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Background: To study the active ingredient and possible mechanism of Huisheng oral liquid in the treatment of lung cancer by network pharmacology. Methods: The active ingredient and drug targets of Huisheng oral liquid were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID), and lung cancer targets were screened using the Gene Expression Omnibus (GEO) database. The drug targets of the effective components of Huisheng oral liquid were matched with disease targets and the obtained intersecting targets were imported into the Search Tool for the Retrieval of Interaction Gene/Proteins (STRING) database to construct a protein-protein interaction (PPI) network. R software and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were used for Gene Ontology (GO) and KEGG enrichment analyses, and Cytoscape software was used to construct a Huisheng oral liquid component target-lung cancer target network. The function and pathway of the therapeutic target of Huisheng oral liquid for lung cancer were analyzed. Results: A total of 1,376 differentially expressed genes (DEGs) of lung cancer were obtained, and 185 potential effective components of Huisheng oral liquid in the treatment of lung cancer were obtained, including quercetin, luteolin, kaempferol, and baicalein. There were 36 intersecting targets between Huisheng oral liquid and lung cancer, and the key targets for lung cancer treatment were CDKN1A, CCNB1, MDM2, CDK1, ErbB2, E2F1, EGFR, etc. Huisheng oral liquid mainly regulates the p53 signaling pathway. Conclusions: The mechanism of Huisheng oral liquid in the treatment of lung cancer is mainly reflected in regulating tumor cell apoptosis, inhibiting angiogenesis, and improving immunity.
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The green synthesis of silver nanoparticles (AgNPs) using a water extract of Ginger (Zingiber officinale) root by microwave irradiation and its antibacterial activities have been reported. However, AgNPs prepared from different parts of ginger root water or ethanol extract by ultrasound synthesis and their antioxidant activity and whether the biogenic could be used to catalyze the reduction of hazardous dye are unknown. This study concentrated on the facile green synthesis of AgNPs prepared from different parts (unpeeled ginger, peeled ginger, and ginger peel) of ginger root water or ethanol extract by the ultrasound-assisted method. We studied their antioxidant activity and catalytic degradation of hazardous dye Direct Orange 26 (DO26) and Direct Blue 15 (DB15). The surface plasmon resonance (SPR) peak of AgNPs was at 428-443 nm. The biogenic AgNPs were approximately 2 nm in size with a regular spherical shape identified from TEM analysis. The ethanol extracts of dried unpeeled ginger and peeled ginger, fresh peeled ginger and ginger peel. The Z. officinale AgNPs synthesized by dried unpeeled ginger ethanol extract showed the best antioxidant activity. Their scavenging activities were significantly better than BHT (p <0.05). The different parts of ginger extracts showed no catalytic degradation activities of DB15 and DO26. Still, the synthesized Z. officinale AgNPs exhibited good catalytic degradation activities, while their ability to catalytic degradation to DB15 was better than DO26. In the additive ratio of 3 mL DB15, 0.1 mL NaBH4 and 0.1 mL AgNPs, the degradation rates of DB15 (or DO26) at 15 min, 30 min and 60 min were only 1.8% (0.9%), 2.8% (1.4%) and 3.5% (1.6%) in the absence of AgNPs. When adding Z. officinale AgNPs prepared from dried ginger peel ethanol extract or fresh ginger peel water extract, the degradation rates of DB15 sharply increased to 97% and 93% after 30 min, respectively. In conclusion, ginger extract has good antioxidant properties. Z. officinale AgNPs biosynthesis from ginger extract exhibit excellent catalytic degradation activities, especially for the ginger peel extract. They have application value in the treatment of textile effluents and provide a new idea and method for the comprehensive development and utilization of ginger resources.
Subject(s)
Citrus sinensis , Metal Nanoparticles , Zingiber officinale , Anti-Bacterial Agents , Antioxidants , Azo Compounds , Ethanol , Green Chemistry Technology , Plant Extracts , Silver , WaterABSTRACT
Background: Sintilimab is an immune checkpoint inhibitor (ICI). It can induce immune-related Adverse Events (irAEs). Severe adverse skin reactions are rare, but the mortality rate is high. We report the first case of successful treatment of adverse skin reactions using traditional Chinese medicine (TCM). Case Description: Here we present the case of a 67-year-old male with advanced lung squamous carcinoma. After 8 cycles of chemotherapy, the patient's disease progressed and the treatment regimen was adjusted to sintilimab combined with albumin paclitaxel and cisplatin. Thirty-two days after this cycle, the patient reported a sporadic rash with pruritus on the face, front chest, and both upper limbs. The area of rash was 40%, and the adverse reaction was grade 3. The level of interleukin-related indicators was above normal. The patient's skin symptoms disappeared after treatment with hormones, TCM, and other drugs. The patient's adverse skin reaction was due to an immune-related toxicity caused by sintilimab, so treatment with sintilimab was suspended. The albumin-paclitaxel plus cisplatin regimen was continued to treat lung cancer. Conclusions: Although rare, case of fatal adverse reaction caused by sintilimab have been reported. We recommend early monitoring and recognition of symptoms. During management, high-dose hormones combined TCM may be helpful.
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BACKGROUND: Many studies have investigated the relationships between vitamins and esophageal cancer (EC). Most of these studies focused on the roles of vitamins in the prevention and treatment of EC, and few studies have examined the changes in vitamin nutritional status and their influencing factors before and after chemotherapy for EC. Chemotherapy may have a considerable effect on EC patients' vitamin levels and hematological indicators. AIM: To research the nutritional status of multiple vitamins in EC patients during chemotherapy and to assess its clinical significance. METHODS: EC patients admitted to our center from July 2017 to September 2020 were enrolled in this study. Serum concentrations of nine vitamins (A, D, E, B9, B12, B1, C, B2 and B6), hemoglobin, total protein, albumin, blood calcium, blood phosphorus concentrations and body mass index (BMI) were measured in all EC patients. The changes in nine vitamins, hematological indicators and BMI were compared before and after two cycles of chemotherapy. The possible influential factors were analyzed. RESULTS: In total, 203 EC patients receiving chemotherapy were enrolled in this study. Varying degrees of vitamin A, D, C and B2 deficiency and weight loss were found in these patients, and the proportions of vitamin B2 and vitamin C deficiencies increased significantly after chemotherapy (both P < 0.05). Serum concentrations of vitamins A, C, B2 and B6 and BMI before and after chemotherapy were statistically significant (all P < 0.05). Multivariate analysis showed that vitamin A levels significantly differed between male and female EC patients, whereas vitamin D concentration significantly differed in EC patients in different stages (all P < 0.05). Correlations were observed between the changes in serum concentrations of vitamin A and C before and after two cycles chemotherapy and the change in BMI (P < 0.05). Hemoglobin, total protein, serum albumin and blood calcium concentrations significantly decreased in EC patients after chemotherapy (all P < 0.05), while the blood phosphorus level significantly increased after chemotherapy (P < 0.05). Using the difference in vitamin concentrations as the independent variables and the difference in BMI as the dependent variable, logistic regression analysis revealed statistically significant differences for vitamin A, vitamin D and vitamin C (F = 5.082, P = 0.002). CONCLUSION: Vitamin A, D, C and B2 were mainly deficient in patients with EC during chemotherapy. Multivitamin supplementation may help to improve the nutritional status, chemotherapy tolerance and efficacy.
Subject(s)
Esophageal Neoplasms , Vitamins , Ascorbic Acid , Esophageal Neoplasms/drug therapy , Female , Humans , Male , Nutritional Status , Vitamin AABSTRACT
Pichia fermentans Z9Y-3 and its intracellular enzymes were inoculated along with S. cerevisiae in synthetic grape must to modulate fruity ester production. The levels of ester-related enzymes, ester precursors, and fruity esters were monitored every 24 h during fermentation. Results showed that the levels of ethyl acetate, acetate higher alcohol esters (AHEs), short chain fatty acid ethyl esters (SFEs), and medium chain fatty acid ethyl esters (MFEs) were significantly enhanced in mixed fermentation. Pearson correlation analysis further revealed that higher alcohols and fatty acids played a more important role in fruity ester production than enzymes; Particularly, the correlation coefficient between fatty acids and MFEs was 0.940. In addition, supplementation of medium chain fatty acids (7.2 mg/L) at the metaphase of single S. cerevisiae fermentation improved ethyl acetate, AHE, SFE, and MFE production by 42.56%, 21.00%, 61.33%, and 90.04%, respectively, although the high level of ethyl acetate might result in off-flavors.
Subject(s)
Esters/chemistry , Esters/metabolism , Fatty Acids/metabolism , Fermentation , Fruit/chemistry , Pichia/metabolism , Saccharomyces cerevisiae/metabolism , Taste , Vitis/chemistry , Vitis/microbiology , Wine/analysisABSTRACT
Radiotherapy is one of the most important treatments for chest tumours. Although there are plenty of strategies to prevent damage to normal lung tissues, it cannot be avoided with the emergence of radiation-induced lung injury. The purpose of this study was to investigate the potential radioprotective effects of glucosamine, which exerted anti-inflammatory activity in joint inflammation. In this study, we found glucosamine relieved inflammatory response and structural damages in lung tissues after radiation via HE staining. Then, we detected the level of epithelial-mesenchymal transition marker in vitro and in vivo, which we could clearly observe that glucosamine treatment inhibited epithelial-mesenchymal transition. Besides, we found glucosamine could inhibit apoptosis and promote proliferation of normal lung epithelial cells in vitro caused by radiation. In conclusion, our data showed that glucosamine alleviated radiation-induced lung injury via inhibiting epithelial-mesenchymal transition, which indicated glucosamine could be a novel potential radioprotector for radiation-induced lung injury.
Subject(s)
Alveolar Epithelial Cells/drug effects , Anti-Inflammatory Agents/therapeutic use , Epithelial-Mesenchymal Transition/drug effects , Glucosamine/therapeutic use , Lung/radiation effects , Pulmonary Fibrosis/prevention & control , Radiation Injuries, Experimental/drug therapy , Radiation Pneumonitis/prevention & control , Radiation-Protective Agents/therapeutic use , Alveolar Epithelial Cells/radiation effects , Animals , Anti-Inflammatory Agents/pharmacology , Apoptosis/drug effects , Colony-Forming Units Assay , Drug Evaluation, Preclinical , Female , Gamma Rays/adverse effects , Glucosamine/pharmacology , Mice , Mice, Inbred C57BL , Pulmonary Fibrosis/etiology , Radiation Pneumonitis/etiology , Radiation-Protective Agents/pharmacology , RatsABSTRACT
Polysaccharides from Laminaria japonica (LJPs) are reported to have various functional properties, but the effects and mechanisms of LJPs on obesity and its related diseases are unclear. This study demonstrated that LJPs prevented diet-induced obesity in a mice model, and improved obesity-related parameters, e.g. fat accumulation in the liver and adipose tissues, body composition, lipids profile, and the morphology of the intestine. Such effects were associated with the modulation of the gut microbiota, involving some members of the Bacteroidetes phylum. Changes in the gut microbiota could improve nutrient utilization, increase microbial metabolites production, and thus regulate lipids metabolism in the body. In short, it sought to indicate that L. japonica can be developed as food supplement for the improvement of metabolic syndrome and the human gut health.
Subject(s)
Gastrointestinal Microbiome/drug effects , Laminaria/chemistry , Metabolic Syndrome/drug therapy , Metabolic Syndrome/microbiology , Polysaccharides/pharmacology , Animals , Diet, High-Fat/adverse effects , Dysbiosis/microbiology , Fatty Acids/chemistry , Fatty Acids/metabolism , Male , Metabolic Syndrome/complications , Metabolic Syndrome/metabolism , Mice , Mice, Inbred BALB C , Nutrients/metabolism , Obesity/complications , Polysaccharides/therapeutic useABSTRACT
It has been demonstrated that excessively activated endoplasmic reticulum stress (ERS) is closely associated with ageing-related diseases and male reproductive dysfunction. Wuzi Yanzong recipe (WZ) is a classical Traditional Chinese Medicine prescription for treatment of male reproductive system diseases. However, it remains unknown whether WZ improves testicular dysfunction with ageing via ERS. In this study, we investigated the protective effects and its mechanism of WZ on testicular dysfunction in ageing rats. The results showed that treatment with WZ for 4 months significantly increased the testicular weight and index, sperm count and viability, and the levels of testosterone and decreased the levels of estradiol. In addition, WZ significantly activated the onset of ERS and prevented germ cell apoptosis by upregulating the expression levels of ERS-responsive proteins GRP78, phospho-PERK, phospho-eIF2α, ATF4, phospho-IRE-1α, XBP1 and ATF6α, and downregulating the expression levels of pro-apoptotic proteins p-JNK, Caspase12 and CHOP in testicular germ cell of ageing rats. Besides, WZ significantly decreased the numbers of TUNEL-positive cells. Taken together, WZ effectively improves ageing-related testicular dysfunction through inhibition of germ cell apoptosis via ERS.
Subject(s)
Aging/drug effects , Apoptosis/drug effects , Drugs, Chinese Herbal/pharmacology , Endoplasmic Reticulum Stress/drug effects , Protective Agents/pharmacology , Spermatozoa/drug effects , Testis/drug effects , Aging/metabolism , Animals , Male , Rats , Rats, Sprague-Dawley , Spermatozoa/metabolism , Testis/metabolismABSTRACT
To study the protective effects of Wuzi Yanzong recipe on testis germ cell apoptosis in natural ageing rats through endoplasmic reticulum stress (ERS), 16-month-old male SPF grade SD rats were randomly divided into three groups: ageing model group, and low and high-dose Wuzi Yanzong recipe groups (WZ, 1 and 4 g·kg⻹), with 10 rats in each group. In addition, 2-month-old SD male rats were used as adult control group. The ageing model group and the adult control group were fed with normal diet for 4 months. WZ groups were given the medicated feed for 4 months. After fasting for 12 hours, the rats were put to death. Then, the testes were immediately collected. The change of testicular tissue morphology was observed by HE staining. The expression levels of ER stress-related proteins GRP78, p-PERK, p-eif2α, ATF4, p-IRE1, XBP1, ATF6 and apoptosis-related proteins CHOP, caspase12 and p-JNK in testes were detected by Western blot. Compared with the ageing model group, Wuzi Yanzong recipe alleviated the morphological changes of testicular tissue. Western blot results showed that Wuzi Yanzong recipe significantly increased the expression levels of endoplasmic reticulum stress-related proteins GRP78, p-PERK, p-eif2α, ATF4, p-IRE1, XBP1, ATF6 and significantly decreased the expression levels of endoplasmic reticulum-induced apoptosis-related proteins CHOP, caspase 12 and p-JNK. In conclusion, Wuzi Yanzong recipe can alleviate the ageing-related apoptosis of testicular germ cells in natural ageing rats by regulating endoplasmic reticulum stress.
Subject(s)
Aging , Apoptosis/drug effects , Drugs, Chinese Herbal/pharmacology , Endoplasmic Reticulum Stress , Germ Cells/drug effects , Testis/drug effects , Animals , Male , Rats , Rats, Sprague-DawleyABSTRACT
To study the protective effects of Wuzi Yanzong recipe on DNA oxidative damage of testis germ cells in natural ageing rats based on Nrf2/HO-1 signaling pathway and base excision repair (BER). In the study, 16-month-old SPF grade male SD rats were randomly divided into three groups, namely ageing model group, and low and high-dose Wuzi Yanzong recipe groups (WZ, 1, 4 g·kg⻹). In addition, 2-month-old SD rats were used as adult control group (10 rats in each group). The ageing model group and the adult control group were fed with normal diet for 4 months. WZ groups were given medicated feed for 4 months. After fasting for 12 hours, the rats were put to death. Then, the testes were immediately removed. The vitality of superoxide dismutase (SOD) and malondialdehyde (MDA) content in testis were detected by xanthine oxidase method and thiobarbituric acid (TBA) method. The levels of Nrf2 and 8-OHdG were detected by immunofluorescence. The protein expression levels of Nrf2, HO-1, NQO1, APE1, OGG1 and XRCC1 were detected by Western blot. Compared with the ageing model group, WZ significantly increased the SOD vitality and decreased MDA content of testis. In addition, immunofluorescence results showed that WZ significantly attenuated testicular DNA oxidative damage and improved antioxidant capacity. Such changes were accompanied by the down-regulation of DNA oxidative damage response protein 8-OHdG levels and the up-regulation of Nrf2 levels. Moreover, Western blot results showed that WZ significantly increased the protein expression levels of Nrf2, HO-1 and NQO1 of the testis germ cells, when compared with ageing model group. In parallel, the protein expression levels of APE1, OGG1 and XRCC1 were significantly decreased. In conclusion, WZ improves ageing-related DNA oxidative damage via Nrf2/HO-1 and BER pathways.
Subject(s)
Testis , Aging , Animals , DNA , Drugs, Chinese Herbal , Male , NF-E2-Related Factor 2 , Oxidative Stress , Rats , Rats, Sprague-DawleyABSTRACT
To study the protective effect of Wuzi Yanzong recipe on testicular DNA damage and apoptosis in natural ageing rats, SPF grade 16-month-old SD male rats were randomly divided into three groups: ageing model group, low and high dose Wuzi Yanzong recipe groups (WZ, 1ï¼ 4 g·kg⻹). In addition, 2-month-old SD rats were used as adult control group (10 rats in each group). The ageing model group and the adult control group were fed with normal diet for 4 months. Wuzi Yanzong groups received medicated feed for 4 months. After fasting for 12 hours, the rats were sacrificed. Then testis tissues were taken and weighed to calculate the testis index. The change of testicular tissue morphology was observed by HE staining. Expression and localization of DNA damage-associated protein ATR were observed by immunofluorescence. The expressions of DNA damage-related proteins γ-H2AX, Chk1, p-p53 and apoptosis-related proteins Bcl-2 and Bax in testes were detected by Western blot. The apoptosis of testis tissue in rats was detected by using TUNEL. The results showed that as compared with the youth control group, the protein expression levels of γ-H2AX, Chk1, p-p53 and Bax were significantly increased while Bcl-2 protein expression level was significantly decreased intestis tissues of ageing model group. Wuzi Yanzong recipe significantly decreased protein expression levels of γ-H2AX, Chk1, p-p53 and Bax and increased Bcl-2 protein expression level as well as Bcl-2/Bax ratio. Immunofluorescence results showed that Wuzi Yanzong recipe could significantly decrease the ageing-induced ATR, increase in testis tissues. TUNEL results showed that Wuzi Yanzong recipe could significantly attenuate the germ cell apoptosis in testicular tissues. All the above results suggest that Wuzi Yanzong recipe could protect the germ cell in testicular tissues of natural ageing rates from DNA damage and apoptosis, and the mechanism may be associated with regulating p53 signaling pathway.
Subject(s)
Drugs, Chinese Herbal , Testis , Aging , Animals , Apoptosis , DNA Damage , Male , Proto-Oncogene Proteins c-bcl-2 , Rats , Rats, Sprague-DawleyABSTRACT
Ulcerative colitis is one of the most common types of inflammatory bowel disease and is multifactorial and relapsing. 6-Gingerol, a component of gingerols extracted from ginger (Zingiber officinale), has been reported to improve ulcerative colitis. The present study aims to investigate the therapeutic efficacy of two analogous forms of 6-gingerol, 8-gingerol, and 10-gingerol, on ulcerative colitis. Colitis was induced in rats through consumption of 5% (w/v) dextran sulfate sodium drinking water for 7 consecutive days. 6-Gingerol, 8-gingerol, and 10-gingerol were then given intraperitoneally at doses of 30 mg kg-1 d-1 for another 7 days, respectively. Body weight change, disease activity index, inflammatory cytokines, and oxidative stress indices were measured, and the colonic tissue injuries were assessed macroscopically and histopathologically. Results showed that all three gingerols attenuated colitic symptoms evoked by dextran sulfate sodium, significantly elevated superoxide dismutase activity, decreased malondialdehyde levels and myeloperoxidase activity in the colon tissue, and markedly reduced the content of tumor necrosis factor alpha and Interleukin 1 beta in the serum. Histological observations showed that all three gingerols obviously accelerated mucosal damage healing. It is concluded that 6-gingerol, 8-gingerol, and 10-gingerol, the three analogues, have a strong and relatively equal efficacy in the treatment of colitis. Copyright © 2017 John Wiley & Sons, Ltd.
Subject(s)
Catechols/pharmacology , Colitis, Ulcerative/drug therapy , Fatty Alcohols/pharmacology , Animals , Colitis, Ulcerative/chemically induced , Colon/drug effects , Colon/pathology , Dextran Sulfate , Disease Models, Animal , Interleukin-1beta/blood , Intestinal Mucosa/drug effects , Intestinal Mucosa/pathology , Male , Malondialdehyde/metabolism , Oxidative Stress/drug effects , Peroxidase/metabolism , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/metabolism , Tumor Necrosis Factor-alpha/bloodABSTRACT
Specnuezhenide (SPN), one of the main ingredients of Chinese medicine "Nü-zhen-zi", has anti-angiogenic and vision improvement effects. However, studies of its effect on retinal neovascularization are limited so far. In the present study, we established a vascular endothelial growth factor A (VEGFA) secretion model of human acute retinal pigment epithelial-19 (ARPE-19) cells by exposure of 150 µM CoCl2 to the cells and determined the VEGFA concentrations, the mRNA expressions of VEGFA, hypoxia inducible factor-1α (HIF-1α) & prolyl hydroxylases 2 (PHD-2), and the protein expressions of HIF-1α and PHD-2 after treatment of 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1, 1.0 µg/mL) or SPN (0.2, 1.0 and 5.0 µg/mL). Furthermore, rat pups with retinopathy were treated with SPN (5.0 and 10.0 mg/kg) in an 80% oxygen atmosphere and the retinal avascular areas were assessed through visualization using infusion of ADPase and H&E stains. The results showed that SPN inhibited VEGFA secretion by ARPE-19 cells under hypoxia condition, down-regulated the mRNA expressions of VEGFA and PHD-2 slightly, and the protein expressions of VEGFA, HIF-1α and PHD-2 significantly in vitro. SPN also prevented hypoxia-induced retinal neovascularization in a rat model of oxygen-induced retinopathy in vivo. These results indicate that SPN ameliorates retinal neovascularization through inhibition of HIF-1α/VEGF signaling pathway. Therefore, SPN has the potential to be developed as an agent for the prevention and treatment of diabetic retinopathy.
Subject(s)
Angiogenesis Inhibitors/pharmacology , Glucosides/pharmacology , Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors , Hypoxia/drug therapy , Ligustrum/chemistry , Pyrans/pharmacology , Retinal Neovascularization/drug therapy , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Angiogenesis Inhibitors/isolation & purification , Animals , Cell Hypoxia , Cell Line , Cobalt/pharmacology , Diabetic Retinopathy/drug therapy , Diabetic Retinopathy/genetics , Diabetic Retinopathy/metabolism , Diabetic Retinopathy/pathology , Disease Models, Animal , Epithelial Cells/cytology , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Gene Expression Regulation , Glucosides/isolation & purification , Humans , Hypoxia/complications , Hypoxia/genetics , Hypoxia/pathology , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor-Proline Dioxygenases/genetics , Hypoxia-Inducible Factor-Proline Dioxygenases/metabolism , Indazoles/pharmacology , Plant Extracts/chemistry , Pyrans/isolation & purification , Rats , Rats, Sprague-Dawley , Retinal Neovascularization/etiology , Retinal Neovascularization/genetics , Retinal Neovascularization/pathology , Retinal Pigment Epithelium/cytology , Retinal Pigment Epithelium/drug effects , Retinal Pigment Epithelium/metabolism , Signal Transduction , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolismABSTRACT
BACKGROUND: It has been reported that formononetin (FMN), one of the main ingredients from famous traditional Chinese medicine "Huang-qi" (Astragalus membranaceus [Fisch] Bunge) for Qi-tonifying, exhibits the effects of immunomodulation and tumor growth inhibition via antiangiogenesis. Furthermore, A. membranaceus may alleviate the retinal neovascularization (NV) of diabetic retinopathy. However, the information of FMN on retinal NV is limited so far. In the present study, we investigated the effects of FMN on the hypoxia-induced retinal NV and the possible related mechanisms. MATERIALS AND METHODS: The VEGF secretion model of acute retinal pigment epithelial-19 (ARPE-19) cells under chemical hypoxia was established by the exposure of cells to 150 µM CoCl2 and then cells were treated with 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1, a potent HIF-1α inhibitor, 1.0 µg/mL) or different concentrations of FMN (0.2 µg/mL, 1.0 µg/mL, and 5.0 µg/mL). The supernatants of cells were collected 48 hours later to measure the VEGF concentrations, following the manufacturer's instruction. The mRNA expressions of VEGF, HIF-1α, PHD-2, and ß-actin were analyzed by quantitative reverse transcription polymerase chain reaction, and the protein expressions of HIF-1α and PHD-2 were determined by Western blot analysis. Furthermore, the rats with retinopathy were treated by intraperitoneal administration of conbercept injection (1.0 mg/kg) or FMN (5.0 mg/kg and 10.0 mg/kg) in an 80% oxygen atmosphere. The retinal avascular areas were assessed through visualization of the retinal vasculature by adenosine diphosphatase staining and hematoxylin and eosin staining. RESULTS: FMN can indeed inhibit the VEGF secretion of ARPE-19 cells under hypoxia, downregulate the mRNA expression of VEGFA and PHD-2, and decrease the protein expression of VEGF, HIF-1α, and PHD-2 in vitro. Furthermore, FMN can prevent hypoxia-induced retinal NV in vivo. CONCLUSION: FMN can ameliorate retinal NV via the HIF-1α/VEGF signaling pathway, and it may become a potential drug for the prevention and treatment of diabetic retinopathy.
Subject(s)
Astragalus propinquus/chemistry , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Isoflavones/pharmacology , Retinal Neovascularization/drug therapy , Signal Transduction/drug effects , Vascular Endothelial Growth Factors/metabolism , Animals , Cell Hypoxia/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/biosynthesis , Isoflavones/administration & dosage , Molecular Structure , Rats , Rats, Sprague-Dawley , Retinal Neovascularization/metabolism , Structure-Activity Relationship , Vascular Endothelial Growth Factors/biosynthesisABSTRACT
To study the toxicokinetics of bakuchiol, hepatic and renal toxicity in rats after single oral administration of Psoraleae Fructus and combined with Glycyrrhizae Radix et Rhizoma, in order to provide scientific evidences for clinical safe medication use. A total of 35 SD rats were randomly divided into seven groups: vehicle (distilled water) control group, Glycyrrhizae Radix et Rhizoma group, positive control (aristolochic acid A) group, Psoraleae Fructus (40 g x kg(-1)) group( both male and female rats), Psoraleae Fructus and Glycyrrhizae Radix et Rhizoma (40 +20) g x kg(-1) group (both male and female rats). HPLC-UV method was used to determine the concentration of bakuchiol in rat plasma at different time points after single oral administration. Plasma alanine transaminase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), plasma creatinine (Cr), N-acetyl-ß-D-glucosaminidase (NAG) and kidney injury molecule 1 (Kim-1) were measured after administration for 24 h. The main toxicokinetics parameters of bakuchiol in rats exert significantly gender difference. When Psoraleae Fructus combination with Glycyrrhizae Radix et Rhizoma, the total area under the plasma concentration-time curve( AUC), C(max), and plasma clearance (CL) of bakuchiol were increased, respectively; CL, half-life (t½) were decreased, and T(max) were prolonged. The biochemical indicators (including ALT, AST, BUN, Cr and KIM-1 level) in different dose of Psoraleae Fructus groups, were found no statistically significant difference when compared with vehicle control group. The level of NAG in both Psoraleae Fructus and compatibility with Glycyrrhizae Radix et Rhizoma groups were significant increased (P < 0.05). There are obvious effects on toxicokinetics of bakuchiol in rats when Psoraleae Fructus combined with Glycyrrhizae Radix et Rhizoma. Renal toxicity induced by Psoraleae Fructus at high dose was observed after single oral administration and no liver damage in rats was found.
Subject(s)
Glycyrrhiza/toxicity , Kidney/drug effects , Liver/drug effects , Phenols/toxicity , Psoralea/toxicity , Administration, Oral , Animals , Female , Male , Phenols/pharmacokinetics , Rats , Rats, Sprague-Dawley , Rhizome/toxicity , ToxicokineticsABSTRACT
Codonopsis, in the family Campanulaceae, is a genus containing 42 species of dicotyledonous herbaceous perennial plants, predominantly found in Central, East and South Asia. Several Codonopsis species are widely used in traditional medicine and are considered to have multiple medicinal properties. Among the Codonopsis species, Codonopsis pilosula (Franch.) Nannf. and C. lanceolata (Sieb. et Zucc.) Benth. & Hook. f. ex Trautv. are more popular than others according to the findings, especially phytochemical and bioactive studies. Phytochemical research shows that Codonopsis species contain mainly polyacetylenes, phenylpropanoids, alkaloids, triterpenoids and polysaccharides, which contribute to multiple bioactivities. However, the mechanisms of their bioactivities need to be further elucidated. The less popular Codonopsis species remain to be studied and exploited. In addition, although a series of methods for the quality evaluation of Codonopsis species have been developed, a feasible and reliable approach to the efficacious and safe use of various Codonopsis species is still needed, with considering botanical origin, chemical constituents and bioactive effects. This review aims to provide up-to-date and comprehensive information on the phytochemistry, bioactivity and quality control of medicinal plants in the genus Codonopsis and to highlight current gaps in knowledge, which is useful for the wider development of the Codonopsis genus.
Subject(s)
Codonopsis/chemistry , Phytochemicals/chemistry , Alkaloids/chemistry , Medicine, Traditional/standards , Plants, Medicinal/chemistry , Polyynes/chemistry , Quality Control , Triterpenes/chemistryABSTRACT
OBJECTIVE: To evaluate the key indicators in the pituitary-target gland axes in the animal model of Shen-yang deficiency syndrome (SYDS). METHODS: The 8 biological indicators [thyroid stimulating hormone (TSH), 3, 3', 5-triiodothyronine (T3), thyroxine (T4), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), adrenocorticotropic hormone (ACTH), and cortisol (CORT)] in the pituitary-target gland axes were grouped using factor analysis. Then the sensitivity of every indicator was calculated according to the sensitivity function defined in this paper, so as to find all the most sensitive indicators in every group as key indicators of SYDS. RESULTS: The key indicators in the early period of SYDS were T, LH, T4, and CORT. The key indicators in the middle period were LH,T, CORT, and ACTH. The key indicators in the late period were LH, T, CORT, and FSH. CONCLUSIONS: T, LH, and CORT were the common key indicators of the three periods, and other different key indicator of SYDS in the early, middle and late period were T4, ACTH, and FSH respectively, which changed from the thyroid axis to the adrenal axis and then to the gonadal axis as the period changed. The key indicators in the late period were mainly in the gonadal axis, showing gonadal dysfunction in the late period.
Subject(s)
Disease Models, Animal , Factor Analysis, Statistical , Yang Deficiency/physiopathology , Animals , Estradiol/analysis , Follicle Stimulating Hormone/analysis , Hydrocortisone/analysis , Luteinizing Hormone/analysis , Male , Pituitary-Adrenal System/physiopathology , Rats , Rats, Sprague-Dawley , Testosterone/analysis , Thyrotropin/analysis , Thyroxine/analysisABSTRACT
This meta-analysis aimed to evaluate the effectiveness of acupuncture or acupressure at the Sanyinjiao (SP6) acupoint in relieving pain associated with primary dysmenorrhea. We searched the scientific literature databases to identify randomized controlled trials. The primary outcome was visual analogue scale (VAS) pain score. Three acupuncture and four acupressure trials were included in the meta-analyses. For the acupuncture analysis, there was no difference in the mean VAS score reduction between the SP6 acupoint and control (GB39 acupoint) groups (-4.935; lower limit = -15.757, upper limit = 5.887; P = 0.371). For the acupressure analysis, there was a significant difference in the mean VAS score after intervention between the SP6 acupoint and control (rest/light touch at SP6/nonacupoint acupressure) groups, favoring the SP6 acupoint group (-1.011; lower limit = -1.622, upper limit = -0.400; P = 0.001). Sensitivity analyses demonstrated good reliability of the meta-analyses findings. These findings suggest that acupuncture at SP6 is not more effective than acupuncture at an unrelated acupoint in the relief from primary dysmenorrhea. Acupressure at SP6 may be effective in the relief from primary dysmenorrhea. High-quality randomized controlled trials are needed to confirm these findings.