Jiedu Decoction Research Articles

Decoding the Mechanism of Huanglian Jiedu Decoction in Treating Pneumonia Based on Network Pharmacology and Molecular Docking.

Huang-Lian-Jie-Du decoction (HLJDD) has been used to treat pneumonia for thousands of years in China. However, our understanding of its mechanisms on treating pneumonia is still unclear. In the present work, network pharmacology was used to analyze the potential active ingredients and molecular mechanisms of HLJDD on treating pneumonia. A total of 102 active ingredients were identified from HLJDD, among which 54 were hit by the 69 targets associated with pneumonia. By performing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, we obtained the main pathways associated with pneumonia and those associated with the mechanism of HLJDD in the treatment of pneumonia. By constructing the protein–protein interaction network of common targets, 10 hub genes were identified, which were mainly involved in the tumor necrosis factor (TNF) signaling pathway, interleukin 17 (IL-17) signaling pathway, and nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway. Moreover, the results of molecular docking showed that the active ingredients of HLJDD had a good affinity with the hub genes. The final results indicate that HLJDD has a greater effect on bacterial pneumonia than on viral pneumonia. The therapeutic effect is mainly achieved by regulating the host immune inflammatory response and oxidative stress reaction, antibacterial microorganisms, alleviating the clinical symptoms of pneumonia, repairing damaged cells, and inhibiting cell migration.

Huanglian Jiedu decoction remodels the periphery microenvironment to inhibit Alzheimer\u2019s disease progression based on the \u201cbrain-gut\u201d axis through multiple integrated omics

BackgroundIn recent years, excellent results have suggested an association between the “brain-gut” axis and Alzheimer’s disease (AD) progression, yet the role of the “brain-gut” axis in AD pathogenesis still remains obscure. Herein, we provided a potential link between the central and peripheral neuroinflammatory disorders in AD progression.MethodsThe Morris water maze (MWM) test, immunohistochemistry, ELISA, ProcartaPlex Multiplex immunoassay, multiple LC-MS/MS methods, and the V3-V4 regions of 16S rRNA genes were applied to explore potential biomarkers.ResultsIn Tg-APP/PS1 mice, gut dysbiosis and lipid metabolism were highly associated with AD-like neuroinflammation. The combination of inflammatory factors (IL-6 and INF-γ), phosphatidylcholines (PCs) and SCFA-producing bacteria were expected to be early diagnostic biomarkers for AD. Huanglian Jiedu decoction (HLJDD) suppressed gut dysbiosis and the associated Aβ accumulation, harnessed neuroinflammation and reversed cognitive impairment.ConclusionTogether, our findings highlighted the roles of neuroinflammation induced by gut dysbiosis and lipid metabolism disorder in AD progression. This integrated metabolomics approach showed its potential to understand the complex mechanisms of HLJDD in the treatment of AD.

Integrating Network Pharmacology and Experimental Models to Investigate the Mechanism of Huanglian Jiedu Decoction on Inflammatory Injury Induced by Cerebral Ischemia.

Unlike single-target Western medicines, traditional Chinese medicines (TCMs) exhibit diverse curative effects against multiple diseases through their “multicomponent” and “multitarget” manifestations. However, the material basis of the major therapeutic diseases and TCM underlying molecular mechanisms remain to be challenged. In the current study, we applied, for the first time, an integrated strategy that combines network pharmacology and experimental evaluation and explored and demonstrated the underlying possible mechanisms of a classic TCM formula, Huanglian Jiedu Decoction (HLJD), in the treatment of cerebral ischemia. First, the herb compound, protein compound, and GO-BP and KEGG pathways were constructed to predict the material basis of HLJD in the treatment of cerebral ischemia and explore the underlying molecular mechanisms. Network pharmacology analysis showed that HLJD treats cerebral ischemia mainly through its anti-inflammatory effect. We used molecular docking to verify that HLJD components have good binding activities to the arachidonic acid pathway enzymes, cyclooxylipase-2 (COX-2) and 5-lipoxygenase (5-LOX). Next, based on the prediction by the network pharmacology analysis, the rat model of middle cerebral artery occlusion (MCAO) was established to verify the efficacy of HLJD. The results showed that HLJD reduces the degree of brain injury in MCAO rats, probably by inhibiting the expression of the 5-LOX pathway and inflammatory response. In conclusion, our study demonstrates the effectiveness of integrating network pharmacology with an experimental study for material basis of the major therapeutic diseases and the underlying molecular mechanisms of TCM.

Observation on Clinical Therapeutic Effect, Toxic and Side Effects of Capecitabine plus Fuzheng Jiedu Decoction Supplemented and Reduced Prescription for Advanced Gastric Cancer

This study deals with observation on clinical therapeutic effect and toxic and side effects of capecitabine plus Fuzheng Jiedu decoction supplemented and reduced prescription for advanced gastric cancer. From January 2011 to January 2014, 145 patients with gastric cancer diagnosed by surgery, gastroscopy and pathology in our hospital, with measurable tumor lesions, were enrolled in this study. They were aged 45-85 y, with mean age (62.3i?±6.7) y, 75 males and 70 females. In the study group, the disease progression time and survival time were 2-19.5 mo and 4.5-24 mo, respectively with 5 cases survived, while those of the control group were 1.5-20 months and 4.2-23 mo, respectively, with 3 cases survived. The t test showed no significant difference between the two groups (p>0.05). The survival rate of 60 cases within 1 y in the study group (87.0 %) was significantly higher than that of the control group (59 cases, 77.9 %), and the difference was significant (p<0.05). The incidence rates of hand-foot syndrome, nausea and vomiting, diarrhea, abdominal pain, liver injury and neurotoxicity in the study group were 21.7 %, 2.9 %, 11.6 %, 7.2 %, 1.4 % and 17.4 %, which were significantly lower than that of the control group (43.4 %, 22.3 %, 25 %, 21.1 %, 11.8 % and 36.8 %) and the chi-square test showed a significant difference (p<0.05). Capecitabine plus Fuzheng Jiedu decoction supplemented and reduced prescription for treating advanced gastric cancer has a good therapeutic effect, less toxic and side effects and the patient’s quality of life is significantly improved. It is worthy of being popularized.

The active ingredients of Huanglian Jiedu Decoction in treating COVID-19 based on network pharmacology, molecular docking and molecular dynamics simulation

The active ingredients of Huanglian Jiedu Decoction in treating COVID-19 based on network pharmacology, molecular docking and molecular dynamics simulation

Anti-inflammatory effect, plasma effective components and therapeutic targets of Huanglian Jiedu Decoction on ulcerative colitis mice

This paper was to investigate the effect of Huanglian Jiedu Decoction(HLJD) on ulcerative colitis(UC) in mice, and determine the effective components in plasma, and virtually screen its therapeutic target, and predict its mechanism. Sixty Balb/c mice were randomly divided into blank group, model group, mesalazine treatment group(0.3 g·kg~(-1)), and HLJD treatment groups(24.66, 12.33, 6.17 g·kg~(-1)). Excepted for the blank group, all the mice in HLJD and mesalazine treatment groups were gavage administration. All mice freely drank 2.5% DSS solution for seven days to induce UC. The disease activity index(DAI) was detected each day. At the end of the experiment, HE staining was used to observe the pathological changes in colon. The content of IL-1β, IL-6 and TNF-α in colon were determined by ELISA. The effective components in plasma were determined by UPLC-Q-TOF-MS. The reverse docking in PharmMapper was used to screen the component targets. The disease targets of UC were collected by searching TTD, OMIM and GeneCards databases. The intersection of the component targets and disease targets was selected as the therapeutic targets. Then the therapeutic targets were imported into the STRING for GO and KEGG enrichment analysis. Discovery Studio was used to simulate the docking between the components and the targets. RESULTS:: showed that the DAI in the model group increased significantly(P&lt;0.05), and the number of inflammatory cells and infiltration degree increased significantly compared with the blank group. The DAI in HLJD treatment group was significantly reduced(P&lt;0.05), and the number and infiltration degree of inflammatory cells were reduced compared with the model group. The ELISA results showed that the levels of IL-1β, IL-6 and TNF-α were increased significantly in the model group(P&lt;0.01) compared with the blank group, and significantly down regulated in the HLJD treatment group(P&lt;0.05) compared with the model group. After UPLC-Q-TOF-MS analyse, ten components were identified. The network pharmacology analysis showed that the action targets were significantly enriched in 129 of biological processes, such as response to organic substance, chemical and oxygen-containing compound, etc., as well as 16 of signal pathways, such as IL-17, TNF and hepatitis B signal pathways, were enriched too. The results of molecular docking showed that limonin, palmatine and berberine could bind to CASP3 and MMP9 by hydrogen bond. In conclusion, HLJD could alleviate the colonic mucosal inflammatory infiltration and mucosal damage in UC mice. The mechanism may be related to the anti-inflammatory effect on UC mice by reducing the levels of IL-1β, IL-6 and TNF-α in colon through limonin, palmatine and berberine regulating IL-17 signal pathway and TNF signal pathway via CASP3 and MMP9 meditated.

Neuraminidase 1 and its Inhibitors from Chinese Herbal Medicines: An Emerging Role for Cardiovascular Diseases.

Neuraminidase, also known as sialidase, is ubiquitous in animals and microorganisms. It is predominantly distributed in the cell membrane, cytoplasmic vesicles, and lysosomes. Neuraminidase generally recognizes the sialic acid glycosidic bonds at the ends of glycoproteins or glycolipids and enzymatically removes sialic acid. There are four types of neuraminidases, named as Neu1, Neu2, Neu3, and Neu4. Among them, Neu1 is the most abundant in mammals. Recent studies have revealed the involvement of Neu1 in several diseases, including cardiovascular diseases, diabetes, cancers, and neurological disorders. In this review, we center the attention to the role of Neu1 in cardiovascular diseases, including atherosclerosis, ischemic myocardial injury, cerebrovascular disease, congenital heart disease, and pulmonary embolism. We also summarize inhibitors from Chinese herbal medicines (CHMs) in inhibiting virus neuraminidase or human Neu1. Many Chinese herbs and Chinese herb preparations, such as Lonicerae Japonicae Flos, Scutellariae Radix, Yupingfeng San, and Huanglian Jiedu Decoction, have neuraminidase inhibitory activity. We hope to highlight the emerging role of Neu1 in humans and potentially titillate interest for further studies in this area.

Huanglian Jiedu Decoction for treatment of multiple myeloma: A protocol for a systematic review and meta-analysis.

Background:Multiple myeloma can lead to lots of clinical problems including pain, fatigue, anemia, infections, renal failure, and so on. Huanglian Jiedu Decoction is a common conservative treatment for this disease in China. Therefore, we conducted a systematic review and meta-analysis to explore the efficacy of Huanglian Jiedu Decoction in the treatment of multiple myeloma.Methods:A systematic literature search for studies will be performed in 8 databases, including PubMed, Web of Science, Embase, the Cochrane library, ClinicalTrials.gov databases, Chinese National Knowledge Infrastructure Database, Wanfang database, and VIP database. The methodological quality of the included studies using the risk bias assessment tool of Cochrane. And the level of evidence for results is assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. Statistical analysis is conducted with Revman 5.3.Results:This systematic review and meta-analysis will provide a synthesis of existed evidences for Huanglian Jiedu Decoction on multiple myeloma.Conclusion:The conclusion of this study will provide evidence to assess effectiveness of Huanglian Jiedu Decoction on multiple myeloma, which can further guide clinical decision-making.INPLASY registration number:INPLASY202060094

A Novel Strategy for Decoding and Validating the Combination Principles of Huanglian Jiedu Decoction From Multi-Scale Perspective.

Traditional Chinese medicine (TCM) formulas treat complex diseases through combined botanical drugs which follow specific compatibility rules to reduce toxicity and increase efficiency. “Jun, Chen, Zuo and Shi” is one of most used compatibility rules in the combination of botanical drugs. However, due to the deficiency of traditional research methods, the quantified theoretical basis of herbal compatibility including principles of “Jun, Chen, Zuo and Shi” are still unclear. Network pharmacology is a new strategy based on system biology and multi-disciplines, which can systematically and comprehensively observe the intervention of drugs on disease networks, and is especially suitable for the research of TCM in the treatment of complex diseases. In this study, we systematically decoded the “Jun, Chen, Zuo and Shi” rules of Huanglian Jiedu Decoction (HJD) in the treatment of diseases for the first time. This interpretation method considered three levels of data. The data in the first level mainly depicts the characteristics of each component in single botanical drug of HJD, include the physical and chemical properties of component, ADME properties and functional enrichment analysis of component targets. The second level data is the characterization of component-target-protein (C-T-P) network in the whole protein-protein interaction (PPI) network, mainly include the characterization of degree and key communities in C-T-P network. The third level data is the characterization of intervention propagation properties of HJD in the treatment of different complex diseases, mainly include target coverage of pathogenic genes and propagation coefficient of intervention effect between target proteins and pathogenic genes. Finally, our method was validated by metabolic data, which could be used to detect the components absorbed into blood. This research shows the scientific basis of “Jun-Chen-Zuo-Shi” from a multi-dimensional perspective, and provides a good methodological reference for the subsequent interpretation of key components and speculation mechanism of the formula.

Comprehensive analysis of Huanglian Jiedu decoction: Revealing the presence of a self-assembled phytochemical complex in its naturally-occurring precipitate

The current study presents a comprehensive analysis to explore the compositions of both the supernatant and naturally-occurring precipitate of Huanglian Jiedu decoction employing ultra-high-performance liquid chromatography hyphenated with quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). Totally 109 constituents (32 alkaloids, 39 flavonoids, 12 iridoids, 9 phenolic acids, and 17 other compounds) were identified from accurate-mass measurements in full-scan MS/data-dependent MS/MS mode of acquisition. Furthermore, a quantitative method was developed for determination of 14 marker compounds in Huanglian Jiedu decoction. Experimental results revealed that all of these marker compounds were present in both the supernatant and naturally-occurring precipitate. Most notably, the contents of baicalin and berberine were significantly higher in the naturally-occurring precipitate than supernatant, presumably due to self-assembly complexation. The formation of the baicalin/berberine complex was comprehensively investigated by electrospray ionization (ESI)-MS, nuclear magnetic resonance (NMR), ultraviolet-visible (UV–vis), Fourier transform infrared (FTIR), and fluorescence spectroscopy, etc. The morphology and size distribution of the baicalin/berberine self-assembled nanoparticles were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). This study provides fundamental scientific evidence of the presence of a self-assembled phytochemical complex in the naturally-occurring precipitate, enabling better understanding of Huanglian Jiedu decoction.

Untargeted metabolomics and lipidomics uncovering the cardioprotective effects of Huanglian Jiedu Decoction on pathological cardiac hypertrophy and remodeling

Ethnopharmacological relevanceAs a classic herbal prescription, Huanglian Jiedu Decoction (HLJDD) exhibits positive effects against cardiac dysfunction. However, its cardioprotective effects and potential mechanism(s) of action still need to be systematically investigated. Aim of the studyThis study aimed to reveal the underlying therapeutic mechanism of HLJDD on transverse aortic constriction (TAC)-induced pathological cardiac hypertrophy and remodeling. Materials and methodsTAC-induced cardiac hypertrophy and remodeling mice model was established to evaluate the therapeutic effects of HLJDD. Serum untargeted metabolomics and lipidomic profiling were performed using ultra-performance liquid chromatography quadrupole-time-of-flight mass spectrometry coupled with multivariate statistical analyses. ResultsOral administration of HLJDD (2.5 g/kg/day, 5.0 g/kg/day) significantly improved the heart morphology, enhanced the heart function, and alleviated the accumulation of fibrosis in the interstitial space and the infiltration of inflammatory cells in TAC-stimulated mice. Serum untargeted metabolomics analysis showed that significant alterations were observed in metabolic signatures between the TAC-model and sham group. Principal component analysis and orthogonal partial least-squares discriminant analysis screened 59 differential metabolic features and 13 metabolites were identified. The disturbed metabolic pathways in TAC group mainly related to lipid metabolism. Further serum lipidomic profiling showed that most lipids including cholesterol esters, ceramides, glycerides, fatty acids and phospholipids were decreased in TAC group and these alterations were reversed after HLJDD intervention. ConclusionHLJDD alleviates TAC-induced pathological cardiac hypertrophy and remodeling, and its potential therapeutic mechanism involves the regulation of lipid metabolism.

Combination of Huanglian Jiedu Decoction and erlotinib delays growth and improves sensitivity of EGFR‑mutated NSCLC cells invitro and invivo via STAT3/Bcl‑2 signaling.

Erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is widely used in the treatment of non-small cell lung cancer (NSCLC). However, erlotinib resistance leads to high mortality in patients with NSCLC, while the activation of STAT3 is closely related to erlotinib resistance. Studies have shown that the main components of Huanglian Jiedu Decoction (HJD) have antitumor effects. Therefore, the anticancer effect of HJD combined with erlotinib on NSCLC cells was investigated. The NSCLC HCC827, HCC827ER, and H1975 cell lines as well as xenograft nude mice were selected as models to study the effects of HJD. The proapoptotic effects of HJD were examined by CCK-8 and apoptosis assays. ELISA, immunostaining, and western blot analysis were also performed. HJD considerably enhanced the anticancer effect of erlotinib in both EGFR-TKI-resistant and -sensitive NSCLC cells. HJD promoted erlotinib-induced apoptosis and caspase 3 activity. The co-treatment also inhibited the expression of Bcl-XL, Bcl-2, and p-STAT3. In addition, siSTAT3 had similar functions with HJD. In particular, the apoptotic rates of erlotinib-stimulated HCC827, HCC827ER, and H1975 cells were enhanced by transfecting siSTAT3. Furthermore, overexpression of STAT3 significantly inhibited HJD-mediated erlotinib sensitization. The combined use of HJD with erlotinib significantly reduced tumor growth in erlotinib-resistant HCC827ER and H1975 ×enografts, induced caspase 3, and inhibited Ki67, STAT3, and Bcl-2 expression. HJD significantly alleviated erlotinib resistance by regulating the STAT3/Bcl-2 signaling pathway, which is a promising method to overcome the EGFR-TKI resistance of NSCLC.

Clinical trait-connected network analysis reveals transcriptional markers of active psoriasis treatment with Liangxue-Jiedu decoction

Ethnopharmacological relevancePsoriasis is a complex recurrent inflammatory skin disease with different pathological changes in different stages. Psoriasis in its active stage, which is comparable to the blood-heat type in traditional Chinese medicine (TCM), has been treated by Liangxue Jiedu Decoction (LJD) in TCM for decades, with proven efficacy. According to TCM theories, LJD has the function of removing heat and pathogenic factors from the blood. Aim of the studyWe aimed to investigate the molecular features associated with the active stage psoriasis and identify genes responding to LJD treatment accompanied by lesion remission. Materials and methodsHealthy volunteers and psoriasis patients who met specific diagnostic criteria were recruited. Twenty-six transcriptomes were profiled from the peripheral blood mononuclear cells (PBMCs) of 10 psoriasis patients (pre- and post-treatment) and 6 healthy volunteers. RNA sequencing data were analyzed using an integrated approach combining differential gene expression analysis (DGEA) and weighted gene co-expression network analysis (WGCNA), by which gene expression was linked to multiple clinical traits, including psoriasis area and severity index (PASI), as well as the improvement rate of skin lesions (ΔPASI). The actions of LJD were then verified using an in vitro cell assay coupled to flow cytometric analysis and RT-PCR. ResultsWe identified four network modules with statistical significance (P < 0.05), two of which connected to the PASI score, while the other two connected to 8-week treatment and ΔPASI, respectively. In psoriasis patients, activated inflammatory pathways and inhibited G-protein signaling genes (GTPase IMAP family member and G protein-coupled receptor) co-occurred, with high expression of CD83 and CD69, and low expression of CD160 and CD180, compared with the health. Accompanying LJD treatment and lesion remission, the expression of CD69 and cell cycle-related genes, including CCNA2, CCNB2, CDK1, and TOP2A, was down-regulated. The inhibitory role of LJD on CD69 expression was confirmed by the decline of activating naïve CD4+ T lymphocytes. ConclusionOur study suggests that active psoriasis is characterized by unbalanced immune status with dendrite cell and lymphocyte-associated inflammatory activation as well as NK cell- and B cell-associated defense response aberrance. LJD played an inhibitory role in T cell activation, a process located downstream pathological cascade of psoriasis.

Molecular Mechanism of the Effect of Huanglian Jiedu Decoction on Type 2 Diabetes Mellitus Based on Network Pharmacology and Molecular Docking.

Background Huanglian Jiedu Decoction (HLJDD) is a Traditional Chinese Medicine (TCM) formula comprising four herbal medicines. This decoction has long been used in China for clinically treating T2DM. However, the molecular mechanism of HLJDD treat for T2DM is still not fully known. Hence, this study was designed to reveal the synergistic mechanism of HLJDD formula in the treatment of T2DM by using network pharmacology method and molecular docking. Methods Retrieving and screening of active components of different herbs in HLJDD and corresponding T2DM-related target genes across multiple databases. Subsequently, STRING and Cytoscape were applied to analysis and construct PPI network. In addition, cluster and topological analysis were employed for the analysis of PPI networks. Then, the GO and KEGG enrichment analysis were performed by using ClueGO tool. Finally, the differentially expressed analysis was used to verify whether the expression of key target genes in T2DM and non-T2DM samples was statistically significant, and the binding capacity between active components and key targets was validated by molecular docking using AutoDock. Results There are 65 active components involved in 197 T2DM-related targets that are identified in HLJDD formula. What is more, 39 key targets (AKT1, IL-6, FOS, VEGFA, CASP3, etc.) and 3 clusters were obtained after topological and cluster analysis. Further, GO and KEGG analysis showed that HLJDD may play an important role in treating T2DM and its complications by synergistically regulating many biological processes and pathways which participated in signaling transduction, inflammatory response, apoptotic process, and vascular processes. Differentially expressed analysis showed that AKT1, IL-6, and FOS were upregulated in T2DM samples and a significant between sample differential expression. These results were validated by molecular docking, which identified 5 high-affinity active components in HLJDD, including quercetin, wogonin, baicalein, kaempferol, and oroxylin A. Conclusion Our research firstly revealed the basic pharmacological effects and relevant mechanisms of the HLJDD in the treatment of T2DM and its complications. The prediction results might facilitate the development of HLJDD or its active compounds as alternative therapy for T2DM. However, more pharmacological experiments should be performed for verification.

Baoyuan Jiedu Decoction Alleviates Cancer-Induced Myotube Atrophy by Regulating Mitochondrial Dynamics Through p38 MAPK/PGC-1α Signaling Pathway

Cancer cachexia is a multifactorial syndrome characterized by continuous body wasting and loss of skeletal muscle. Impaired mitochondria function is closely associated with muscle atrophy in cancer cachexia. Our previous study confirmed the effectiveness of Baoyuan Jiedu decoction (BJD) in inhibiting cancer-induced muscle atrophy in an in vivo model. However, little is known about its mechanisms in regulating mitochondria dysfunction. In this study, we evaluated the therapeutic effect and action mechanisms of BJD against atrophy both in the Lewis-conditioned medium induced C2C12 myotube atrophy model and in a BALB/c mice xenograft model using mouse colon cancer C26 cells. The mitochondrial content was tested by 10-Non-ylacridine orange staining. Expressions of related proteins and mRNAs were detected by western blotting (WB) and qPCR, respectively. As a result, 18 major components were identified in BJD by ultra-high performance liquid chromatography-quadrupole (UHPLC-Q) Exactive analysis. As shown in the in vitro results, BJD treatment prevented prominent myotube atrophy and increased the myotube diameter of C2C12 cells. Besides, BJD treatment increased mitochondrial content and ATPase activity. Furthermore, the protein and mRNA expressions that were related to mitochondrial functions and generation such as cytochrome-c oxidase IV, Cytochrome C, nuclear respiratory factor 1, and mitochondrial transcription factor A were significantly increased in BJD treatment compared to the control group. The in vivo results showed that BJD treatment prevented body weight loss and improved the gastrocnemius index in cachexia mice. Moreover, the expressions of Atrogin-1 and muscle RING-finger protein-1 were decreased by BJD treatment. Mechanically, BJD increased the expression of peroxisome proliferator-activated receptor-gamma coactivator 1, and consistently, inhibited the expression of p38 MAPK and its phosphorylation both in vivo and in vitro. Taken together, this study identified that BJD effectively relieved cancer-induced myotube atrophy and provided a potential mechanism for BJD in regulating mitochondrial dynamics through p38 MAPK/PGC-1α signaling pathway.

Susceptibility of Mature Staphylococcus Biofilms to Chinese Herbal Decoction Sanhuang Jiedu: An In Vitro Study.

Background External socking and washing with the Chinese herbal Sanhuang Jiedu decoction (SHJD) can effectively control local limb infections with bone and implant exposure. However, the antibiofilm activities of this decoction in vitro have not yet been investigated. Therefore, the aim of this study was to examine the effects and characteristics of SHJD on the mature biofilms of multidrug-resistant staphylococci on a titanium surface. Methods Biofilm-forming methicillin-resistant Staphylococcus epidermidis ATCC 35984 and S. aureus ATCC 43330, and non-biofilm-forming S. epidermidis ATCC 12228 were selected as the experimental strains. The mature biofilms were prepared on titanium surfaces. The five experimental groups were based on dilution concentrations (DC) of SHJD: the control group (biofilm incubated with 0.85% NaCl solution), the SHJD (DC:1/8) group (initial SHJD solution was diluted 1/8), the SHJD (DC:1/4) group, the SHJD (DC:1/2) group, and the SHJD (DC:1/1) group (initial SHJD solution). The effects of SHJD on the mature biofilms were observed with the bacterial spread plate method, crystal violet (CV) staining, scanning electron microscopy, and confocal laser scanning microscopy. Results After culture in tryptic soy broth for 72 h, ATCC 43300 and ATCC 35984 produced mature biofilms and ATCC 12228 did not. The optical density value of ATCC 12228 was 0.11 ± 0.02, significantly lower than that of ATCC 35984 (0.42 ± 0.05) or ATCC 43300 (0.41 ± 0.03) (P < 0.05). The mature biofilms of ATCC 43300 and ATCC 35984 clearly disintegrated when incubated for 12–24 h with SHJD (DC:1/1) or SHJD (DC:1/2), showing only scattered bacterial adhesion. In the SHJD (DC:1/4) group, although many residual bacterial colonies still clustered together, presenting a biofilm structure, it was very looser than that in the SHJD (DC:1/8) group in which the biofilm was similar to that in the control group. For ATCC 12228, only colony adhesion was observed, and the number of colonies decreased as the concentration of SHJD or the culture period increased. The quantitative results for the bacterial spread plate and CV staining showed significant differences between the SHJD groups (P < 0.05). Conclusion SHJD has antibiofilm activity against multidrug-resistant Staphylococcus strains. It weakens or disrupts already-formed mature biofilms on titanium surfaces in a concentration- and incubation time-dependent manner.

Alleviation of Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome in Rats by Yiqi Huayu Jiedu Decoction: A Tandem Mass Tag-Based Proteomics Study.

BackgroundTo study the effect of Yiqi Huayu Jiedu Decoction (YQHYJD) on protein expression in the lung tissue of acute respiratory distress syndrome (ARDS) rats and to explore the underlying molecular therapeutic mechanism of YQHYJD.MethodsSprague Dawley rats were administered with YQHYJD by oral gavage for 1 week. The rats were injected with lipopolysaccharide (LPS) to induce ARDS. The lung injury was assessed pathologically. Differentially expressed proteins (DEPs) were screened by quantitative proteomics and analyzed using bioinformatic tools, such as Metascape and Kyoto Encyclopedia of Genes and Genomes (KEGG) mapper. DEPs were verified by parallel reaction monitoring (PRM).ResultsYQHYJD alleviated the LPS-induced pathological damage of lung tissue in rats. There were 134 DEPs among the YQHYJD treatment and model groups. The Genomes pathway analyses revealed that the DEPs were closely related to immune system pathway. The mass spectrometry analysis revealed that YQHYJD exhibits a protective effect on lung tissue by significantly upregulating hematopoietic cell kinase (Hck), phospholipid phosphatase 3 (Plpp3), myristoylated-alanine rich C-kinase substrate (Marcks), and Actin-related protein 2/3 complex subunit 2 (Arpc2), which are related to Fc gamma receptor-mediated phagocytosis pathway.ConclusionYQHYJD can alleviate the lung injury of ARDS rats by regulating the Fc gamma receptor-mediated phagocytosis pathway, which is related to immune system.

Chinese herbal medicine Baoyuan Jiedu decoction inhibits the accumulation of myeloid derived suppressor cells in pre-metastatic niche of lung via TGF-β/CCL9 pathway

Baoyuan Jiedu (BYJD for short) decoction, a traditional Chinese medicine formula, is composed of Astragalus, Ginseng, Aconite root, Honeysuckle, Angelica, Licorice, which has the functions of nourishing qi and blood, enhancing immune function, improving quality of life and prolonging survival time of tumor patients. The present study aimed to investigate the effect and mechanism of BYJD decoction on reversing the pre-metastatic niche. We showed that BYJD decoction could prolong the survival time of 4T1 tumor-bearing mice. Moreover, we found that the BYJD decoction inhibited the formation of lung pre-metastatic niche and inhibited recruitment of myeloid derived suppressor cells (MDSCs) in the lung. Mechanistically, we showed that the proteins and genes expression of TGF-β, Smad2, Smad3, p-Smad2/3, Smad4, CCL9 in the TGF-β/CCL9 signaling pathway were suppressed by BYJD decoction. In line with the above findings, our results confirm that BYJD decoction inhibits the accumulation of MDSC in pre-metastatic niche of lung via TGF-β/CCL9 pathway.

Huanglian Jiedu Decoction ameliorates DSS-induced colitis in mice via the JAK2/STAT3 signalling pathway

BackgroundUlcerative colitis (UC) is an intestinal disease which was characterized by intestinal inflammation, mucosal injury and fibrosis. In this paper, the effect of Huanglian Jiedu Decoction (HJD), a well-known traditional Chinese medicine with significant anti-inflammatory effect, on dextran sulphate sodium (DSS)-induced UC in mice and inhibition of JAK2/STAT3 pathway were investigated.MethodsBALB/c mice were randomly divided into 6 groups: HJD group (high, medium and low dose), USAN group, UC group, and control group. UC in mice were induced through free access to 3% DSS solution. After being treated with HJD for 8 days, all animals were sacrifice. Pathological examination of colonic specimen was performed by H&E staining. Cytokines (TNF-α, IL-6, and IL-1β) in colon were assayed by ELISA and immunofluorescence, MPO in colon and ATT in serum were detected by ELISA. Moreover, mice in HJD group and UC group were treated with AG490 to inhibit the expression of JAK2 protein, then the expression of JAK2 and STAT3 protein in colon was determined by western blotting and immunofluorescence staining. Furthermore, KI67 in colon was examined by immunohistochemistry, and apoptosis was detected by TUNEL staining, and collagen deposition was assayed by Masson staining after JAK2/STAT3 pathway in UC mice was inhibited by HJD.ResultsAfter mice being treated with HJD, the symptoms (weight loss and haematochezia) of UC were alleviated, and the contents of inflammatory cytokines (TNF-α, IL-6 and IL-1β) and MPO in colon were significantly decreased. The expression of JAK2 and STAT3 protein was reduced after administration with HJD. After JAK2/STAT3 pathway being inhibited with HJD, the cell apoptosis, collagen deposition and immunoreactivity of macrophage in colon were significantly reduced, but the expression of Ki67 was markedly enhanced in both UC group and HJD group compare with control group.ConclusionsHJD treatment can alleviate intestinal mucosal damage and has the protective effect on UC by downregulating JAK2 and STAT3 expression to reduce inflammation via JAK2/STAT3 pathway.

Ancient Chinese Medicine Herbal Formula Huanglian Jiedu Decoction as a Neoadjuvant Treatment of Chemotherapy by Improving Diarrhea and Tumor Response.

BackgroundDiarrhea is a major gastrointestinal complication in cancer patients receiving chemotherapy. Prognosis and treatment of chemotherapy-induced diarrhea (CID) remain unsatisfactory. This study aims to explore the potential of an ancient Chinese Medicine herbal formula Huanglian Jiedu Decoction (HLJDD) as an adjuvant treatment on CID.MethodHLJDD extract was prepared by GMP manufacturing standard with quality and stability being checked. 5-fluorouracil (5-Fu) and irinotecan (CPT-11)-induced diarrhea model in mice was established and pre-, co- and post-treatment of HLJDD was implemented. Mechanism of action was explored by detecting related protein expression. In addition, the effect of HLJDD on diarrhea and tumor response induced by clinical regimens FOLFOX and FOLFIRI was measured in murine orthotopic colorectal cancer model.ResultsHLJDD exhibited consistency in quality and stability after 24-month storage. Pre-treatment of HLJDD, but not co-treatment or post-treatment, could significantly improve the diarrhea score, body weight loss and intestinal damage in 5-Fu- and CPT-11-treated mice. Pre-treatment of HLJDD reduced cell apoptosis in the intestine of chemotherapy-treated mice, and promoted renewal of intestinal cell wall. CD44 was predicted as the potential target of HLJDD-containing compounds in CID. HLJDD pre-treatment induced presentation of CD44-postive cells in the intestine of chemotherapy-treated mice, and initiated expression of stemness-associated genes. Transcriptional products of the downstream Wnt signaling of CD44 were elevated. Furthermore, pre-treatment of HLJDD could significantly improve the tumor response of clinical chemotherapy regimens FOLFOX and FOLFIRI in orthotopic colorectal cancer, and reduce diarrhea and intestinal damage. Conclusion: Our study suggests the potential of HLJDD as a neoadjuvant treatment of chemotherapy by reducing diarrhea and improving tumor response.