupled with SCIEX OS software for characterizing the chemical composition in SXC. The data collection was conducted using a Waters UPLCTM HSS T3 (2.1 × 100 mm, 1.8 µm) in a binary elution system. The SCIEX OS software coupled with multivariable processing techniques was used to screen absorbed prototypes in serum after oral administration of SXC. The structural identification of the components was performed by MS/MS fragmentation mechanism. Results A total of 113 components from SXC were tentatively characterized, including 38 saponins, 13 flavonoids, 10 phenylpropanoids, 9 alkaloids, 20 organic acids, and 23 others. Based on the in vitro composition results, 21 absorbed prototypes in rat serum were identified, mainly including alkaloids, flavonoids, phenylpropanoids, and saponins. Conclusion It was concluded that an integrative UPLC-Q-TOF-MS method coupled with SCIEX OS software could be successfully applied for the components’ characterization of SXC in vitro and in vivo, which laid a reliable scientific basis for promoting the discovery of material basis and the improvement of quality control of SXC.