Network Pharmacology Study on Herb Pair Bletilla striata-Galla chinensis in the Treatment of Chronic Skin Ulcers.

BACKGROUND: Herb pair Bletilla striata-Galla chinensis (BS-GC) is a classic combination of topical traditional Chinese medicine formulae in the treatment of chronic skin ulcers (CSUs). OBJECTIVE: The aim of this study is to explore the effective active ingredients of BS-GC, as well as the core targets and signal transduction pathways of its action on CSUs. METHODS: The ingredients of BS-GC were obtained from TCMSP and HERB databases. The targets of all active ingredients were retrieved from the SwissTargetPrediction database. The targets of CSUs were obtained from OMIM, GeneCards, Drugbank, and DisGeNET databases. A drug-disease target protein-protein interaction (PPI) network was constructed to select the most core targets, and an herb-ingredient-target network was built by utilizing Cytoscape 3.7.2. Furthermore, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes database (KEGG) analysis and verified the results of network pharmacology through molecular docking. RESULTS: A total of 40 active ingredients from the herb pair BS-GC were initially screened, and a total of 528 targets were retrieved. Meanwhile, the total number of CSU targets was 1032. Then, the number of common targets between BS-GC and CSUs was 107. The 13 core targets of herb pair BS-GC with CSUs were filtered out according to the PPI network, including AKT1, TNF, EGFR, BCL2, HIF1A, MMP-9, etc. The 5 main core active ingredients were 1-(4-Hydroxybenzyl)-2-methoxy-9,10-dihydrophenanthrene-4,7-diol, 1-(4- Hydroxybenzyl)-4-methoxy-9,10-dihydrophenanthrene-2,7-diol, physcion, dihydromyricetin, and myricetin. The main biological processes were inflammation, oxidative stress, and immune response, involving the AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, NF-κB signaling pathway, and calcium signaling pathway. Molecular docking results showed good binding activity between the 5 main core active ingredients and 13 core targets. CONCLUSION: This study predicted the core targets and signal transduction pathways in the treatment of CSUs to provide a reference for further molecular mechanism research.

Fine-Scale analysis of both wild and cultivated horned galls provides insight into their quality differentiation.

BACKGROUND: Galla chinensis is a traditional Chinese medicine (TCM) produced due to the interaction between the Fordinae aphids and the Rhus plant species. Horned galls with high tannin content are the most widely cultivated gall type, and Wufeng county of Hubei province in China is the center of cultivation. However, long-term artificial cultivation and domestication of horned galls to meet the increasing production demand have led to quality degradation. Understanding the reasons underlying quality degradation is urgent for horned gall production and application. The present study used a combination of metabolic, genetic, and ecological analyses to investigate the quality and genetic differentiation of the horned galls under long-term domestication as well as the potential relationships between them. RESULTS: Analysis of gallic acid content and other three phenotypic traits (fresh weight, gall size, and wall thickness) revealed quality differentiation of horned galls collected from five locations in Wufeng, in which the cultivated samples from Wang Jiaping (WJP) showed the highest degradation. Genetic differentiation between the cultivated and wild Rhus chinensis trees in WJP, and between WJP and the other populations was detected based on SSR molecular markers, however, no significant difference in genetic structure was seen for the aphid populations. Among the various ecological factors examined, temperature was identified as the primary one affecting the quality of horned galls. CONCLUSIONS: Both genetic and ecological factors caused quality differentiation of horned galls. The collection of diverse germplasm of host trees and aphids will help reduce the quality degradation of horned galls in Wufeng.

Bioinformatics-based and molecular docking study on the mechanism of action of Galla chinensis in the treatment of diabetic foot ulcers.

Based on transcriptome sequencing and molecular biology, the active ingredient of Galla chinensis in the treatment of diabetic foot ulcers was identified, and its mechanism of action was analyzed.

(1) Searching for the main components of the compounds contained in G. chinensis in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and literature research. (2) Prediction of their targets using the PubChem, SwissTargetPrediction, and BATMAN databases. (3) The CTD, Genecards. and NCBI databases were used to mine the transcriptome sequencing data for target genes related to diabetic foot ulcers. (4) Cytoscape 3.7.0 software was used to construct protein/gene interaction network maps for G. chinensis. (5) GO and KEGG analysis was carried out using the DAVID database. (6) Heatmap and volcano map analysis was carried out with R software. (7) The preliminary validation and visualization of molecular docking were performed using AutoDockVina and PyMOL software. After the screening of TCMSP and literature research, we obtained nine active ingredients of G. chinensis, 53 targets for diabetic foot ulcers; 40 biological processes, 30 cell compositions, and 30 molecular functions by GO analysis; and 24 signaling pathways, including the HIF-1 signaling pathway and VEGF signaling pathway. were obtained by KEGG analysis. The molecular docking results showed that the main active ingredients of Galla chinensis had good binding activities with their corresponding target proteins. In this study, G. chinensis was analyzed for its potential value in the treatment of diabetic foot ulcers due to its anti-inflammatory and wound-healing effects.

Galla Chinensis, a Traditional Chinese Medicine: Comprehensive review of botany, traditional uses, chemical composition, pharmacology and toxicology.

ETHNOPHARMACOLOGICAL RELEVANCE: Galla chinensis (GC), a traditional Chinese medicine (TCM), has a wide range of pharmacological properties which have been widely used for more than 1400 years. Based on shape, GC is divided into two groups: jiaobei and dubei. It is a bitter, sour, cold and astringent substance which is usually used for treating diarrhea, constipation, bleeding, cough, vomiting, sweating, hemorrhoids, and anal and uterine prolapse. It is distributed in Japan, North Korea, and all parts of China. AIM OF STUDY: This study was aimed at carrying out a comprehensive overview of the current status of research on Galla chinensis (GC) for better understanding of it characteristics, while providing a clear direction for future studies. It has aroused the interest of researchers, leading to development of medicinal value, expansion of its application, and provision of wider and more effective drug choices. This study was focused on the traditional uses, botany, chemical composition, pharmacology and toxicology of GC. Finally, the study focused on possible future research directions for GC. MATERIALS AND METHODS: A comprehensive analysis was done based on academic papers, pharmaceutical monographs, ancient medicinal works, and drug standards of China. This review used Galla and Galla chinensis as keywords for retrieval of information on GC from online databases such as PubMed, Elsevier, CNKI, Web of Science, Google Scholar, SCI hub, and Baidu academic. RESULTS: It was found that the chemical constituents of GC included tannins, phenolic acid, amino acids and fatty acid, with polyphenol compounds (especially tannins and gallic acid) as the distinct components. In vitro and in vivo studies revealed that GC exerted numerous biological effects such as anti-caries, antibacterial, antiviral, anticancer, and antioxidant effects. The therapeutic effect of GC was attributed mainly to the biological properties of its bioactive components. CONCLUSIONS: GC is an important TCM which has potential benefit in the treatment of a variety of diseases. However, the relationship amongst the structure and biological activity of GC and its components, mechanism of action, toxicity, pharmacokinetics and target organs need to be further studied. Quality control and quality assurance programs for GC need to be further developed. There is need to study the dynamics associated with the accumulation of chemical compounds in GC as well as the original plants and aphid that form GC.

Tannins extract from Galla Chinensis can protect mice from infection by Enterotoxigenic Escherichia coli O101.

BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) is classically associated with acute secretory diarrhea, which induces 2 million people death in developing countries over a year, predominantly children in the first years of life. Previously, tannins (47.75%) were extracted from Galla Chinensis and prepared as Galla Chinensis oral solution (GOS) which showed significant antidiarrheal activity in a castor oil-induced diarrhea in mice. Whether the tannins extract were also effective in treatment of ETEC-induced diarrhea was determined in this study. METHODS: Mice were randomly divided into 6 groups (n = 22). The mice in the normal and untreated groups were given normal saline. Three GOS-treated groups were received different concentrations of GOS (5, 10 and 15%, respectively) at a dose of 10 mL/kg. Mice in the positive control group were fed with loperamide (10 mg/kg). The treatment with GOS started 3 days before infection with ETEC and continued for 4 consecutive days after infection. On day 3, mice were all infected with one dose of LD50 of ETEC, except those in the normal group. Survival of mice was observed daily and recorded throughout the study. On days 4 and 7, samples were collected from 6 mice in each group. RESULTS: GOS could increase the survival rate up to 75%, while in the untreated group it is 43.75%. The body weights of mice treated with 15% GOS were significantly increased on day 7 in comparison with the untreated group and the normal group. GOS-treatment recovered the small intestine coefficient enhanced by ETEC-infection. The diarrhea index of mice treated with GOS was significantly decreased. GOS increased the levels of IgG and sIgA in the terminal ileum and decreased the levels of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1ß, IL-6 and IL-8) in serum. GOS could increase the amount of intestinal probiotics, Lactobacilli and Bifidobacteria. GOS could alleviate colon lesions induced by ETEC-infection. GOS showed higher potency than loperamide. CONCLUSIONS: GOS could be a promising drug candidate for treating ETEC infections.

[Study on commodity specification and grade standard and quality evaluation of Galla Chinensis].

This paper is aimed to study the commodity specification and grade standard of Galla Chinensis,for standardizing market order and guide the market circulation,and provide a basis for standardization of Galla Chinensis. With 33 samples of Galla Chinensis from market as the object of the research,the herbal textual research and market research were carried out. Then the grading indicator were selected by the descriptive statistics,principal component analysis and cluster analysis,combining with production practice,the commodity specification and grade standard of Galla Chinensis were set out. The data of moisture,ash,gallic acid as the internal index were used to analyze the relationship between the quality difference between grades and the appearance characters and the intrinsic composition. Herbal textual research and market research found that the high quality of Galla Chinensis characterized with large,complete,wall thick,grayish brown characteristics,and Galla Chinensis could be divided into gallnuts and horned gall. Through principal component analysis and cluster analysis,combining actual production and herbal record,screening,the length,diameter,single weight,the number of 500 g were determined as 4 grading indicators,the commodity specification was divided into two: gallnuts and horned gall,the grades was divided into two: selected goods and mixed goods. The result of correlation analysis showed there was no significant correlation between the internal index and the appearance characters of Galla Chinensis. The result of multiple comparison showed that the ash content of the selected goods was smaller than that of the mixed goods,but it did not reach significant. The content of gallic acid of the selected goods and the mixed goods of gallnuts were higher than selected goods of horned gall,and higher than mixed goods of horned galls. Using the length,diameter,single weight,the number of 500 g as the appearance characters index. Combining with the herbal textual research and market research,we have divided two specifications and two grades for the commodity specification and grade standard of Galla Chinensis,which can provide a basis for industry standards and national standards.

[Transformation and attribution of drug properties in Galla Chinesis fermented Baiyaojian based on cold and heat syndrome rats].

To reveal the transformation and attribution of drug properties in Galla Chinesis fermented Baiyaojian by studying the effect of Galla Chinesis and Baiyaojian on cold and heat syndrome rats. Euthyrox was used to induce the hyperthyrosis model,ice water stimulation was used to induce the cold syndrome model,and different concentrations of Galla Chinesis and Baiyaojian water decoction were administrated by gavage for 15 d continuously. Symptom indexes were evaluated,content of pyruvic acid( PA),ATPase activity in liver and contents of DA,T4,cAMP,5-HT,NE,17-OHCS,TRH and TSH in serum were assayed by enzyme linked immunosorbent assay and spectrophotometry. The rectal temperature,water consumption and body weight of heat syndrome rats in model group were increased,cAMP,NE,17-OHCS,TRH and PA were increased,TSH,Na-K ATPase and Ca-Mg ATPase were increased significantly( P<0. 01),while 5-HT was decreased,compared with those of the blank group( P< 0. 05),the contents of T4,DA,NE,TSH,TRH,cAMP and 17-OHCS were decreased significantly( P<0. 01),PA and Ca-Mg ATPase in WG and BG groups were decreased compared with those of the model group( P<0. 05),and the Galla Chinesis content of WG group was lower than that of BG group,while the contents of 5-HT in WG and BG groups were increased,and the Galla Chinesis content of WG group was higher than that of BG group,with no significant difference of viscera index between heat syndrome rats in blank group,model group and drug groups. The rectal temperature,water consumption and body weight of cold syndrome rats in model group were decreased,DA,T4,cAMP,NE,17-OHCS,TRH,TSH,PA,Na-K ATPase and Ca-Mg ATPase of rats in model group were decreased,whereas 5-HT was increased compared with those of the blank group( P<0. 05),the indexes of heart,lung and kidney were significantly higher than those in the blank group( P<0. 05). Both Galla Chinesis and Baiyaojian can significantly alleviate the symptoms of heat syndrome rats caused by levothyroxine sodium. Galla Chinesis has a better effect than Baiyaojian,but cannot alleviate the symptoms of cold syndrome caused by ice water stimulation,suggestting that the decoction of Galla Chinesis and Baiyaojian are both cold,but Galla Chinesis is colder than Baiyaojian. Cold property in Galla Chinesis fermented Baiyaojian can be relieved. In clinical application,the property of " slight cold" is more accurate than " neutral property" for Baiyaojian.

Transformation and attribution of drug properties in Galla Chinesis fermented Baiyaojian based on cold and heat syndrome rats / 中国中药杂志

To reveal the transformation and attribution of drug properties in Galla Chinesis fermented Baiyaojian by studying the effect of Galla Chinesis and Baiyaojian on cold and heat syndrome rats. Euthyrox was used to induce the hyperthyrosis model,ice water stimulation was used to induce the cold syndrome model,and different concentrations of Galla Chinesis and Baiyaojian water decoction were administrated by gavage for 15 d continuously. Symptom indexes were evaluated,content of pyruvic acid( PA),ATPase activity in liver and contents of DA,T4,cAMP,5-HT,NE,17-OHCS,TRH and TSH in serum were assayed by enzyme linked immunosorbent assay and spectrophotometry. The rectal temperature,water consumption and body weight of heat syndrome rats in model group were increased,cAMP,NE,17-OHCS,TRH and PA were increased,TSH,Na-K ATPase and Ca-Mg ATPase were increased significantly( P<0. 01),while 5-HT was decreased,compared with those of the blank group( P< 0. 05),the contents of T4,DA,NE,TSH,TRH,cAMP and 17-OHCS were decreased significantly( P<0. 01),PA and Ca-Mg ATPase in WG and BG groups were decreased compared with those of the model group( P<0. 05),and the Galla Chinesis content of WG group was lower than that of BG group,while the contents of 5-HT in WG and BG groups were increased,and the Galla Chinesis content of WG group was higher than that of BG group,with no significant difference of viscera index between heat syndrome rats in blank group,model group and drug groups. The rectal temperature,water consumption and body weight of cold syndrome rats in model group were decreased,DA,T4,cAMP,NE,17-OHCS,TRH,TSH,PA,Na-K ATPase and Ca-Mg ATPase of rats in model group were decreased,whereas 5-HT was increased compared with those of the blank group( P<0. 05),the indexes of heart,lung and kidney were significantly higher than those in the blank group( P<0. 05). Both Galla Chinesis and Baiyaojian can significantly alleviate the symptoms of heat syndrome rats caused by levothyroxine sodium. Galla Chinesis has a better effect than Baiyaojian,but cannot alleviate the symptoms of cold syndrome caused by ice water stimulation,suggestting that the decoction of Galla Chinesis and Baiyaojian are both cold,but Galla Chinesis is colder than Baiyaojian. Cold property in Galla Chinesis fermented Baiyaojian can be relieved. In clinical application,the property of " slight cold" is more accurate than " neutral property" for Baiyaojian.

Study on commodity specification and grade standard and quality evaluation of Galla Chinensis / 中国中药杂志

This paper is aimed to study the commodity specification and grade standard of Galla Chinensis,for standardizing market order and guide the market circulation,and provide a basis for standardization of Galla Chinensis. With 33 samples of Galla Chinensis from market as the object of the research,the herbal textual research and market research were carried out. Then the grading indicator were selected by the descriptive statistics,principal component analysis and cluster analysis,combining with production practice,the commodity specification and grade standard of Galla Chinensis were set out. The data of moisture,ash,gallic acid as the internal index were used to analyze the relationship between the quality difference between grades and the appearance characters and the intrinsic composition. Herbal textual research and market research found that the high quality of Galla Chinensis characterized with large,complete,wall thick,grayish brown characteristics,and Galla Chinensis could be divided into gallnuts and horned gall. Through principal component analysis and cluster analysis,combining actual production and herbal record,screening,the length,diameter,single weight,the number of 500 g were determined as 4 grading indicators,the commodity specification was divided into two: gallnuts and horned gall,the grades was divided into two: selected goods and mixed goods. The result of correlation analysis showed there was no significant correlation between the internal index and the appearance characters of Galla Chinensis. The result of multiple comparison showed that the ash content of the selected goods was smaller than that of the mixed goods,but it did not reach significant. The content of gallic acid of the selected goods and the mixed goods of gallnuts were higher than selected goods of horned gall,and higher than mixed goods of horned galls. Using the length,diameter,single weight,the number of 500 g as the appearance characters index. Combining with the herbal textual research and market research,we have divided two specifications and two grades for the commodity specification and grade standard of Galla Chinensis,which can provide a basis for industry standards and national standards.

Anti-carious Effects of Galla chinensis: A Systematic Review.

As a natural traditional Chinese medicine, Galla chinensis has been widely used since ancient times for its astringency, stypticity, detoxification, and antibacterial activity. Our group has concentrated on the research about its potential of being an applicable anti-caries agent. The crude extract and some other components purified from it show remarkable efficacy on anticaries, and the most likely mechanism is proposed through specific research. For the fact that crude drugs consist of numerous compounds, and their bioactivity is a result of synergistic effects and/or antagonistic effects of several compounds, it is difficult to clarify the exact mechanism and evaluate the safety and effectiveness of G. chinensis. This review article systematically summarizes previous findings from the following aspects: (1) inhibitory effect on oral bacteria; (2) the demineralization inhibition property; (3) the remineralization-enhancing property; and (4) stability and toxicity evaluation, and thus indicates the further research direction.

Acute and subchronic toxicity as well as evaluation of safety pharmacology of Galla chinensis solution.

Galla chinensis has been popularly used in traditional Chinese medicine which is beneficial for the treatment of various diseases, such as inflammation, dysentery, toxicosis and sore. However, it has not previously been evaluated for safety through systematic toxicological studies. In the present study, acute and subchronic oral toxicity studies and safety pharmacology evaluation of Galla chinensis solution (GCS) were conducted in specific pathogen-free (SPF) Sprague-Dawley (SD) rats. Acute administration of GCS was done as single dose from 3333 mg to 6912 mg per kg/bodyweight (bw) and subchronic toxicity study for 30 days was done by daily oral administration of GCS at doses of 500, 1500 and 2500 mg/kg body weight in SPF SD rats. The acute toxicity study showed the LD50 of GCS was greater than 5000 mg/kg. The results of sunchronic toxicity study showed that the no-observed effect level of GCS was lesser than 1500 mg/kg bw day, which suggested three times higher than that of recommended dose for clinical applications (500 mg/kg bw day). The dose at 2500 mg/kg bw day of GCS may slow down the growth of rats and lead to degeneration and necrosis of tissue cells to some extent. In the safety pharmacology study, GCS did not produce any side effects to rats in central nervous system, cardiovascular system and respiratory system. Therefore, from the results of the study presented herein, it could be concluded that the use of appropriate levels (one to three times of recommended dose for clinical applications) of GCS as a topical preparations is considered safe.

Observation of Antibacterial Activity of Galla Chinensis etc. 14 Kinds of Traditional Chinese Medicine against 112 Strains of Staphlococcus Aureus in Vitro / 中国中医药信息杂志

Objective To evaluate the antibacterial activity of Galla chinensis etc.14 kinds of TCM against 112 strains of Staphylococcus aureus in vitro. Method Deterimination of antibacterial activity of Galla chinensis etc.against 112 strains of Staphylococcus aureus was performed by using new agar dilution method. Results The antibacterial efficiency of Galla chinensis, Forsythia suspensa and Acacia catechu (L.) Willd against 112 strains Staphylococcus aureus was good, and the MIC90 was 0.102, 0.244, 1.19 mg/mL respectively. Conclusion Galla chinensis etc. 14 kinds of TCM had strong antibacterial activity agsinst 112 srains of Staphylococcus aureus.