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BACKGROUND: Alopecia is one of the most common adverse effects of chemotherapy. It reduces the patient's self-esteem and quality of life and the effect of therapy. Scalp cooling is the only verified current method for prevention but success is not guaranteed, particularly after receiving anthracycline-based combinations. Low-level light therapy has been clinically proven to inhibit the progress of androgenic alopecia. A previous study using human subjects shows limited benefits for low-level light therapy for patients who suffer chemotherapy-induced alopecia but an increase in the number of probes and the optimization of light sources may improve the efficacy. This study determines the efficacy of low-level light therapy for the prevention of chemotherapy-induced hair loss for patients with breast cancer using a randomized controlled trial. METHODS: One hundred six eligible breast cancer patients were randomly distributed into a low-level light therapy group and a control group, after receiving chemotherapy. Subjects in the low-level light therapy group received 12 courses of intervention within 4 weeks. Subjects in the control group received no intervention but were closely monitored. The primary outcome is measured as the difference in the hair count in a target area between the baseline and at the end of week 4, as measured using a phototrichogram (Sentra scalp analyzer). The secondary outcomes include the change in hair count at the end of week 1, week 2, and week 3 and hair width at the end of week 1, week 2, week 3, and week 4, as measured using a phototrichogram, and the change in distress, the quality of life, and self-esteem due to chemotherapy-induced alopecia, at the end of week 4, as measured using a questionnaire. DISCUSSION: This study improves cancer patients' quality of life and provides clinical evidence. TRIAL REGISTRATION: Registered at ClinicalTrials.gov- NCT05397457 on 1 June 2022.
Subject(s)
Breast Neoplasms , Low-Level Light Therapy , Humans , Female , Quality of Life , Head Protective Devices , Alopecia/chemically induced , Alopecia/prevention & control , Alopecia/drug therapy , Scalp , Antibiotics, Antineoplastic/adverse effects , Breast Neoplasms/drug therapy , Randomized Controlled Trials as TopicABSTRACT
Glioma is the most common tumor of the nervous system. The diffuse growth and proliferation of glioma poses great challenges for its treatment. Here, Transcriptomic analysis revealed that Rac GTPase activating protein 1 (RACGAP1) is highly expressed in glioma. RACGAP1 has been shown to play an important role in the malignant biological progression of a variety of tumors. However, the underlying role and mechanism in glioma remain poorly understood. By using quantitative real-time polymerase chain reaction (qRT-PCR), western blot, immunohistochemistry and Orthotopic mouse xenografts, we confirmed that knockdown of RACGAP1 impeded cell proliferation in glioma and prolonged the survival of orthotopic mice. Interestingly, we also found that inhibiting the expression of RACGAP1 reduced the expression of minichromosome maintenance 3 (MCM3) through RNA-seq and rescue assay, while Yin Yang 1 (YY1) transcriptionally regulated RACGAP1 expression. Furthermore, T7 peptide-decorated exosome (T7-exo) is regard as a promising delivery modality for targeted therapy of glioma, and the T7-siRACGAP1-exo significantly improved the survival time of glioma bearing mice. These results suggested that targeting RACGAP1 may be a potential strategy for glioma therapy.
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BACKGROUND: α-Viniferin, the major constituent of the roots of Caragana sinica (Buc'hoz) Rehder with a trimeric resveratrol oligostilbenoid skeleton, was demonstrated to possess a strong inhibitory effect on xanthine oxidase in vitro, suggesting it to be a potential anti-hyperuricemia agent. However, the in vivo anti-hyperuricemia effect and its underlying mechanism were still unknown. PURPOSE: The current study aimed to evaluate the anti-hyperuricemia effect of α-viniferin in a mouse model and to assess its safety profile with emphasis on its protective effect on hyperuricemia-induced renal injury. METHODS: The effects were assessed in a potassium oxonate (PO)- and hypoxanthine (HX)-induced hyperuricemia mice model by analyzing the levels of serum uric acid (SUA), urine uric acid (UUA), serum creatinine (SCRE), serum urea nitrogen (SBUN), and histological changes. Western blotting and transcriptomic analysis were used to identify the genes, proteins, and signaling pathways involved. RESULTS: α-Viniferin treatment significantly reduced SUA levels and markedly mitigated hyperuricemia-induced kidney injury in the hyperuricemia mice. Besides, α-viniferin did not show any obvious toxicity in mice. Research into the mechanism of action of α-viniferin revealed that it not only inhibited uric acid formation by acting as an XOD inhibitor, but also reduced uric acid absorption by acting as a GLUT9 and URAT1 dual inhibitor as well as promoted uric acid excretion by acting as a ABCG2 and OAT1 dual activator. Then, 54 differentially expressed (log2 FPKM ≥ 1.5, p ≤ 0.01) genes (DEGs) repressed by the treatment of α-viniferin in the hyperuricemia mice were identified in the kidney. Finally, gene annotation results revealed that downregulation of S100A9 in the IL-17 pathway, of CCR5 and PIK3R5 in the chemokine signaling pathway, and of TLR2, ITGA4, and PIK3R5 in the PI3K-AKT signaling pathway were involved in the protective effect of α-viniferin on the hyperuricemia-induced renal injury. CONCLUSIONS: α-Viniferin inhibited the production of uric acid through down-regulation of XOD in hyperuricemia mice. Besides, it also down-regulated the expressions of URAT1 and GLUT9 and up-regulated the expressions of ABCG2 and OAT1 to promote the excretion of uric acid. α-Viniferin could prevent hyperuricemia mice from renal damage by regulating the IL-17, chemokine, and PI3K-AKT signaling pathways. Collectively, α-viniferin was a promising antihyperuricemia agent with desirable safety profile. This is the first report of α-viniferin as an antihyperuricemia agent.
Subject(s)
Hyperuricemia , Uric Acid , Mice , Animals , Interleukin-17/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Hyperuricemia/drug therapy , Hyperuricemia/chemically induced , Kidney , Xanthine Oxidase/metabolismABSTRACT
Resilience enables mental elasticity in individuals when rebounding from adversity. In this study, we identified a microcircuit and relevant molecular adaptations that play a role in natural resilience. We found that activation of parvalbumin (PV) interneurons in the primary auditory cortex (A1) by thalamic inputs from the ipsilateral medial geniculate body (MG) is essential for resilience in mice exposed to chronic social defeat stress. Early attacks during chronic social defeat stress induced short-term hyperpolarizations of MG neurons projecting to the A1 (MGA1 neurons) in resilient mice. In addition, this temporal neural plasticity of MGA1 neurons initiated synaptogenesis onto thalamic PV neurons via presynaptic BDNF-TrkB signaling in subsequent stress responses. Moreover, optogenetic mimicking of the short-term hyperpolarization of MGA1 neurons, rather than merely activating MGA1 neurons, elicited innate resilience mechanisms in response to stress and achieved sustained antidepressant-like effects in multiple animal models, representing a new strategy for targeted neuromodulation.
Subject(s)
Auditory Cortex , Mice , Animals , Auditory Cortex/metabolism , Thalamus/physiology , Neurons/metabolism , Geniculate Bodies , Interneurons/physiology , Parvalbumins/metabolismABSTRACT
Objective:To investigate the effect of early intervention with electroacupuncture (EA) on the gut microbiota in a mouse model of post-traumatic stress disorder(PTSD).Methods:Totally 32 C57BL/6 mice were randomly assigned to the following 4 groups ( n=8 for each group): Control group, EA group, PTSD group and PTSD+ EA group.After 7 days acclimation, mice in the PTSD group and PTSD+ EA group were subjected to modified single prolonged stress (mSPS). Mice in the EA group and PTSD+ EA group received EA (2/15 Hz, 1 mA, dilatational wave, 30 min/d) on "Baihui" for 7 days. Mice in the Control group and PTSD group received false stimulation (stimulated the same acupiont without electricity) for 7 days. Seven days after the last stimulation, elevated plus maze test and fear conditioning test were conducted to observe the effect of EA on PTSD-like behavior of mice. At the same time, feces of the mice were collected for gut microbiota detection by 16S rRNA sequencing.SPSS 19.0 was used for statistical analysis.One-way ANOVA was used for multiple group comparison and Bonferrani test was done for further pairwise comparision. Results:(1) There were statistically differences in the open arm activity time of the elevated plus maze test and the immobility time in contextual and cued fear conditioning test among the four groups ( F=6.93, 5.26, 14.51, all P<0.01). In the elevated plus maze test, mice in PTSD group ((60.17±15.52) s) showed significant less time in the open arms than mice in Control group((96.37±14.62) s) and PTSD+ EA group ((86.89±15.02) s) (both P<0.05). In the fear conditioning test, mice in PTSD group ((121.99±29.67) s, (130.82±29.11) s) showed significant increased immobility time both in contextual and cued fear conditioning tests than mice in Control group((74.50±26.65) s, (39.50±23.52) s) and PTSD+ EA group ((76.77±22.60) s, (102.17±3.39) s)(both P<0.05). (2) There were no significant differences among the four groups in the alpha diversity of gut microbiota ( F=0.79-2.45, all P>0.05). (3)Correlation analysis showed that 13 gut microbiotas were negatively correlated with the immobility time in contextual fear conditioning test, 2 gut microbiotas were positively correlated with it; 7 gut microbiotas were negatively correlated with the immobility time in cued fear conditioning test, 1 gut microbiota was positively correlated with it; 3 gut microbiotas were positively correlated with time spent in open arms of elevated plus maze test. Conclusion:Early intervention with EA can improve anxiety-fear like behaviors and gut microflora disorder in PTSD model mice.
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ObjectiveBy comparing the differences in composition and content of volatile components between Atractylodis Macrocephalae Rhizoma(AMR)and bleaching AMR, bran-fried AMR and bran-fried bleaching AMR, the effect of processing with rice-washed water on the volatile components in AMR and bran-fried AMR were investigated. MethodHeadspace gas chromatography-mass spectrometry(HS-GC-MS)was used to determine the volatile components in raw products, bran-fried products and their processed products with rice-washed water. GC conditions were programmed temperature(starting temperature of 50 ℃, rising to 140 ℃ at 10 ℃·min-1, maintained for 5 min, then rising to 210 ℃ at 4 ℃·min-1), splitting ratio of 10∶1, high purity helium as the carrier gas and a solvent delay time of 3 min. MS conditions were an electron bombardment ion source(EI) with an electron collision energy of 70 eV, ion source temperature of 230 ℃, and the detection range of m/z 20-650. The relative contents of the components were determined by the peak area normalization method, the obtained sample data were subjected to principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) by SIMCA 14.1 software, and the differential components of AMR and bleaching AMR, and bran-fried AMR and bran-fried bleaching AMR were screened according to variable importance in the projection(VIP) value>1 and P<0.05. ResultA total of 71 volatile components were identified, including 53 in AMR, 50 in bleaching AMR, 51 in bran-fried AMR, and 44 in bran-fried bleaching AMR. OPLS-DA results showed that there were significant differences between AMR and bleaching AMR, bran-fried AMR and bran-fried bleaching AMR, but not between AMR samples from different origins. The compound composition of AMR and bleaching AMR, bran-fried AMR and bran-fried bleaching AMR did not change, but the contents of monoterpenes and sesquiterpenes changed significantly. ConclusionSignificant changes in the contents of volatile components were observed in AMR and bleaching AMR, bran-fried AMR and bran-fried bleaching AMR, among them, 1,2-dimethyl-4-methylidenecyclopentene, 9,10-dehydro-isolongifolene, γ-elemene, zingiberene, atractylone, silphinene, modhephene and (1S,4S,4aS)-1-isopropyl-4,7-dimethyl-1,2,3,4,4a,5-hexahydronaphthalene can be used as candidate differential markers of volatile components of AMR before and after processing with rice-washed water.
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This study aimed to evaluate the efficacy of Qi-supplementing and Yin-nourishing Chinese patent medicine in the treatment of early diabetic nephropathy(DN) by network Meta-analysis to explore the Chinese patent medicine with optimal efficacy and provide references for preventing renal deterioration and delaying the progression of early DN. Eight databases, including CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science, were searched for clinical randomized controlled trial(RCT) of Qi-supplementing and Yin-nourishing Chinese patent medicines in the treatment of early DN. After the literature mee-ting the inclusion criteria was screened, the quality of the literature was evaluated using the Cochrane risk-of-bias tool, and network Meta-analysis was performed using the BUGSnet package in R 4.2.1. Seventy-two research articles with a sample size of 6 344 cases were included, involving eight Chinese patent medicines and seven outcome indicators. The results of the network Meta-analysis showed that(1)in terms of improving urinary albumin excretion rate(UAER), Chinese patent medicines combined with conventional treatment were superior to conventional treatment, and Qiyao Xiaoke Capsules + conventional treatment was optimal.(2)In terms of reducing serum crea-tinine(Scr), Bailing Capsules + conventional treatment had superior efficacy.(3)In terms of reducing 24-hour urine total protein(24hUTP), Shenyan Kangfu Tablets + conventional treatment and Jinshuibao Capsules + conventional treatment had equivalent efficacy, and Shenyan Kangfu Tablets + conventional treatment was superior.(4)In terms of improving fasting blood glucose(FBG), Shenyan Kangfu Tablets + conventional treatment had superior efficacy.(5)In terms of improving total cholesterol(TC), Qiyao Xiaoke Capsules +conventional treatment had superior efficacy.(6)In terms of reducing triglyceride(TG), Bailing Capsules + conventional treatment had superior efficacy.(7)In terms of safety, the occurrence of adverse reactions was reported in seven interventions, but due to the large clinical heterogeneity, the quantitative analysis could not be performed. Overall, Qi-supplementing and Yin-nourishing Chinese patent medicines combined with conventional treatment were superior to conventional treatment alone in the treatment of early DN. The results showed that Qi-supplementing and Yin-nourishing Chinese patent medicines combined with conventional treatment had good clinical efficacy, and they could significantly reduce renal function indicators such as UAER, Scr, and 24hUTP, and reduce blood sugar and blood lipid, which can provide evidence-based support for the treatment of early DN. However, due to the differences in the quantity and quality of the included research articles, large-sample, multi-center, high-quality studies are still needed for further verification.
Subject(s)
Humans , Diabetic Nephropathies/drug therapy , Nonprescription Drugs/therapeutic use , Qi , Network Meta-Analysis , Capsules , Drugs, Chinese Herbal/therapeutic use , Tablets , Diabetes Mellitus/drug therapyABSTRACT
Background: Increasing lines of evidence indicate that traditional Chinese exercise (TCE) has potential benefits in improving chronic low back pain (CLBP) symptoms. To assess the clinical efficacy of TCE in the treatment of CLBP, we performed a systematic review of existing randomized controlled trials (RCTs) of CLBP and summarized the neural mechanisms underlying TCE in the treatment of CLBP. Methods: A systematic search was conducted in four electronic databases: PubMed, Embase, the Cochrane Library, and EBSCO from January 1991 to March 2022. The quality of all included RCTs was evaluated by the Physiotherapy Evidence Database Scale (PEDro). The primary outcomes included pain severity and pain-related disability. Results: A total of 11 RCTs with 1,256 middle-aged and elderly patients with CLBP were included. The quality of all 11 included RCTs ranged from moderate to high according to PEDro. Results suggested that TCE could considerably reduce pain intensity in patients with CLBP. Overall, most studies did not find any difference in secondary outcomes (quality of life, depression, and sleep quality). Conclusion: The neurophysiological mechanism of TCE for treating CLBP could be linked to meditation and breathing, posture control, strength and flexibility training, and regulation of pain-related brain networks. Our systematic review showed that TCE appears to be effective in alleviating pain in patients with CLBP.
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Objective: To investigate the preventive effects of Ilex cornuta aqueous extract (ICAE) on high-fat diet (HFD)-induced fatty liver of mice and its mechanisms. Materials and Methods: Twenty-six male KM (Kunming) mice were divided into 3 groups, including the control group (n = 9), fed with normal diet; HFD group (n = 9), fed with HFD; ICAE + HFD group (n = 8), fed with HFD and administered with ICAE (3 g·kg-1·d-1) at the same time for 10 weeks. Body weight, liver weight, intra-abdominal and subcutaneous fat weight, serum triglyceride (TG), total cholesterol (TC), and blood glucose were determined to evaluate the preventive effects of ICAE on obesity. The average 24 h food consumption of the mice was monitored for 5 times in the 9th week of the experiment to investigate the effects of ICAE on food intake. Serum alanine transaminase (ALT) and aspartate aminotransferase (AST) were assayed to observe the influences of HFD and ICAE on liver function. HE staining was adopted to observe the influence of ICAE on the morphology of adipose tissue and liver tissue. Hepatic TG and TC content assay and oil red O staining were used to evaluate the influences of ICAE on HFD-induced fatty liver, and the protein expression of peroxisome proliferator-activated receptors γ (PPARγ) and adipose differentiation-related protein (ADRP) in liver were examined by immunoblotting. Results: ICAE treatment significantly reduced the increase of body weight, intra-abdominal, and subcutaneous fat and liver weight induced by HFD (P < 0.001), but has no influence on food intake; ICAE treatment attenuated the elevation of serum TG, TC, and glucose, as well as serum ALT and AST (P < 0.01, P < 0.05, P < 0.001) and dramatically decreased the content of TG in liver (P < 0.01), but has no influence on hepatic TC content. HE staining and oil red O staining showed that ICAE significantly reduced HFD-induced white adipocyte hypertrophy and significantly inhibited lipid accumulation in liver. Immunoblotting showed that the protein levels of PPARγ and ADRP were significantly increased by HFD induction, which can be dramatically reduced by ICAE treatment (P < 0.05, P < 0.0001). Conclusion: ICAE has preventive effects on HFD-induced obesity and fatty liver in mice, exerted beneficial effects upon HFD-induced hepatic injury. The preventive effects of ICAE on fatty liver are concerned with the downregulation of PPARγ and ADRP protein expression in liver.
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PURPOSE: To investigate the effect of Glabridin (GLD) in Aspergillus fumigatus keratitis and its associated mechanisms. METHODS: Aspergillus fumigatus (A. fumigatus) conidia was inoculated in 96-well plate, and minimal inhibitory concentration (MIC) and biofilm formation ability were evaluated after GLD treatment. Spore adhesion ability was evaluated in conidia infected human corneal epithelial cells (HCECs). Keratitis mouse model was created by corneal intrastromal injection with A. fumigatus conidia, and GLD treatment started at the day after infection. The number of fungal colonies was calculated by plate count, and degree of corneal inflammation was assessed by clinical score. Flow cytometry, myeloperoxidase (MPO), and immunofluorescence staining (IFS) experiments were used to assess neutrophil infiltrations. PCR, ELISA and Western blot were conducted to determine levels of TLR4, Dectin-1 as well as downstream inflammatory factors. RESULTS: GLD treatment suppressed the proliferation, biofilm formation abilities and adhesive capability of A. fumigatus. In mice upon A. fumigatus infection, treatment of GLD showed significantly decreased severity of corneal inflammation, reduced number of A. fumigatus in cornea, and suppressed neutrophil infiltration in cornea. GLD treatment obviously inhibited mRNA and protein levels of Dectin-1, TLR4 and proinflammatory mediators such as IL-1ß, HMGB1, and TNF-α in mice corneas compared to the control group. CONCLUSION: GLD has antifungal and anti-inflammatory effects in fungal keratitis through suppressing A. fumigatus proliferation and alleviating neutrophil infiltration, and repressing the expression of TLR4, Dectin-1 and proinflammatory mediators.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antifungal Agents/therapeutic use , Aspergillosis/drug therapy , Aspergillus fumigatus/physiology , Corneal Ulcer/drug therapy , Eye Infections, Fungal/drug therapy , Isoflavones/therapeutic use , Phenols/therapeutic use , Animals , Aspergillosis/microbiology , Aspergillus fumigatus/drug effects , Biofilms/drug effects , Blotting, Western , Corneal Ulcer/microbiology , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Eye Infections, Fungal/microbiology , Female , Flow Cytometry , Lectins, C-Type/metabolism , Mice , Mice, Inbred C57BL , Microbial Sensitivity Tests , Neutrophil Infiltration , Polymerase Chain Reaction , Toll-Like Receptor 4/metabolismABSTRACT
ObjectiveBy comparing the composition and content changes of the volatile components in Atractylodis Rhizoma before and after processing with rice-washed water, the effect of rice-washed water processing on volatile components in Atractylodis Rhizoma was investigated. MethodHeadspace-gas chromatography-mass spectrometry (HS-GC-MS) was used to detect the volatile components in rhizomes of Atractylodes chinensis and A. lancea, and their processed products of rice-washed water. Chromatographic conditions were programmed temperature (starting temperature of 50 ℃ for 2 min, rising to 120 ℃ with the speed of 10 ℃·min-1, then rising to 170 ℃ at 2.5 ℃·min-1, and rising to 240 ℃ at 10 ℃·min-1 for 3 min), the inlet temperature was 280 ℃, the split ratio was 10∶1, and the solvent delay time was 3 min. The conditions of mass spectrometry were electron bombardment ionization (EI) with ionization temperature at 230 ℃ and detection range of m/z 20-650. Then the relative content of each component was determined by the peak area normalization method. SIMCA 14.1 software was used to perform unsupervised principal component analysis (PCA) and supervised orthogonal partial least squares-discriminant analysis (OPLS-DA) on each sample data, the differential components of Atractylodis Rhizoma and its processed products were screened by the principle of variable importance in the projection (VIP) value>1. ResultA total of 60 components were identified, among which 40 were rhizomes of A. chinensis and 38 were its processed products, 46 were rhizomes of A. lancea and 47 were its processed products. PCA and OPLS-DA showed that the 4 kinds of Atractylodis Rhizoma samples were clustered into one category respectively, indicating that the volatile components of the two kinds of Atractylodis Rhizoma were significantly changed after processing with rice-washed water, and there were also significant differences in the volatile components of rhizomes of A. lancea and A. chinensis. The compound composition of Atractylodis Rhizoma and its processed products was basically the same, but the content of the compounds was significantly different. The differential components were mainly concentrated in monoterpenoids and sesquiterpenoids, and the content of monoterpenoids mostly showed a decreasing trend. ConclusionAfter processing with rice-washed water, the contents of volatile components in rhizomes of A. lancea and A. chinensis are significantly changed, and pinene, 3-carene, p-cymene, ocimene, terpinolene, atractylon, acetic acid and furfural can be used as difference markers before and after processing.
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ObjectiveTo identify the chemical constituents of Alismatis Rhizoma before and after processing with salt-water by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS), and to investigate the changes of terpenoids in Alismatis Rhizoma before and after processing with salt-water. MethodUPLC-Q-TOF-MS was used to detect with 0.1% formic acid aqueous solution (A)-acetonitrile (B)as mobile phase for gradient elution (0-0.01 min, 20%B; 0.01-5 min, 20%-40%B; 5-40 min, 40%-95%B; 40-42 min, 95%B; 42-42.1 min, 95%-20%B; 42.1-45 min, 20%B), electrospray ionization (ESI) was selected for collection and detection in positive ion mode with the scanning range of m/z 100-1 250 and ion source temperature at 500 ℃. The data were analyzed by PeakView 1.2.0.3, the components were identified according to the primary and secondary MS data, and combined with the reference substance and literature. After normalized treatment by MarkerView 1.2.1, the MS data were analyzed by principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA), and then the differential components before and after processing were screened. The content changes of differential components were analyzed according to the relative peak area. ResultA total of 30 components were identified under positive ion mode, including 28 prototerpene triterpenes and 2 sesquiterpenes. The results of PCA and OPLS-DA showed that there were significant differences in components from Alismatis Rhizoma before and after processing with salt-water, and 10 differential components (alisol B 23-acetate, alisol I, alismol, 11-deoxy-alisol B 23-acetate, alisol B, alisol C, 11-deoxy-alisol B, alisol G, 11-deoxy-alisol C and alisol A) were screened, and the contents of alisol G and alisol A decreased significantly after processing. ConclusionUPLC-Q-TOF-MS can comprehensively and accurately identify the chemical constituents in raw and salt-processed products of Alismatis Rhizoma. It takes a great difference in the contents of chemical constituents before and after processing, and the difference of substituents is the main reason for this differences, which can provide reference for determining the material basis of efficacy changes of Alismatis Rhizoma before and after processing with salt-water.
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ObjectiveTo identify the chemical constituents of Alismatis Rhizoma before and after processing with salt-water by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS), and to investigate the changes of terpenoids in Alismatis Rhizoma before and after processing with salt-water. MethodUPLC-Q-TOF-MS was used to detect with 0.1% formic acid aqueous solution (A)-acetonitrile (B)as mobile phase for gradient elution (0-0.01 min, 20%B; 0.01-5 min, 20%-40%B; 5-40 min, 40%-95%B; 40-42 min, 95%B; 42-42.1 min, 95%-20%B; 42.1-45 min, 20%B), electrospray ionization (ESI) was selected for collection and detection in positive ion mode with the scanning range of m/z 100-1 250 and ion source temperature at 500 ℃. The data were analyzed by PeakView 1.2.0.3, the components were identified according to the primary and secondary MS data, and combined with the reference substance and literature. After normalized treatment by MarkerView 1.2.1, the MS data were analyzed by principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA), and then the differential components before and after processing were screened. The content changes of differential components were analyzed according to the relative peak area. ResultA total of 30 components were identified under positive ion mode, including 28 prototerpene triterpenes and 2 sesquiterpenes. The results of PCA and OPLS-DA showed that there were significant differences in components from Alismatis Rhizoma before and after processing with salt-water, and 10 differential components (alisol B 23-acetate, alisol I, alismol, 11-deoxy-alisol B 23-acetate, alisol B, alisol C, 11-deoxy-alisol B, alisol G, 11-deoxy-alisol C and alisol A) were screened, and the contents of alisol G and alisol A decreased significantly after processing. ConclusionUPLC-Q-TOF-MS can comprehensively and accurately identify the chemical constituents in raw and salt-processed products of Alismatis Rhizoma. It takes a great difference in the contents of chemical constituents before and after processing, and the difference of substituents is the main reason for this differences, which can provide reference for determining the material basis of efficacy changes of Alismatis Rhizoma before and after processing with salt-water.
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ObjectiveBy comparing the composition and content changes of the volatile components in Atractylodis Rhizoma before and after processing with rice-washed water, the effect of rice-washed water processing on volatile components in Atractylodis Rhizoma was investigated. MethodHeadspace-gas chromatography-mass spectrometry (HS-GC-MS) was used to detect the volatile components in rhizomes of Atractylodes chinensis and A. lancea, and their processed products of rice-washed water. Chromatographic conditions were programmed temperature (starting temperature of 50 ℃ for 2 min, rising to 120 ℃ with the speed of 10 ℃·min-1, then rising to 170 ℃ at 2.5 ℃·min-1, and rising to 240 ℃ at 10 ℃·min-1 for 3 min), the inlet temperature was 280 ℃, the split ratio was 10∶1, and the solvent delay time was 3 min. The conditions of mass spectrometry were electron bombardment ionization (EI) with ionization temperature at 230 ℃ and detection range of m/z 20-650. Then the relative content of each component was determined by the peak area normalization method. SIMCA 14.1 software was used to perform unsupervised principal component analysis (PCA) and supervised orthogonal partial least squares-discriminant analysis (OPLS-DA) on each sample data, the differential components of Atractylodis Rhizoma and its processed products were screened by the principle of variable importance in the projection (VIP) value>1. ResultA total of 60 components were identified, among which 40 were rhizomes of A. chinensis and 38 were its processed products, 46 were rhizomes of A. lancea and 47 were its processed products. PCA and OPLS-DA showed that the 4 kinds of Atractylodis Rhizoma samples were clustered into one category respectively, indicating that the volatile components of the two kinds of Atractylodis Rhizoma were significantly changed after processing with rice-washed water, and there were also significant differences in the volatile components of rhizomes of A. lancea and A. chinensis. The compound composition of Atractylodis Rhizoma and its processed products was basically the same, but the content of the compounds was significantly different. The differential components were mainly concentrated in monoterpenoids and sesquiterpenoids, and the content of monoterpenoids mostly showed a decreasing trend. ConclusionAfter processing with rice-washed water, the contents of volatile components in rhizomes of A. lancea and A. chinensis are significantly changed, and pinene, 3-carene, p-cymene, ocimene, terpinolene, atractylon, acetic acid and furfural can be used as difference markers before and after processing.
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ObjectiveTo analyze changes of the chemical composition in Euodiae Fructus before and after processing with Coptidis Rhizoma decoction, so as to provide scientific basis for elucidating the processing mechanism of this decoction pieces. MethodUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was performed on a Titank C18 column (2.1 mm×100 mm, 1.8 μm), the mobile phase was 0.1% formic acid aqueous solution-acetonitrile for gradient elution, the column temperature was set at 40 ℃, the flow rate was 0.25 mL·min-1. Electrospray ionization (ESI) was used to scan in positive and negative ion modes, and the scanning range was m/z 50-1 250. The chemical constituents in Euodiae Fructus were identified before and after processing by reference substance comparison, database matching and literature reference, and MarkerView™ 1.2.1 software was used to normalize the obtained data, SIMCA-P 14.1 software was employed to perform principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) on MS data of raw and processed products to screen the differential components before and after processing. ResultA total of 50 compounds were identified, including 48 kinds of stir-fried products with Coptidis Rhizoma decoction and 44 kinds of raw products. After processing, six compounds were added, including danshensu, noroxyhydrastinine, oxyberberine, 13-methylberberrubine, protopine and canadine. However, two kinds of compounds, including (S)-7-hydroxysecorutaecarpine and wuchuyuamide Ⅱ, were not detected after processing. In general, after processing, the overall contents of phenolic acids and flavonoids decreased significantly, the overall content of limonoids increased, and the overall content of alkaloids did not decrease insignificantly. The results of PCA and OPLS-DA showed that there were significant differences in the composition and content of the chemical components of Euodiae Fructus before and after processing, and a total of 12 variables such as quercetin, dihydrorutaecarpine and dehydroevodiamine were obtained by screening. ConclusionEuodiae Fructus stir-fried with Coptidis Rhizoma decoction mainly contains phenolic acids, flavonoids, limonoids and alkaloids. The composition and content of the chemical components have some changes before and after processing. The addition of processing excipients and hot water immersion are the main reasons for the difference, which can provide experimental basis for interpretation of the processing mechanism of this characteristic processed products of Euodiae Fructus.
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Calixarenes are reportedly excellent activators that can remarkably improve the transport efficiencies of cell penetrating peptides. We employed eight calixarenes to systematically study the influence of structure on activation efficiency, which revealed that the scaffold, head group, and alkyl chain are all significant factors for activation efficiency by affecting affinities with the peptide and membrane.
Subject(s)
Calixarenes/pharmacology , Peptides/metabolism , Biological Transport/drug effects , Calixarenes/chemistry , Drug Evaluation, Preclinical , Humans , Molecular StructureABSTRACT
BACKGROUND: There is no effective therapy for silicosis, and Dahuang Zhechong pill (DHZCP), an ancient Chinese medicine prescription, may have a therapeutic effect on silicosis. This study aims to verify the efficacy and safety of DHZCP in silicosis. METHODS: This is a randomized controlled clinical trial done at Panzhihua Second People's Hospital (Panzhihua City, Sichuan Province, China). Participants diagnosed with silicosis were recruited and randomized to the conventional treatment group (CG) or DHZCP combined with the conventional treatment group (DG). Forced vital capacity % predicted (FVC%), diffusing capacity of the lung for carbon monoxide % predicted (DLCO%), six-minute walk distance (6MWD), peripheral oxygen (SpO2), King's Brief Interstitial Lung Disease Questionnaire (K-BILD), and safety outcomes were measured at baseline and 9 weeks. RESULTS: Fifty-six participants (28 in each group) completed the study, and 53 of them (26 in DG and 27 in CG) completed pulmonary function. At 9 weeks, compared with no DHZCP, DHZCP treatment was associated with significant improvements in FVC% (mean ± SD, 95%CI) (8.2 ± 3.9, 0.3 to 16.0), DLCO% (8.6 ± 3.5, 1.5 to 15.7), SpO2 (3.8 ± 0.7, 2.3 to 5.2), and K-BILD total score (6.0 ± 2.3, 1.4 to 10.7). And, there were no statistical differences of safety outcomes between the two groups. Eight patients accepting DHZCP developed mild diarrhea during the first week, which subsequently resolved on its own. CONCLUSION: DHZCP could improve the pulmonary function, the quality of life, and the exercise capacity of silicosis patients.
ABSTRACT
BACKGROUND: Hyperuricemia (HUA) is an important risk factor for gout, renal dysfunction and cardiovascular diseases. The whole plant of Persicaria capitata (Buch.-Ham. ex D. Don) H. Gross, namely Persicaria capitata herba, is a well-known ethnic herb with potent therapeutic effects on urinary tract infections and urinary calculus, yet previous reports have only focused on its effect on urinary tract infections. PURPOSE: To evaluate the therapeutic potential of P. capitata herba against gout by investigating its antihyperuricemia and antigouty arthritis effects and possible mechanisms. METHODS: The ethanol extract (EP) and water extract (WP) of P. capitata herba were prepared by extracting dried and ground whole plants of P. capitata with 75% ethanol and water, respectively, followed by removal of solvents and characterization by UHPLC-Q-TOF/MS. The antihyperuricemia and antigouty arthritis effects of the two extracts were evaluated in a potassium oxonate- and hypoxanthine-induced hyperuricemia mouse model and a monosodium urate crystal (MSUC)-induced acute gouty arthritis mouse model, respectively. The mechanisms were investigated by testing their effects on the expression of correlated proteins (by Western blot) and mRNAs (by RT-PCR). RESULTS: UHPLC-HRMS fingerprinting and two chemical markers (i.e., quercetin and quercitrin) determination were used for the characterization of the WP and EP extracts. Both WP and EP extracts showed pronounced antihyperuricemia activities, with a remarkable decline in serum uric acid and a marked increase in urine uric acid in hyperuricemic mice. Unlike the clinical xanthine oxidase (XOD) inhibitor allopurinol, WP and EP did not show any distinct renal toxicities. The underlying antihyperuricemia mechanism involves the inhibition of the activity and expression of XOD and the downregulation of the mRNA and protein expression of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1). The extracts of P. capitata herba also demonstrated remarkable anti-inflammatory activity in MSUC-induced acute gouty arthritis mice. The mechanism might involve inhibitory effects on the expression of proinflammatory factors. CONCLUSIONS: The extracts of P. capitata herba possessed pronounced antihyperuricemia and antigouty arthritis effects and were, therefore, promising natural medicines for hyperuricemia-related disorders and gouty arthritis. The use of P. capitata herba for the treatment of urinary calculus may be, at least to some degree, related to its potential as an antihyperuricemia and antigouty arthritis drug.
Subject(s)
Arthritis, Gouty , Hyperuricemia , Animals , Arthritis, Gouty/drug therapy , Hyperuricemia/chemically induced , Hyperuricemia/drug therapy , Mice , Oxonic Acid , Plant Extracts/pharmacology , Uric Acid , Xanthine OxidaseABSTRACT
Bupleuri Radix, serving as the sovereign medicinal in many antidepressant compound preparations, has been proved effective in treating depression in mice, but its effect on the intestinal flora remains unclear. The present study aimed to investigate the effects of Bupleurum chinense(one of the original materials of Bupleuri Radix) on the behaviors and the diversity of intestinal flora of depressed mice. A depression mouse model was induced by repeated social defeat stress. Specifically, C57 BL/6 J male mice were exposed to the attack from the CD-1 mice. Then, C57 BL/6 J male mice were divided into a depression group and a B. chinense group, with normal saline and B. chinense administered(ig) respectively. Sucrose preference test and tail suspension test were conducted during and after the experiment respectively, to analyze the effects of B. chinense on the behaviors of the depressed mice. The feces were collected after the experiment. The V3-V4 16 S rDNA regions of intestinal flora of mice in each group were sequenced by Ion S5 TMXL for the analysis of the number of operational taxonomic units(OTUs), richness, alpha and beta diversity indexes, and differential phyla and genera. The results indicated that B. chinense could decrease depressive-like behaviors of mice, increase sucrose preference, and shorten the time of immobility in tail suspension test. After B. chinense intervention, the relative abundance of Firmicutes was significantly decreased, while that of Bacteroidetes was increased at the phylum level. At the genus level, the relative abundance of Lactobacillus and Lachnoclostridium decreased(P<0.05), while that of Bacteroides, Alistopes, etc. was elevated(P<0.05). The findings demonstrate that B. chinense can regulate the intestinal flora and improve the depressive-like behaviors of mice with depression.
Subject(s)
Bupleurum , Gastrointestinal Microbiome , Animals , Feces , Lactobacillus , Mice , Mice, Inbred C57BLABSTRACT
Roselle (Hibiscus sabdariffa L.) plants, whose calyces are used for production of beverages or jams, are mainly cultivated in Taitung County of eastern Taiwan. Since 2016, large crown galls were observed on the roselle plants in the commercial plantations at Taimali and Jinfong Townships of Taitung County. A follow-up survey in July and August of 2017 revealed spreading of this disease to the neighboring areas including Beinan and Dawu Townships. Disease incidence was estimated to be 0.6-10%. Galls of varying sizes (2-15 cm in diameter) were usually found on the roots and crowns of the roselle plants, starting with small swellings at the infection sites. Galls were light-colored, and smooth and tender in texture at the early stage, but later turned dark-colored, and appeared rough and woody. In some cases, adventitious roots extruding from the larger crown galls could be seen. Isolation of the causal agent was performed by quadrantally streaking bacterial suspension made from surface-sterilized, macerated galls on trypticase soy agar (TSA). After incubating at 28°C for 5 days, single colonies were transferred onto new TSA plates for further cultivation at 28°C. Finally, circular, convex, viscous and milky white colonies with smooth surface similar to colony morphology of Agrobacterium tumefaciens C58 were obtained for further identification. First, all six candidate isolates (TZ-1, TL1-2, TL2-1, TD1-1, TD1-24 and TD2-1) were identified as Agrobacterium spp. using the partial sequences of the 16S rRNA gene (accession numbers MW205820 to MW205825 in the GenBank database). The selected isolates also showed some biochemical and physiological characteristics similar to A. tumefaciens, including oxidase positive, growth at 35°C and in 2% NaCl, and alkalinity from litmus milk. Moreover, they were tested negative for utilization of citrate and acid production on potato dextrose agar (PDA) supplemented with calcium carbonate. Under a transmission electron microscope, the bacterium was rod-shaped and possessed peritrichous flagella. By means of multiplex PCR using primers designed for differentiation of Agrobacterium rubi, Agrobacterium vitis and Agrobacterium biovars 1 and 2, a 184 bp product was detected in all six isolates, indicating that they all belong to Agrobacterium biovar 1. Furthermore, the recA allele of each isolate was PCR amplified using primers F2898/F2899, and recA sequence analysis assigned all six isolates to A. tumefaciens genomospecies G7 (GenBank accession numbers MZ570905-MZ570910). Pathogenicity assay was carried out by inoculating the stems of 2-week-old roselle seedlings through wounds made with a sterile needle with bacteria on it. The inoculated seedlings were kept in plastic bags to maintain high humidity. Symptoms similar to those observed in the field developed at the inoculation sites after 7 days, and Koch's postulates were fulfilled when the bacteria re-isolated from the galls were also identified as A. tumefaciens genomospecies G7 using recA gene sequence analysis. To our knowledge, this is the first report of crown gall disease caused by A. tumefaciens on Hibiscus sabdariffa in Taiwan. This disease may potentially damage the roselle industry if no action is taken to stop its spreading. Identification of the causal agent of roselle crown gall disease could help us further investigate its ecology and develop integrated pest management strategies for prevention of this disease in the future.