Integrative analysis of bone-formation associated genes and immune cell infiltration in osteoporosis, and the prediction of active ingredients in targeted traditional Chinese medicine

Objective To explore the differential expression and mechanisms of bone formation-related genes in osteoporosis(OP)leveraging bioinformatics and machine learning methodologies;and to predict the active ingredients of targeted traditional Chinese medicine(TCM)herbs.Methods The Gene Expression Omnibus(GEO)and GeneCards databases were employed to conduct a comprehensive screening of genes and disease-associated loci pertinent to the pathogenesis of OP.The R package was utilized as the analytical tool for the identification of differentially expressed genes.Least absolute shrinkage and selection operator(LASSO)logis-tic regression analysis and support vector machine-recursive feature elimination(SVM-RFE)algorithm were employed in defining the genetic signature specific to OP.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses for the selected pivotal genes were conducted.The cell-type identification by estimating rela-tive subsets of RNA transcripts(CIBERSORT)algorithm was leveraged to examine the infiltra-tion patterns of immune cells;with Spearman’s rank correlation analysis utilized to assess the relationship between the expression levels of the genes and the presence of immune cells.Coremine Medical Database was used to screen out potential TCM herbs for the treatment of OP.Comparative Toxicogenomics Database(CTD)was employed for forecasting the TCM ac-tive ingredients targeting the key genes.AutoDock Vina 1.2.2 and GROMACS 2020 softwares were employed to conclude analysis results;facilitating the exploration of binding affinity and conformational dynamics between the TCM active ingredients and their biological targets.Results Ten genes were identified by intersecting the results from the GEO and GeneCards databases.Through the application of LASSO regression and SVM-RFE algorithm;four piv-otal genes were selected:coat protein(CP);kallikrein 3(KLK3);polymeraseγ(POLG);and transient receptor potential vanilloid 4(TRPV4).GO and KEGG pathway enrichment analy-ses revealed that these trait genes were predominantly engaged in the regulation of defense response activation;maintenance of cellular metal ion balance;and the production of chemokine ligand 5.These genes were notably associated with signaling pathways such as ferroptosis;porphyrin metabolism;and base excision repair.Immune infiltration analysis showed that key genes were highly correlated with immune cells.Macrophage M0;M1;M2;and resting dendritic cell were significantly different between groups;and there were signifi-cant differences between different groups(P<0.05).The interaction counts of resveratrol;curcumin;and quercetin with KLK3 were 7;3;and 2;respectively.It shows that the interac-tions of resveratrol;curcumin;and quercetin with KLK3 were substantial.Molecular docking and molecular dynamics simulations further confirmed the robust binding affinity of these bioactive compounds to the target genes.Conclusion Pivotal genes including CP;KLK3;POLG;and TRPV4;exhibited commendable significant prognostic value;and played a crucial role in the diagnostic assessment of OP.Resveratrol;curcumin;and quercetin;natural compounds found in TCM;showed promise in their potential to effectively modulate the bone-forming gene KLK3.This study provides a sci-entific basis for the interpretation of the pathogenesis of OP and the development of clinical drugs.

A review on cocrystal of active ingredients in traditional Chinese medicine

In the development of new drugs products,especially the development of traditional Chinese medicine active ingredients,solubility and oral bioavailability are the main factors which are restricting the development of new drugs,whereas the physicochemical properties of active ingredients are the key element to affecting these factors.Pharmaceutical cocrystal provides an excellent opportunity to develop new drugs with excellent physical and chemical properties such as melting point,solubility,stability and bioavailability while retaining the pharmacological properties of individuals active pharmaceutical ingredients among pharmaceutical cocrystal compounds.Traditional Chinese herbal medicine has the characteristics of multiple pathways and multiple targets,mainly because it contains many active ingredients,like cocrystals thereof with many components.The active ingredients extracted from traditional Chinese herbal medicine have a wide range of pharmacological activities,but most of the active ingredients affect the development of traditional Chinese medicine active ingredients due to their physical and chemical properties such as solubility.Traditional Chinese medicine pharmaceutical cocrystals can not only improve the physical and chemical properties of drugs without changing the internal structure of drugs,so as to provide a new scheme for the development of traditional Chinese medicine active ingredients.This paper reviews the research progress of active ingredients of traditional Chinese medicine pharmaceutical cocrystal.The preparation methods of cocrystals are summarized and the advantages of cocrystals are illustrated with examples.

Application of Caenorhabditis elegans in screening active ingredients of traditional Chinese medicine

People continue to recognize the important role of Chinese medicine in the treatment of diseases,and there is an urgent need to clarify the mechanism of Chinese medicine.Because of the multi-target and multi-component characteristics of traditional Chinese medicine,it is difficult to elaborate from a single perspective.As a high-quality animal model,Caenorhabditis elegans with the characteristics of small size and fast reproduction,has been widely used in traditional Chinese medicine activity experiments.In this article,Caenorhabditis elegans,as model organisms used to screen the active components of traditional Chinese medicine were reviewed.

Impacts of Active Ingredients of Three Traditional Chinese Medicine on Immune Effect of PCV2 Vaccine

[ Objective ] The paper was to screen the active ingredients of traditional Chinese medicine （ TCM）, which significantly enhanced the immune effect of porcine circovirus type 2 （PCV2） vaccine. [Method]Sixty-six 14-day-old piglets were randomly divided into 11 groups, including immune control group, blank control group and nine drug groups. Piglets that were reared for 21 d were intramuscularly injected with 2 mL of inactivated vaccine in cervical region expect for blank control group. Piglets in nine drug groups were administrated with 5 mL of matrine, scutellarin and astragalus polysaecharide （ASP） at three doses （ high dose 12 mg, medium dose 8 nag, low dose 4 mg） three days before and after immunization; piglets in blank control group and irmnune control group were administrated with equal volume of normal saline. Five piglets were randomly selected from each group to collect venous blood at 7, 14, 21 and 28 d post immunization, and the PCV2 antibody level, the concentration of specific immunoglobulin [gG, the changes in peripheral blood lymphocyte subsets, and the content of serum IL-2 and IFN-γ were determined. [ Result] The immunological effects of active ingredients of three TCM on PCV2 vaccine all enhanced at different degree. The effects of scutellarin middle dose group was the best. [ Conclusion ] Scutellarin could be used as a candidate drug for PCV2 vaccine immunoenhancer.

Advances in Pharmacological Research on Active Components of Traditional Chinese Medicine in the Treatment of Inflammatory Bowel Disease-related Bowel Cancer

In recent years,with the modern development of traditional medicine,the research on the treatment of inflammatory bowel disease and bowel cancer is increasingly deep.This paper reviews the pharmacological research progress of flavonoids,alkaloids,polyphenols,polysaccharides,steroids and saponins in the treatment of inflammatory bowel disease and canceration.

Pharmacokinetics of Two Ingredients of the Compound Chinese Herbal Medicine Transdermal Preparation in Cows

The topical administration of the compound Chinese herbal medicine transdermal preparation has been widely used in treating the mastitis of cows. In order to understand the metabolic process, four cows suffering from clinical mastitis were selected for the pharmacokinetic study. The transdermal preparation was applied to the diseased part of breast. Then the plasma and milk samples were collected respectively at 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, and 36 h, The concentrations of baicalin and phillyrin in plasma and milk were determined by HPLC and the data of time-concentrations were analyzed by the pharmacokinetic software. The results showed that two ingredients in the plasma were not detectable, but they in the milk had linear relationship with the time. The peak concentration of baicalin [（2.84 ±0.15）μg mL^-1] appeared at （4.93 ± 0.35） h, AUC0.1OQ was （27.32 ± 7.91） mg L^-1 h^-1, and the mean retention time was （28.31 ±0.49） h. The peak concentration of phillyrin [（0.49 ± 0.41） μg mL^-1] achieved at （3.68 ± 3.14） h, AUC0-LOQ was （4.10± 0.31） mg L^-1 h^-1, and the mean retention time was （14.52 ± 0.02） h. These suggested that two ingredients had slow absorbing speed and high absorbing degree. They could not be eliminated in a short time, thus exerted the topical curative effect.

Inhibition of growth and metastasis of triple-negative breast cancer targeted by Traditional Chinese Medicine Tubeimu in orthotopic mice models

Objective： Triple-negative breast cancer（TNBC） is highly invasive and metastatic, which is in urgent need of transformative therapeutics. Tubeimu（TBM）, the rhizome of Bolbostemma paniculatum（Maxim.） Franquet, is one of the Chinese medicinal herbs used for breast diseases since the ancient times. The present study evaluated the efficacy, especially the anti-metastatic effects of the dichloromethane extract of Tubeimu（ETBM） on TNBC orthotopic mouse models and cell lines.Methods： We applied real-time imaging on florescent orthotopic TNBC mice model and tested cell migration and invasion abilities with MDA-MB-231 cell line. Digital gene expression sequencing was performed and Kyoto Encyclopedia of Genes and Genomes（KEGG） analysis applied to explore the pathways influenced by ETBM.Moreover, quantitative real-time polymerase chain reactions（q RT-PCR） and Western blot were delivered to confirm the gene expression changes.Results： ETBM exhibited noticeable control on tumor metastasis and growth of TNBC tumors with no obvious toxicity. In compliance with this, it also showed inhibition of cell migration and invasion in vitro. Its impact on the changed biological behavior in TNBC may be a result of decreased expression of integrin β1（ITGβ1）, integrin β8（ITGβ8） and Rho GTPase activating protein 5（ARHGAP5）, which disabled the focal adhesion pathway and caused change in cell morphology.Conclusions： This study reveals that ETBM has anti-metastatic effects on MDA-MB-231-GFP tumor and may lead to a new therapeutic agent for the integrative treatment of highly invasive TNBC.

Chinese medicine active ingredients or monomers increase neuronal synaptic plasticity

Totally three articles focusing on Schisandra N-butanol extract effects on hippocampal CA1 synaptic morphology and plasticity in ovarectomized mice, as well as catalpol and GBE50 effects on neuronal synaptic plasticity in the motor cortex following cerebral ischemia were published in three issues. We hope that our readers find these papers useful to their research.

Research Progress of Traditional Chinese Medicine in Treating Irritable Bowel Syndrome Based on Network Pharmacology and Molecular Docking Technology

In recent years,using network pharmacology and molecular docking technology to reveal the therapeutic targets of irritable bowel syndrome(IBS)has become a research hotspot.This paper summarizes 31 studies of traditional Chinese medicine for IBS by domestic and foreign scholars,and expounds the action mechanism of single drug,drug pair and compound prescription in the treatment of IBS from the aspects of drug activity,action target,biological process and pathway analysis.It also discusses the shortcomings and prospects of network pharmacology and molecular docking technology in the field of traditional Chinese medicine research,and provides reference for expanding the research ideas of traditional Chinese medicine in treating IBS.

Progress on antioxidant activity of single or compound traditional Chinese medicine

Oxidative stress plays a key role in the pathogenesis of various diseases.Nature antioxidants derived from traditional Chinese medicine protect the cells and tissues from oxidative stress by scavenging free radicals and reactive oxygen species,therefore have a great potential in delaying ageing process and preventing oxidative stress-related disease.In this article,the antioxidant benefits of common single and compound traditional Chinese medicine in protecting tissues from injury are reviewed,along with identification of the various constituents that possess antioxidant activity and its mechanism were reviewed.

A Systematic Review on Chemical Constituents of Suanzaoren Decoction, a Traditional Chinese Medicine Prescription

Traditional Chinese Medicine prescription Suanzaoren decoction (SZRD) is composed of Ziziphi Spinosae Semen, Chuanxiong Rhizoma, Anemarrhenae rhizoma, Poria and Licorice. It was used to treat central nervous system diseases such as insomnia and anxiety for thousands of years. This paper aims to systematically understand varieties and quantities of compounds and clarify chemical components of SZRD, subsequently to further provide the reference for phytochemistry and pharmacology researches of SZRD. Our results showed that SZRD contained 145 components, including flavonoids, triterpenoids, steroids, coumarins, phthalides, and volatile oils, etc., while five-single herbs contain 1104 components. Only in terms of compound number, there were 80 common components in SZRD and its five herbs, which accounted for 6.8% of total compounds in all 5 herbs and 55.2% of compounds in SZRD. The components of SZRD were not simply the sum of one in every single herb. It is necessary to perform parallel studies among SZRD and its herbs. This review discussed the problems that existed in the chemical research of SZRD and pointed out the direction for its further research.

Similarity measurement of Chinese medicine ingredients for cold-hot nature identification

Objective:Nature theory of Chinese medicine (CM) is the core basic theory of Traditional Chinese Medicine (TCM), in which cold-hot nature is the focus of research. Studies have found that CM ingredients are the material basis for the production of medicine natures. Therefore, it is speculated that CMs with similar composition of substances should have similar medicinal nature. Modern work studies cold-hot medicine of CMs with chemical fingerprinting technology because the chemical fingerprint data of CM can reflect the whole composition of CM ingredients. Methods:To verify the hypothesis above, in this work, we study quantifying the similarity of CM ingredients to fingerprint similarity, and explore the relationship between the composition of CMs and cold-hot nature. Firstly, we utilize ultraviolet (UV) spectrum technology to analyze 61 CMs, which have clear cold-hot nature (including 30 ‘cold’ CMs and 31 ‘hot’ CMs). Secondly, with the constructed fingerprint database of CMs, a distance metric learning algorithm is studied to metric the similarity of UV fingerprints. Finally, a retrieval scheme is proposed to build a predictive identification model to identify cold-hot nature of CMs. Results:By means of numerous experiment analyses, ultraviolet spectrum data of petroleum ether solvent can better represent CMs to distinguish between cold and hot natures. Comparing with existing classical models, the proposed identification scheme has better predictive performance. Conclusion:The experimental results prove our inference that CMs with similar composition of substances should have similar medicinal nature. The proposed prediction model is proved to be effective and feasible.

Perspectives in application of biosensors for the modernization of traditional Chinese medicine

Biosensor is an instrument which is sensitive to biological material and converts its concentration into electrical signals.Organisms such as enzymes, antibodies, tissues, cells and so on can selectively identify specific substances. Thesemolecular recognition functions can be combined with the target, such as the binding of antibodies and antigens, and thebinding of enzymes to the substrate through the recognition process. Biosensor has the advantages of high specificity,high sensitivity, fast reaction speed, low cost and easy operation. It has wide application prospect in food, pharmacy,chemical industry, clinical examination, biomedicine, environmental monitoring and so on, especially as a newtechnology means, in the field of modern herbal medicine research influence. Studies have demonstrated that thebiosensing technology has been applied to, traditional Chinese medicine （TCM） targets, isolation and purification ofTCM, the mechanism of TCM, quality control of TCM, the active ingredients detection of TCM and other basicresearches. Biosensor technology has made an important contribution to the research of modern herbal medicine, and hasbecome a Hot-spot in future research.

Research progress of traditional Chinese medicine monomers in intervening colorectal cancer by regulating MAPK signaling pathway

The incidence rate and mortality rate of colorectal cancer in China are increasing year by year.Finding effective therapeutic strategies and interventions,especially exploring“highly effective and low toxic”drugs to prevent“inflammation-cancer”transformation,treat primary tumors,prevent tumor metastasis and reduce the toxicity and increase efficiency of existing therapies has become a hot topic of domestic and foreign scholars.The advantage of traditional Chinese medicine in the treatment of colorectal cancer is to reduce the postoperative recurrence rate,improve patients’symptoms and the quality of life of“tumor survivors”and prolong the survival time.This paper summarizes the tumor treatment strategies and research prospects of traditional Chinese medicine targeting mitogen activated protein kinase by sorting out the mechanism of traditional Chinese medicine extracts or effective components intervening colorectal cancer by regulating mitogen activated protein kinase signal pathway in tumor cells in recent years.

Research Progress of Chinese Medicine Used in Treating COVID-19

The outbreak of COVID-19 has brought great health threat to human beings all over the world,it also brings great challenges to the development of medicine.Several traditional Chinese medicines have good effects on treating pneumonia patients in COVID-19.In this article,the active composition,pharmacological mechanism and clinical practice of these traditional Chinese medicines were reviewed.This will be of positive significance to the further research and clinical application of traditional Chinese medicine for treating COVID-19 pneumonia.

Antioxidant Activity of 50 Traditional Chinese Medicinal Materials Varies with Total Phenolics

This study was designed to determine the total phenolic content of 50 herbs and to examine their antioxidant potential. In the sample preparation, 60% ethanol was chosen as the extraction solvent for the subsequent experiments. Folin-Cicolteau phenol reagent and a colorimetric method were used to determine the total phenolic content of the selected herbs. The result showed that total phenolic content of those herbs ranged from 2 to 185 mg/g. In antioxidant assay, the ferric reducing/antioxidant power (FRAP) values ranged from 2 to 134 mg GAE/g;the IC50 values of DPPH?·, ·OH and ?scavenging were in the range of 0.06 - 5.50 mg/mL, 0.017 - 0.636 mg/mL and 0.050 - 0.681 mg/mL respectively. Flos caryophylli was the exceptant in the ?scavenging assay because there was no linear relation between the concentration and the scavenging percentage. Compared to gallic acid, ascorbic acid and butylated hydroxytoluene (BHT) in antioxidant assay as positive control, the most potential antioxidant herbs were Cacumen platycladi, Radix et Rhizoma rhei, Rhizoma rhodiolae crenulatae, and Rhizoma sanguisorbae with considerable content of phenolics. Especially, a positive and significant correlation was found between the total phenolic content and FRAP value or DPPH· scavenging percentage.

Multi-layered effects of Codonopsis Radix on the immune system

Recent research has highlighted the potential of Codonopsis Radix to modulate the immune system,making it a promising candidate for treating chronic inflammatory and cardiovascular diseases,tumors,and aging.However,because of the complex immune activities of its various components,a comprehensive understanding of Codonopsis Radix immune-regulating properties is still lacking.This knowledge gap hinders its widespread utilization in clinical practice.Therefore,this review aimed to assess the impact of Codonopsis Radix on the immune system and elucidate its underlying mechanisms.Additionally,we compared the immunomodulatory effects of different active ingredients derived from Codonopsis Radix to provide a theoretical basis for future investigations on immunomodulation.

Traditional Chinese medicine for activating blood circulation and detoxifying in unstable angina pectoris:A systematic review and meta-analysis

Objective:The purpose of this review was to evaluate the effectiveness of traditional Chinese medicine for activating blood circulation and detoxifying(ABCD)in patients with unstable angina pectoris.Methods:We performed an electronic literature search of six medical databases for relevant articles published up to December 2014.Randomized controlled trials that compared ABCD Chinese medicine(alone or alongside conventional drugs)with conventional drugs or other Chinese medicines alone were included.A meta-analysis was performed for the following outcome measures:reduction of angina symptoms,electrocardiogram improvement,blood lipid levels,inflammatory factor levels,and plasma fibrinogen levels.Results:In total,11 moderate-to low-quality studies involving 686 patients were included.The evidence indicated that ABCD Chinese medicine exhibited superior effectiveness in relieving angina symptoms compared with conventional drugs[relative risk,1.23;95%confidence interval,1.05e1.44];however,electrocardiogram improvement was not very significant(relative risk,1.21;95%confidence interval,0.91e1.62).Moreover,ABCD Chinese medicine exhibited superior anti-inflammatory,anticoagulant,and lipid-lowering effects compared with other medicines.Conclusions:Within the methodological limitations of the included studies,our results suggest that ABCD Chinese medicine is beneficial for the treatment of unstable angina pectoris.

Effects of ginger moxibustion combined with Chinese medicine iontophoresis on patients with primary dysmenorrhea

Objective:To observe the effects of Ginger moxibustion combined with iontophoresis with traditional Chinese medicine on the improvement of symptoms, serum platelet activating factor (PAF) level and uterine artery pulsation index in patients with primary dysmenorrhea.Methods 114 patients with primary dysmenorrhea who were treated in our hospital from August 2017 to February 2019 were divided into two groups according to the different treatment schemes. 57 patients in the control group were treated with ibuprofen capsules, and 57 patients in the study group were treated with Ginger moxibustion combined with iontophoresis with traditional Chinese medicine. After three menstrual cycles of treatment, the curative effect was evaluated and the improvement of symptoms was counted. PAF, PAF-AH and platelet adhesion rate were compared, uterine artery hemodynamics was measured, and levels of serum hs-CRP and IL-6 were measured.Results The overall response rate of the study group was significantly higher than that of the control group (P < 0.05). After treatment, the scores of different symptoms in the two groups were significantly lower than those before treatment (P < 0.05), and the scores of different symptoms in the study group were significantly lower than those in the control group (P < 0.05). After treatment, PAF and platelet adhesion rate in the two groups were significantly lower than those before treatment (P < 0.05), PAF-AH was significantly higher than that before treatment (P < 0.05), and PAF and platelet adhesion rate in the study group were significantly lower than those in the control group (P < 0.05), PAF-AH was significantly higher than that in the control group (P < 0.05). After treatment, the pulsation index, resistance index and peak systolic-diastolic ratio in the study group were significantly lower than those before treatment (P < 0.05), and the pulsation index, resistance index and peak systolic-diastolic ratio in the study group were significantly lower than those in the control group (P < 0.05). After treatment, the levels of serum hs-CRP and IL-6 in the two groups were significantly lower than those before treatment (P < 0.05), and the levels of serum hs-CRP and IL-6 in the study group were significantly lower than those in the control group (P < 0.05).Conclusions Ginger moxibustion combined with iontophoresis with traditional Chinese medicine is helpful to improve the overall response rate of primary dysmenorrhea treatment, reduce the score levels of different symptoms, rationally improve PAF, PAF-AH, platelet adhesion rate, and the pulse index, resistance index, peak systolic-diastolic ratio are decreased significantly, and serum hs-CRP and IL-6 levels tend to be normal.

Development of Chinese herbal medicine for sensorineural hearing loss

According to the World Health Organization’s world report on hearing,nearly 2.5 billion people worldwide will suffer from hearing loss by 2050,which may contribute to a severe impact on individual life quality and national economies.Sensorineural hearing loss(SNHL)occurs commonly as a result of noise exposure,aging,and ototoxic drugs,and is pathologically characterized by the impairment of mechanosensory hair cells of the inner ear,which is mainly triggered by reactive oxygen species accumulation,inflammation,and mitochondrial dysfunction.Though recent advances have been made in understanding the ability of cochlear repair and regeneration,there are still no effective therapeutic drugs for SNHL.Chinese herbal medicine which is widely distributed and easily accessible in China has demonstrated a unique curative effect against SNHL with higher safety and lower cost compared with Western medicine.Herein we present trends in research for Chinese herbal medicine for the treatment of SNHL,and elucidate their molecular mechanisms of action,to pave the way for further research and development of novel effective drugs in this field.