Alginate oligosaccharide assimilation by gut microorganisms and the potential role in gut inflammation alleviation.

Dietary fiber metabolism by gut microorganisms plays important roles in host physiology and health. Alginate, the major dietary fiber of daily diet seaweeds, is drawing more attention because of multiple biological activities. To advance the understanding of alginate assimilation mechanism in the gut, we show the presence of unsaturated alginate oligosaccharides (uAOS)-specific alginate utilization loci (AUL) in human gut microbiome. As a representative example, a working model of the AUL from the gut microorganism Bacteroides clarus was reconstructed from biochemistry and transcriptome data. The fermentation of resulting monosaccharides through Entner-Doudoroff pathway tunes the metabolism of short-chain fatty acids and amino acids. Furthermore, we show that uAOS feeding protects the mice against dextran sulfate sodium-induced acute colitis probably by remodeling gut microbiota and metabolome. IMPORTANCE: Alginate has been included in traditional Chinese medicine and daily diet for centuries. Recently discovered biological activities suggested that alginate-derived alginate oligosaccharides (AOS) might be an active ingredient in traditional Chinese medicine, but how these AOS are metabolized in the gut and how it affects health need more information. The study on the working mechanism of alginate utilization loci (AUL) by the gut microorganism uncovers the role of unsaturated alginate oligosaccharides (uAOS) assimilation in tuning short-chain fatty acids and amino acids metabolism and demonstrates that uAOS metabolism by gut microorganisms results in a variation of cell metabolites, which potentially contributes to the physiology and health of gut.

IiAGL6 participates in the regulation of stamen development and pollen formation in Isatis indigotica.

The AGL6 (AGMOUSE LIKE 6) gene is a member of the SEP subfamily and functions as an E-class floral homeotic gene in the development of floral organs. In this study, we cloned IiAGL6, the orthologous gene of AGL6 in Isatis indigotica. The constitutive expression of IiAGL6 in Arabidopsis thaliana resulted in a late-flowering phenotype and the development of curly leaves during the vegetative growth period. Abnormal changes in floral organ development were observed during the reproductive stage. In woad plants, suppression of IiAGL6 using TRV-VIGS (tobacco rattle virus-mediated virus-induced gene silencing) decreased the number of stamens and led to the formation of aberrant anthers. Similar changes in stamen development were also observed in miRNA-AGL6 transgenic Arabidopsis plants. Yeast two-hybrid and BiFC tests showed that IiAGL6 can interact with other MADS-box proteins in woad; thus, playing a key role in defining the identities of floral organs, particularly during stamen formation. These findings might provide novel insights and help investigate the biological roles of MADS transcription factors in I. indigotica.

Unraveling the serial glycosylation in the biosynthesis of steroidal saponins in the medicinal plant Paris polyphylla and their antifungal action.

Sugar-sugar glycosyltransferases play important roles in constructing complex and bioactive saponins. Here, we characterized a series of UDP-glycosyltransferases responsible for biosynthesizing the branched sugar chain of bioactive steroidal saponins from a widely known medicinal plant Paris polyphylla var. yunnanensis. Among them, a 2'-O-rhamnosyltransferase and three 6'-O-glucosyltrasferases catalyzed a cascade of glycosylation to produce steroidal diglycosides and triglycosides, respectively. These UDP-glycosyltransferases showed astonishing substrate promiscuity, resulting in the generation of a panel of 24 terpenoid glycosides including 15 previously undescribed compounds. A mutant library containing 44 variants was constructed based on the identification of critical residues by molecular docking simulations and protein model alignments, and a mutant UGT91AH1Y187A with increased catalytic efficiency was obtained. The steroidal saponins exhibited remarkable antifungal activity against four widespread strains of human pathogenic fungi attributed to ergosterol-dependent damage of fungal cell membranes, and 2'-O-rhamnosylation appeared to correlate with strong antifungal effects. The findings elucidated the biosynthetic machinery for their production of steroidal saponins and revealed their potential as new antifungal agents.

The effect of JuanBiQiangGu granules in combination with methotrexate on joint inflammation in rheumatoid arthritis: a randomized controlled trial.

Background: Rheumatoid arthritis (RA) joint inflammation severely affects joint function and quality of life in patients and leads to joint deformities and limb disability. The non-steroidal anti-inflammatory drugs used in the treatment of RA do not fully control the progression of joint inflammation and bone destruction and have notable adverse reactions. Traditional Chinese medicine formula JuanBiQiangGu Granules (JBQG) are commonly used for the treatment of RA inflammation and delay of bone destruction, but has not been evaluated through high-quality clinical studies. There is a pressing need for well-designed, randomized, parallel, controlled clinical studies to evaluate the exact effect of JBQG on RA joint inflammation and improvement of patient quality of life. Methods: This is a randomized, parallel, controlled clinical study in which 144 patients with rheumatoid arthritis who met the inclusion criteria were randomly assigned to 2 groups in a 1:1 ratio. The JBQG group received methotrexate 7.5 mg qw and JBQG granules 8 mg tid, while the MTX group received methotrexate 7.5 mg qw. The endpoint was 12 weeks after treatment. Relevant indices at baseline, 4 weeks, 8 weeks, and 12 weeks after treatment were observed and recorded, and DAS28-ESR, HAQ-DI, and Sharp scores were recorded for each patient. Blood samples were collected to test for CRP, ESR, TNF-α, IL-1ß, IL-6, IL-17, and INF-γ, and adverse reactions and liver and kidney function (AST, ALT, Cr, BUN) were recorded for safety assessment. After 12 weeks of treatment, the effect of JBQG granules on disease activity, improvement in bone damage, and patient quality of life scores and safety in RA patients were evaluated. Results: A total of 144 subjects completed treatment (71 in the JBQG group and 73 in the MTX group) and were included in the analysis. At baseline, there were no significant differences between the groups in terms of the observed indicators (p > 0.05). After treatment, 76.06% of patients in the JBQG group had DAS28-ESR levels below or equal to Low, including 45.07% in Remission and 5.63% in High, compared to 53.1% in the MTX group below or equal to Low, 12.33% in Remission, and 17.81% in High. CRP was significantly reduced (8.54 ± 5.87 vs. 11.86 ± 7.92, p < 0.05, p = 0.005), ESR was significantly reduced (15.1 ± 6.11 vs. 21.96 ± 9.19, p < 0.0001), TNF-α was significantly reduced (1.44 ± 0.83 vs. 1.85 ± 1.07, p < 0.05, p = 0.011), IL-17 was significantly reduced (0.53 ± 0.33 vs. 0.71 ± 0.38, p < 0.05, p = 0.004), and INF-γ was significantly reduced (3.2 ± 1.51 vs. 3.89 ± 1.77, p < 0.05, p = 0.014). The median (IQR) OPG in the JBQG group was 2.54 (2.21-3.01), significantly higher than in the MTX group 2.06 (1.81-2.32), p < 0.0001), and the median (IQR) ß-CTX in the JBQG group was 0.4 (0.32-0.43), significantly lower than in the MTX group 0.55 (0.47-0.67), p < 0.0001). The median (IQR) VSA scores were 2 (1-3), a decrease from 3 (2-4) in the MTX group (p < 0.0001). The median (IQR) Sharp scores were 1 (1-2), a decrease from 2 (1-2) in the MTX group, but the difference was not statistically significant (p > 0.05, p = 0.28). The median (IQR) HAQ-DI scores were 11 (8-16), significantly lower than in the MTX group 26 (16-30) (p < 0.0001). The median (IQR) AST in the JBQG group was 16 (12-20), with a significant difference compared to the MTX group 19 (13-25) (p < 0.01, p = 0.004); the median (IQR) ALT in the JBQG group was 14 (10-18), with a significant difference compared to the MTX group 16 (11-22.5) (p < 0.05, p = 0.015). There were no statistically significant differences in Cr or BUN (p > 0.05). Conclusion: JuanBiQiangGu Granules can be used to treat patients with rheumatoid arthritis, alleviate joint inflammation, reduce the incidence of adverse reactions to methotrexate, and has good safety. Clinical Trial Registration: http://www.chinadrugtrials.org.cn/index.html; identifier: ChiCTR2100046373.

Berberine targets the electron transport chain complex I and reveals the landscape of OXPHOS dependency in acute myeloid leukemia with IDH1 mutation.

Metabolic reprogramming, a newly recognized trait of tumor biology, is an intensively studied prospect for oncology medicines. For numerous tumors and cancer cell subpopulations, oxidative phosphorylation (OXPHOS) is essential for their biosynthetic and bioenergetic functions. Cancer cells with mutations in isocitrate dehydrogenase 1 (IDH1) exhibit differentiation arrest, epigenetic and transcriptional reprogramming, and sensitivity to mitochondrial OXPHOS inhibitors. In this study, we report that berberine, which is widely used in China to treat intestinal infections, acted solely at the mitochondrial electron transport chain (ETC) complex I, and that its association with IDH1 mutant inhibitor (IDH1mi) AG-120 decreased mitochondrial activity and enhanced antileukemic effect in vitro andin vivo. Our study gives a scientific rationale for the therapy of IDH1 mutant acute myeloid leukemia (AML) patients using combinatory mitochondrial targeted medicines, particularly those who are resistant to or relapsing from IDH1mi.

Compatibility of Polygonati Rhizoma and Angelicae Sinensis Radix enhance the alleviation of metabolic dysfunction-associated fatty liver disease by promoting fatty acid ß-oxidation.

Jiuzhuan Huangjing Pills (JHP) composed of Polygonati Rhizoma (PR) and Angelicae Sinensis Radix (ASR) remedied mitochondria to cure metabolic dysfunction-associated fatty liver disease (MAFLD). However, a comparison of the anti-MAFLD ability between JHP prescription and PR and ASR single-medicines in MAFLD has not been performed, and the action mechanisms and substances remain unknown. Our results show that JHP, PR and ASR decreased serum and liver lipid levels. The effects of JHP were stronger than those of PR and ASR. JHP, PR and ASR afforded protection to mitochondrial ultrastructure, and regulated oxidative stress and energy metabolism in mitochondria. JHP also regulated the expression of ß-oxidation genes, which were not regulated by PR and ASR. JHP-, PR- and ASR-derived components in mitochondrial extracts regulated oxidative stress, energy metabolism, and ß-oxidation gene expression and alleviated cellular steatosis. Four, six and eleven compounds were identified in mitochondrial extracts from PR-, ASR- and JHP-treated rats, respectively. The data suggest that JHP, PR and ASR alleviated MAFLD by remedying mitochondria, while the ability of JHP was stronger than that of PR and ASR, which was involved with the ß-oxidation promotion. The compounds identified may be the main ingredients in the three extracts active in MAFLD improvement.

Secoiridoids from the traditional Chinese medicine Swertia pseudochinensis.

Detailed phytochemical investigation on the traditional Chinese medicine Swertia pseudochinensis Hara led to the isolation of ten undescribed secoiridoids and fifteen known analogs. Their structures were elucidated by extensive spectroscopic analysis (including 1D and 2D NMR, and HRESIMS). Selected isolates were assayed for their anti-inflammatory and antibacterial activities, and moderate anti-inflammatory activity via inhibiting the secretion of cytokines IL-6 and TNF-α in macrophages RAW264.7 induced by LPS were observed. Antibacterial activity against Staphylococcus aureus was not found at 100 µM.

Systematic analysis of MYB transcription factors related to the geniposide biosynthesis in Gardenia jasminoides Ellis based on whole genome / 药学学报

MYB transcription factors are involved in the regulation of various secondary metabolites biosynthesis. Gardenia jasminoides Ellis is the commonly used Chinese herbal medicine, and its main active ingredient is geniposide. Here, leaves and flower buds at different developmental stages of G. jasminoides were used to explore MYB transcription factors related to geniposide biosynthesis based on genome and transcriptome analysis. Transcriptome data analysis showed that, different from the expression of the common pathway genes for terpenoid biosynthesis, the expression level of genes in the specific pathway of geniposide biosynthesis was significantly higher in flower buds than in leaves, which was the same as the organ accumulation pattern of this component. And the promoter regions of geraniol synthase, iridoid synthase and geniposidic acid methyltransferase involved in the specific pathway all contained multiple MYB-binding sites. A total of 105 MYB transcription factors were obtained by annotating the coding genes of G. jasminoides, which were divided into 68 1R-MYB, 33 R2R3-MYB, 3 3R-MYB and 1 atypical MYB transcription factor according to the number of conserved domain. Based on the analysis of phylogenetic tree and quantitative real-time PCR, three candidate MYB transcription factors related to geniposide biosynthesis were selected, including potential positive regulation factor GjMYB23 and negative regulation factors GjMYB31 and GjMYB73. The results of this study will lay a foundation for searching the regulation of geniposide biosynthesis and further analysis of the quality formation mechanism of G. jasminoides, so as to promote the breeding of excellent varieties of G. jasminoides.

Electroacupuncture Alleviates Functional Constipation in Mice by Activating Enteric Glial Cell Autophagy via PI3K/AKT/mTOR Signaling / 中国结合医学杂志

OBJECTIVE@#To investigate autophagy-related mechanisms of electroacupuncture (EA) action in improving gastrointestinal motility in mice with functional constipation (FC).@*METHODS@#According to a random number table, the Kunming mice were divided into the normal control, FC and EA groups in Experiment I. The autophagy inhibitor 3-methyladenine (3-MA) was used to observe whether it antagonized the effects of EA in Experiment II. An FC model was established by diphenoxylate gavage. Then the mice were treated with EA stimulation at Tianshu (ST 25) and Shangjuxu (ST 37) acupoints. The first black stool defecation time, the number, weight, and water content of 8-h feces, and intestinal transit rate were used to assess intestinal transit. Colonic tissues underwent histopathological assessment, and the expressions of autophagy markers microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 were detected by immunohistochemical staining. The expressions of phosphoinositide 3-kinases (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) signaling pathway members were investigated by Western blot and quantitative reverse transcription-polymerase chain reaction, respectively. The relationship between enteric glial cells (EGCs) and autophagy was observed by confocal immunofluorescence microscopy, localization analysis, and electron microscopy.@*RESULTS@#EA treatment shortened the first black stool defecation time, increased the number, weight, and water content of 8-h feces, and improved the intestinal transit rate in FC mice (P<0.01). In terms of a putative autophagy mechanism, EA treatment promoted the expressions of LC3 and Beclin-1 proteins in the colonic tissue of FC mice (P<0.05), with glial fibrillary acidic protein (GFAP) and LC3 significantly colocalized. Furthermore, EA promoted colonic autophagy in FC mice by inhibiting PI3K/AKT/mTOR signaling (P<0.05 or P<0.01). The positive effect of EA on intestinal motility in FC mice was blocked by 3-MA.@*CONCLUSION@#EA treatment can inhibit PI3K/AKT/mTOR signaling in the colonic tissues of FC mice, thereby promoting EGCs autophagy to improve intestinal motility.

Research on the formulation and revision of radiological parameters in the "Standards for Drinking Water Quality（GB5749-2022）" in China / 中华预防医学杂志

The radioactive safety of drinking water has attracted increasing public concern. The newly issued Standards for Drinking Water Quality (GB5749-2022) in China has revised the radiological parameters. This article provides an overview of the main sources, levels of radionuclides in drinking water, and summarized the individual doses criterion and adverse health effects associated with exposure of the public to radionuclides from drinking-water. It analyzes and discusses the relevant revision content of radiological parameters, including the guidance values for screening gross α and gross β, subtracting the contribution of potassium-40 from gross β activity when the gross β activity concentration exceeds the screening level, and the basis for establishing the limit values of reference indices uranium and radium-226. Specific implementation and evaluation suggestions are also proposed.

In vivo identification of the pharmacodynamic ingredients of Polygonum cuspidatum for remedying the mitochondria to alleviate metabolic dysfunction-associated fatty liver disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a chronic liver disease that currently lacks approved pharmacological treatment options. The mechanisms and active ingredients of Polygonum cuspidatum (PC) that regulate the mitochondria to relieve MAFLD have not been assessed. Thus, this study was designed to explore the bioactive components of PC extract in regulating mitochondria to alleviate high-fat diet-induced MAFLD using mitochondrial pharmacology and pharmacochemistry. Our results demonstrate that PC protected the mitochondrial ultrastructure and inhibited oxidative stress and energy metabolism disorder in the liver mitochondria. Furthermore, PC-derived components in the liver mitochondria attenuated oxidative stress and restored the energy metabolism of fat emulsion-induced steatosis in L02 cell. Sixteen compounds were identified in the liver-mitochondrial extracts of PC-treated rats. The antisteatotic effects of three identified monomers and anti-MAFLD ability of the monomer group were confirmed. Collectively, our data suggest that the extract of PC can alleviate lipid metabolism disorder in MAFLD by protecting the mitochondrial ultrastructure, reducing oxidative stress injury, and promoting energy metabolism. The sixteen identified compounds were potentially the main effective ingredients of PC in treating MAFLD. Thus, PC shows potential in treating MAFLD and related mitochondrial dysfunction. The proposed strategy to identify the ingredients of herbal medicines based on mitochondrial pharmacology and pharmacochemistry presents a new approach in exploring the pharmacodynamic components of herbal medicines that regulate mitochondria in preventing and treating diseases.

[Application of near infrared spectroscopy to predict contents of various lactones in chromatographic process of Ginkgo Folium].

This study established a method for rapid quantification of terpene lactone, bilobalide, ginkgolide C, ginkgolide A and ginkgolide B in the chromatographic process of Ginkgo Folium based on near infrared spectroscopy(NIRS). The effects of competitive adaptive reweighting sampling(CARS), random frog(RF), and synergy interval partial least squares(siPLS) on the performance of partial least squares regression(PLSR) model were compared to the reference values measured by HPLC. Among them, the correlation coefficients of prediction(Rp) of validation sets of terpene lactone, bilobalide, and ginkgolide C were all higher than 0.98, and the relative standard errors of prediction(RSEPs) were 5.87%, 6.90% and 6.63%, respectively. Aiming at ginkgolide A and ginkgolide B with relatively low content, the genetic algorithm joint extreme learning machine(GA-ELM) was used to establish the optimized quantitative analysis model. Compared with CARS-PLSR model, the CARS-GA-ELM models of ginkgolide A and ginkgolide B exhibited a reduction in RSEP from 15.65% to 8.52% and from 21.28% to 10.84%, respectively, which met the needs of quantitative ana-lysis. It has been proved that NIRS can be used for the rapid detection of various lactone components in the chromatographic process of Ginkgo Folium.

A Novel Method for Identifying Parkin Binding Agents in Complex Preparations of Herbal Medicines.

Parkin is a crucial E3 ubiquitin ligase for initiating mitophagy through the PINK1/Parkin pathway. Regulating the expression and activity of parkin can remedy mitophagy and human disease. We developed an efficient method to isolate natural parkin ligands from herbal medicines by combining centrifugal ultrafiltration and liquid chromatography/mass spectrometry. The heterologous expression technology identified functionally active and pure parkin proteins. After evaluating the reliability of the method using DL-selenomethionine and DL-dithiothreitol as positive controls, this method was successfully applied to capture parkin ligands from Polygoni Cuspidati Rhizoma et Radix and Sophorae Flavescentis Radix. LC/MS identified seven novel parkin-targeting compounds, namely, 7,4'-dihydroxy-5-methoxy-8-(γ, γ-dimethylallyl)-flavanone, kushenol I, kurarinone, sophoraflavanone G, torachrysone-8-O-glucoside, apigenin, and emodin, supported by the molecular docking analysis. Five of the seven novel compounds (kushenol I, kurarinone, sophoraflavanone G, apigenin, and emodin) can activate parkin in in vitro autoubiquitination assays. Meanwhile, kushenol I and kurarinone had antisteatosis activity in fat emulsion-damaged human hepatocytes. These results confirmed the effectiveness of the method for identifying parkin ligands from complex preparations, useful to advance drug discovery from medicinal herbs.

The Impact of Traditional Chinese Medicine on Mitophagy in Disease Models.

Mitophagy plays an important role in maintaining mitochondrial quality and cell homeostasis through the degradation of damaged, aged, and dysfunctional mitochondria and misfolded proteins. Many human diseases, particularly neurodegenerative diseases, are related to disorders of mitochondrial phagocytosis. Exploring the regulatory mechanisms of mitophagy is of great significance for revealing the molecular mechanisms underlying the related diseases. Herein, we summarize the major mechanisms of mitophagy, the relationship of mitophagy with human diseases, and the role of traditional Chinese medicine (TCM) in mitophagy. These discussions enhance our knowledge of mitophagy and its potential therapeutic targets using TCM.

Research progress and prospects for the use of plant metabolomics in quality evaluation of traditional Chinese medicinal materials / 药学学报

The quality of traditional Chinese medicine has a direct impact on the effectiveness and safety of its use, and is the premise necessary to ensure the healthy development of the traditional Chinese medicine industry. Comprehensive and accurate control and evaluation of the quality of medicinal materials is of great significance to the traditional Chinese medicine industry, but the complexity and dynamics of the chemical composition of medicinal materials makes their quality evaluation a challenge. Plant metabolomics provides an integrated and comprehensive analysis that is consistent with the holistic approach of traditional Chinese medicine. Chemical information therein promotes the establishment of a traceable system and provides new ideas and methods for the quality evaluation of medicinal materials. Plant metabolomics in the quality evaluation of medicinal materials is gradually increasing, and the core is the screening and identification of differential metabolites or specific marker compounds by means of stoichiometry. This study focused on the main factors that affect the quality of medicinal materials, such as origin, environmental adversity, varieties, harvest time, commercial specification and TCM processing. We describe the research progress in plant metabolomics combined with chemometrics analysis for the quality control and evaluation of medicinal materials, summarize existing problems, identify trends, and propose future research directions. Metabolomics plays an increasingly important role in the quality evaluation of medicinal materials, but the absolute qualitative and quantitative information of metabolomics needs to be further developed, and a single 'omics' technique is not sufficient for an in-depth analysis of medicinal value. In the future, standardization of plant metabolomics methods and a more complete database should be actively promoted, and plant metabolomics should be integrated into quality marker exploration. Plant metabolomics will need to be integrated with other 'omics' methods to improve the quality and evaluation system of medicinal materials.

A study on the rapidly non-destructive detection method of Huoxiang Zhengqi oral liquid using near infrared spectroscopy / 药学学报

Based on near infrared spectroscopy and high performance liquid chromatography, this paper established the regression relationship between near infrared spectroscopy and index component content of Huoxiang Zhengqi oral liquid, so as to realize the rapid detection of index component content based on near infrared spectroscopy. Magnolol, honokiol and hesperidin were used as the quality indexes of Huoxiang Zhengqi oral liquid. After using the first derivative and normalization pretreatment method, characteristic variables were screened by CARS, and the correction model was finally established by partial least-squares regression (PLSR) method. The method accuracy was evaluated with the external validation, and the prediction results were tested for significance. The results indicated that when the near infrared spectrum was scanned through the bottle, the model's correlation coefficients of prediction (Rp) were higher than 0.99, the root mean square errors of the prediction models (RMSEP) were all less than 0.008 4, and the relative standard errors of prediction set (RSEP) were all less than 2.83%. There was no significant difference in the predicted results between these two kinds of model. The models established in the non-destructive way have good performance and high prediction accuracy. The rapid and nondestructive way has application value in the quality control of Huoxiang Zhengqi oral liquid.

The role of acupuncture in the treatment of women with pain in endometriosis: A protocol for systematic review and meta-analysis.

BACKGROUND: Given the high numbers of recent cases related to Endometriosis, acupuncture has become a first line of treatment to alleviate the discomfort caused by endometriosis. Numerous studies have reported that acupuncture has a distinct effect when treating the discomfort caused by endometriosis. The primary advantages include various treatment methods, simple administration, minimal adverse reactions, and having no impact on the intrauterine environment. This study aims to elucidate the role of acupuncture in treating pain associated with endometriosis. METHODS: The authors will search 6 online-based databases to find Randomized Controlled Trials related to determining the role of acupuncture in treating pain from endometriosis. The assessed primary outcomes include the clinical effective rate, variation in the level of pain, and variation in peripheral blood CA-125 level. A comprehensive meta-analysis statistical software will be used to conduct all analyses. RESULTS: This study will assess the role of acupuncture when it is used to treat pain arising from endometriosis. CONCLUSION: The conclusions presented in the metanalysis will present a scientific-based theoretical framework and a standardized clinical guidance for treating endometriosis-related pain. ETHICS AND DISSEMINATION: This systematic review and meta-analysis does not require an ethics approval as it does not collect any primary data from patients. OSF REGISTRATION NUMBER: September 28, 2021.osf.io/htukv. (https://osf.io/htukv/).

Jiuzhuan Huangjing Pills relieve mitochondrial dysfunction and attenuate high-fat diet-induced metabolic dysfunction-associated fatty liver disease.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common global chronic liver disease. Jiuzhuan Huangjing Pills (JHP) have been used for the treatment of human disease for over a thousand years, but their efficacy and underlying mechanism(s) of action against MAFLD are unknown. We investigated the alleviating effects of JHP on high-fat diet (HFD)-induced MAFLD. METHODS: In vitro and in vivo methods were used to evaluate the effects of JHP on MAFLD. L02 adipocyte models were induced by fat emulsion and adipocytes were treated with JHP for 24 h. MAFLD rat models were induced by HFD-feeding and were intragastrically administered JHP for 12 weeks. Changes in fat accumulation, L02 cell damage, body weight, food intake, histological parameters, organ indexes, biochemical parameters, and mitochondrial indicators including ultrastructure, oxidative stress, energy metabolism, and fatty acid metabolism were investigated. RESULTS: JHP attenuated the increase in levels of total cholesterol, triglyceride, low density lipoprotein cholesterol, alanine transaminase, and aspartate transaminase levels, and significantly increased high density lipoprotein cholesterol. JHP up-regulated levels of glutathione (GSH) and superoxide dismutase (SOD), and down-regulated malondialdehyde (MDA). JHP afforded protection to the mitochondrial ultrastructure, and inhibited the HFD-induced increase in MDA and the reduction of SOD, GSH, ATP synthase, and complex I and II, in liver mitochondria. JHP regulated the expression of ß-oxidation genes, including acyl-CoA dehydrogenase, cyl-CoA dehydrogenase long chain, carnitine palmitoyltransferase 1A, carnitine palmitoyltransferase 1B, peroxisomal proliferator-activated receptor-gamma coactivator-1α and peroxide proliferator activated receptor α. CONCLUSION: JHP alleviates HFD-induced MAFLD through the protection of mitochondrial function.

Tiaobu Feishen therapy inhibits inflammation induced by cigarette smoke extracts in a human monocyte/macrophage cell line.

OBJECTIVE: To study the mechanistic effects of Tiaobu Feishen therapy (TBFS) on inflammation induced by cigarette smoke extract (CSE) in a human monocyte/macrophage cell line. METHODS: The human monocyte/macrophage cell line THP-1 was stimulated with 10 % CSE in the presence or absence of Bufei Yishen formula (BYF), Bufei Jianpi formula (BJF) and Yiqi Zishen formula (YZF). All formulations contained serum. Pro-inflammatory cytokines were measured in the supernatants using enzyme-linked immunosorbent assay. The activity of STAT3 DNA binding was detected using electrophoretic mobility shift assay and janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway activation was assessed using Western blotting. RESULTS: The results showed that BYF, BJF and YZF treatment strongly decreased the CSE-induced secretion of interleukin (IL)-6, IL-8, tumor necrosis factor-α and matrix metalloproteinase-9 by THP-1 cells. Furthermore, BYF, BJF and YZF treatment attenuated STAT3 DNA binding capacity and JAK2 and STAT3 were shown to be phosphorylated. CONCLUSION: The data revealed that BYF, BJF and YZF effectively inhibited a CSE-induced inflammatory response in THP-1 cells by limiting activation of the JAK2/STAT3 pathway.

Resveratrol inhibits MUC5AC expression by regulating SPDEF in lung cancer cells.

BACKGROUND: MUC5AC was recently identified to play important roles in the proliferation and metastasis of malignant mucinous lung tumor cells. Resveratrol (Res), a natural compound with anticancer effects in lung cancer cells, has been reported to inhibit mucin production in airway epithelial cells. This study aimed to investigate the inhibitory effect of Res on MUC5AC expression in lung mucinous adenocarcinoma cells and the potential mechanisms. METHODS: Mucus-producing A549 human lung carcinoma cells were used to test the effects of Res on SPDEF and MUC5AC expression. Gene and protein expression was assessed by real-time quantitative PCR (qPCR), immunofluorescence and western blotting assays. SPDEF lentivirus was used to upregulate SPDEF expression levels in mucus-producing A549 human lung carcinoma cells. Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) assay. RESULTS: Res decreased MUC5AC expression in an SPDEF-dependent manner in mucus-producing A549 human lung carcinoma cells, and this change was accompanied by decreased ERK expression and AKT pathway activation. Moreover, SPDEF was found to be overexpressed in lung adenocarcinoma (LUAD), especially in mucinous adenocarcinoma. In-vitro functional assays showed that overexpression of SPDEF reduced the chemosensitivity of A549 cells to cisplatin (DDP). In addition, Res treatment increased A549 cell chemosensitivity to DDP by inhibiting the SPDEF-MUC5AC axis. CONCLUSION: Our results indicate that the SPDEF-MUC5AC axis is associated with DDP sensitivity, and that Res decreases SPDEF and MUC5AC expression by inhibiting ERK and AKT signaling in A549 cells, which provides a potential pharmacotherapy for the prevention and therapeutic management of mucinous adenocarcinoma.