Traditional Chinese Medicine Herbal Formula Research Articles

Intranasal administration of the essential oil from Perillae Folium ameliorates social defeat stress-induced behavioral impairments in mice

Ethnopharmacological relevancePerillae Folium, the leaves and twigs of Perilla frutescens (L.) Britton, has been included in many traditional Chinese medicine herbal formulas to treat depression. However, the precise antidepressant mechanism of the essential oil from Perillae Folium (PFEO) has not been fully investigated. Aim of the studyTo assess the effects and potential mechanisms of PFEO on depression using animal models and network pharmacology analysis. Materials and methodsPFEO was intranasally administered to a mouse model of social defeat stress (SDS). The antidepressant effects of PFEO on SDS-induced mice were evaluated using behavioral tests. Enzyme-linked immunosorbent assay (ELISA) and western blot were performed to measure the levels of depression-related biomarkers in the hippocampus and serum of the mice. The chemical compounds of PFEO were determined using gas chromatography-mass spectrometry (GC-MS). Network pharmacology and molecular docking analyses were conducted to investigate the potential bioactive components of PFEO and the mechanisms underlying the antidepressant effects. To validate the mechanisms of the bioactive compounds, in vitro models using PC12 and BV2 cells were established and the blood-brain barrier (BBB) permeability was evaluated. ResultsThe intranasal administration of PFEO suppressed SDS-induced depression in mice by increasing the time spent in the social zone and the social interactions in the social interaction test and by decreasing the immobility time in the tail suspension and forced swimming tests. Moreover, the PFEO treatment reduced the SDS-induced anxiety-like behavior, as inferred from the increased activity in the central zone observed in the open field test and in the open arms observed in the elevated plus maze test. PFEO administration recovered the SDS-induced decrease in the levels of 5-HT, NE, gamma-aminobutyric acid (GABA), and p-ERK in the hippocampus of mice. Furthermore, the increased serum corticosterone level was also attenuated by the PFEO treatment. A total of 21 volatile compounds were detected in PFEO using GC-MS, among which elemicin (15.52%), apiol (15.16%), and perillaldehyde (12.79%) were the most abundant ones. The PFEO compounds targeted 32 depression-associated genes, which were mainly related to neural cells and neurotransmission pathways. Molecular docking indicated good binding affinities between the bioactive components of PFEO (apiol, β-caryophyllene, elemicin, and myristicin) and the key targets, including ACHE, IL1B, IL6, MAOB, SLC6A2, SLC6A3, SLC6A4, and tumor necrosis factor. Among the four compounds, β-caryophyllene, elemicin, and myristicin were more effective in reducing neurotoxicity and neuroinflammation. Elemicin showed the highest BBB permeability rate. ConclusionsThis study shows the antidepressant activities of PFEO in an SDS-induced mouse model and suggests its potential mechanisms of action: regulation of the corticosterone levels, hippocampal neurotransmitters, and ERK signaling. Apiol, β-caryophyllene, elemicin, and myristicin may be the main contributors to the observed effects induced by PFEO. Further studies are needed to fully elucidate the underlying mechanisms and the main PFEO bioactive components.

Nutrients and Botanical Medicines in Systemic Lupus Erythematosus

Lupus is a chronic autoimmune disease which can affect multiple systems throughout the body, characterized by the formation and deposition of autoantibodies and immune complexes in vital organs. The goals of standard lupus treatment include the prevention of chronic organ damage and reduction of disease flares, and may include hydroxychloroquine, corticosteroids, and immunosuppressives. A number of botanical medicines or nutrients may have a role alongside conventional management of lupus. These include green tea extract, curcumin, Traditional Chinese Medicine herbal formulas, N-acetylcysteine, vitamin D, and fish oil. This article reviews the clinical evidence for these nutrient or herbal medicine-based interventions and discusses outcomes in people with lupus.

Wogonin, a Bioactive Ingredient from Huangqi Guizhi Formula, Alleviates Discogenic Low Back Pain via Suppressing the Overexpressed NGF in Intervertebral Discs.

To investigate whether wogonin, a key bioactive ingredient of Huangqi Guizhi formula (HQGZ formula; a Traditional Chinese Medicine herbal formula) according to network pharmacology analysis, has analgesic effects on discogenic low back pain (LBP) via regulating the nerve growth factor (NGF) in intervertebral discs (IVDs). The lumbar IVDs of rats were punctured to discogenic LBP, and the therapeutic effect of orally administrated HQGZ for discogenic LBP was investigated by measuring mechanical and cold allodynia and histological analysis. A network pharmacology analysis was conducted to search for bioactive ingredients from the HQGZ formula, and wogonin was suggested to be the most possible bioactive ingredient for LBP treatment. Subsequently, the analgesic effect of wogonin was investigated in the LBP model, and the gene expression of propain peptides in the bilateral dorsal root ganglia was analyzed using RT-PCR. Finally, immunohistochemical staining was performed for NGF expression of NGF in the IVDs to determine whether wogonin treatment would ameliorate NGF-induced LBP. Oral administration of HQGZ for two weeks significantly ameliorated puncture-induced IVD degeneration (IDD) and LBP. In addition, the network pharmacology analysis revealed that wogonin, quercetin, and kaempferol were the potential candidate components of HQGZ for LBP treatment. Furthermore, we proved that wogonin had significant analgesic effects in the LBP model. Finally, wogonin was demonstrated to suppress the upregulated NGF in the IVD and ameliorate NGF-induced LBP in rats. The HQGZ formula has significant analgesic effects for LBP. In addition, the bioactive ingredient of wogonin was extracted from HQGZ and ameliorated LBP by suppressing the overexpressed NGF in degenerated IVDs. Therefore, wogonin has potential to be alternative treatment for LBP in clinical.

QiHuangYiShen Granules Modulate the Expression of LncRNA MALAT1 and Attenuate Epithelial-Mesenchymal Transition in Kidney of Diabetic Nephropathy Rats.

QiHuangYiShen granules (QHYS), a traditional Chinese herbal medicine formula, have been used in clinical practice for treating diabetic kidney disease for several years by our team. The efficacy of reducing proteinuria and delaying the decline of renal function of QHYS has been proved by our previous studies. However, the exact mechanism by which QHYS exerts its renoprotection remains largely unknown. Emerging evidence suggests that lncRNA MALAT1 is abnormally expressed in diabetic nephropathy (DN) and can attenuate renal fibrosis by modulating podocyte epithelial-mesenchymal transition (EMT). In the present study, we aimed to explore whether QHYS could modulate lncRNA MALAT1 expression and attenuate the podocyte EMT as well as the potential mechanism related to the Wnt/β-catenin signal pathway. SD rats were fed with the high-fat-high-sucrose diet for 8 weeks and thereafter administered with 30 mg/kg streptozotocin intraperitoneally to replicate the DN model. Quality control of QHYS was performed using high-performance liquid chromatography. QHYS were orally administered at 1.25, 2.5, and 5 g/kg doses, respectively, to the DN model rats for 12 weeks. Body weight, glycated haemoglobin, blood urea nitrogen, serum creatinine, 24-h proteinuria, and kidney index were measured. The morphologic pathology of the kidney was evaluated by Hematoxylin-eosin and Masson's trichrome staining. The expression level of lncRNA MALAT1 was determined by quantitative real-time polymerase chain reaction. In addition, the expression levels of podocyte EMT protein markers and Wnt/β-catenin pathway proteins in renal tissues were evaluated by Western blotting and immunohistochemistry. The results showed that QHYS significantly reduced 24-h proteinuria, blood urea nitrogen, kidney index, and ameliorated glomerular hypertrophy and collagen fiber deposition in the kidney of DN rats. Importantly, QHYS significantly downregulated the expression level of lncRNA MALAT1, upregulated the expression of nephrin, the podocyte marker protein, downregulated the expression of desmin and FSP-1, and mesenchymal cell markers. Furthermore, QHYS significantly downregulated the expression levels of Wnt1, β-catenin, and active β-catenin. Conclusively, our study revealed that QHYS significantly reduced proteinuria, alleviated renal fibrosis, and attenuated the podocyte EMT in DN rats, which may be associated with the downregulation of lncRNA MALAT1 expression and inhibition of the Wnt/β-catenin pathway.

Ontology characterization, enrichment analysis, and similarity calculation‐based evaluation of disease–syndrome–formula associations by applying SoFDA

AbstractClinical symptom‐based diagnosis and therapy play a crucial role in personalized medicine and drug discovery. The syndromes, distinctive groups of clinical symptoms summarized by traditional Chinese medicine (TCM) theories and clinical experiences, are used as the core diagnostic criteria and therapeutic guidance in TCM. However, there is still a lack of standardized data, information, and intrinsic molecular basis to help TCM syndromes better classify diseases and guide tailored medications. To address this problem, we built the first integrated web platform, SoFDA (http://www.tcmip.cn/Syndrome/front/), with a curated ontology of 319 TCM syndromes, 8045 diseases, and 1359 TCM herbal formulas and their relationships with genes, diseases, and formulas. This platform proposed an association measurement by calculating Jaccard/Cosine similarities between TCM syndromes and their related biomedical entities with case and control validations. On this basis, the SoFDA platform enables biomedical and pharmaceutical scientists to rank and filter the most promising associations for disease diagnosis and tailored interventions. Conversely, the targeted gene sets and symptom sets can also be associated with TCM syndromes, formulas, and diseases for function illustration. Notably, SoFDA explores the multi‐way associations among diseases, TCM syndromes, symptom genes, herbal formulas, drug targets, and pathways in heterogeneous biomedical networks with lots of customization. The protocol here implements all the analyses above using the SoFDA platform. Collectively, SoFDA may provide insights into the biological basis of disease‐specific TCM syndromes and the underlying molecular mechanisms, as well as a tailored treatment for single or multiple symptoms within a syndrome.

Data Mining-Based Analysis for Salt-Related Traditional Chinese Medicine Herbal Formulas in the Treatment of Urogenital Dysfunctions

To analyze the rules of salt-related traditional Chinese medicine herbal formulas of urogenital dysfunctions using data mining, the results could provide novel prescriptions and give suggestions to clinical application. The data mining methods used in this study including frequency analysis, cluster analysis and association rule. A total of 108 formulas involving 141 herbs were included in this study. The most frequently used herb is Poria (Fuling). The top three categories were deficiency-tonifying herbs (34.07 %), astringent herbs (11.85 %) and emetic herbs (10.09 %). The properties of the herbs were mainly being warm (403), cold (334) and calm (304). The tastes of the herbs were mainly sweet (699) and bitter (316). The main meridian tropisms were kidney meridian of foot-shaoyin (726), liver meridian of foot-Jueyi (418), spleen meridian of foot-Taiyin (406). The main formulas for spermatorrhea are Yangxin Zishen pill (71). The top two formulas of stranguria were Bixie Fenqing decoction (1354). According to the cluster analysis, the high-frequency herbs were divided into 8 salt-related categories. According to association rule analysis, 16 common salt-related couplets medicines were obtained. The treatment of urogenital dysfunctions is mostly clearing, tonifying and astringing methods. The law of medicines compatibility and the application of meridian ushering herbs have high reference value for the clinical treatment of urogenital dysfunctions.

Advances in basic research of traditional Chinese medicine herbal formulae in the treatment of non-small cell lung cancer

Today, there is an increasing rate of morbidity and mortality in lung cancer worldwide. In China, lung cancer is also the leading cause of cancer-related death in China. The distinctive herbal therapy from traditional Chinese medicine (TCM) has shown good efficacy in treating lung cancer principally by inhibiting tumor growth or improving the anti-tumor immune response according to considerable experimental studies, which also justifies the concept of dispelling pathogenic qi and strengthening healthy qi in TCM.

Anticancer potential of indirubins in medicinal chemistry: Biological activity, structural modification, and structure-activity relationship.

Indirubin is the crucial ingredient of Danggui Longhui Wan and Qing-Dai, traditional Chinese medicine herbal formulas used for the therapy of chronic myelocytic leukemia in China for hundreds of years. Although the monomeric indirubin has been used in China for the treatment human chronic myelocytic leukemia. However, due to low water solubility, poor pharmacokinetic properties and low therapeutic effects are the major obstacle, and had significantly limited its clinical application. Consequently, the attractive anticancer profile of indirubin has enthused numerous researchers to discover novel indirubin derivatives with improved pharmacodynamic activity as well as good pharmacokinetic property. In this paper, we comprehensively review the recent progress of anticancer potential of indirubins, structural modification and structure-activity relationship, which may provide useful direction for the further development of novel indirubins with improved pharmacological profiles for the treatment of various types of cancer.

Traditional Chinese Medicine formula FTZ protects against polycystic ovary syndrome through modulating adiponectin-mediated fat-ovary crosstalk in mice

Ethnopharmacological relevanceFuFang ZhenZhu TiaoZhi (FTZ) is a hospitalized traditional Chinese medicine herbal formula with documented metabolic benefits. Polycystic ovary syndrome (PCOS) characterized by ovarian dysfunction and insulin resistance represents one of the most common endocrine disorders in close association with metabolic dysfunction in premenopausal women.Aim of The Study: The present study aimed to investigate the preventive effect of FTZ on letrozole-induced experimental PCOS and its associated insulin resistance in mice. Materials and methodsPrepubertal female mice in the experimental groups (letrozole and FTZ) received continuous infusion of letrozole (50 μg/day) for 35 days. FTZ was administrated to mice by oral gavage daily at dosage of 2.892 g/kg body weight for 5 weeks. All groups of mice were fed a high-fat diet (HFD). Ovary and adipose tissue were collected from all mice after 5 weeks and adiponectin, testosterone, estradiol, and luteinizing hormone level determined. ResultsLetrozole-induced morphological changes in the ovary, including a decreased number of corpora lutea and antral follicles, and increased cystic follicles, were significantly attenuated in FTZ-treated mice. Additionally, FTZ treatment notably reversed PCOS-related disruption of estrous status. PCOS-related insulin resistance was markedly alleviated. Mechanistically, FTZ treatment notably enhanced circulating level and transcriptional abundance of adiponectin in adipose tissue, thereby orchestrating fat-ovary crosstalk. ConclusionsOur data collectively demonstrate that FTZ exerted preventive benefits in an experimental model of PCOS, at least partially by potentiating the production of adiponectin from adipose tissues. This suggests that FTZ is a promising treatment for PCOS.

Analysis of Chinese Herbal Formulae Recommended for COVID-19 in Different Schemes in China: A Data Mining Approach.

Novel coronavirus pneumonia (NCP), or coronavirus disease 2019 (COVID-19), is a worldwide health threat that has affected millions of people globally. Traditional Chinese medicine (TCM) has been introduced for the treatment of COVID-19. However, efficacy differs among herbal medicines, and the ideal prescription pattern for TCM herbal formulae for COVID-19 treatment needs to be explored. Therefore, the data mining method has been used in this study to analyze the TCM prescription pattern for COVID-19. The aim of this study was to analyze the TCM prescription pattern in Regional Schemes in China for COVID-19 in order to provide a new reference for the use of TCM in COVID-19 treatment. By searching the TCM treatment protocols of COVID-19 in 23 Regional Schemes, TCM syndromes and herbal medicines were analyzed by data mining. The Ancient and Modern Medical Case Cloud Platform (V2.1 personal Edition) was used to perform frequency statistics, correlation analysis, and cluster analysis. A total of 82 TCM syndromes and 171 Chinese herbal medicines were found. The course of the disease can be divided into the early stage, middle stage, severe stage, and recovery stage. In the early stage, the focus is primarily on resolving dampness, dispelling cold, and diffusing the lungs. In the middle stage, the treatment priority is clearing heat and resolving toxins, promoting lung function, and relieving asthma. In the severe stage, the focus is on tonifying Qi, restoring Yang, and relieving the depletion of Yin and Yang. In the recovery stage, the main treatment is to invigorate the spleen and regulate Qi, tonify Qi, nourish Yin, and clear residual disease. There are certain differences between the Regional Schemes and the Nation Schemes, but the core prescription pattern of the former is consistent with the latter. The effectiveness of these 171 Chinese herbs include but are not limited to inhibiting COVID-19, strengthening immune system function, preventing heart failure, acting as antioxidants, oxidative stress inhibitory effects, maintaining organ function, and improving leukocyte survival. This study may help to improve understanding of TCM herbal prescription pattern, practices, reveal the efficacy of combinations of Chinese herbs, and provide new ideas for TCM treatment for COVID-19.

The Effects of a Traditional Chinese Medication on Children with Attention-Deficit/Hyperactivity Disorder.

Objective: This feasibility study examined the effects of a particular Traditional Chinese Medicine (TCM) herbal formula on attention-deficit/hyperactivity disorder (ADHD) and related problem behaviors. Design: A total of 79 participants aging 6-12 years consumed a granulated TCM herbal formula twice daily over a period of 3 months and underwent assessments at months 0, 3, and 6. Changes in ADHD symptoms and related behaviors were measured using the ADHD rating scale-IV (ADHD-RS-IV), child behavior checklist (CBCL), children's global sssessment scale (CGAS), as well as the clinical global impressions-severity (CGI-S) and improvement (CGI-I) scales. Results: Repeated measures mixed model analyses revealed significant differences in scores across time on all ADHD-RS-IV and CBCL subscales as well as on the CGAS, CGI-S, and CGI-I scales. Pairwise comparisons between months 0 and 3 as well as months 0 and 6 indicated significant improvements in scores. Scores also did not differ significantly between months 3 and 6. The results may suggest that this particular TCM formula possesses potential therapeutic qualities in the treatment of ADHD. Furthermore, changes in ADHD symptoms generally appear to be stable 3 months after discontinuation. However, these findings could also be attributed to placebo effects as well as reporting biases. Conclusion: This particular TCM formula may prove to be a useful adjunctive treatment for children with ADHD, and randomized controlled trials need to be conducted to evaluate its efficacy.

The effects of a new, improved Chinese medicine, Gengnianchun formula granules, on hot flushes, depression, anxiety, and sleep in Chinese peri- and postmenopausal women: a randomized placebo-controlled trial.

The aim of the study was to investigate the effectiveness and safety of a new, improved herbal formula of a traditional Chinese medicine, improved Gengnianchun (I-GNC), on hot flushes, depression, anxiety, and sleep in peri- and postmenopausal women in China. A randomized, single-blind, placebo-controlled trial of peri- and postmenopausal women with Kupperman Index (KMI) scores of 15 or higher was conducted for 12 weeks. Hot flush frequencies, KMI scores, Hamilton depression scale scores, Hamilton anxiety scale scores, and Pittsburgh Sleep Quality Index scores were evaluated. Each outcome was evaluated every 4 weeks. Ninety-eight participants completed the study. The I-GNC formula significantly reduced the mean (SD) frequency of hot flushes from 7 (4.554) to 1.2 (1.675) in the I-GNC group and from 6.74 (3.43) to 3.66 (2.635) in the placebo group (P < 0.01). The KMI (P < 0.01), Hamilton depression scale (P < 0.01), and Hamilton anxiety scale (P < 0.01) scores decreased in both groups after treatment, and significant differences were observed between the two groups (P < 0.01); however, no significant difference in the Pittsburgh Sleep Quality Index score was observed. I-GNC had no effect on serum follicle-stimulating hormone or E2 levels. There were no obvious adverse effects. The traditional Chinese medicine herbal formula I-GNC can alleviate the symptoms of menopausal syndrome and improve quality of life among peri- and postmenopausal women. I-GNC is safe and has no notable adverse effects.

Advances in anti hepatic fibrotic therapy with Traditional Chinese Medicine herbal formula.

The process of liver fibrogenesis includes a number of common and etiology-dependent or independent mechanisms and events. Up to now, there are still insufficient approved biological or chemical therapies directly targeting and reversing advanced fibrosis. The key is that once liver fibrosis is triggered, it presents a complex network control model with the activation of HSCs as the core, resulting in poor efficacy of treatment. Traditional Chinese medicine (TCM) has unique advantages in treating hepatic fibrosis because of its syndrome differentiation and treatment and comprehensive pharmacological effects of multi-channel, multi-level and multi-target. However, TCM's advantages were rarely discussed as previous reviews focused on the active ingredients of TCM and single Chinese Medicine. Therefore, this paper focuses on TCM herbal formulae's pharmacological role, target and related mechanisms in the treatment of liver fibrosis. This paper will focus on the pharmacological role, target and related mechanisms of TCM herbal formulae in the treatment of liver fibrosis. We collect English literatures or Chinese literatures with English Abstract on the treatment of liver fibrosis with TCM herbal formulae from databases including PubMed, Wiley InterScience, Science Direct OnSite/Elsevier, Ovid, Excerpta Medica Database, SpringLink, CNKI and China Biomedical Literature Database. Based on previous literatures, we summarize the TCM herbal formulae with definite anti-hepatic fibrosis effects. To some extent, classical or modern TCM herbal formulae including Yinchenhao Decoction (YCHD), Xiayuxue Decoction (XYXD), Xiaochaihutang (XCHT), Yiguanjian Decoction (YGJ), Huangqi Decoction (HQD), Dahuang Zhechong Pills (DHZC), Fuzheng Huayu Formula (FZHY), Fufang Biejia Ruangan Tablets (FFBJRG), Anluo Huaxian Pills (ALHX) and Compound 861 (Cpd861) have anti-hepatic fibrosis effect both on patients with liver fibrosis and animal models with liver fibrosis. According to the principle of syndrome differentiation and treatment, Liver fibrosis patients with different syndromes are treated with different herbal formula, which increases the difficulty of clinical efficacy research. YCHD and XYXD research lack randomized and controlled clinical trials. XCHT, YGJ and HQD research has small sample sizes despite randomized and controlled clinical trials. In contrast, most modern herbal formulae have randomized and controlled clinical trials. For instance, FZHY and ALHX recently published the research results of the combination of entecavir in the treatment of patients with chronic hepatitis B liver fibrosis or cirrhosis. Compared to anti-viral treatment with entecavir alone, this method has improved the reversion rate of liver fibrosis but still needs syndrome classification therapy of TCM. TCM Herbal formulae have a good prospect in treating liver fibrosis, but its composition of multiple drugs and a wide range of targets intensify the difficulty of studying their anti-hepatic fibrosis mechanisms. Future research needs to further study the anti-hepatic fibrosis mechanisms and select corresponding TCM herbal formula to treat patients with different syndromes of liver fibrosis or the same patient with different syndromes at different stages to achieve better curative results.

Jiao-tai-wan inhibits inflammation of the gut-brain-axis and attenuates cognitive impairment in insomnic rats.

Jiao-tai-wan is a well-known traditional Chinese herbal medicine formula that is used to treat insomnia and systemic inflammation. Studies indicate chronic insomnia might contribute to the prevalence of cognitive impairment. The role of systemic inflammation and intestinal permeability in the progression of neurodegenerative diseases attracts much attention. This study aimed to investigate if Jiao-tai-wan plays a role in promoting the repair of the intestinal epithelial barrier to suppress systemic inflammation and cognitive impairment in sleep-deprived (SD) rats. Male obesity-resistant SD rats were partially sleep-deprived for 16 weeks. During the last 8 weeks, they were treated with Jiao-tai-wan. A Morris water maze was used to analyze their cognitive ability. Aβ42 and proinflammation cytokines in the cerebrospinal fluid, tissue, or serum were determined using enzyme-linked immunosorbent assay or polymerase chain reaction. Intestinal permeability was detected using the fluorescein isothiocyanate-dextran perfusion assay method. Plasma lipopolysaccharide (LPS) levels were detected with Tachypleus Amebocyte Lysate. Western bolt was used in the signaling pathway analysis. Sleep deprivation deteriorated the performance of rats in the Morris water maze and increased the Aβ42, caspase3, IL-6, and TNF-α levels in their brains. The intestinal TLR4/NF-κB pathway was activated with an increase in the expression of IL-6 and TNF-α. The expression of tight junction proteins was also decreased in the intestinal tissue. This increased the intestinal permeability and circulation of LPS, LPS binding protein, IL-6, and TNF-α. Treatment with Jiao-tai-wan could partly reverse these changes. Jiao-tai-wan has the potential to attenuate systemic inflammation and cognitive impairment in partially sleep-deprived rats. The possible underlying mechanism is by preventing an inflammation trigger being transferred through the gut-brain-axis.

Identification of Constituents Affecting the Secretion of Pro-Inflammatory Cytokines in LPS-Induced U937 Cells by UHPLC-HRMS-Based Metabolic Profiling of the Traditional Chinese Medicine Formulation Huangqi Jianzhong Tang.

Within non-communicable diseases, chronic inflammatory conditions represent one of the biggest challenges for modern medicine. Traditional Chinese Medicine (TCM) has been practiced over centuries and has accumulated tremendous empirical knowledge on the treatment of such diseases. Huangqi Jianzhong Tang (HQJZT) is a famous TCM herbal formula composed of Radix Astragali, Ramulus Cinnamomi, Radix et Rhizoma Glycyrrhizae Praeparata cum Melle, Radix Paeoniae Alba, Rhizoma Zingiberis Recens, Fructus Jujubae and Saccharum Granorum (maltose), which has been used for the treatment of various chronic inflammatory gastrointestinal diseases. However, there is insufficient knowledge about its active constituents and the mechanisms responsible for its effects. The present study aimed at identifying constituents contributing to the bioactivity of HQJZT by combining in vitro cytokine production assays and LC-MS metabolomics techniques. From the HQJZT decoction as well as from its single herbal components, extracts of different polarities were prepared. Phytochemical composition of the extracts was analyzed by means of UPLC-QTOF-MS/MS. The inhibitory effects of the extracts on TNF-α, IL-1β and IFN-γ production were studied in U937 cells. Phytochemical and pharmacological bioactivity data were correlated by orthogonal projection to latent structures discriminant analysis (OPLS-DA) in order to identify those HQJZT constituents which may be relevant for the observed pharmacological activities. The investigations resulted in the identification of 16 HQJZT constituents, which are likely to contribute to the activities observed in U937 cells. Seven of them, namely calycosin, formononetin, astragaloside I, liquiritigenin, 18β-glycyrrhetinic acid, paeoniflorin and albiflorin were unambiguously identified. The predicted results were verified by testing these compounds in the same pharmacological assays as for the extracts. In conclusion, the anti-inflammatory activity of HQJZT could be substantiated by in vitro pharmacological screening, and the predicted activities of the OPLS-DA hits could be partially verified. Moreover, the benefits and limitations of MVDA for prediction pharmacologically active compounds contributing to the activity of a TCM mixture could be detected.

Antitumor Effects of Ruyiping on Cell Growth and Metastasis in Breast Cancer.

Background: Ruyiping is an effective traditional Chinese herbal medicine formula for preventing postoperative recurrence and metastasis of breast cancer. However, the exact function and underlying mechanism of Ruyiping in breast cancer remain unclear. Materials and Methods: After breast cancer cell lines MDA-MB-231 and MDA-MB-468 were treated with Ruyiping, the CCK8, colony formation, wound-healing, and transwell invasion assays were used to examine cell proliferation, migration, and invasion, respectively. Flow cytometry was performed to examine the effect of Ruyiping on cell cycle distribution. Western blot was performed to examine the expression of related proteins, and the activity of MMP9 was detected using Gelatin zymography assay. Results: Ruyiping treatment significantly inhibited cell proliferation and viability of MDA-MB-231 and MDA-MB-468 cells. Ruyiping was also revealed to trigger cell cycle arrest at the G2 phase in MDA-MB-231 and MDA-MB-468 cells. Moreover, Ruyiping suppressed the migration and invasion abilities of MDA-MB-231 and MDA-MB-468 cells in vitro. Furthermore, Ruyiping blocked the activity of MMP9 in MDA-MB-231 and MDA-MB-468 cells. Additionally, western blotting showed that Ruyiping attenuated epithelial-to-mesenchymal transition (EMT) of breast cancer through downregulation of N-cadherin, Vimentin, Snail1, and Snail2 and upregulation of E-cadherin. The authors observed that the components of Ruyiping Pseudobulbus Cremastra seu pleiones polysaccharide and curcumol showed significant suppression in the growth and invasion of breast cancer cell. Conclusions: The observations of this study suggest the antitumor properties of Ruyiping in cell growth and invasion of breast cancer, which are modulated by induction of cell cycle arrest and reduction of MMP9 and EMT.

Dai-Zong-Fang, A Traditional Chinese Herbal Formula, Ameliorates Insulin Resistance in db/db Mice.

Intricate health problems, such as insulin resistance (IR) and its associated diseases, call for multi-targeted therapies with few side effects. Based on traditional Chinese medicine (TCM), Dai-Zong-Fang (DZF) is an herbal formula mainly composed of Rhizoma Coptidis (Huanglian) and Fructus Aurantii Immaturus (Zhishi), of which berberine and naringin are the main constituents. Though DZF has been clinically used for treatment of IR and metabolic syndrome for decades, its mechanism in vivo remains unknown. In the present study, we observed that both DZF and metformin, the first-line drug for type 2 diabetes, ameliorated insulin resistance with significant improvement of oral glucose tolerance test (OGTT) and homeostasis model assessment of IR (HOMA-IR) level in diabetic C57BL/Ksj-Lepr db−/− (db/db) mice. Low-density lipoprotein cholesterol (LDL-C) and fatty acids (FAs) also decreased in the blood. Higher dose of DZF (1 g·kg−1), but not metformin (0.25 g·kg−1), alleviated hepatic steatosis with reduced liver weight and hepatic lipid accumulation and provided protection from hepatic injury with lower alanine aminotransferase and aspartate aminotransferase and increased hepatic superoxide dismutase activity in db/db mice. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) showed a decrease in FA synthase gene (Fasn) and an increase in FA oxidation gene Ppara expression. Western blot demonstrated that both DZF and metformin activated 5′ AMP-activated protein kinase (AMPK) but inhibited Notch intracellular domain (NICD) and Hairy/enhancer-of-split 1 (Hes1) of Notch signaling pathway in the liver. DZF also dramatically improved the ultrastructure of skeletal muscles, AMPK phosphorylation, and GLUT4 translocation. DZF also promoted FA transport and oxidation with Cd36 and Cpt1b up-regulation in the skeletal muscle. In conclusion, DZF improves insulin sensitivity by reducing hepatic lipids through AMPK activation and Notch signal pathway inhibition and enhancing energy metabolism in the skeletal muscle via AMPK. This study provides insights into the treatment of complex conditions, such as IR, where TCM herbal formulas exert multipronged effects through correlating pathways.

Design of new traditional Chinese medicine herbal formulae for treatment of type 2 diabetes mellitus based on network pharmacology

In the present study, 28 Chinese medicinal herbs belonging to traditional Chinese medicine (TCM) for the treatment of type 2 diabetes were selected to explore the application of network pharmacology in developing new Chinese herbal medicine formulae for the treatment of type 2 diabetes mellitus (T2DM). These herbs have the highest appearance rate in the literature, and their compounds are listed. The human protein–protein interaction network and the T2DM disease protein interaction network were constructed. Then, the related algorithm for network topology was used to perform interventions on the interaction network of disease proteins and normal human proteins to test different Chinese herbal medicine compound combinations, according to the information on the interaction of compounds–targets in two databases, namely TarNet and the Medicinal Plants Database. Results of the intervention scores indicate that the method proposed in this study can provide new effective combinations of Chinese herbal medicines for T2DM. Network pharmacology can effectively promote the modernization and development of TCM.

Rotective effect of Fengliao-Changweikang extracts, a traditional Chinese herbal medicine formula,on mucosa in rat with chronic gastritis

Background: Fengliao-Changwei-Kang(FCK), the Chinese patent drug, is a famous traditional Chinese herbal medicine formula. It has a significant effect on the clinic treatment of gastrointestinal diseases including gastritis, enteritis and diarrhea for many years. However, there is few research on the protective effects of FCK on the gastric mucosa of chronic gastritis (CG) model rat. Objective: The present study aimed to explore the effects of FCK extract on mucosa in rats with Chronic Gastritis.Materials and Methods: 50 SD mice were randomly divided into 5 groups with 10 in each group（five per sex). The groups are respectively control group, model group, low, middle and high FCK extracts (FCK I, II and III) group. The CG rat model was induced by synthetic methods. FCK I, II and III group were administrated with FCK extracts at 2.16g• kg, 4.32g• kg, 8.94g• kg once per day for 21 consecutive days, and the control group and model group were administrated the same volume of distilled water at 10mL/kg once per day. 16 hours after the last administration, the rats were anesthetized and their blood and stomach were drawn from vena cava and abdominal cavity. The serum levels of EGF was measured by enzyme linked immunosorbent assay(ELISA) method, the expression of growth factor receptor (EGFR) in gastric mucosa was detected by immunohistochemical method, and the mRNA expressions of NF-κB p65 was detected in-situ hybridization.Results: The inflammation grades and the expressions of NF-κB p65 mRNA in gastric mucosa of the model group were markedly higher than those of the control group (P&lt;0.05). The inflammation grades of gastric mucosa and the expressions of NF-κB p65 mRNA in gastric mucosa the FCK extract group are significantly lower than those of the model group, and the FCK extract group at 8.64g/kg could greatly increase the serum levels of EGF and the expressions of EGFR in gastric mucosa. High EGF level was found in FCK extract group at 4.32g/kg, but low in FCK extract groups at 2.16g/kg. There were no marked differences among the rats from control group, model group and FCK extract group on ratio of Ll/L2 (P&gt;0.05).Conclusions: FCK extract could alleviate mucosal inflammation by down regulating the expressions of NF-κB p65 mRNA and promote tissue repair by up regulating EGFR expression in gastric mucosa cell.Keywords: chronic gastritis; fengliao-changwei-kang extract; epidermal growth factor receptor; nuclear factor kappa B.

PROTECTIVE EFFECT OF FENGLIAO-CHANGWEIKANG EXTRACTS, A TRADITIONAL CHINESE HERBAL MEDICINE FORMULA,ON MUCOSA IN RAT WITH CHRONIC GASTRITIS

Background: Fengliao-Changwei-Kang(FCK), Chinese patent drug, is a famous traditional Chinese herbal medicine formula, which is effectively used to cure gastrointestinal disease including gastritis, enteritis and diarrhea in the clinic for many years. However, little research has been focused on the protective effects of FCK on the gastric mucosa of chronic gastritis (CG) model rat.&#x0D; Objective: The present study aimed to explore the effects of FCK extract on mucosa in rats with Chronic Gastritis.&#x0D; Materials and Methods: The CG rat model was induced by synthetic methods. The serum levels of EGF was measured by enzyme linked immunosorbent assay(ELISA) method, the expression of growth factor receptor (EGFR) in gastric mucosa was detected by immunohistochemical method, the mRNA expressions of NF-κB p65 was detected in-situ hybridization.&#x0D; Results: In the model group, the inflammation grades of gastric mucosa and the expressions of NF-κB p65 mRNA in gastric mucosa were markedly higher than those of the control group (P0.05).&#x0D; Conclusions: FCK extract could alleviate mucosal inflammation by down regulating the expressions of NF-κB p65 mRNA and promote tissue repair by up regulating EGFR expression in gastric mucosa cell.