Immunomodulatory Effects of Yu-Ping-Feng Formula on Primary Sjögren's Syndrome: Interrogating the T Cell Response.

Ethnopharmacological treatments have shown beneficial effects in the clinical practice of autoimmune disorders. However, the underlying mechanism of immunomodulatory effects remains challenging, given the complicate composition of herbal medicines. Here, we developed an immunological approach to interrogate the T helper cell response. Through data mining we hypothesized that Chinese medicine formula, Yu-Ping-Feng (YPF) might be a promising candidate for treating primary Sjögren's syndrome (pSS), a common autoimmune disease manifested by exocrine gland dysfunction. We took advantage of a mouse model of experimental Sjögren's syndrome (ESS) that we previously established for YPF formula treatment. YPF therapy ameliorated the ESS pathology in mice with active disease, showing improved salivary function and decreased serum levels of autoantibodies. Phenotypic analysis suggested that both effector T and B cells were significantly suppressed. Using co-culture assay and adoptive transfer models, we demonstrated that YPF formula directly restrained effector/memory T cell expansion and differentiation into Th17 and T follicular helper (Tfh) cells, the key subsets in ESS pathogenesis. Importantly, we recruited 20 pSS patients and conducted a pilot study of 8-week therapy of YPF formula. YPF treatment effectively improved fatigue symptoms, exocrine gland functions and reduced serum IgG/IgA levels, while effector T and B cell subsets were significantly decreased. There was a trend of reduction on disease activity, but not statistically significant. Together, our findings suggested a novel approach to assess the immunomodulatory effects of YPF formula, which may be favorable for patients with autoimmune disorders.

Five-layer-funnel filtering mode discovers effective components of Chinese medicine formulas: Zhishi-Xiebai-Guizhi decoction as a case study.

BACKGROUND: How to screen and identify the effective components in the complex substance system is one of the core issues in achieving the modernization of traditional Chinese medicine (TCM) formulas. However, it is still challenging to systematically screen out the effective components from the hundreds or thousands of components in a TCM formula. PURPOSE: An innovative five-layer-funnel filtering mode stepwise integrating chemical profile, quantitative analysis, xenobiotic profile, network pharmacology and bioactivity evaluation was successfully presented to discover the effective components and implemented on a case study of Zhishi-Xiebai-Guizhi decoction (ZXG), a well-known TCM formula for coronary heart disease (CHD). METHODS: Initially, the chemical profile of ZXG was systemically characterized. Subsequently, the representative constituents were quantitatively analyzed. In the third step, the multi-component xenobiotics profile of ZXG was systemically delineated, and the prototypes absorbed into the blood were identified and designated as the primary bioavailable components. Next, an integrated network of "bioavailable components-CHD targets-pathways-therapeutic effects" was constructed, and the crucial bioavailable components of ZXG against CHD were screened out. Lastly, the bioactivities of crucial bioavailable components were further evaluated to pinpoint effective components. RESULTS: First of all, the chemical profile of ZXG was systemically characterized with the detection of 201 components. Secondly, 37 representative components were quantified to comprehensively describe its content distribution characteristics. Thirdly, among the quantified components, 24 bioavailable components of ZXG were identified based on the multi-component xenobiotic profile. Fourthly, an integrated network led to the identification of 11 crucial bioavailable components against CHD. Ultimately, 9 components (honokiol, magnolol, naringenin, magnoflorine, hesperidin, hesperetin, naringin, neohesperidin and narirutin) exhibiting myocardial protection in vitro were identified as effective components of ZXG for the first time. CONCLUSION: Overall, this innovative strategy successfully identified the effective components of ZXG for the first time. It could not only significantly contribute to elucidating the therapeutic mechanism of ZXG in the treatment of CHD, but also serve as a helpful reference for the systematic discovery of effective components as well as ideal quality markers in the quality assessment of TCM formulas.

Traditional Chinese medicine and mitophagy: A novel approach for cardiovascular disease management.

BACKGROUND: Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide, imposing an enormous economic burden on individuals and human society. Laboratory studies have identified several drugs that target mitophagy for the prevention and treatment of CVD. Only a few of these drugs have been successful in clinical trials, and most studies have been limited to animal and cellular models. Furthermore, conventional drugs used to treat CVD, such as antiplatelet agents, statins, and diuretics, often result in adverse effects on patients' cardiovascular, metabolic, and respiratory systems. In contrast, traditional Chinese medicine (TCM) has gained significant attention for its unique theoretical basis and clinical efficacy in treating CVD. PURPOSE: This paper systematically summarizes all the herbal compounds, extracts, and active monomers used to target mitophagy for the treatment of CVD in the last five years. It provides valuable information for researchers in the field of basic cardiovascular research, pharmacologists, and clinicians developing herbal medicines with fewer side effects, as well as a useful reference for future mitophagy research. METHODS: The search terms "cardiovascular disease," "mitophagy," "herbal preparations," "active monomers," and "cardiac disease pathogenesis" in combination with "natural products" and "diseases" were used to search for studies published in the past five years until January 2024. RESULTS: Studies have shown that mitophagy plays a significant role in the progression and development of CVD, such as atherosclerosis (AS), heart failure (HF), myocardial infarction (MI), myocardial ischemia/reperfusion injury (MI/RI), cardiac hypertrophy, cardiomyopathy, and arrhythmia. Herbal compound preparations, crude extracts, and active monomers have shown potential as effective treatments for these conditions. These substances protect cardiomyocytes by inducing mitophagy, scavenging damaged mitochondria, and maintaining mitochondrial homeostasis. They display notable efficacy in combating CVD. CONCLUSION: TCM (including herbal compound preparations, extracts, and active monomers) can treat CVD through various pharmacological mechanisms and signaling pathways by inducing mitophagy. They represent a hotspot for future cardiovascular basic research and a promising candidate for the development of future cardiovascular drugs with fewer side effects and better therapeutic efficacy.

Optimization of the Zhou Tian Formula extraction technology based on AHP-CRITIC method and analysis of transfer efficiency of key components based on HPLC fingerprinting.

INTRODUCTION: Zhou Tian Formula (ZTF) is an antidepressant traditional Chinese medicine utilized widely in clinical settings for the treatment of patients with depression. However, shortcomings persist in its extraction technology and quality control. OBJECTIVE: This study aimed to propose a methodology for ZTF extraction technology based on the analytic hierarchy process (AHP)-criteria importance through intercriteria correlation (CRITIC) method and to establish a quality control framework for the efficient transfer of index components. METHOD: Firstly, we analyzed the chemical components of ZTF and determined the optimal extraction technology. Secondly, we calculated the transfer efficiency of the index components during the conversion of water decoction to extract powder and subsequently to granules. Thirdly, we established HPLC fingerprints for 15 batches of ZTF water decoction, extract powder, and granules. We employed SIMCA software to analyze the chemicals responsible for variations in quality among different batches of ZTF granules. RESULTS: We determined the optimal extraction process. The average transfer efficiency of ferulic acid, puerarin, mirificin, isoferulic acid, and calycosin during the conversion of water decoction to extract powder and subsequently to granules exceeded 41%. The HPLC fingerprints of ZTF exhibited a similarity exceeding 0.890. Variable importance in projection values indicated that calycosin, ferulic acid, and puerarin were the primary contributors to quality variations. CONCLUSIONS: The AHP-CRITIC method, coupled with an orthogonal array design, could be used for exploring extraction technology. In addition, the rules governing the transfer of index components from water decoction to extract powder, and subsequently to granules, could be applied for the evaluation and quality assessment of ZTF.

Traditional Chinese medicine formulae: A complementary method for the treatment of polycystic ovary syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a prevalent female endocrine condition that significantly affects women of all age groups and is characterized by metabolic dysfunction. The efficacy of existing pharmaceutical interventions for the treatment of PCOS remains inadequate. With a rich history and cultural significance spanning thousands of years, Traditional Chinese Medicine (TCM) is extensively employed for treating a variety of ailments and can serve as a supplementary therapy for managing PCOS. Multiple clinical observations and laboratory tests have unequivocally demonstrated the substantial effectiveness and safety of TCM formulae in treating PCOS, and further investigations are currently in progress. AIM OF THE STUDY: To summarize the TCM formulae commonly employed in the clinical management of PCOS, examine their therapeutic benefits, investigate their mechanism of action, active constituents, and establish the correlation between efficacy, mechanism of action, and active constituents. MATERIALS AND METHODS: We conducted a comprehensive search on PubMed, Web of Science, and China national knowledge infrastructure (CNKI) using the following keywords: "Polycystic Ovary Syndrome", "Traditional Chinese Medicine Decoctions", "Traditional Chinese Medicine formulae", "Traditional Chinese Medicine", "Clinical Observation", "Mechanism", "Treatment", "Pharmacology", and various combinations of these terms. From January 1, 2006 until October 7, 2023, (inclusive). RESULTS: This paper summarized the clinical effectiveness, mechanism of action, and active components of 8 TCM formulae for the treatment of PCOS. Our research indicates that TCM formulae can potentially treat PCOS by enhancing the levels of hyperandrogenism and other endocrine hormones, decreasing insulin resistance and hyperinsulinemia, and controlling chronic low-grade inflammation, among other modes of action. In addition, we found an association between epigenetics and TCM formulae for the treatment of PCOS. CONCLUSION: TCM formulae have specific advantages in the treatment of Polycystic Ovary Syndrome (PCOS). They achieve therapeutic benefits by targeting several pathways and connections, attracting considerable interest and playing a vital role in the treatment of PCOS. TCM formulae can be used as an adjunctive therapy for the treatment of PCOS.

An UHPLC-QTOF-MS-based strategy for systematic profiling of chemical constituents and associated in vivo metabolites of a famous traditional Chinese medicine formula, Yinchenhao decoction.

Yinchenhao decoction (YCHD), a famous traditional Chinese medicine formula, has been applied for relieving jaundice in China for more than 1800 years. However, the material basis for YCHD is still unclear, and the chemical composition and metabolism characteristic in vivo are undefined, making the potential effective constituents and mechanism of action unclear. Herein, an ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS)-based strategy was applied for the chemical profiling of YCHD, as well as their in vivo prototypes and global metabolites that defined the metabolome. Our results showed that a total of 139 chemicals were identified in YCHD, including 28 organic acids, 12 monoterpenoids, five diterpenes, three triterpenoids, 17 iridoids, 23 anthraquinones, 26 flavonoids, four coumarins and 21 other types. Moreover, 58 prototypes and 175 metabolites were found in rat biological samples after oral administration of YCHD; those distributed in plasma, liver, intestine and feces were suggested to be potentially effective substances. Oxidation, hydrogenation, decarboxylation and conjugations with methyl, sulfate and glucuronate were considered as the predominant metabolic pathways in vivo. In conclusion, this is a systemic study of chemical constituents and in vivo metabolome profiles of YCHD, contributing to the material basis understanding and further mechanism research.

Traditional Chinese Medicine formula, Sanwujiao granule, attenuates ischemic stroke by promoting angiogenesis through early administration.

ETHNOPHARMACOLOGICAL RELEVANCE: Ischemic stroke (IS) is one of the most lethal diseases with the insufficient pharmacology therapeutic approach. Sanwujiao granule (SW) is widely used for IS in China with little known about its underlying mechanism. AIM OF THE STUDY: To investigate the characteristics of therapeutic effects and potential mechanisms of SW against IS. MATERIALS AND METHODS: The fingerprint of SW was applied by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Three different drug treatment strategies, including prophylactic administration, early administration and delayed administration, were applied in rats' permanent middle cerebral occlusion (pMCAO) model. The Garcia neurological deficit test, adhesive removal test, rotarod test, TTC and TUNEL staining were performed to evaluate the pathological changes. The transcriptomic analysis was used to predict the potential mechanism of SW. The vascular deficiency model of Tg(kdrl:eGFP) zebrafish larvae and oxygen-glucose deprivation model on bEnd.3 cells were used to verify SW's pharmacological effect. qRT-PCR, immunofluorescent staining and Western Blot were applied to detect the expression of genes and proteins. The network pharmacology approach was applied to discover the potential bioactive compounds in SW that contribute to its pharmacological effect. RESULTS: SW early and delayed administration attenuated cerebral infarction, neurological deficit and cell apoptosis. The transcriptomic analysis revealed that SW activated angiogenesis-associated biological processes specifically by early administration. CD31 immunofluorescent staining further confirmed the microvessel intensity in peri-infarct regions was significantly elevated after SW early treatment. Additionally, on the vascular deficiency model of zebrafish larvae, SW showed the angiogenesis effect. Next, the cell migration and tube formation were also observed in the bEnd.3 cells with the oxygen-glucose deprivation induced cell injury. It's worth noting that both mRNA and protein levels of angiogenesis factor, insulin-like growth factor 1, were significantly elevated in the pMCAO rats' brains treated with SW. The network pharmacology approach was applied and chasmanine, karacoline, talatisamine, etc. were probably the main active compounds of SW in IS treatment as they affected the angiogenesis-associated targets. CONCLUSIONS: These results demonstrate that SW plays a critical role in anti-IS via promoting angiogenesis through early administration, indicating that SW is a candidate herbal complex for further investigation in treating IS in the clinical.

Potential mechanism of Qinggong Shoutao pill alleviating age-associated memory decline based on integration strategy.

CONTEXT: Qinggong Shoutao Wan (QGSTW) is a pill used as a traditional medicine to treat age-associated memory decline (AAMI). However, its potential mechanisms are unclear. OBJECTIVE: This study elucidates the possible mechanisms of QGSTW in treating AAMI. MATERIALS AND METHODS: Network pharmacology and molecular docking approaches were utilized to identify the potential pathway by which QGSTW alleviates AAMI. C57BL/6J mice were divided randomly into control, model, and QGSTW groups. A mouse model of AAMI was established by d-galactose, and the pathways that QGSTW acts on to ameliorate AAMI were determined by ELISA, immunofluorescence staining and Western blotting after treatment with d-gal (100 mg/kg) and QGSTW (20 mL/kg) for 12 weeks. RESULTS: Network pharmacology demonstrated that the targets of the active components were significantly enriched in the cAMP signaling pathway. AKT1, FOS, GRIN2B, and GRIN1 were the core target proteins. QGSTW treatment increased the discrimination index from -16.92 ± 7.06 to 23.88 ± 15.94% in the novel location test and from -19.54 ± 5.71 to 17.55 ± 6.73% in the novel object recognition test. ELISA showed that QGSTW could increase the levels of cAMP. Western blot analysis revealed that QGSTW could upregulate the expression of PKA, CREB, c-Fos, GluN1, GluA1, CaMKII-α, and SYN. Immunostaining revealed that the expression of SYN was decreased in the CA1 and DG. DISCUSSION AND CONCLUSIONS: This study not only provides new insights into the mechanism of QGSTW in the treatment of AAMI but also provides important information and new research ideas for the discovery of traditional Chinese medicine compounds that can treat AAMI.

Application of data mining algorithms in research on traditional Chinese medicine formula / 中国药房

In recent years， data mining algorithms have been widely employed in scientific research within the field of traditional Chinese medicine （TCM）. The data mining algorithms are used to effectively handle and analyze the complex data in TCM formulas， providing a rational explanation for the mechanism of action. This method has proven particularly useful in uncovering patterns of compatibility and frequent combinations of herbs in TCM， thereby enhancing the reliability and accuracy of clinical diagnosis， target screening， and the study of new drugs. This paper reviews and analyzes 147 papers on TCM formula research that utilize data mining algorithms. The results indicate that data mining algorithms play a unique advantage in six sub- areas， including the study on the mechanism of action in TCM formula， the dose-efficacy of TCM formulas， the identification of core drugs pairs/groups， mining the relationships among “formulas-drug-symptom”， the discovery of new formulas， and mining the compatibility law. Notably， association rules and clustering algorithms are the most representative.

Research progress of traditional Chinese medicine in improving hepatic fibrosis based on inhibiting pathological angiogenesis.

Hepatic fibrosis is the formation of scar tissue in the liver. This scar tissue replaces healthy liver tissue and can lead to liver dysfunction and failure if left untreated. It is usually caused by chronic liver disease, such as hepatitis B or C, alcohol abuse, or non-alcoholic fatty liver disease. Pathological angiogenesis plays a crucial role in the development of hepatic fibrosis by promoting the growth of new blood vessels in the liver. These new vessels increase blood flow to the damaged areas of the liver, which triggers the activation of hepatic stellate cells (HSCs). HSCs are responsible for producing excess collagen and other extracellular matrix proteins that contribute to the development of fibrosis. Pathological angiogenesis plays a crucial role in the development of hepatic fibrosis by promoting the growth of new blood vessels in the liver. These new vessels increase blood flow to the damaged areas of the liver, which triggers the activation of HSCs. HSCs are responsible for producing excess collagen and other extracellular matrix proteins that contribute to the development of fibrosis. Traditional Chinese medicine (TCM) has been found to target pathological angiogenesis, thereby providing a potential treatment option for hepatic fibrosis. Several studies have demonstrated that TCM exhibits anti-angiogenic effects by inhibiting the production of pro-angiogenic factors, such as vascular endothelial growth factor and angiopoietin-2, and by reducing the proliferation of endothelial cells. Reviewing and highlighting the unique TCM recognition of treating hepatic fibrosis by targeting pathological angiogenesis may shed light on future hepatic fibrosis research.

Brain and serum metabolomic studies reveal therapeutic effects of san hua decoction in rats with ischemic stroke.

San Hua Decoction (SHD) is a traditional four-herbal formula that has long been used to treat stroke. Our study used a traditional pharmacodynamic approach combined with systematic and untargeted metabolomics analyses to further investigate the therapeutic effects and potential mechanisms of SHD on ischemic stroke (IS). Male Sprague-Dawley rats were randomly divided into control, sham-operated, middle cerebral artery occlusion reperfusion (MCAO/R) model and SHD groups. The SHD group was provided with SHD (7.2 g/kg, i.g.) and the other three groups were provided with equal amounts of purified water once a day in the morning for 10 consecutive days. Our results showed that cerebral infarct volumes were reduced in the SHD group compared with the model group. Besides, SHD enhanced the activity of SOD and decreased MDA level in MCAO/R rats. Meanwhile, SHD could ameliorate pathological abnormalities by reducing neuronal damage, improving the structure of damaged neurons and reducing inflammatory cell infiltration. Metabolomic analysis of brain and serum samples with GC-MS techniques revealed 55 differential metabolites between the sham and model groups. Among them, the levels of 12 metabolites were restored after treatment with SHD. Metabolic pathway analysis showed that SHD improved the levels of 12 metabolites related to amino acid metabolism and carbohydrate metabolism, 9 of which were significantly associated with disease. SHD attenuated brain inflammation after ischemia-reperfusion. The mechanisms underlying the therapeutic effects of SHD in MCAO/R rats are related to amino acid and carbohydrate metabolism.

Progress on traditional Chinese medicine in improving hepatic fibrosis through inhibiting oxidative stress.

Hepatic fibrosis is a common pathological process that occurs in the development of various chronic liver diseases into cirrhosis and liver cancer, characterized by excessive deposition of the extracellular matrix. In the past, hepatic fibrosis was thought to be a static and irreversible pathological process. In recent years, with the rapid development of molecular biology and the continuous in-depth study of the liver at the microscopic level, more and more evidence has shown that hepatic fibrosis is a dynamic and reversible process. Therefore, it is particularly important to find an effective, simple, and inexpensive method for its prevention and treatment. Traditional Chinese medicine (TCM) occupies an important position in the treatment of hepatic fibrosis due to its advantages of low adverse reactions, low cost, and multi-target effectiveness. A large number of research results have shown that TCM monomers, single herbal extracts, and TCM formulas play important roles in the prevention and treatment of hepatic fibrosis. Oxidative stress (OS) is one of the key factors in the occurrence and development of hepatic fibrosis. Therefore, this article reviews the progress in the understanding of the mechanisms of TCM monomers, single herbal extracts, and TCM formulas in preventing and treating hepatic fibrosis by inhibiting OS in recent years, in order to provide a reference and basis for drug therapy of hepatic fibrosis.

[A Novel Chinese Medicine Formula Inhibits Non-small Cell Lung Cancer by Triggering Oxidative Stress Dependent on Pentose Phosphate Pathway].

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the most lethal malignancies worldwide. A novel Chinese medicine formula-01 (NCHF-01) has shown significant clinical efficacy in the treatment of NSCLC, but the mechanism of this formula in the treatment of NSCLC is not fully understood. The aim of this study is to investigate the molecular mechanism of NCHF-01 in inhibiting NSCLC. METHODS: Lewis lung cells (LLC) tumor bearing mice were established to detect the tumor inhibitory effect of NCHF-01. The morphological changes of tissues and organs in LLC tumor-bearing mice were detected by hematoxylin-eosin (HE) staining. NSCLC cells were treated by NCHF-01. The effects of cell viability and proliferation were detected by MTT and crystal violet staining experiment. Flow cytometry was used to detect cell cycle, apoptosis and reactive oxygen species (ROS). Network pharmacology was used to predict the mechanism of its inhibitory effect of NSCLC. Western blot and immunohistochemistry (IHC) were used to detect the expression of related proteins. RESULTS: NCHF-01 can inhibit tumor growth in LLC tumor-bearing mice, and has no obvious side effects on other tissues and organs. NCHF-01 could inhibit cell viability and proliferation, induce G2/M phase arrest and apoptosis, and promote the increase of ROS level. Network pharmacological analysis showed that NCHF-01 exerts anti-NSCLC effects through various biological processes such as oxidative stress and central carbon metabolism. NCHF-01 can reduce the protein expression and enzyme activity of the key enzymes 6-phosphate glucose dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) in the pentose phosphate pathway (PPP). CONCLUSIONS: NCHF-01 can inhibit NSCLC through oxidative stress dependent on the PPP.

Integrated network pharmacology and experimental validation to explore the potential pharmacological mechanism of Qihuang Granule and its main ingredients in regulating ferroptosis in AMD.

BACKGROUND: Qihuang Granule (QHG) is a traditional prescription  that has exhibited potential in safeguarding against age-related maculopathy (AMD). Salvia miltiorrhiza (SM) and Fructus lycii (FL) are the main components of QHG. Ferroptosis, a newly discovered, iron-dependent, regulated cell death pathway, have been implicated in the pathogenesis of AMD. This study delves into the intricate mechanism by which SM/FL and QHG confer protection against AMD by modulating the ferroptosis pathway, employing a combination of network pharmacology and experimental validation. METHODS: Bioactive compounds and potential targets of SM and FL were gathered from databases such as TCMSP, GeneCard, OMIM, and FerrDb, along with AMD-related genes and key genes responsible for ferroptosis regulation. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction (PPI) network were performed to discover the potential mechanism. The construction of an interaction network involving AMD, ferroptosis, SM/FL potential target genes was facilitated by the STRING database and realized using Cytoscape software. Subsequent validation was accomplished through molecular docking and in vitro cell experiments. RESULTS: Noteworthy active compounds including quercetin, tanshinone IIA, luteolin, cryptotanshinone, and hub targets such as HIF-1α, EGFR, IL6, and VEGFA were identified. KEGG enrichment unveiled the HIF-1 signalling pathway as profoundly enriched, and IL6 and VEGF were involved. The molecular docking revealed the significant active compounds with hub genes and quercetin showed good binding to HIF-1α, which is involved in inflammation and angiogenesis. Experimental results verified that both herbs and QHG could regulate key ferroptosis-related targets in the retinal pigment epithelium and inhibit the expression of HIF-1α, VEGFA, and IL-6, subsequently increase cell viability and decrease the ROS content induced by H2O2. CONCLUSION: This study demonstrates the molecular mechanism through which SM/FL and QHG protect against AMD and emerges as a plausible mechanism underlying this protection.

[Clinical centralized safety monitoring and evaluation of traditional Chinese medicine formula granules].

Traditional Chinese medicine(TCM) formula granules are highly praised for the advanced, convenient, and modern use of Chinese medicinal materials. The safety of TCM formula granules has long been a concern of regulatory authorities and the medical industry. A multi-center, prospective, open, non-interventional, and centralized monitoring was carried out for the patients treated with TCM formula granules in 252 medical institutions from February 5, 2020 to April 19, 2022. All the case data and the incidence of adverse drug reactions/events were recorded. This study evaluated the safety of TCM formula granules, aiming to provide a reference for the clinically use. A total of 20 547 patients were included in this study. Four adverse events were recorded, including 3 adverse drug reactions with an adverse drug reaction rate of 0.015%, all of which occurred in the digestive system. There was no serious adverse event, and no factors related to adverse drug reactions/events were identified. The incidence of adverse drug reactions/events associated with China Resources Sanjiu Medical & Pharmaceutical Co., Ltd. TCM formula granules was rare, which proved their safety in clinical use. A comprehensive data mining and objective analysis was carried out for the medicines with high frequency in TCM formula granules, the commonly used medicine pairs and combinations, and departmental medication. The drug use characteristics, prescription rules, and departmental use of TCM formula granules were summarized, which can shed light on the prescription compatibility and clinical application.

Comprehensive online two-dimensional liquid chromatography coupled to hybrid linear ion trap Orbitrap mass spectrometry with optimized dilution and modulation for analysis of Huangqi Guizhi Wuwu decoction.

Huangqi Guizhi Wuwu decoction (HGWD), as a classical formula, has been used for thousands of years in China. In this work, a comprehensive strategy was proposed for characterizing the chemical profile of HGWD based on online two-dimensional hydrophilic interaction and reversed-phase liquid chromatography coupled with hybrid linear ion trap-Orbitrap mass spectrometry (online HILIC × RP-ESI/HRMS/MSn). The compounds in HGWD were first separated by the combined use of an XBridge amide column (150 × 4.6 mm, 3.5 µm) and Accucore C18 column (50 mm × 4.6 mm, 2.6 µm). Modulation with assistant technology, including trap columns and online dilution, was optimized and developed to decrease potential analyte loss and improve the resolution of the system. Subsequently, the accurate mass was determined by high-resolution Orbitrap and MSn fragment data by a hybrid linear ion trap (LTQ). In total, 170 chemical constituents were unambiguously identified or tentatively characterized in both positive and negative ion modes. Our study demonstrated that the proposed online HILIC × RP system coupled to the LTQ-Orbitrap MS platform is an efficient analytical technique for characterizing the chemical profile of multicomponent systems.

Transcriptomics reveals the molecular regulation of Chinese medicine formula on improving bone quality in broiler.

Skeletal disorder is of concern to the poultry industry as it affects animal welfare and production performance. Traditional Chinese medicine could improve bone quality and reduce the incidence of bone disease, but the molecular regulation of Chinese medicine formula (CMF) on improving bone quality in broilers is still unclear. This study was performed to research the effects of CMF on skeletal performance of Cobb broilers and reveal the molecular regulation. A total of 120 one-day-old Cobb broilers were randomly allocated into 4 equal groups of 30 chickens, with 5 replicates and 6 chickens in each replicate. The control (CON) group was fed a diet without CMF, while the CMF1, CMF2, and CMF3 groups were supplemented with different CMF at 6,000 mg/kg diet, respectively. The broilers were raised to 60 d of age, then bone tissues were collected for biomechanical properties, micro-CT detection and transcriptomic sequencing analysis. The results showed that CMF3 improved the biomechanical properties of broiler tibia, via increasing the elastic modulus (P < 0.05), yield strength (P > 0.05), maximum stress (P < 0.05) and fracture stress (P < 0.05) of the tibia. Micro-CT analysis indicated that CMF3 increased the bone mineral density (BMD), bone volume/total volume (BV/TV), bone surface density (BS/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and decreased the trabecular separation (Tb.Sp) of femur cancellous bone (P < 0.05). RNA-seq analysis revealed 2,177 differentially expressed genes (DEGs) (|log2FoldChange| ≥ 1, FDR < 0.05) between the CMF3 group and CON group. Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) analysis showed 13 pathways mostly associated with bone growth and development and bone metabolism, and we identified 39 bone-related DEGs. This study suggests that CMF3 could improve bone strength and bone microstructure of broilers, and showed a positive effect on bone performance. Our research could provide a theoretical reference for the development of pollution-free feed additives to improve the skeletal performance of broilers, which could help promote healthy farming of chickens.

Integrating network pharmacology and experimental validation to decipher the mechanism of the Chinese herbal prescription modified Shen-Yan-Fang-Shuai formula in treating diabetic nephropathy.

CONTEXT: Diabetic nephropathy (DN) is the main cause of end-stage renal disease. Modified Shen-Yan-Fang-Shuai formula (M-SYFSF) has excellent clinical efficacy in treating diabetic kidney disease. However, the potential mechanism of M-SYFSF remains unknown. OBJECTIVE: To investigate the mechanism of M-SYFSF against DN by network pharmacological analysis and biological experiments. MATERIALS AND METHODS: Utilizing a web-based pharmacology database, the potential mechanisms of M-SYFSF against DN were identified. In vivo experiments, male SD rats were injected with streptozotocin (50 mg/kg) and got uninephrectomy to construct a model of DN. M-SYFSF (11.34 g/kg/d) was gavaged once per day for 12 weeks after model establishment. In vitro experiments, human proximal tubular cells (HK-2) were performed with advanced glycation end-products (AGEs) (100 µg/mL), then intervened with M-SYFSF freeze-dried powder. Pathological staining, WB, IHC, ELISA were conducted to explore the mechanism of M-SYFSF against DN. RESULTS: Network pharmacological analysis showed that MAPK pathway was the potential pathway. Results showed that compared with the Model group, M-SYFSF significantly reduced 24h urine albumin, UACR, and serum creatinine levels (54.90 ± 26.67 vs. 111.78 ± 4.28, 8.87 ± 1.69 vs. 53.94 ± 16.01, 11.56 ± 1.70 vs. 118.70 ± 49.57, respectively), and improved renal pathological changes. Furthermore, the intervention of M-SYFSF reduced the expression of pro-inflammatory cytokines and inhibited the activation of MAPK pathway in AGEs-treated HK-2 cells. DISCUSSION AND CONCLUSION: M-SYFSF is likely to reduce inflammation in DN by inhibiting the MAPK pathway. It provides a theoretical basis for the clinical application of M-SYFSF in the treatment of DN.

The mechanisms of Huangqi Guizhi Wuwu decoction in treating ischaemic stroke based on network pharmacology and experiment verification.

CONTEXT: Huangqi Guizhi Wuwu Decoction (HGWD) is effective in treating ischaemic stroke (IS). However, its mechanism of action is still unclear. OBJECTIVE: Network pharmacology integrated with in vivo experiments were used to clarify the underlying mechanisms of HGWD for treating IS. MATERIALS AND METHODS: TCMSP, GeneCards, OMIM and STRING were used to retrieve and construct visual protein interaction networks for the key targets. The AutoDock tool was used for molecular docking between key targets and active compounds. The neuroprotective effect of HGWD were verified in a middle cerebral artery occlusion (MCAO) model rat. The Sprague-Dawley (SD) rats were divided into sham, model, low-dose (5 g/kg, i.g.), high-dose (20 g/kg, i.g.), and nimodipine (20 mg/kg, i.g.) groups once daily for 7 days. The neurological scores, brain infarct volumes, lipid peroxidation, inflammatory cytokines, Nissl bodies, apoptotic neurons, and signalling pathways were all investigated and evaluated in vivo. RESULTS: Network pharmacology identified 117 HGWD targets related to IS and 36 candidate compounds. GO and KEGG analyses showed that HGWD anti-IS effects were mainly associated with PI3K-Akt and HIF-1 signalling pathways. HGWD effectively reduced the cerebral infarct volumes (19.19%), the number of apoptotic neurons (16.78%), and the release of inflammatory cytokines, etc. in MCAO rats. Furthermore, HGWD decreased the levels of HIF-1A, VEGFA, Bax, cleaved caspase-3, p-MAPK1, and p-c-Jun while increasing the expression of p-PI3K, p-AKT1, and Bcl-2. DISCUSSION AND CONCLUSION: This study initially elucidated the mechanism of HGWD anti-IS, which contributed to the further promotion and secondary development of HGWD in clinical practice.

The traditional Chinese medicines treat chronic heart failure and their main bioactive constituents and mechanisms.

Chronic heart failure (CHF) is a severe public health problem with increasing morbidity and mortality, any treatment targeting a single session is insufficient to tackle this. CHF is characterized by reduced cardiac output resulting from neurohumoral dysregulation and cardiac remodeling, which might be related to oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, autophagy, mitochondrial function, and angiogenesis. These molecular mechanisms interact with each other through crosstalk. Historically, Chinese medicinal herbs have been widely applied in the treatment of CHF, and therapeutic effects of Chinese medicinal herbs and their ingredients have been scientifically confirmed over the past decades. Traditional Chinese medicine (TCM) with multiple components can confront the different pathogenesis of CHF through multiple targets. This review analyzes commonly used TCM patent drugs and TCM decoctions that are applicable to different stages of CHF based on clinical trials. Diverse bioactive ingredients in Chinese medicinal herbs have been found to treat CHF via multiple molecular mechanisms. This review comprehensively covers the key works on the effects and underlying mechanisms of TCM, herbal ingredients and synergistic effects of constituent compatibility in treating CHF, providing additional ideas to address this threat.