Clinical application value of Huanglian Jiedu Pills in improving syndrome of excess heat and fire toxin based on phase Ⅱ clinical trial study on plasma ATP, 4-HNE, and ACTH levels / 中国中药杂志

A randomized, double-blind, placebo-controlled, multi-center phase Ⅱ clinical trial design was used in this study to recruit subjects who were in line with the syndrome of excess heat and fire toxin, and were diagnosed as recurrent oral ulcers, gingivitis, and acute pharyngitis. A total of 240 cases were included and randomly divided into a placebo group and a Huanglian Jiedu Pills group. The clinical efficacy of Huanglian Jiedu Pills in treating the syndrome of excess heat and fire toxin was evaluated by using the traditional Chinese medicine(TCM) syndrome scale. Enzyme-linked immunosorbent assay(ELISA) was used to determine and evaluate the levels of adenosine triphosphate(ATP), 4-hydroxynonenal(4-HNE), and adrenocorticotropic hormone(ACTH) in plasma of the two groups before and after administration and to predict their application value as clinical biomarkers. The results showed that the disappearance rate of main symptoms in the Huanglian Jiedu Pills group was 69.17%, and that in the placebo group was 50.83%. The comparison between the Huanglian Jiedu Pills group and the placebo group showed that 4-HNE before and after administration was statistically significant(P<0.05). The content of 4-HNE in the Huanglian Jiedu Pills group decreased significantly after administration(P<0.05), but that in the placebo group had no statistical significance and showed an upward trend. After administration, the content of ATP in both Huanglian Jiedu Pills group and placebo group decreased significantly(P<0.05), indicating that the energy metabolism disorder was significantly improved after administration of Huanglian Jiedu Pills and the body's self-healing ability also alleviated the increase in ATP level caused by the syndrome of excess heat and fire toxin to a certain extent. ACTH in both Huanglian Jiedu Pills group and placebo group decreased significantly after administration(P<0.05). It is concluded that Huanglian Jiedu Pills has a significant clinical effect, and can significantly improve the abnormal levels of ATP and 4-HNE in plasma caused by the syndrome of excess heat and fire toxin, which are speculated to be the effective clinical biomarkers for Huanglian Jiedu Pills to treat the syndrome of excess heat and fire toxin.

Tissue distribution of Qingfei Paidu Decoction based on HPLC-MS/MS / 中国中药杂志

The tissue distribution of Qingfei Paidu Decoction was studied by HPLC-MS/MS in vivo. Hypersil GOLD C_(18) column(2.1 mm×50 mm, 1.9 μm) was used for gradient elution with acetonitrile as the mobile phase A and 0.1% formic acid solution as the mobile phase B. High-resolution liquid chromatography-mass spectrometry in both positive and negative ion scanning mode and multiple response monitoring(MRM) mode was employed to analyze the behaviors of the active components of Qingfei Paidu Decoction in diffe-rent tissues. The results showed that 19, 9, 17, 14, 22, 19, 24, and 2 compounds were detected in plasma, heart, liver, spleen, lung, kidney, large intestine, and brain, respectively. The compounds belonged to 8 groups, covering 14 herbs in the prescription. After administration with Qingfei Paidu Decoction, the compounds were rapidly distributed in various tissues, especially in the lung, liver, large intestine, and kidney. The majority of the compounds displayed secondary distribution. This study comprehensively analyzed the distribution rules of the main active components in Qingfei Paidu Decoction and provided a basis for the clinical application.

Comprehensive evaluation system for quality of Chinese medicinal decoction pieces based on "experience-ingredients-activity-electronic sensing" / 中国中药杂志

Quality evaluation of Chinese medicinal decoction pieces is vital for the development of the downstream industries, and is an important channel for implementing the strategy of "higher quality, higher price, and priority for the high quality" for traditional Chinese medicine. At the moment, the quality of Chinese medicinal decoction pieces is mainly evaluated based on chemical component examination. Considering the weak preliminary research foundation and poor research conditions, traditional experience-based evaluation is undervalued in the quality rating of Chinese medicinal decoction pieces. However, traditional experience is a summary of the quality of Chinese medicinal materials based on clinical experience, which thus can be a potential basis for the quality evaluation of the decoction pieces. It is a challenge in the evaluation of Chinese medicinal decoction pieces to objectify the traditional experience-based evaluation from multiple aspects such as chemistry, effect, and characterization via modern techniques. Therefore, this study developed the "experience-ingredients-activity-electronic sensing" evaluation system for Chinese medicinal decoction pieces on the basis of experience-based assessment, chemical ingredients that can truly reflect the traditional experience, biological effect assessment, and electronic sensory evaluation, which is expected to quantify the traditional experience of quality evaluation of Chinese medicinal decoction pieces via chemistry, biology, and sensory simulation. The evaluation system can serve as a reference for clinical experience-based quality evaluation of Chinese medicinal decoction pieces.

Historical Evolution and Modern Clinical Application of Qingxin Lianzi Yin / 中国实验方剂学杂志

Qingxin Lianzi Yin （QXLZY）， as an ancient classical formula for clearing the heart and nourishing the Yin， was composed of nine herbs （Scutellariae Radix， Ophiopogonis Radix， Lycii Cortex， Plantaginis Semen， Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle， Nelumbinis Semen， Poria， Astragali Radix and Ginseng Radix et Rhizoma）， coming from Prescriptions of the Bureau of Taiping People's Welfare Pharmacy. It could clear away the heart-fire， promote the interaction of the heart and kidney， replenish Qi and Yin， and stop strangury-turbidity. It was used to treat gonorrhea of urination， seminal emission， restlessness， wasting-thirst and so on. At present， the usage and dosage of QXLZY and its addition and subtraction are different in clinical practice. Most of the studies just focus on its clinical efficacy， and there is few review literature reflecting its historical evolution. Based on this， this paper systematically clarified the historical evolution， composition， preparation， interpretation， function， and modern clinical application of QXLZY. This work has been explained the historical evolution of QXLZY， and found that it was wildly used in modern clinical， especially suitable for the treatment of chronic urinary system diseases. At the same time， QXLZY also had significant therapeutic effects on neurasthenia， stomatitis， diabetic nephropathy and other aspects. Through the comprehensive analysis of ancient and modern literature， this work explores the true connotation of QXLZY from the perspective of traditional Chinese medicine theory， which can point out the direction of the clinical application and positioning of this famous classical formula after it comes into the market， and also can provide reference basis for its subsequent in-depth research and development.

Identification of chemical constituents of Xiaoer Chiqiao Qingre Granules based on UHPLC-LTQ-Orbitrap-MS/MS and network pharmacology analysis / 中国中药杂志

This study aimed to qualitatively analyze the chemical components in Xiaoer Chiqiao Qingre Granules(XRCQ) by UHPLC-LTQ-Orbitrap-MS/MS and identify its material basis. The absorbed components in plasma were combined for exploring the potential action mechanism by integrated network pharmacology. ACQUITY UPLC HSS T3(2.1 mm×100 mm, 1.8 μm) column and mobile phase system of 0.1% formic acid solution(A)-acetonitrile(B) were used for gradient elution, followed by high resolution liquid chromatography-mass spectrometry in both positive and negative ion scanning modes. According to the precise relative molecular mass and MS/MS fragment ions, a total of 124 chemical components were identified in XRCQ by the comparison with references and literature reports, among which 29 compounds were completely confirmed by comparison with reference substances. Then, the main absorbed components of XRCQ in plasma were also analyzed and clarified by UHPLC-LTQ-Orbitrap-MS/MS. BATMAN-TCM and SwissTargetPrediction were used for target prediction of absorbed components in plasma. Following the plotting of association network with Cytoscape 3.8.2, the core targets were subjected to GO and KEGG pathway enrichment analysis and a component-target-pathway network was constructed. A total of eight main targets of XRCQ against fever in children were obtained together with eight absorbed components in plasma, including glycyrhydinic acid, hesperidin, emodin, reticuline, daidzein, magnolignan C, magnolignan A, and magnolaldehyde D. It was inferred that XRCQ might improve alimentary system abnormality, inflammatory response, oxidative stress, and endocrine disorder through tumor necrosis factor, PI3 K-AKT, and other signaling pathways. The present study comprehensively expounded the chemical profiles of XRCQ and the main absorbed components in plasma and predicted the potential mechanism of XRCQ based on integrated network pharmacology, which has provided certain theoretical reference for the clinical application of XRCQ.

Identification and attribution of chemical constituents of Qingfei Paidu Decoction based on UHPLC-LTQ-Orbitrap-MS technology / 中国中药杂志

UHPLC-LTQ-Orbitrap-MS was developed for the identification of chemical constituents in Qingfei Paidu Decoction, which will clarify its material basis. ACQUITY UHPLC HSS T3 chromatography column(2.1 mm×100 mm, 1.8 μm) was used with 0.1% formic acid(B)-acetonitrile(A) as the mobile phase in gradient elution. The decoction was detected by high-resolution liquid chromatography-mass spectrometry equipped with an ESI ion source in positive and negative mode. Based on the accurate mass measurements, retention time, mass fragmentation patterns combined with comparison of reference and literature reports, a total of 87 major compounds including 43 flavonoids, 9 alkaloids, 4 triterpenoid saponins, 1 sesquiterpene, 2 coumarins, 10 phenolic acids and 18 other compounds were tentatively screened and characterized. UHPLC-LTQ-Orbitrap-MS was employed to comprehensively elucidate the chemical components in Qingfei Paidu Decoction, which basically covered 20 Chinese medicines except gypsum in Qingfei Paidu Decoction. These collective results provide a scientific basis for further research on the quality control standard of Qingfei Paidu Decoction.

Identification and attribution of chemical compounds of Pudilan Antiphlogistic Oral Liquid / 中国中药杂志

UPLC-ESI-Orbitrap-MS/MS was used to analyze,identify and attribute the chemical constituents in Pudilan Antiphlogistic Oral Liquid. The analysis was performed on an Agilent Eclipse XDB-C18(4.6 mm × 150 mm,3.5 μm) with a gradient mobile phase of methanol-0.1% formic solution system at the flow rate of 0.5 m L·min-1. The sample volume was 2 μL. The column temperature was30 ℃. The high-resolution orbitrap mass spectrometry was used as detector,with electrospray ion source in both positive and negative models,and the MS scanning ranged between m/z 50 and 2 000. Based on the analysis of mass spectrometry and literature reports,79 compounds were confirmed,including 30 alkaloids,28 organic acids,18 flavonoids and 3 coumarins. Finally,39 compounds,such as rutin,esculetin,gallic acid,caffeic acid,cichoric acid,were identified from Taraxacum mongolicum; 11 compounds,such as baicalin,baicalein,apigenin,chrysin,oroxylin A,were identified from Scutellaria baicalensis; 13 compounds,such as arginine,proline,hypoxanthine,epigoitrin,indirubin,were identified from Isatis indigotica; and 18 compounds,such as dehydrocheilanthifoline,oxysanguinarine,corynoline,protopine,spallidamine,were identified from Corydalis bungeana. After the analysis of chemical model and attribution,the contents of some compounds were high in Pudilan Antiphlogistic Oral Liquid,such as baicalin,wogonoside,baicalein,wogonin,apigenin,chrysin,skullcapflavonⅡ,oroxylin A,cichoric acid,chlorogenic acid,caffeic acid,esculetin,dehydrocheilanthifoline,dihydrosanguinarine,protopine,corynoline and indirubin. The established method is simple,accurate,rapid,sensitive and reproducible,and thus suitable for the qualitative identification and quantitative determination of Pudilan Antiphlogistic Oral Liquid,which lays a foundation for the systematic quality control and the establishment of whole-course traceability system of active ingredients.

Study of screening pseudoallergenic substances of Shuanghuanglian injection / 中国中药杂志

In this study, chemistry, biology and pharmacology were combinated to screen pseudoallergenic substances of Shuang-huanglian injection (SHLI) so that to establish a scientific and systematic approach to screen pseudoallergenic substances of traditional Chinese medicine injections. The mouse pseudoallergic reaction models were used to screen the pseudoallergic reaction of SHLI's intermediate extract and the intermediate extract's component or ingredient. Among the three intermediates of Shuanghuanglian injection (extract of Scutellaria baicalensis, extract of Lonicera japonica, extract of Forsythia suspensa) , pseudoallergic action of Forsythia suspensa was the strongest, Forsythia suspesnsa's pseudoallergic reaction mainly associated with the composition with largerchemical polarity. Further it was found that forsythiaside A and arctiin which existed in the the composition with largerchemical polarity caused obvious pseudoallergic reactions. SHLI with removal forsythoside A with the technology of HPLC-MS displayed reduced pseudoallergic reaction and a significant improved safety. This study provided a scientific basis for SHLI process improvements and also offered idea and research foundation for screening pseudoallergenic substances injections in other TCM injections.

Huanglian jiedu decoction active fraction protects ipsilateral thalamus injury in MCAO rats through regulating astrocytes / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the protective effects of the Huanglian Jiedu decoction aqueous extract and its active fraction, which consists of total alkaloids, total flavonoids and total iridoid, on the thalamus of cerebral ischemia in rats.</p><p><b>METHOD</b>The rat model of middle cerebral artery occlusion (MCAO) was chosen. Male SD rats were randomly divided into sham-operation group, model group, aqueous extract group (800 mg x kg(-1)), total alkaloids group(44 mg x kg(-1)), total flavonoids group (50 mg x kg(-1)) and the total iridoid group (80 mg x kg(-1)). The rats were administered the appropriate drugs intragastrically once a day, for 7 days after surgery. An equivalent volume of saline was given in the sham surgery and model groups. The HE staining was adopted to observe the pathological changes. Determination of Glu and gamma-GABA in thalamus were detected by HPLC with fluorescence detection. The expression of GAD65 was examined with immunohistochemistry and double staining with uorescent-conjugated antibodies against GFAP and Cx43 was chosen in this study.</p><p><b>RESULT</b>The neurons degenerated in MCAO rats after cerebral ischemia 7 d. The content of Glu, gamma-GABA decreased (P < 0.05), the expression of GAD65 reduced (P < 0.05) and the expression of GFAP and Cx43 increased (P < 0.01) in thalamus of rats compared with sham-operation group. Huanglian Jiedu decoction aqueous extract, total alkaloids, total flavonoids and total iridoid reduced the degeneration of neurons. Total flavonoids could promote the expression of GAD65 (P < 0.05) and decrease the expression of GFAP and Cx43 (P < 0.01) in thalamus compared with model group while it could also increased the content of Glu,gamma-GA BA to normal levels. Compared with model group, Huanglian Jiedu decoction aqueous extract, total alkaloids and total iridoid could raise the expression of Cx43, and Huanglian Jiedu decoction aqueous extract could also increase the expression of GAD65 (P < 0.05). The expression of GFAP in Huanglian Jiedu decoction aqueous extract group, total alkaloids group and total iridoid group were not different compared with model group while the content of gamma-GABA decreased (P < 0.05) compared with sham-operation group.</p><p><b>CONCLUSION</b>The degeneration of nerve cells, the reduction of neurotransmitter amino acids content, the aberrant activation of astrocytes and the abnormal expression of GFAP and Cx43 will appear in thalamus of MCAO rats after ischemia. Huanglian Jiedu decoction total flavonoids could relieve the injury of nerve cell through inhibiting the abnormal activation of astrocytes and regulating the expression of GFAP and GAD65.</p>

Study on action mechanism of adjuvant therapeutic effect compound Ejiao slurry in treating cancers based on network pharmacology / 中国中药杂志

Recently, compound Ejiao slurry (FFEJJ) had been applied to treat cancer patients in clinic, with obvious curative effect. In this study, data and literatures were collected from the TCM chemical component database to establish the chemical component database of FFEJJ. Afterwards, MetaDrug software was used to predict the targets of FFEJJ and obtain the compound-target network. Next, the compound-target network was compared and analyzed to obtain the "compound-target-tumor target" heterogeneous network. Besides, further analysis was made on gene functions and metabolic pathway. The results indicated that FFEJJ could directly resist tumors by regulating cancer cell differentiation, growth, proliferation and apoptosis, and show an adjuvant therapeutic effect by enriching the blood and increasing the immunity.

LC-FT-ICR-MS analysis of the prototypes and metabolites in rat plasma after administration of huang-lian-jie-du decoction / 药学学报

To obtain chemical constituent information of rat plasma after oral administration of Huang-Lian-Jie-Du Decoction (HLJDD), a LC-FT-ICR-MS method has been established, and both positive and negative ions scan modes were include in the analysis. By comparing their retention time, high resolution mass data of HLJDD extracts, blank plasma and dosed plasma, 38 constituents, including 22 prototype compounds and 16 metabolites, were detected in rat plasma after oral administration of HLJDD. In the 22 prototype compounds, 16 constituents were determined unambiguously by comparing with references. In the analysis of metabolites, phase II reactions like glucuronidation and sulfation were the major biotransformation pathways of HLJDD. M11 was observed as the only phase I metabolite in present experiment. The results will be beneficial for the further pharmacokinetics and pharmacological evaluations of HLJDD.

In vitro anti-proliferation effect of peptides from cinobufacini injection / 药学学报

Cinobufacini is an aqueous extract of Bufo bufo gargarizans Cantor dried skin, which has been widely used for cancer therapy in China. So far, its active components are still not very clear. In previous reports, bufadienolides with low-concentration were usually studied because of their anticancer effects. However, the high polarity constituents in cinobufacini are less investigated. The present study found that more than 50% contents of cinobufacini were water-soluble peptides. Then, in vitro anticancer experiments were carried out, including human stomach cancer cell lines BGC823 and MCG803, human colon cancer cell lines DLD-1 and HT-29, and human pancreatic cancer cell line MIAPACA-2. The IC50 for these cell lines model were ranged from 25-123 microgmL(-1). The results indicated that these peptides showed similar activity with cinobufacini injection. As a conclusion, this study provides a new and further understanding of anticancer components in cinobufacini injection.

Action mechanisms of complementary and alternative medicine therapies for rheumatoid arthritis / 中国结合医学杂志

Rheumatoid arthritis (RA) is characterized as a chronic inflammatory disease in joints and concomitant destruction of cartilage and bone. Cartilage extracellular matrix components, such as type II collagen and aggrecan are enzymatically degraded by matrix metalloproteinases (MMPs) and aggrecanases in RA. Currently, treatments targeting cytokines, including anti-tumor necrosis factor (TNF) α antibodies, soluble TNF receptor, anti-interleukin (IL)-6 receptor antibody, and IL-1 receptor antagonist, are widely used for treating RA in addition to antiantiinflammatory agents and disease-modifying antirheumatic drugs (DMARDs), such as inflmethotrexate, but these treatments have some problems, especially in terms of cost and the increased susceptibility of patients to infection in addition to the existence of low-responders to these treatments. Therefore, therapeutics that can be safely used for an extended period of time would be preferable. Complementary and alternative medicines including traditional Chinese medicines (TCM) have been used for the arthritic diseases through the ages. Recently, there are many reports concerning the anti-arthritic action mechanisms of TCM-based herbal formulas and crude herbal extracts or isolated ingredients. These natural herbal medicines are thought to moderately improve RA, but they exert various actions for the treatment of RA. In this review, the current status of the mechanism exploration of natural compounds and TCM-based herbal formulas are summarized, focusing on the protection of cartilage destruction in arthritic diseases including RA and osteoarthritis.

Studies on chemical constituents and volatile oil of Xiaochengqi decoction / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents and volatile oil of Xiaochengqi decoction.</p><p><b>METHOD</b>The constituents in decoction were separated by means of column chromatography and their structures were identified by spectral data and compared with literature data. As well as the volatile oil of Xiaochengqi Fang were analyzed and identified by GC-MS.</p><p><b>RESULT</b>Eleven compounds were isolated and identified as chrysophanol (1), physcion (2), magnolol (3), beta-sitosterol (4), sitosterol trans-cinnamic acid (5), emodin (6), aloe emodin (7), rhein (8), gallic acid (9), chrysophanol-8-O-beta-D-glucopyranoside (10), aurantiamarin (11). The volatile oils extracted with steam distillation from Xiaochengqi were identified 67 components, and the main components are including.</p><p><b>CONCLUSION</b>All of the eleven compounds were isolated from Xiaochengqi decoction for the first time and the study on their activities in Chinese prescription is being carried out. D-limonene (42.61%), p-cymene (16.43%), and 8-terpinene (14.46%).</p>

Study on preparation technology of plumula nelumbinis Alkaloid Dripping Pill and determination of content by HPLC / 中国中药杂志

<p><b>OBJECTIVE</b>To determine the optimum technical parameters through controlling the different factors and the content of Dripping Pill.</p><p><b>METHOD</b>Time of dissolution, spherical degree and pill weight as parameters, the influential factors were investigated by orthogonal test and then to determine the content of liensinine, isoliensinine, neferine in plumula nelumbinis Alkaloid Dripping Pill.</p><p><b>RESULT</b>The optimum condition: 75% PEG4000 as matrix, methyl-silicon oil as refrigerant, 4 cm dripping distance, 10 degrees C refrigerant, 30 drippings per minute.</p><p><b>CONCLUSION</b>The good quality pills can be produced through this process and the HPLC determination method is simple, reliable and can be used in the quality control of plumula nelumbinis Alkaloid Dripping Pill.</p>

Solubilities of ephedrine and d-pseudo-ephedrine from different sizes of ultramicro-particles of the compound traditional Chinese herbs Maxing Shigan decoction / 中国中药杂志

<p><b>OBJECTIVE</b>To compare the solubilities of ephedrine and d-pseudo-ephdrine in the compound of traditional Chinese drugs--Maxing Shigan decoction with and without ultramicro-pulverizations using a RP-HPLC procedure.</p><p><b>METHOD</b>The analytical column was a YMC ODS-C18(4.6 mm x 150 mm,4 microm). A mixture of water-acetonitrile-sodium dodecyl sulfate-phosphorous acid (650:350:5:1) was used as the mobile phase at flow rate of 1.5 mL x min(-1). The column temperature was 50 degrees C and the wavelength was 210 nm.</p><p><b>RESULT</b>In this way, ephedrine and d-pseudo-ephedrine of the compound samples can be separated well and showed significant differences before and after the ultramicro-pulverizations.</p><p><b>CONCLUSION</b>For the Maxing Shigan decoction, the dissolution rates and solubilites of ephedrine and d-pseudo-ephedrine ultramicro-pulverization were greatly improved.</p>

Study on preparation of refined Xiong-gui sustained release pills / 中国中药杂志

<p><b>OBJECTIVE</b>To optimize the molding formula of refined Xiong-gui sustained release pills, types and assorted dosages of water-soluble and non water-soluble drug carrier were studied.</p><p><b>METHOD</b>An orthogonal design was performed to sift the pill formulation. The processing conditions were determining in terms of roundness, hardness, viscosity, fluidity, easily drop.</p><p><b>RESULT AND CONCLUSION</b>According to the final optimal formula, the amount of drug release can be detected instantly, while remaining over 80% at 10 h.</p>

Studies on chemical constitutents in roots of Jasminum sambac / 中国中药杂志

<p><b>OBJECTIVE</b>To isolate and identify the chemical constitutents in roots of Jasminum sambac.</p><p><b>METHOD</b>The compounds were isolated by means of chromatography and the structures were identified on the basis of physical and spectral data.</p><p><b>RESULT</b>Dotriacontanoic acid, dotriacontanol, oleanolic acid, daucosterol and hesperidin were elucidated.</p><p><b>CONCLUSION</b>All compounds were found in this plant for the first time.</p>