ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: To explore the differences in the anti-inflammatory efficacy and mechanisms of the Miao medicine, both raw and after processing, using the "sweat soaking method" of Radix Wikstroemia indica (RWI). AIM OF THE STUDY: The purpose of this study was to explore the differences in the anti-inflammatory efficacy and mechanism of action before and after the processing of the Miao medicine (RWI) using the "sweat soaking method." MATERIALS AND METHODS: Network pharmacology technology was used to construct the "drug-component target-pathway-disease" network, and the main anti-inflammatory pathways of RWI were identified. Rat models of collagen-induced arthritis were established. The changes in body weight, swelling rate of the foot pad and ankle joint, arthritis index, thymus index, spleen index, pathological changes of the ankle joint, and the content of inflammatory cytokines (IL-1ß, IL-2, IL-6, IL-10, TNF-α, and NO) were used as indices to evaluate the effect of RWI on rats with collagen-induced arthritis before and after its processing. Plasma and urine samples were collected from the rats, and the potential biomarkers of, and metabolic pathways underlying the anti-inflammatory effects of RWI before and after processing were identified using 1H-Nuclear magnetic resonance metabolomics combined with a multivariate statistical analysis. RESULTS: Eleven key anti-inflammatory targets of IL6, IL-1ß, TNF, ALB, AKT1, IFNG, INS, STAT3, EGFR, TP53, and SRC were identified by network pharmacology. The PI3K-Akt signaling pathway, steroid hormone biosynthesis, arginine biosynthesis, arginine and proline metabolism, tryptophan metabolism, and other pathways were mainly involved in these effects. Pharmacodynamic studies found that both raw and processed RWI products downregulated inflammatory factors in rats with collagen-induced arthritis and alleviated the pathological changes. A total of 41 potential pathways for the anti-inflammatory effects of raw RWI products and 36 potential pathways for the anti-inflammatory effects of processed RWI products were identified by plasma and urine metabolomics. The common pathways of network pharmacology and metabolomics were steroid hormone biosynthesis, arginine biosynthesis, arginine and proline metabolism, and tryptophan metabolism. CONCLUSIONS: The anti-inflammatory effect of RWI was mainly related to the regulation of steroid hormone biosynthesis, arginine biosynthesis, arginine and proline metabolism, and tryptophan metabolism. Finally, the "sweat soaking method" enhanced the anti-inflammatory effect of RWI.
Subject(s)
Arthritis, Experimental , Drugs, Chinese Herbal , Wikstroemia , Rats , Animals , Arthritis, Experimental/chemically induced , Arthritis, Experimental/drug therapy , Arthritis, Experimental/pathology , Sweat/chemistry , Phosphatidylinositol 3-Kinases , Tryptophan , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/analysis , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Arginine , Steroids , Hormones , ProlineABSTRACT
This study aims to systematically evaluate the clinical efficacy and safety of Kushen Gelatum combined with antibiotics for treating bacterial vaginosis. The randomized controlled trial(RCT) of Kushen Gelatum for treating bacterial vaginosis were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, and Cochrane Library with the time interval from inception to January 2023. Data were extracted from the included RCT by 2 investigators, including the sample size, characteristics of patients, interventions and controls, outcome indicators, and adverse effects. The Cochrane collaboration network's bias risk assessment tool was used for methodolo-gical quality evaluation of the included trials. RevMan 5.4 was employed to perform the Meta-analysis. A total of 19 RCTs were inclu-ded, involving 1 980 patients with bacterial vaginosis. Meta-analysis showed that, compared with nitroimidazoles alone, Kushen Gelatum + nitroimidazoles improved the total response rates in terms of clinical symptoms and laboratory tests(RR=1.24, 95%CI[1.13, 1.36], P<0.000 01), laboratory tests(RR=1.16, 95%CI[1.06, 1.26], P=0.000 9), and clinical symptoms(RR=1.26, 95%CI[1.08, 1.46], P=0.003), and reduced the leukocyte esterase positive rate(RR=0.29, 95%CI[0.17, 0.48], P<0.000 01) and the recurrence rate(RR=0.37, 95%CI[0.23, 0.58], P<0.000 1). Compared with lincomycin antibiotics(clindamycin) alone, Kushen Gelatum + lincomycin antibiotics(clindamycin) improved the total response rates in terms of clinical symptoms and laboratory tests(RR=1.18, 95%CI[1.06, 1.31], P=0.003) and laboratory tests(RR=1.27, 95%CI[1.04, 1.54], P=0.02), reduced the recurrence rate(RR=0.20, 95%CI[0.05, 0.75], P=0.02), and shortened the time to relief of burning sensation(MD=-1.70, 95%CI[-2.15,-1.26], P<0.000 01), vaginal itching(MD=-0.82, 95%CI[-1.30,-0.34], P=0.000 8), and abnormal leucorrhea(MD=-1.52, 95%CI[-1.98,-1.06], P<0.000 01). Compared with nitroimidazoles + probiotics, Kushen Gelatum + nitroimidazoles + probiotics improved the total response rate in terms of clinical symptoms and laboratory tests(RR=1.18, 95%CI[1.02, 1.36], P=0.03) and reduced the recurrence rate(RR=0.27, 95%CI[0.09, 0.76], P=0.01). Kushen Gelatum combined with antibiotics demonstrates a potential therapeutic effect on bacterial vaginosis, whereas the number and quality of the relevant clinical studies remain to be improved. The process of clinical trial should be standardized to improve the quality of evidence, so as to provide strong evidence to guide the application of Kushen Gelatum in clinical practice.
Subject(s)
Nitroimidazoles , Vaginosis, Bacterial , Female , Humans , Anti-Bacterial Agents/adverse effects , Clindamycin/adverse effects , Vaginosis, Bacterial/drug therapy , Vaginosis, Bacterial/chemically induced , Nitroimidazoles/adverse effectsABSTRACT
This study aimed to observe the effect of terpinen-4-ol(T4O) on the proliferation of vascular smooth muscle cells(VSMCs) exposed to high glucose(HG) and reveal the mechanism via the Krüppel-like factor 4(KLF4)/nuclear factor kappaB(NF-κB) signaling pathway. The VSMCs were first incubated with T4O for 2 h and then cultured with HG for 48 h to establish the model of inflammatory injury. The proliferation, cell cycle, and migration rate of VSMCs were examined by MTT method, flow cytometry, and wound healing assay, respectively. The content of inflammatory cytokines including interleukin(IL)-6 and tumor necrosis factor-alpha(TNF-α) in the supernatant of VSMCs was measured by enzyme-linked immunosorbent assay(ELISA). Western blot was employed to determine the protein levels of proliferating cell nuclear antigen(PCNA), Cyclin D1, KLF4, NF-κB p-p65/NF-κB p65, IL-1ß, and IL-18. The KLF4 expression in VSMCs was silenced by the siRNA technology, and then the effects of T4O on the cell cycle and protein expression of the HG-induced VSMCs were observed. The results showed that different doses of T4O inhibited the HG-induced proliferation and migration of VSMCs, increased the percentage of cells in G_1 phase, and decreased the percentage of cells in S phase, and down-regulated the protein levels of PCNA and Cyclin D1. In addition, T4O reduced the HG-induced secretion and release of the inflammatory cytokines IL-6 and TNF-α and down-regulated the expression of KLF4, NF-κB p-p65/NF-κB p65, IL-1ß, and IL-18. Compared with si-NC+HG, siKLF4+HG increased the percentage of cells in G_1 phase, decreased the percentage of cells in S phase, down-regulated the expression of PCNA, Cyclin D1, and KLF4, and inhibited the activation of NF-κB signaling pathway. Notably, the combination of silencing KLF4 with T4O treatment further promoted the changes in the above indicators. The results indicate that T4O may inhibit the HG-induced proliferation and migration of VSMCs by down-regulating the level of KLF4 and inhibiting the activation of NF-κB signaling pathway.
Subject(s)
Interleukin-18 , NF-kappa B , NF-kappa B/genetics , NF-kappa B/metabolism , Interleukin-18/metabolism , Proliferating Cell Nuclear Antigen/genetics , Cyclin D1/metabolism , Tumor Necrosis Factor-alpha/metabolism , Muscle, Smooth, Vascular , Cell Proliferation , Signal Transduction , Cytokines/metabolism , Glucose/toxicity , Glucose/metabolismABSTRACT
A side-stream tank which was in parallel with the anoxic tank was used to improve the performance of an Anaerobic-Anoxic-Oxic process. The partial mixtures from the anaerobic tank were injected into the side-stream tank with the initial nitrite nitrogen (NO2--N) concentrations of 10 mg/L and 20 mg/L. When the initial NO2--N concentration in the tank was 20 mg/L, total nitrogen and total phosphorus removal efficiencies of the A2/O process increased from 72% and 48% to 90% and 89%, respectively. 2.23 mg/L of nitric oxide (NO) were observed in the side-stream tank. The abundance of Nitrosomonas sp. and Nitrospira sp. were varied from 0.98% and 6.13% to 2.04% and 1.13%, respectively. The abundances of Pseudomonas sp. and Acinetobacter sp. were increased from 0.81% and 0.74% to 6.69% and 5.48%, respectively. NO plays an important role for improving the nutrients removal of the A2/O process in the side-stream nitrite-enhanced strategy.
Subject(s)
Nitrites , Waste Disposal, Fluid , Nitric Oxide , Anaerobiosis , Rivers , Nitrogen Dioxide , Bioreactors , Phosphorus , Nitrogen , Nutrients , Sewage , DenitrificationABSTRACT
In this work, twenty-five water-soluble constituents were isolated from the bulbs of Lilium davidii var. unicolor, including two new compounds termed liliumtides A and B (1-2), and seventeen known compounds (3-4, 6-13, 15, 17, 21-25) isolated from the genus of Lilium for the first time. Their structures were established using high-resolution electrospray ionization mass spectroscopy and 1D and 2D nuclear magnetic resonance data. To confirm furtherly the absolute configuration of liliumtide A, and to accumulate enough sample to study the anti-insomnia effect, a total synthesis for liliumtide A was achieved by four steps. The pentobarbital-induced sleeping time test showed that compared with the blank control group, the liliumtide A decreased sleep latency and significantly increased the sleep time. These results suggested that liliumtide A could be investigated as a natural anti-insomnia lead compound in the pharmaceutical and food industries.
Subject(s)
Lilium , Lilium/chemistry , Molecular Structure , Plant Roots/chemistryABSTRACT
The antimicrobial effect of 21 nature spices essential oils (EOs) on marinated chicken was investigated and response surface analysis was applied to obtain the optimal combination. Cassia bark EO, cinnamon EO, tea tree EO, and angelica EO had the best antibacterial effect. Their inhibition zone diameters (IZD) were 23 mm, 21 mm, 15 mm, and 12 mm, and their minimal bactericidal concentrations (MBC) were 1.25 µL/mL, 1.25 µL/mL, 10.00 µL/mL, 20.00 µL/mL. Using the Box-Behnken Design model, with the minimum total number of spoilage bacteria as the evaluation index, the optimal mixture was cassia bark EO 2.40 µL/mL, cinnamon EO 1.00 µL/mL, tea tree EO 3.50 µL/mL, and angelica EO 9.00 µL/mL. Compared with the control group, the total number of colonies was reduced by 1.3 log unites at the 12th sampling day, and the protein degradation process was slowed down owing to the preservative addition. These results indicate the potential application of nature extracts in chicken and other meat preservation.
Subject(s)
Oils, Volatile , Spices , Animals , Anti-Bacterial Agents/pharmacology , Chickens , Cinnamomum zeylanicum , Microbial Sensitivity Tests/veterinary , Oils, Volatile/pharmacology , Plant Extracts/pharmacology , TeaABSTRACT
Pressure injury (PI) is a worldwide health problem that has attracted widespread attention from scientific and clinical research communities. PI incidence correlates with the increase of the aging population. In this situation, it is crucial to select effective and affordable drugs for patients and healthcare systems. Herein, we report a case of a 94-year-old female with a stage 2 PI wound, which was treated topically using a novel combination of mixed powders: metronidazole and nano pearl powders. Metronidazole is the preferred option to treat infected wounds due to its excellent antibacterial ability. However, some drawbacks have limited the use of metronidazole in PI wound management, such as its poor capacity to accelerate wound closure. Pearl powder has a strong capacity to promote wound healing and closure but has not been effective at resisting wound infection. To take advantage of powdered drugs' wound treatment properties and accelerate PI wound healing, we prepared powdered mixtures for wound application. Both drugs are cost-effective and were beneficial to wound healing. Therefore, the combination of metronidazole and pearl powders offer a promising choice to patients with PI wounds.
Subject(s)
Metronidazole , Pressure Ulcer , Wound Infection , Aged , Aged, 80 and over , Female , Humans , Anti-Bacterial Agents/therapeutic use , Metronidazole/therapeutic use , Powders , Wound Healing , Wound Infection/drug therapyABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Coptis chinensis Franch (CCF), also known as Huang Lian in China, is a traditional Chinese medicine that commonly used for more than 2000 years. Clinically, CCF often used as anti-inflammatory, immune regulation and other effects. It has been reported that the decoction containing CCF can be used for the treatment of benign prostatic hyperplasia (BPH) or lower urinary tract symptoms (LUTS). AIM OF THE STUDY: This research aims to investigate the effect of CCF on inhibition of BPH development in vivo and in vitro, and further identify the active compound (s) and the possible mechanism involved in BPH-related bladder dysfunction. MATERIALS AND METHODS: Oestrodial/testosterone-induced BPH rat model was established as the in vivo model. The prostate index (PI) was calculated, the pathogenesis was analyzed and the micturition parameters were determined in the shamed-operated, BPH model and BPH + CCF groups after 4-week administration. The tension in detrusor strips was then assessed upon KCl or ACh stimulation with or without incubation of CCF or active compounds. To further investigate the signaling involved, rat detrusor cells were cultured as the in vitro models, the instantaneous calcium influx was measured and the ROCK-1 expression was detected. RESULTS: Increased PI value and the aggravated prostatic pathology were observed with voiding dysfunction in BPH rats, which were significantly blocked by oral CCF taken. ACh or KCl-induced contractile responses in detrusor strips were significantly inhibited and the micturition parameters were improved when incubation with CCF or its active compounds such as berberine. Both CCF and berberine suppressed the cellular calcium influx and ROCK-1 expression upon ACh stimulation, demonstrating that berberine was one of the active compounds that contributed to CCF-improved micturition symptoms and function. CONCLUSIONS: Taken together, our findings give evidence that CCF and its active compound berberine inhibited BPH and bladder dysfunction via Ca2+ and ROCK signaling, supporting their clinical use for BPH and BPH-related LUTS treatment.
Subject(s)
Berberine/therapeutic use , Coptis , Lower Urinary Tract Symptoms/drug therapy , Muscle Contraction/drug effects , Prostatic Hyperplasia/drug therapy , Urinary Bladder/drug effects , Animals , Berberine/isolation & purification , Berberine/pharmacology , Cells, Cultured , Lower Urinary Tract Symptoms/physiopathology , Male , Muscle Contraction/physiology , Organ Culture Techniques , Prostatic Hyperplasia/physiopathology , Rats , Rats, Wistar , Urinary Bladder/physiologyABSTRACT
The outbreak of COVID-19 raises an urgent need for the therapeutics to contain the emerging pandemic. However, no effective treatment has been found for SARS-CoV-2 infection to date. Here, we identified puerarin (PubChem CID: 5281807), quercetin (PubChem CID: 5280343) and kaempferol (PubChem CID: 5280863) as potential compounds with binding activity to ACE2 by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Molecular docking analysis showed that puerarin and quercetin exhibit good binding affinity to ACE2, which was validated by surface plasmon resonance (SPR) assay. Furthermore, SPR-based competition assay revealed that puerarin and quercetin could significantly affect the binding of viral S-protein to ACE2 receptor. Notably, quercetin could also bind to the RBD domain of S-protein, suggesting not only a receptor blocking, but also a virus neutralizing effect of quercetin on SARS-CoV-2. The results from network pharmacology and bioinformatics analysis support a view that quercetin is involved in host immunomodulation, which further renders it a promising candidate against COVID-19. Moreover, given that puerarin is already an existing drug, results from this study not only provide insight into its action mechanism, but also propose a prompt application of it on COVID-19 patients for assessing its clinical feasibility.
ABSTRACT
CONTEXT: Ganoderma lucidum (Leyss.ex Fr.) Karst (Ganodermataceae) is a fungus that has been used in traditional Chinese medicine. OBJECTIVE: This is the first investigation of the lipid-lowering and anti-atherosclerotic effects of Ganoderma lucidum spore ethanol extract (EEG) in hyperlipidemic rabbits. MATERIALS AND METHODS: Fifty-four Japanese rabbits were randomly divided into six groups (n = 9): control, model, atorvastatin and three EEG groups (6, 24 and 96 mg/kg/day, p.o.). Control group was administered a normal diet and other groups were administered a high-fat diet to induce hyperlipidaemia and atherosclerosis for 14 weeks. During this time, lipid profiles were recorded; lipid testing and histopathological examination of aorta and liver were conducted. LXRα and its downstream genes expression in the liver and small intestine were examined. The effect of EEG on macrophage cholesterol efflux and ABCA1/G1 expression was observed under silenced LXRα expression. RESULTS: EEG reduced serum cholesterol (20.33 ± 3.62 mmol/L vs 34.56 ± 8.27 mmol/L for the model group) and LDL-C, reduced the area of arterial plaques (24.8 ± 10% vs 53.9 ± 15.2% for the model group) and Intima/Medium thickness ratio, increased faecal bile acid content, upregulated LXRα, CYP7A1, ABCA1/G1, ABCG5/G8 expression in the liver, small intestine and macrophages. After silencing LXRα in macrophages, the ability of EEG to promote cholesterol efflux was inhibited. DISCUSSION AND CONCLUSION: EEG exert lipid-lowering and anti-atherosclerotic effects via upregulating expression of LXRα and downstream genes associated with reverse cholesterol transport and metabolism. However, whether PPARα/γ are involved in the up-regulation of LXR expression by EEG remains to be elucidated.
Subject(s)
Atherosclerosis/drug therapy , Hyperlipidemias/drug therapy , Lipid Metabolism/drug effects , Reishi/chemistry , Animals , Atherosclerosis/pathology , Cholesterol/metabolism , Diet, High-Fat , Disease Models, Animal , Ethanol/chemistry , Humans , Hyperlipidemias/pathology , Liver X Receptors/genetics , Liver X Receptors/metabolism , Macrophages/drug effects , Male , Rabbits , Spores, Fungal , THP-1 Cells , Up-RegulationABSTRACT
BACKGROUND AND OBJECTIVE: Mycoplasmal pneumonia (MP) can lead to inflammation, multiple system immune damage, and mixed infection in children. The pathogenesis is still unclear. Shuang-Huang-Lian (SHL) oral liquid can treat acute upper respiratory tract infection, acute bronchitis and light pneumonia. However, our current understanding of the molecular mechanisms supporting its clinical application still lags behind due to the lack of researches. It is difficult to understand the overall sensitization mechanism of SHL oral liquid. The purpose is to explain the mechanism of action of drugs in this study, which is useful to ensure the safety of medication for children. METHODS: The therapeutic mechanism of SHL oral liquid was investigated by a system pharmacology approach integrating drug-likeness evaluation, oral bioavailability prediction, ADMET, protein-protein interaction worknet, Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes database pathway performance, C-T-P network construction and molecular docking. RESULTS: A total of 18 active ingredients contained in SHL oral liquid and 53 major proteins were screened out as effective players in the treatment of M. pneumoniae disease through some related pathways and molecular docking. The majority of targets, hubs and pathways were highly related to anti-mycoplasma therapy, immunity and inflammation process. CONCLUSION: This study shows that the anti-bacterial effect of SHL oral liquid has multicomponent, multi-target and multi-pathway phenomena. The proposed approach may provide a feasible tool to clarify the mechanism of traditional Chinese medicines and further develop their therapeutic potentials.
Subject(s)
Anti-Infective Agents/chemistry , Drugs, Chinese Herbal/chemistry , Pneumonia, Mycoplasma/drug therapy , Respiratory Tract Infections/drug therapy , Small Molecule Libraries/chemistry , Anti-Infective Agents/pharmacokinetics , Databases, Genetic , Drug Evaluation, Preclinical , Drugs, Chinese Herbal/pharmacokinetics , Gene Expression Regulation/drug effects , Gene Ontology , Humans , Medicine, Chinese Traditional , Molecular Docking Simulation , Protein Binding , Signal Transduction , Small Molecule Libraries/pharmacologyABSTRACT
Liver fibrosis is a common part of the pathological development of many chronic liver diseases. As liver fibrosis progresses, it may lead to cirrhosis, portal hypertension, liver decompensation, liver tumours, and death. Camellia oil (Camellia oleifera Abel.) is widely used as an edible oil in China. It has a wide range of biological activities and is used as a traditional medicine to treat conditions such as burns and stomach pains. However, whether camellia oil can ameliorate liver fibrosis remains unclear. We constructed a liver fibrosis model induced by carbon tetrachloride (CCl4) and then confirmed the role of camellia oil in liver fibrosis by biochemical examination, histopathological morphology, immunohistochemistry, and western blot analysis. We found that camellia oil ameliorated histopathological lesions, improved liver function and antioxidant capacity, decreased the expression of TGF-ß1 and α-SMA proteins, and downregulated the expression of the pro-apoptotic proteins in CCl4-induced liver fibrosis. Therefore, these results suggest that camellia oil attenuates CCl4-induced liver fibrosis in mice, and its mechanism may function via reduction of hepatocyte apoptosis to inhibit hepatic stellate cell (HSC) activation. Camellia oil may provide a potential new treatment for liver fibrosis as an auxiliary treatment by addition of the edible oil to the daily diet.
Subject(s)
Camellia , Hepatocytes/drug effects , Liver Cirrhosis/prevention & control , Plant Oils/pharmacology , Animals , Apoptosis/drug effects , Carbon Tetrachloride , Disease Models, Animal , Male , Mice , Mice, Inbred C57BL , Phytotherapy , Plant Oils/therapeutic useABSTRACT
OBJECTIVE: To explore the effect of iron supplement intake on gestational diabetes mellitus(GDM) in early and middle pregnancy. METHODS: From February to April 2017, a prospective study was conducted among 807 early pregnant women in a prenatal clinic of a maternal and child medical institution in Chengdu City through purposive sampling. Data on maternal demographic characteristics was collected through questionnaire in early pregnancy. In early and middle pregnancy, the information of iron supplement intake were collected with questionnaire, 3-day 24 hour dietary recall method was used to assess maternal diet. According to the WHO recommendation, 60 mg/d iron supplementation during pregnancy was used as the dividing point, <60 mg/d iron supplementation was used as the low level group, and ≥60 mg/d iron supplementation was used as the high level group. At the 24 th to 28 th pregnant week, the oral glucose tolerance test(OGTT) was conducted, and GDM was diagnosed according to the Guidelines for the Diagnosis and Treatment of Pregnancy Diabetes in China(2014). Multivariate unconditional Logistic regression model was used to analyze the effect of iron supplement intake on gestational diabetes mellitus(GDM) in early and middle pregnancy. RESULTS: A total of 739 valid samples were followed up, the age was(28. 22±3. 75) years old. In early and middle pregnancy, the rate of taking iron supplementation was 5. 0% and 67. 9%, 3. 8% and 47. 1% of them iron supplement intake was more than 60 mg/d. After adjustmenting for body mass index, age, dietary iron, etc. Multivariate unconditional Logistic regression analysis showed that there was a positive correlation between the average intake of iron supplement and the occurrence of GDM in women during the second trimester of pregnancy(OR=1. 059, 95%CI 1. 016-1. 104). Compared with the lower iron supplement intake(<60 mg/d) women in midpregnancy, the risk of GDM was 1. 406 times(95%CI 1. 019-1. 939)in the higher iron supplement intake(≥60 mg/d) women. No correlation was found between iron intake in early pregnancy and the occurrence of GDM. CONCLUSION: Iron supplement intake during pregnancy may increase the risk of GDM. Appropriate intake of iron supplement for pregnant women is worth discussing.
Subject(s)
Diabetes, Gestational , Dietary Supplements , Iron, Dietary/administration & dosage , Adult , China , Female , Humans , Pregnancy , Prospective Studies , Young AdultABSTRACT
The inherited polyglutamine (polyQ) expansion diseases are characterized by progressive accumulation of aggregation-prone polyQ proteins, which may provoke proteostasis imbalance and result in significant neurotoxicity. Using polyQ transgenic Caenorhabditis elegans models, we find that Kai-Xin-San (KXS), a well-known herbal formula traditionally used to treat mental disorders in China, can alleviate polyQ-mediated neuronal death and associated chemosensory deficiency. Intriguingly, KXS does not reduce polyQ aggregation in vitro as demonstrated by Thioflavin-T test, but does inhibit polyQ aggregation in C. elegans models, indicating an indirect aggregation-inhibitory mechanism. Further investigation reveals that KXS can modulate two key arms of the protein quality control system, that is, heat shock response and autophagy, to clear polyQ aggregates, but has little effect on proteasome activity. In addition, KXS is able to reduce oxidative stress, which is involved in proteostasis and neurodegeneration, but has no effect on life span or dietary restriction response. To examine potential interaction of the four component herbs of KXS, a dissection strategy was used to study the effects of differential herbal combinations in C. elegans polyQ models. While the four herbs do contribute additively to KXS function, Panax ginseng is found to be the most effective constituent. Taken together, these findings not only demonstrate the neuroprotective ability of KXS but also suggest its potential as a proteostasis regulator in protein aggregation disorders and provide an insight into the mechanism studies of traditionally used complex prescriptions and their rationality.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Neurotoxicity Syndromes/prevention & control , Peptides/toxicity , Proteostasis/drug effects , Animals , Animals, Genetically Modified , Behavior, Animal/drug effects , Caenorhabditis elegans , Disease Models, Animal , Drugs, Chinese Herbal/therapeutic use , Neurotoxicity Syndromes/metabolism , Neurotoxicity Syndromes/pathology , Oxidative Stress/drug effects , Proteasome Endopeptidase Complex/drug effects , Proteasome Endopeptidase Complex/metabolism , Protein Aggregation, Pathological/metabolism , Protein Aggregation, Pathological/prevention & control , Proteome/drug effects , Proteome/metabolismABSTRACT
OBJECTIVE: To investigate the apoptosis of CD34+CD38--KG1a leukemia stem cells induced by Qinba selenium-mushroom extract(FA-2-b-ß), and its related mechanism. METHODS: CD34+CD38---KG1a cells were isolated from KG1a cell line by magnetic activated cell sorting. The proliferation ability of KG1a stem cells treatd by various concentration of FA-2-b-ß(1.2-2.4 mg/ml) in vitro for 24 and 48 hours were tested by cell counting Kit-8(CCK8). Flow cytometry was used to detect the apoptosis rate of KG1a stem cells in each group after treated by FA-2-b-ß in vitro. Expression of BAX,BCL-2,Casepase-3 and Cyclin D1 protein were detected by Western blot. RESULTS: The proportion of CD34+CD38---KG1a stem cells was (95.35±2.63ï¼% after immunomagnetic isolation. The proliferation of KG1a stem cells was inhibited significantly by FA-2-b-ß, which shows a time- and dose-dependent manner (24 h,r=0.943; 48 h,r=0.976). Flow cytometry shows that with the increasing of drug concentration, the apoptosis was also increased, when KG1a stem cells was treated by FA-2-b-ß for 24 h. Western blot indicated that the expression of apoptosis-related protein BAX and Casepase-3 were up-regulated, the expression of BCL-2 and Cyclin D1 were down-regulated. CONCLUSION: FA-2-b-ß can regulate proliferation and apoptosis KG1a stem cells, the involved mechanism may be related with the activation of mitochondrial-mediated apoptotic pathway.
Subject(s)
Neoplastic Stem Cells , ADP-ribosyl Cyclase 1 , Antigens, CD34 , Apoptosis , Cell Line, Tumor , Cell Proliferation , Humans , Membrane Glycoproteins , SeleniumABSTRACT
BACKGROUND: Chronic simple pharyngitis (CSP) is a common clinical chronic respiratory inflammation with persistent and intransigent symptoms. We analyzed the clinical data to find the evidence that herbal tea, a traditional Chinese medicine treatment in China, could improve the symptoms of CSP patients in a simple way. METHODS: We systematically reviewed the clinical data of randomized controlled treatments from April 2019 and evaluated the results using the improved Jadad scale and the Cochrane bias risk assessment tool. RevMan 5.3 software was used for chart analysis. In addition, we used Excel to conduct frequency statistics on Chinese herbs from included articles and analyze its medication rules. RESULTS: Among the collection of 161 articles, 6 RCTs published in Chinese journals were included in this review. The methodological quality of the treatments was low, and most of them only provide diagnostic criteria. Inclusion and exclusion criteria were not specified, and none of the 6 RCTs used the blind method on the result evaluator. Furthermore, only one RCT evaluated the baseline level variance. For these reasons, we did not make a network meta-analysis. CONCLUSIONS: The traditional Chinese herbs involved in herbal tea did have ingredients to alleviate CSP symptoms. However, our research showed that the current research could not draw any credible conclusions on the curative effect of herbal tea, which indicated that the overall level of TCM clinical research needs to be improved to evaluate the efficacy of herbal tea.
ABSTRACT
Estrogens and androgens play critical roles during benign prostatic hyperplasia (BPH) development. Estrogen receptors (ERs), androgen receptor (AR) and aromatase, the key conversion enzyme of androgen to estrogen, are thought to be the effective targets for BPH treatment. Bakuchiol (Ba)-containing herb Psoralea corylifolia has been long-termed used for BPH patients in traditional Chinese medicine while the role and regulatory mechanism of Ba involved remain unclear. Human prostatic cell lines WPMY-1 and BPH-1 and oestrodial/testosterone-induced BPH rats were used as the in vitro and in vivo models. Ba significantly inhibited the proliferation of WPMY-1 and BPH-1 cells. In E2/T-induced BPH model, Ba treatment also significantly inhibited the enlargement of prostate, decreased PI values, reduced the thickness of periglanular smooth muscle layer, and down-regulated the expressions of PCNA and smooth muscle cell marker α-SMA, all of which were highly induced in BPH rats. Moreover, the basal and PGE2-induced expressions of aromatase were reduced in Ba-stimulated WPMY-1 cells, while the expression of ERß was highly increased in Ba-stimulated BPH-1 cells, both of which are consistent with the findings in Ba group in vivo. Ba induced ERE activity in BPH-1 cells as E2 did; however, silence of ERß not ERα, blocked Ba-induced ERE activity while E2 still exhibited the significant ERE activity, indicating the regulation of estrogen signaling by Ba is particularly via ERß. In conclusion, by down-regulation of stromal aromatase and up-regulation of epithelial ERß, Ba contributes to the balance of estrogen and androgen signaling and further inhibits BPH development.
Subject(s)
Aromatase/metabolism , Estrogen Receptor beta/metabolism , Phenols/therapeutic use , Prostatic Hyperplasia/drug therapy , Animals , Aromatase/genetics , Cell Line , Cell Proliferation/drug effects , Down-Regulation/drug effects , Estradiol/pharmacology , Estrogen Receptor beta/genetics , Estrogens/pharmacology , Humans , Male , Mice , Phenols/pharmacology , Prostatic Hyperplasia/genetics , Prostatic Hyperplasia/metabolism , RAW 264.7 Cells , Rats, Wistar , THP-1 Cells , Testosterone/pharmacology , Up-Regulation/drug effectsABSTRACT
Phosphorus (P) deficiency is one of the main growth-limiting factors for plants. However, arbuscular mycorrhizal (AM) symbiosis can significantly promote P uptake. Generally, PHT1 transporters play key roles in plants' P uptake, and thus, PHT1 genes have been investigated in some plants, but the regulation and functions of these genes in wheat (TaPHT1) during AM symbiosis have not been studied in depth. Therefore, a comprehensive analysis of TaPHT1 genes was performed, including sequence, phylogeny, cis-elements, expression, subcellular localization and functions, to elucidate their roles in AM-associated phosphate transport and immunity. In total, 35 TaPHT1s were identified in the latest high-quality bread wheat genome, 34 of which were unevenly distributed on 13 chromosomes, and divided into five groups. Sequence analysis indicated that there are 11 types of motif architectures and five types of exon-intron structures in the TaPHT1 family. Duplication mode analysis indicated that the TaPHT1 family has expanded mainly through segmental and tandem duplication events, and that all duplicated gene pairs have been under purifying selection. Transcription analysis of the 35 TaPHT1s revealed that not only known the mycorrhizal-specific genes TaPht-myc, TaPT15-4B (TaPT11) and TaPT19-4D (TaPT10), but also four novel mycorrhizal-specific/inducible genes (TaPT3-2D, TaPT11-4A, TaPT29-6A, and TaPT31-7A) are highly up-regulated in AM wheat roots. Furthermore, the mycorrhizal-specific/inducible genes are significantly induced in wheat roots at different stages of infection by colonizing fungi. Transient Agrobacterium tumefaciens-mediated transformation expression in onion epidermal cells showed that TaPT29-6A is a membrane-localized protein. In contrast to other AM-specific/inducible PHT1 genes, TaPT29-6A is apparently required for the symbiotic and direct Pi pathway. TaPT29-6A-silenced lines exhibited reduced levels of AM fungal colonization and arbuscules, but increased susceptibility to biotrophic, hemi-biotrophic and necrotrophic pathogens. In conclusion, TaPT29-6A was not only essential for the AM symbiosis, but also played vital roles in immunity.
Subject(s)
Mycorrhizae/metabolism , Phosphate Transport Proteins/genetics , Phosphates/metabolism , Phosphorus/metabolism , Plant Proteins/genetics , Triticum/genetics , Gene Expression Regulation, Plant , Plant Roots/genetics , Symbiosis/physiology , Triticum/metabolismABSTRACT
Microbes play important roles in the transport and transformation of selenium (Se) in the environment, thereby influencing plant resistance to Se and Se accumulation in plant. The objectives are to characterize the bacteria with high Se tolerance and reduction capacity and explore the significance of microbial origins on their Se tolerance, reduction rate and efficiency. Two bacterial strains were isolated from a naturally occurred Se-rich soil at tea orchard in southern Anhui Province, China. The reduction kinetics of selenite was investigated and the reducing product was characterized using scanning electron microscopy and transmission electron microscopy-energy dispersive spectroscopy. The bacteria were identified as Lysinibacillus xylanilyticus and Lysinibacillus macrolides, respectively, using morphological, physiological and molecular methods. The results showed that the minimal inhibitory concentrations (MICs) of selenite for L. xylanilyticus and L. macrolides were 120 and 220 mmol/L, respectively, while MICs of selenate for L. xylanilyticus and L. macrolides were 800 and 700 mmol/L, respectively. Both strains aerobically reduced selenite with an initial concentration of 1.0 mmol/L to elemental Se nanoparticles (SeNPs) completely within 36 hr. Biogenic SeNPs were observed both inside and outside the cells suggesting either an intra- or extracellular reduction process. Our study implied that the microbes from Se-rich environments were more tolerant to Se and generally quicker and more efficient than those from Se-free habitats in the reduction of Se oxyanions. The bacterial strains with high Se reduction capacity and the biological synthesized SeNPs would have potential applications in agriculture, food, environment and medicine.
Subject(s)
Bacillaceae/drug effects , Bacillaceae/metabolism , Selenious Acid/metabolism , Selenium/metabolism , Selenium/toxicity , Aerobiosis/drug effects , Bacillaceae/growth & development , Bacillaceae/physiology , Biodegradation, Environmental , Biotransformation/drug effects , Hydrogen-Ion Concentration , Nanoparticles/chemistry , Oxidation-Reduction , Selenium/analysis , Selenium/chemistry , Soil/chemistry , Soil MicrobiologyABSTRACT
BACKGROUND: The increase in multidrug-resistant tuberculosis (MDR-TB) severely hampers tuberculosis prevention and control in China, a country with the second highest MDR-TB burden globally. The first nationwide drug-resistant tuberculosis surveillance program provides an opportunity to comprehensively investigate the epidemiological/drug-resistance characteristics, potential drug-resistance mutations, and effective population changes of Chinese MDR-TB. METHODS: We sequenced 357 MDR strains from 4600 representative tuberculosis-positive sputum samples collected during the survey (70 counties in 31 provinces). Drug-susceptibility testing was performed using 18 anti-tuberculosis drugs, representing the most comprehensive drug-resistance profile to date. We used 3 statistical and 1 machine-learning methods to identify drug-resistance genes/single-nucleotide polymorphisms (SNPs). We used Bayesian skyline analysis to investigate changes in effective population size. RESULTS: Epidemiological/drug-resistance characteristics showed different MDR profiles, co-resistance patterns, preferred drug combination/use, and recommended regimens among 7 Chinese administrative regions. These factors not only reflected the serious multidrug co-resistance and drug misuse but they were also potentially significant in facilitating the development of appropriate regimens for MDR-TB treatment in China. Further investigation identified 86 drug-resistance genes/intergenic regions/SNPs (58 new), providing potential targets for MDR-TB diagnosis and treatment. In addition, the effective population of Chinese MDR-TB displayed a strong expansion during 1993-2000, reflecting socioeconomic transition within the country. The phenomenon of expansion was restrained after 2000, likely attributable to the advances in diagnosis/treatment technologies and government support. CONCLUSIONS: Our findings provide an important reference and improved understanding of MDR-TB in China, which are potentially significant in achieving the goal of precision medicine with respect to MDR-TB prevention and treatment.