Research progress in chemical constituent and pharmacological activity of Punica granatum L / 中国药科大学学报

@#Punica granatum L.(pomegranate) is a medicinal plant belonging to the genus Punica Linn..The peel, seed, flower, leaf and root of P.granatum is widely used as traditional medicine in China.Phytochemical studies showed that the major chemical constituents of P.granatum were tannins, flavonoids, terpenes, alkaloids, phenolic acids, anthocyanins, fatty acids, etc.Biological studies on extracts and active ingredients of P.granatum show some bioactivities, such as antioxidant, hypoglycemic, anti-inflammatory, anti-tumor, antibacterial activities.Herein, the chemical constituents and pharmacological effects of different parts of pomegranate were reviewed, providing a theoretical basis for the further research and utilization of pomegranate.

Therapeutic effects of the extract of Sancao Formula, a Chinese herbal compound, on imiquimod-induced psoriasis via cysteine-rich protein 61 / 中西医结合学报

OBJECTIVE@#Psoriasis is a common chronic inflammatory skin disease that is prone to recurrence, and the proinflammatory factor, cysteine-rich protein 61 (Cyr61), is important in its pathophysiology. Long-term clinical practice has shown that Sancao Formula (SC), a Chinese herbal compound, is effective in the treatment of psoriasis, but the precise mechanism remains unknown. In this study, we investigate the mechanism by which SC extract alleviates imiquimod (IMQ)-induced psoriasis.@*METHODS@#The expression of Cyr61 in psoriatic lesions and normal healthy skin was detected using immunohistochemical analysis to investigate the biological role of Cyr61 in models of psoriatic inflammation. A psoriatic mouse model was established by topical application of IMQ, and the effect of topical application of SC extract was evaluated using the psoriasis area and severity index (PASI) score, hematoxylin-eosin staining, and histopathological features of the skin. Next, a HaCaT cell inflammation model was established using interferon-γ (IFN-γ), and the effect of SC extract on the mRNA and protein levels of Cyr61 and intercellular cell adhesion molecule-1 (ICAM-1) was confirmed using Western blot and quantitative real-time polymerase chain reaction analyses.@*RESULTS@#Immunohistochemical staining showed that the expression of Cyr61 in psoriatic lesions was higher than that in normal skin samples (78.26% vs 41.18%, P < 0.05), and the number of Cyr61-positive cells in psoriatic lesions was also significantly higher than in normal skin (18.66 ± 2.51 vs 4.33 ± 1.52, P < 0.05). Treatment in mice with IMQ-induced psoriasis showed that SC extract could significantly improve the inflammatory phenotype, PASI score (10.875 ± 0.744 vs 3.875 ± 0.582, P < 0.05), and pathological features compared with those in IMQ model group; SC treatment was also associated with decreased levels of Cyr61 and ICAM-1. In the IFN-γ-induced inflammatory cell model, the mRNA and protein levels of Cyr61 and ICAM-1 were upregulated, while the SC extract downregulated the levels of Cyr61 and ICAM-1.@*CONCLUSION@#The results provide a theoretical basis for the involvement of Cyr61 in the pathogenesis of psoriasis, and suggest that SC should be used to target Cyr61 for the prevention of psoriasis recurrence.

Study on the mechanism of active components of Liupao tea on 3CLpro based on HPLC-DAD fingerprint and molecular docking technique.

Liupao tea, a drink homologous to medicine and food. It can treat dysentery, relieve heat, remove dampness, and regulate the intestines and stomach. The objective of this study is to explore the material basis and mechanism of Liupao tea intervention in COVID-19 and to provide a new prevention and treatment programme for COVID-19. We used high performance liquid chromatography to analyze the extract of Liupao tea and establish its fingerprint. The main index components of the fingerprint were determined using SARS-COV-2 3-chymotrypsin-like protease (3CLpro ), and an in vitro drug screening model based on fluorescence resonance energy transfer was used to evaluate its inhibitory activity in vitro. The fingerprint results showed that the alcohol extract of Liupao tea contained gallic acid, epigallocatechin gallate (EGCG), caffeine, epicatechin gallate, rutin, and ellagic acid. The molecular docking binding energies of the six index components of SARS-CoV-2 3Clpro were all less than -5.0 kJ/mol and showed strong binding affinity. The results of in vitro activity showed that the IC50 of EGCG was 8.84 µmol/L, which could inhibit SARS-CoV-2 3Clpro to a certain extent. This study unleashed that EGCG has a certain inhibitory effect on SARS-CoV-2 3CLpro , and Liupao tea has a certain significance as a tea drink for the prevention of COVID-19. PRACTICAL APPLICATIONS: The objective of this study was to explore the material basis and mechanism of Liupao tea intervention in COVID-19 and to provide a new prevention and treatment programme for COVID-19. The molecular docking binding energies of the six index components of Liupao tea with SARS-CoV-2 3CLpro were all less than -5.0 kJ/mol, among them, the enzyme activity experiment shows that EGCG has a certain inhibitory effect on SARS-CoV-2 3CLpro , it can be used as a potential SARS-CoV-2 3CLpro inhibitor. We predicted that the understandings gained in the current research may evidence that Liupao tea has a certain significance as a tea drink for the prevention of COVID-19.

Effect of Fluid Sheer Stress on Atherosclerosis and Progress of Research on Treatment of Sheer Stress Injury with Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Cells in the arterial wall are constantly subjected to the shear stress generated by the blood flow. Shear stress plays a pivotal role in the formation of atherosclerosis. The endothelial cells located between the blood and the vessel wall have a unique response to the shear stress of the blood flow， which can convert mechanical stimulation into intracellular signals， thereby affecting the pathological process of atherosclerosis. Endothelial function is not only regulated by hormones， growth factors and other biochemical substances， but also affected by mechanical forces such as blood flow shear stress. Physiologically， shear stress can play an anti-atherosclerotic role in maintaining the homeostasis of endothelial cells. Pathological shear stress will lead to endothelial dysfunction and promote the progression of atherosclerosis. Under the mediation of different shear stress， the endothelial function can be regulated through epigenetic pathways or mechanically sensitive cation channels. Therefore， it is necessary to understand how various signal transduction pathways are affected by pathological shear stress， so as to cause endothelial dysfunction and atherosclerosis. Traditional Chinese medicine（TCM） has been increasingly recognized for its curative effect in treating atherosclerosis， with the advantages of few side effects， multiple targets and multiple mechanisms. In recent years， the understanding of the anti-atherosclerosis mechanism of TCM mediated by shear stress has gradually deepened. This review will take endothelial function as the breakthrough point， systematically sort out the influence of shear stress on the pathological process of atherosclerosis and the related molecular mechanisms. Meanwhile， it is the first time to summarize the latest research progress of Chinese medicine against shear stress damage by sorting out the existing literature. This article mainly clarify the relationship between shear stress， endothelial function， atherosclerosis and TCM， in order to provide a theoretical basis for the clinical treatment and pathological mechanism of atherosclerosis.

Advances in Research on Pharmacological Effect of Astragaloside Ⅳ on Cardiovascular and Cerebrovascular Diseases / 中国实验方剂学杂志

Astragalus membranaceus has the effect of tonifying Qi and solid surface， diuretic support poison， discharging pus and astringent sores to produce muscle. It is not only used for syndromes such as deficiency of lung and temper， deficiency of spleen and diarrhea， but also for stroke， chest obstruction and other diseases. Due to the complex chemical composition and diverse pharmacological effect of Astragalus membranaceus， and the main role in invigorating qi and activating blood circulation has not been clarified. Astragaloside Ⅳ is one of its main active ingredients. In recent years， more and more studies on Astragaloside Ⅳ have been conducted at home and abroad. It has been reported that it has the medicinal value of enhancing immune function， strengthening heart and lowerin blood glucose， diuresis， anti-aging and anti-fatigue， et al， and has extensive pharmacological activity. Among them， the role of cardiovascular and cerebrovascular diseases in particular has attracted increasing attention. Cardiovascular and cerebrovascular diseases are ischemic or hemorrhagic diseases occurring in the heart， brain and systemic tissues due to blood viscosity， atherosclerosis， hypertension， hyperlipidemia， etc.， including cardiovascular and cerebrovascular diseases. Such diseases are a serious threat to mankind and are the leading cause of death worldwide. At present， western medicine is the main treatment， with many adverse reactions and poor long-term prognosis. TCM believes that the imbalance of qi and blood is the basic pathogenesis of this kind of disease. Qi deficiency and blood stasis are more common.At present， Astragaloside Ⅳ in the treatment of cardiovascular and cerebrovascular diseases in a number of studies， and achieved some results， but this review in recent years， Astragaloside Ⅳ in the treatment of cardiovascular and cerebrovascular diseases play the pharmacological activity， in order to explore whether Astragaloside Ⅳ is the main role of astragalus qi to find a theoretical basis for material basis， but also for the innovation of traditional Chinese medicine drug research and development of theoretical basis and practical guidance.

Identification of Hypertension Subgroups through Topological Analysis of Symptom-Based Patient Similarity / 中国结合医学杂志

OBJECTIVE@#To obtain the subtypes of the clinical hypertension population based on symptoms and to explore the relationship between hypertension and comorbidities.@*METHODS@#The data set was collected from the Chinese medicine (CM) electronic medical records of 33,458 hypertension inpatients in the Affiliated Hospital of Shandong University of Traditional Chinese Medicine between July 2014 and May 2017. Then, a hypertension disease comorbidity network (HDCN) was built to investigate the complicated associations between hypertension and their comorbidities. Moreover, a hypertension patient similarity network (HPSN) was constructed with patients' shared symptoms, and 7 main hypertension patient subgroups were identified from HPSN with a community detection method to exhibit the characteristics of clinical phenotypes and molecular mechanisms. In addition, the significant symptoms, diseases, CM syndromes and pathways of each main patient subgroup were obtained by enrichment analysis.@*RESULTS@#The significant symptoms and diseases of these patient subgroups were associated with different damaged target organs of hypertension. Additionally, the specific phenotypic features (symptoms, diseases, and CM syndromes) were consistent with specific molecular features (pathways) in the same patient subgroup.@*CONCLUSION@#The utility and comprehensiveness of disease classification based on community detection of patient networks using shared CM symptom phenotypes showed the importance of hypertension patient subgroups.

Non-targeted metabolomics study and biomarker screening of prehypertensive liver-fire hyperactivity syndrome based on UPLC-Q-Exactive MS technology / 中国中药杂志

In this study, patients with prehypertensive liver-fire hyperactivity syndrome(LFHS) were selected as the research objects. The plasma samples of healthy volunteers and patients with prehypertensive LFHS were analyzed by non-targeted metabolomics based on UPLC-Q-Exactive MS. The differential biomarkers and metabolic pathways were screened out by multivariate statistics and metabolic pathway analysis, which revealed the characteristics of metabolic patterns of the syndrome. Thirty-three potential biomarkers such as androsterone and lysophosphatidylcholine and 16 related metabolic pathways such as steroid hormone metabolism and lipid metabolism were identified, and a partial least squares-discriminant analysis(PLS-DA) model of traditional Chinese medicine(TCM) syndromes was preliminarily constructed: Y =-0.070X_(13)-0.006X_8+ 0.040X_5-0.152X_1+0.131X_(10)+0.036X_(11)+0.043X_(23)+0.076X_(16)+0.132X_(20)+0.081X_(19)-0.101X_(31)+0.082X_(15)-0.038X_9+0.079X_(24). The predictive value of the model was 88.1%, and the explanatory power was 88.4%. In this study, the characteristic metabolic pattern of the prehypertensive LFHS was distinguished and revealed by metabolomics. The constructed PLS-DA model is expected to provide an objective basis for the identification of TCM syndromes in prehypertension, and inspiration for exploring the biological basis of TCM syndromes at small-molecular and overall levels.

Research status of berberine in treatment of kidney disease / 解放军医学杂志

Kidney, as an important metabolic organ of humans, has many functions such as excreting metabolic waste, maintaining electrolyte and acid-base balance, controlling blood pressure and secreting hormones. Kidney disease is a common disease which endangers human health and has become a global public health problem. The rapid increase in the number of patients with kidney disease and the continuously increased treatment costs have brought a heavy burden to society and families. Western medicine is developing rapidly in the treatment of kidney diseases and has a definite effect, but improper using of Western medicine may easily aggravate kidney damage. In recent years, Chinese medicine and monomers have been widely recognized and applied in the treatment of kidney disease due to the advantages of multiple targets and pathways. Berberine (BBR) is a quinoline alkaloid extracted mainly from the Chinese medicine Coptis Chinesis Franch, and has a variety of pharmacological effects and excellent renal protection. BBR has the therapeutic characteristics of multi-target and multi-channel, which make it have great potential in the treatment of renal diseases. The pharmacological mechanism of BBR, including anti-oxidative stress, anti-inflammatory, lowering blood sugar, blood pressure and blood lipid, anti-tumor, etc. and combined with the clinical application of BBR in diabetic nephropathy, acute kidney injury and renal cancer, etc. has been summarized in present paper, so as to provide new ideas for the treatment of kidney disease and lay the foundation for the integration of Chinese and Western medicine.

Effect of electroacupuncture on SIRT1/NF-κB signaling pathway in adipose tissue of obese rats / 中国针灸

OBJECTIVE@#To explore the effect of electroacupuncture (EA) on insulin sensitivity, adipose tissue inflammatory reaction and silent information regulation factor 1(SIRT1)/nuclear factor kappa B (NF-κB) signaling pathway in obese rats.@*METHODS@#A total of 100 SPF-grade Wistar male rats were collected. Thirteen rats of them were selected randomly as the normal group and fed with common forage, and the rest rats were fed with high-fat forage. Eight weeks later, 39 rats that met the obesity criteria were randomized into a model group, an EA group and a sham-EA group, 13 rats in each one. In each group, 3 rats were collected randomly and the hyperinsulinemic-euglycemic clamp was exerted to record glucose infusion rate (GIR) so as to determine insulin sensitivity. Afterwards, in the EA group, EA was applied to "Zusanli" (ST 36), "Fenglong" (ST 40), "Zhongwan" (CV 12) and "Guanyuan" (CV 4), stimulated with continuous wave, 2 Hz in frequency, 1 mA in current intensity, for 15 min. The treatment was given once every 2 days, 3 times a week, for 8 weeks totally. In the sham-EA group, the needles were inserted shallowly at the sites, 5 mm lateral to each of the acupoints stimulated in the EA group, and the electrodes were attached to the needle handles, but without electric stimulation exerted. The rest management was the same as the EA group. Before and after intervention, the body mass and the insulin sensitivity were measured. After intervention, the white adipose tissue was collected from the kidney in the rats. Western blot was adopted to detect the relative protein expressions of SIRT1, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and acetylated NF-κB (Ac-NFκB). The real-time fluorescence quantitative PCR was used to detect the mRNA expressions of SIRT1, IL-6 and TNF-α. The immunofluorescence double labeling method was applied to detect the co-expression of SIRT1 and Ac-NFκB in adipose tissue.@*RESULTS@#After fed with high-fat forage for 8 weeks, the body mass was significantly increased and GIR decreased in the rats of the model group as compared with the normal group (0.05). Compared with the normal group, in the model group, the protein and mRNA expressions of SIRT1 in adipose tissue were decreased, and the protein expression of Ac-NFκB increased, the protein and mRNA expressions of IL-6 and TNF-α increased (0.05). The results of immunofluorescence double labeling showed that SIRT1 and Ac-NFκB were co-expressed in adipose tissue.@*CONCLUSION@#Electroacupuncture significantly reduces the body mass, inflammatory reaction conditions of adipose tissue and improves insulin sensitivity in obese rats. Regarding the potential mechanism, after the activation of SIRT1/NF-κB signaling pathway by electroacupuncture, and down-regulates the transcription of downstream inflammatory factors.

Study on the Intervention Effects of Pinggan Prescription () on Spontaneously Hypertensive Rats Based on Metabonomic and Pharmacodynamic Methods / 中国结合医学杂志

OBJECTIVE@#To investigate the effects of Pinggan Prescription (, PGP) on hypertension by the associated methods of metabonomic and pharmacodynamic.@*METHODS@#A total of 32 male spontaneously hypertensive rats (SHRs) were randomly divided into two groups by using the random number table method: a treatment group (n=18) and a model group (n=14). The Wistar rats (n=14) were used as the normal group. Different prescription were used to intervene three groups: the treatment group in which PGP extract was administered orally at a dose of 18.336 g/kg (PGP/body weight), and the model group in which physiological saline was administered at the equivalent dose. The same treatment was applied to the normal group as the model group. The blood pressure was measured by tail-cuff method, and pharmacodynamic indexes including cyclic adenosine monophosphate (cAMP) and angiotensin II (Ang II) were tested by enzyme-linked immunosorbent assay. The plasma samples from three groups were detected by gas chromatography-mass spectrometry (GC-MS).@*RESULTS@#Compared with the model group, blood pressure of treatment group was obviously reduced after continuous curing with PGP (P<0.01). The pharmacodynamic results illustrated that the content of Ang II increased with the raised blood pressure and the cAMP expressed the converse trend. After curing with PGP, the content of Ang II decreased, the difference between model group and treatment group was significant (P<0.01), and the cAMP expressed the converse trend. Five potential biomarkers were identified, including arachidonic acid, hexadecanoic acid, elaidic acid, octadecanedioic acid and 9,12-octadecadienoic acid. These metabolites had shown significantly changes as followed: arachidonic acid, hexadecanoic acid and elaidic acid were significantly higher and octadecanedioic acid and 9,12-octadecadienoic acid were lowered in the model group than those in the normal group. After the treatment of PGP, the metabolites had the trends of returning to normal along with the reduced blood pressure.@*CONCLUSIONS@#PGP intervention for hypertension played a major role in the metabolism of arachidonic acid and linoleic acid. Metabonomic with pharmacodynamic methods could be potentially powerful tools to investigate the mechanism of Chinese medicine.

Discussion on Feasibility of Establishing Macro-micro Syndrome Differentiation System of Traditional Chinese Medicine Based on Scale and Omics / 中国实验方剂学杂志

Syndrome is the basis and essence of the treatment according to syndrome differentiation theory in traditional Chinese medicine(TCM), which comprehensively summarizes the overall reaction state of the organism under the influence of internal and external factors, and has subjective and qualitative characteristics. But the test indexes of modern medicine for diagnosing diseases have the objective and quantitative characteristics. The subjective and qualitative TCM syndromes can be quantitatively treated and combined with the objective and quantitative modern test indexes, this method provides a new idea for the modernization of syndrome differentiation system of TCM. In this paper, the prehypertension with syndrome of upper hyperactivity of liver Yang was taken as an example, a syndrome discriminant model was set up by using the technique of scale and metabonomics, and the feasibility of establishing macro-micro syndrome differentiation system of TCM was also discussed. This paper has important guiding significance for realizing the objectification of diagnosis of TCM syndrome and the standardization of the treatment according to syndrome differentiation theory of TCM.

Lipidomics study on intervention by Uncaria on hepatic metabolic disorder in spontaneously hypertensive rats / 药学学报

In this paper, the lipidomics was used to analyze the changes to address how Uncaria interrupts lipid metabolism in the liver of spontaneously hypertensive rats, and to explore the mechanism of action of Uncaria. All the experiments were approved by the animal protection and use committee of Shandong University of Traditional Chinese Medicine. UHPLC-Q Extractive orbitrap high-resolution mass spectrometry was used to collect lipid metabolite information of the rat livers. Through pattern recognition, matters with noticeable differences were recognized. Mass spectrum and data base searching helped to identify the potential biomarkers. Pattern recognition results indicated that the rats from control versus SHR group showed clear differences. Compared with the rats from the control group, there are decreases in sphosphatidylcholine, phosphatidic acid, diacylglycerol and sphingomyelin in rats from the SHR group, however lysophosphatidylcholine, triglyceride, linoleic acid, arachidonic acid and ceramide are increased. Uncaria could regulate the disorder of lipid metabolism by interfering with glycerophospholipid, sphingolipid, linoleic acid, and arachidonic acid metabolic pathways. This study provided the mechanistic understanding of the impact of Uncaria on lipid metabolism and revealed the lipid metabolism pathways affected to offer the explanation for the complex mechanism of action.

Study on influence of different storage environments and packaging materials on quality of Citri Reticulatae Pericarpium / 中国中药杂志

Traditional Chinese herbs are readily contaminated by mold that produced mycotoxins which are closly related to the herbs' external factors and external environments during the storage process. In this study, Citri Reticulatae Pericarpium was used as example, and the characteristics of traits, water content, active components (naringin, hesperidin, sinensetin, naringin, tangeretin) and the accumulation of aflatoxins (AFs) were selected as the evaluation indexes. Citri Reticulatae Pericarpium was stored under different environments and packaging materials for 12 months, and then the quality changes and mildew of Citri Reticulatae Pericarpium were examined. The results showed that the color of Citri Reticulatae Pericarpium was deepened after storage, but without mildew phenomenon. Besides, the sample storage in kraft paper and woven bags had varying degrees of moth phenomenon after 12 months storage, and the water content exceeded the limit of Chinese Pharmacopoeia. In addition, the contents of the five active constituents obviously decreased, especially for hesperidin, which did not meet the pharmacopoeia standard after storage. AFs were not detected in any of the tested samples. According to the results, we conclude that low temperature and humidity environment is more suitable for the storage of Citri Reticulatae Pericarpium, and that packaging materials should be further investigated. This study is of great significance for preventing the mold to contaminate the traditional Chinese medicine and ensuring the quality, effectiveness and safety of TCMs.

Identification and quality evaluation of Tripterygium wilfordii / 中国中药杂志

With the extensive clinical application of Tripterygium wilfordii, there are many counterfeit products on the market. Traditional technology can not effectively identify the authenticity of the traditional Chinese medicine. Therefore, a strategy of accurate identification and quality evaluation of Tripterygium based on DNA barcode and chemical fingerprint spectrum was established. Based on DNA barcode technology, HMMer annotation method of hidden Markov model and K2P model were used to analyze genetic distance.BLAST1, nearest distance and phylogenetic tree (NJ-tree) methods were used to assess the identification efficiency of the ITS2 barcode. The fingerprint of 27 T. wilfordii was established by UPLC-PDA method, and the similarity of the fingerprint of different sources was evaluated. The main components of T. wilfordii were determined by LC-MS/MS. The results revealed that the intraspecific genetic distances of T. wilfordii were lower than the interspecific genetic distances between T. wilfordii and its adulterants. The results of similarity search showed that ITS2 sequence was used to identify T. wilfordii and its adulterants. The clustering of T. wilfordii and its adulterants was clear in the tree of NJ cluster, and 12 of 27 samples were identified as true T. wilfordii.The chemical fingerprint spectrum research indicates that the feature one region can distinguish the false product of tripterygium glycosides more intuitively. The cluster analysis of HCA-thermal map showed that the contents of six active components of T. wilfordii from different habitats were significantly different, which could be used to evaluate the quality of T. wilfordii. This paper is of guiding significance for the accurate identification and quality evaluation of Tripterygium medicinal plants.

[The present situation and countermeasures of Uighur medicine compound].

Uighur medicine compound, which created and used by Uighur nationality, is under the guidance of the Uighur medical theory system of herbal formula and dialectical use of minority nationality conventional medicines. In recent years, Uighur medicine attracted more and more attention of people which have used and were using it. Combining the history of Uighur medicine, this article summarizes the Uighur resources, medicinal materials, drugs preparation, ancient documents, and the establishment of the clinical evaluation system and so on, and then analyzes the status quo and the existing problems in Uighur medicine compound research and industry. On this basis, we put forward countermeasures and suggestions for the development of Uighur medicine.

Clinical Characteristics of Patients with Drug-induced Liver Injury.

BACKGROUND: Drug is an important cause of liver injury and accounts for up to 40% of instances of fulminant hepatic failure. Drug-induced liver injury (DILI) is increasing while the diagnosis becomes more difficult. Though many drugs may cause DILI, Chinese herbal medicines have recently emerged as a major cause due to their extensive use in China. We aimed to provide drug safety information to patients and health carers by analyzing the clinical and pathological characteristics of the DILI and the associated drug types. METHODS: A retrospective analysis was conducted in 287 patients diagnosed with DILI enrolled in our hospital from January 2011 to December 2015. The categories of causative drugs, clinical and pathological characteristics were reviewed. RESULTS: Western medicines ranked as the top cause of DILI, accounting for 163 out of the 287 DILI patients (56.79%) in our study. Among the Western medicine, antituberculosis drugs were the highest cause (18.47%, 53 patients) of DILI.   Antibiotics (18 patients, 6.27%) and antithyroid (18 patients, 6.27%) drugs also ranked among the major causes of DILI. Chinese herbal medicines are another major cause of DILI, accounting for 36.59% of cases (105 patients). Most of the causative Chinese herbal medicines were those used to treat osteopathy, arthropathy, dermatosis, gastropathy, leukotrichia, alopecia, and gynecologic diseases. Hepatocellular hepatitis was prevalent in DILI, regardless of Chinese herbal medicine or Western medicine-induced DILI. CONCLUSIONS: Risks and the rational use of medicines should be made clear to reduce the occurrence of DILI. For patients with liver injury of unknown origin, liver tissue pathological examination is recommended for further diagnosis.

The multiple constituents study of Danhuang Quyu Capsule based on UPLC-Q-Orbitrap HRMS / 中草药

Objective In order to clarify the chemical constituents in traditional Chinese medicine (TCM) compound preparation of Danhuang Quyu Capsule and establish an efficient analysis method for the identification of the complex components in TCM accurately and rapidly. Methods An ultra-high performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry (UPLC-Q-Orbitrap HRMS) was used to perform an identification analysis of the chemical constituent in the Danhuang Quyu Capsule.This objective was achieved mainly depending on the information of the accurate mass and the multistage fragment ions obtained by UPLC-Q-Orbitrap, comparing the relative retention time and the massspectrometricdata of the standardsubstance and consulting the reference literature. Results Fifty nine compounds were identified in this study, including the flavones, phthalides, anthraquinones, alkaloids, monoterpene glycosides, organic acids, and other categories. Conclusion This study can identify various chemical constituents of Danhuang Quyu Capsule systematically, accurately and rapidly. What's more, the scientific theory basis will be provided for thepharmacodyamic material basis and the quality control of this drug at the same time. Key words: Danhuang Quyu Capsule; UPLC-Q-Orbitrap HRMS; flavones; phthalides; monoterpene glycosides

Clinical Characteristics of Patients with Drug-induced Liver Injury / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Drug is an important cause of liver injury and accounts for up to 40% of instances of fulminant hepatic failure. Drug-induced liver injury (DILI) is increasing while the diagnosis becomes more difficult. Though many drugs may cause DILI, Chinese herbal medicines have recently emerged as a major cause due to their extensive use in China. We aimed to provide drug safety information to patients and health carers by analyzing the clinical and pathological characteristics of the DILI and the associated drug types.</p><p><b>METHODS</b>A retrospective analysis was conducted in 287 patients diagnosed with DILI enrolled in our hospital from January 2011 to December 2015. The categories of causative drugs, clinical and pathological characteristics were reviewed.</p><p><b>RESULTS</b>Western medicines ranked as the top cause of DILI, accounting for 163 out of the 287 DILI patients (56.79%) in our study. Among the Western medicine, antituberculosis drugs were the highest cause (18.47%, 53 patients) of DILI.   Antibiotics (18 patients, 6.27%) and antithyroid (18 patients, 6.27%) drugs also ranked among the major causes of DILI. Chinese herbal medicines are another major cause of DILI, accounting for 36.59% of cases (105 patients). Most of the causative Chinese herbal medicines were those used to treat osteopathy, arthropathy, dermatosis, gastropathy, leukotrichia, alopecia, and gynecologic diseases. Hepatocellular hepatitis was prevalent in DILI, regardless of Chinese herbal medicine or Western medicine-induced DILI.</p><p><b>CONCLUSIONS</b>Risks and the rational use of medicines should be made clear to reduce the occurrence of DILI. For patients with liver injury of unknown origin, liver tissue pathological examination is recommended for further diagnosis.</p>

L-citrulline for protection of endothelial function from ADMA-induced injury in porcine coronary artery.

Endogenous nitric oxide synthase (eNOS) inhibitor asymmetric dimethylarginine (ADMA) is a cardiovascular risk factor. We tested the hypothesis that L-citrulline may ameliorate the endothelial function altered by ADMA in porcine coronary artery (PCA). Myograph study for vasorelaxation, electrochemical measurement for NO, RT-PCR, and Western blot analysis for expression of eNOS, argininosuccinate synthetase (ASS), and p-eNOS(ser1177) were performed. cGMP was determined by enzyme immunoassay. Superoxide anion (O2.(-)) production was detected by the lucigenin-enhanced chemiluminescence method. Compare with controls (96.03% ± 6.2%), the maximal relaxation induced by bradykinin was significantly attenuated (61.55% ± 4.8%, p<0.01), and significantly restored by L-citrulline (82.67 ± 6.4%, p<0.05) after 24 hours of ADMA exposure. Expression of eNOS, p-eNOS(ser1177), and ASS in PCA significantly increased after L-citrulline incubation. L-citrulline also markedly restored the NO production, and cGMP level which was reduced by ADMA. The increased O2.(-) production by ADMA was also inhibited by L-citrulline. L-citrulline restores the endothelial function in preparations treated with ADMA by preservation of NO production and suppression of O2.(-) generation. Preservation of NO is attributed to the upregulation of eNOS expression along with activation of p-eNOS(ser1177). L-citrulline improves endothelium-dependent vasodilation through NO/ cGMP pathway.

Formula Optimization in Renshen Jianxin Capsule Based on Uniform Design and Anti-myocardial Ischemia Effect / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To realize quadratic formula optimization of Renshen Jianxin Capsule (RJC) by screening Chinese herbs with major anti-myocardial ischemia effect in RJC and optimize their optimal dosages.</p><p><b>METHODS</b>By following "uniform design-pharmacodynamic experiment-mathematical modeling-formula optimization", authors employed U10(10(8)) uniform design in the experiment. Eight Chinese herbs contained in RJC were taken as observatory factors. Electrocardiograph (ECG) changes of myocardial ischemia induced by isoproterenol were taken as pharmacodynamic indices. The mathematical model between herbal factors and pharmacodynamic indices was established using stepwise regression analysis to screen Chinese herbs with major anti-myocardial ischemia effect. Their optimal dosages were optimized using the grid algorithm.</p><p><b>RESULTS</b>The regression equation was y =1. 7889 -0. 3247 Ginseng xSalvia Miltiorrhiza -0. 0663 Astragalus membranaceus xOriental Waterplantain tuber. Forecasting factors included were Ginseng, Salvia Miltiorrhiza, Astragalus membranaceus, and Oriental Waterplantain tuber. The optimal formula dosage calculated by the grid algorithm was Ginseng 1. 62 g, Astragalus membranaceus 4. 62 g, Salvia Miltiorrhiza 2. 43 g, and Oriental Waterplantain tuber 1. 66 g.</p><p><b>CONCLUSION</b>Uniform design combined with stepwise regression analysis and grid algorithm were able to realize quadratic formula optimization of RJC.</p>