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On December 22,2021,the United States Food and Drug Administration approved the first main protease inhibitor,i.e.,oral antiviral nirmatrelvir(PF-07321332)/ritonavir(Paxlovid),for the treatment of early severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Nirmatrelvir inhibits SARS-CoV-2 infection,but high doses or long-term treatment may cause embryonic developmental toxicity and changes in host gene expression.The chiral structure of nirmatrelvir plays a key role in its antiviral activity.Ritonavir boosts the efficacy of nirmatrelvir by inactivating cytochrome P450 3A4 expression and occupying the plasma protein binding sites.Multidrug resistance protein 1 inhibitors may increase the efficacy of nirmatrelvir.However,Paxlovid has many contraindications.Some patients treated with Paxlovid experience a second round of coronavirus disease 2019(COVID-19)symptoms soon after re-covery.Interestingly,the antiviral activity of nirmatrelvir metabolites,such as compounds 12-18,is similar to or higher than that of nirmatrelvir.Herein,we review the advances and challenges in using nirmatrelvir and its derivatives with the aim of providing knowledge for drug developers and physicians in the fight against COVID-19.
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Berberine (BBR) is known as a classic drug for intestinal infection treatment.BBR inhibits intestinal bacteria,which is the core of its role in the treatment of intestinal infection.With the survival of local intestinal bacteria and its related metabolites on the physiological and pathological functions of the body continue to recognize the impact of it,more and more literatures have presented the effect of BBR through the impact of intestinal bacteria on the body glycol-lipid metabolism,even brain function.This allows us to re-understand the pathophysiology of BBR in inhibiting gut microbiome.In this paper,the antibacterial activity of BBR was reviewed and analyzed.The possible molecular target of BBR was analyzed according to the characteristics of prokaryotes gene expression,which was helpful to the in-depth study of BBR on intestinal bacteria.Thus,a more comprehensive understanding of the pharmacological effects of BBR is given.
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There have been many reports on berberine (BBR) effect of the inhibition on gut bacteria,but more from the protein level.In view of the preference of BBR for DNA binding,we here investigated the expression of BBR from the transcriptional expression level of the gene.The results showed that BBR had a higher affinity for UP element of Escherichia coli (E.coli) gene,and the transcription initiation region of this element contained TATA base sequence.The expression of genes sulA,recA and 16S which contain the genes of the UP element regulatory elements in the upstream of the promoter could be suppressed by BBR,and the expression of lpxC,secG and mutT which did not contain the genes of the UP element regulatory elements in the upstream of the promoter could not be inhibited by BBR.It is shown that the TATA sequence is the target of BBR.This result provides a new perspective for exploring the effect of BBR's inhibition of microbiota from gene transcription.
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Caenorhabditis elegans (C.elegans), has developed into an useful model for biomedical research, particularly in the targets of novel drugs and the related mechanism.C.elegans, combining with cost-effective cultivation, simple biological structure, make for high-throughput screenings in vivo model.In this review, we explore the feasibility of C.elegans in drug activity evaluation of complex systems.Because of the body independence of C.elegans, it provided good platform for the efficacy and mechanism of research on new drugs as well as Chinese herbal extract in vivo, showing a good prospect.
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This study was aimed to observe the effect ofpomegranate leaf tennis and Ananas coumosus leaf phenols on the growth of lactating mice through breast milk. Intragastric administration of different doses of drug was given to maternal mice. The general condition of newborn mice, body weight, tail length and organ coefficient of liver-related factors regulating the expression of lipid metabolism were observed. The results showed that both pomegranate leaf tennis and A. coumosus leaf phenols can obviously affect the growth and development of newborn mice through breast milk. And the effect of pomegranate leaf tennis was stronger than A. coumosus leaf phenols. Meanwhile, it obviously downregulated the expression of liver-related lipid metabolism enzymes in newborn mice. It was concluded that pomegranate leaf tennis and A. coumosus leaf phenols can affect the growth and development of newborn mice through breast milk. Its effect was related to the influence of lipid metabolism enzyme in the liver. Attention should be paid on taking this medication during lactation. Its clinical significance still required in-depth study.
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This study was aimed to observe effect of pomegranate leaf tannin and ellagic acid on primary rat adipocyte differentiation and lipid metabolism-related factor expression. Primary rat preadipocyte was in vitro cultured to observe the effect of pomegranate leaf tannin and ellagic acid on lipid fat cells as well as mRNA expression of its related factor. The results showed that pomegranate leaf tannin and ellagic acid had obvious inhibition effect on fat formation in fat cells. It had certain inhibition effect on activities of lipoprotein lipase (LPL) and glucose-3-phosphate dehydrogenase (GPDH). It promoted fat decomposition and reduced intracellular lipid content. It upregulated PPARγ and fatty acid-binding protein (aP2). It downregulated obese (ob) gene level. It was concluded that pomegranate leaf tannin can inhibit fat generation of fat cells and promote fat metabolism. Ellagic acid was its main active ingredient, which had the same effect as pomegranate leaf tannin.
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This article was aimed to study the quality control of pineapple leaf in order to further develop the appli-cations of pineapple leave as medicinal resources. The tissue structure of pineapple leaf was observed by tissue biop-sy assay. Thin-layer chromatography (TLC) was employed on the qualitative identification of ananasate in the leave. The p-coumaric acid and ananasate were detected with high-performance liquid chromatography (HPLC) assay in the content determination. The results showed that pineapple leaf can be divided into the upper and lower leaf epidermis with stoma under microscope observation. Ananasate of the leave can be indentified clearly by TLC. HPLC method can accurately detect the content of p-coumaric acid and ananasate of pineapple leave. There are different contents of p-coumaric acid and ananasate of pineapple leave in different origins. In Y unnan province, the contents of p-coumaric acid and ananasate of pineapple leave are the highest; while the contents of p-coumaric acid and ananasate in Guangxi province are the lowest. It was concluded that ananasate can be used in the quality identification. The p-coumaric acid and ananasate can be used in the quantitative determination in the better control of the quality of pineapple leaf.
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This article was aimed to study the general reproductive toxicity in mice in order to give a better evalua-tion of the medicinal plant of pineapple leaves (A nanas comasus L). Adult male and female mice were orally admin-istered with pineapple leaves. And then, each of the male and female mice was put together in one cage for mating. The mating success females were fed continuously. The experimental observation was conducted in pregnancy, fetal development, as well as the offspring of mice. The results showed that in addition to a large dose of pineapple leaves (4 g·kg-1) of the parental male rats having a lower body weight, pineapple leaves did not significantly affect on other parameters. There were no significant effects on pregnant mice and their offspring of mice. It was concluded that the pineapple leaves did not influence the general reproductive function of mice apparently.
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This article was aimed to study the antioxidant and antihyperlipidemic effect of total phenolic composition prepared from pineapple (A nanas comosus L.) leave. It had a rapid absorption after intragastric administration and the principle ingredient, p-coumaric acid, reached the peak concentration after 5 minutes of administration. The mice model with single intragastric administration of lipid and glucose were used in the observation of changes on postprandial glucose, lipid and intestinal lipase at different time points after drug administration. The results showed that phenols of pineapple leave can inhibit triglyceride and glucose absorption in certain extent. No significant effect was observed on inhibition at 30 minutes after the phenol administration. However, the intestinal lipase activity was obviously inhibited in normal mice and the intestinal lipase activity decline caused by acute lipid consumption can be reversed. It was concluded that the phenols pineapple leave may inhibit the absorption of lipids with correlation to lipase activity. It had certain regulation effect on the high postprandial glucose and fat absorption.
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Brazilein is one of the active ingredients of a Chinese medicine Caesalpinia sappan L. This study was aimed to test the vasodilator effect of brazilein on vascular smooth muscle cells in vitro from the perspective of molecular biology. The results showed that brazilein mainly acted through the influence of potassium ion channels, reducing membrane depolarization in order to affect the vessel relaxation. This effect can be influenced by blocking 5-HT receptor, and, simultaneously, correlating with the regulation of intracellular calcium ion concentration, affecting calmodulin and downregulating MLCP. In addition, the alterations of cAMP, PKA and PGI2 were involved in the pharmacological process of brazilein.
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<p><b>OBJECTIVE</b>To observe the effect of Euphorbia kansui (E. KS) alcohol extracts on urination and kidney-related expressions of mice injected with normal saline and to discuss its impact on kidney.</p><p><b>METHOD</b>Mice intraperitoneally injected with normal saline were observed for urination and changes in kidney-related histiocytic factors of after intragastrical administration of E. KS and compared with normal mice.</p><p><b>RESULT</b>E. KS alcohol extracts can promote urination of mice injected with normal saline and enhance peripheral serum creatinine, with no obvious pathological change showed in tissue sections. It had a certain effect on reducing AQP2 expression and enhancing TNF-alpha expression.</p><p><b>CONCLUSION</b>Euphorbia kansui in large dose has a remarkable effect on kidney but may be accompanied with pathological reactions to some extent, especially the dose of 1.2 g x kg(-1). The pathological reactions may be related with increased serum creatinine and TNF-alpha expression.</p>
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Animais , Masculino , Camundongos , Aquaporina 2 , Genética , Euphorbia , Interleucina-1beta , Genética , Rim , Metabolismo , Camundongos Endogâmicos ICR , Extratos Vegetais , Farmacologia , RNA Mensageiro , Fator de Necrose Tumoral alfa , Genética , MicçãoRESUMO
<p><b>OBJECTIVE</b>To study the allergen in key processes during the production of Fufang Kushen injection by IgG promoter-HepG2 cells in vitro.</p><p><b>METHOD</b>By transfecting a IgG promoter-regulating the expression of green fluorescent protein(GFP) plasmid into HepG2 cells, this transferred cells were incubated with common allergens (like puerarin, ovalbumin, LPS or Sal typhoid vi polysaccharide vaccine), excipients using in Fufang Kushen injection (NaOH, acetic acid, Tween-80 and ethanol) and samples from the key production processes of the injection for 30 minutes . Fluorescent photographs were analyzed the fluorescence intensity of the cells by using an image analysis software.</p><p><b>RESULT</b>All of common allergens significantly increased the IgG expression. Two of the excipicents, acetic acids and Tween-80 were shown to increased the IgG expression, while others had no effect on IgG expression. In the 8 samples from the key processes in the production of Fufang Kushen injection, two of them stimulated IgG expression.</p><p><b>CONCLUSION</b>IgG promoter-HepG2 cells are highly sensitive and specific to allergens, and thus can be applied to rapid screening of allergens in components and injections in transcriptional level. It is possible to use the IgG-promoter HepG2 cells in a real-time monitoring of allergens in the production processes of Chinese medicine injections.</p>
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Humanos , Alérgenos , Alergia e Imunologia , Medicamentos de Ervas Chinesas , Química , Regulação da Expressão Gênica , Alergia e Imunologia , Células Hep G2 , Imunoglobulina G , Genética , Injeções , Medicina Tradicional Chinesa , Padrões de Referência , Regiões Promotoras Genéticas , Genética , Controle de QualidadeRESUMO
<p><b>OBJECTIVE</b>To investigate the alteration of inflammasome and receptor during IgG promoter transfected to HepG2 cells.</p><p><b>METHOD</b>By assay of Elisa to evaluate the secretion of IL-1 beta, IL-8, TNF-alpha and MCP-1 after puerarine and LPS administration, and by assay of real time PCR to evaluate the expression of mRNA of IL-1 beta, IL-8,TNF-alpha and MCP-1, as well as the receptors of TLR2, 4 and NOD2, MyD88.</p><p><b>RESULT</b>IgG promoter did not active innate immunity and enhance the expression and secretion of inflammasome in HepG2. Puerarine did not active the inflammasome either. LPS activated the innate immunity and increased the secretion of IL-8, TNF-alpha and MCP-1.</p><p><b>CONCLUSION</b>IgG-HepG2 cells could be used specifically as the model of allergy type II for ingredients screening. It is suggested that puerarine was suite for the activator for this type of allergy as positive control.</p>
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Humanos , Alérgenos , Alergia e Imunologia , Medicamentos de Ervas Chinesas , Química , Regulação da Expressão Gênica , Alergia e Imunologia , Células Hep G2 , Imunidade Inata , Alergia e Imunologia , Imunoglobulina G , Genética , Inflamassomos , Alergia e Imunologia , Regiões Promotoras Genéticas , Genética , TransfecçãoRESUMO
<p><b>OBJECTIVE</b>To investigate brazilein's role in energy metabolism of cerebral ischemia-reperfusion in mice.</p><p><b>METHOD</b>Fourty mice were randomly divided into the sham group, ischemia group, brazilein 5 mg x kg(-1) group and brazilein 10 mg x kg(-1) group, each with ten cases. Cerebral ischemia model was the built. Mice were injected with brazilein three days before the operation, then they were killed. Cerebrum homogenate was prepared for the detecting of ATP, ADP, AMP and lactic acid by HPLC, expressions of MCT1 and MCT2 in mRNA level by RT-PCR.</p><p><b>RESULT</b>The lactic acid in cerebrum increased sharply 20 minutes after cerebral ischemia and decreased 1 hour after reperfusion, then returned to the normal level 24 hours after reperfusion. The charge of energy decreased significantly at the beginning of the ischemia-reperfusion, and the charge restored 1 hour after reperfusion though it was still much lower than the normal level at the time point of 24 hours. Moreover, MCT1 and MCT2 upregulated accompanied with the increase of lactate, MCT2 mRNA enhanced in brazilein 5 mg x kg(-1) group (P < 0.05) while both the two factors increased in brazilein 10 mg x kg(-1) group (P < 0.01).</p><p><b>CONCLUSION</b>Brazilein might protect neurons by changing the charge of energy.</p>
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Animais , Humanos , Masculino , Camundongos , Benzopiranos , Isquemia Encefálica , Tratamento Farmacológico , Genética , Metabolismo , Modelos Animais de Doenças , Metabolismo Energético , Expressão Gênica , Indenos , Camundongos Endogâmicos ICR , Transportadores de Ácidos Monocarboxílicos , Genética , Metabolismo , Distribuição Aleatória , Traumatismo por Reperfusão , Tratamento Farmacológico , Genética , Metabolismo , Simportadores , Genética , MetabolismoRESUMO
<p><b>OBJECTIVE</b>To construct an effective system screening and evaluating possible injections and components inducing allergy type II.</p><p><b>METHOD</b>Transfect IgG promoter-regulated green fluorescent protein expressing plasmid into RPMI-8226 cell. The number of fluorescent cells after drug treatment was calculated and statistically evaluated.</p><p><b>RESULT</b>Tween 80 can suppress the expression of IgG effectively, and puerarin has activity of stimulating IgG expression, and the system has no response to KCl-treatment. No effect of Yuxingcao (Herba Houttuyniae) injection on this system is observed.</p><p><b>CONCLUSION</b>IgG promoter-drove green fluorescent protein expressing cell line can be used as system screening injections and components inducing allergy type II based on stimulating IgG promoter activity. Tween 80 can suppress the expression of IgG at the transcriptional level. Four batches of Yuxingcao injection cannot induce allergy type II by activating IgG expression.</p>
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Humanos , Masculino , Linhagem Celular Tumoral , Expressão Gênica , Proteínas de Fluorescência Verde , Genética , Metabolismo , Imunoglobulina G , Genética , Injeções , Extratos Vegetais , Farmacologia , Plantas Medicinais , Química , Plasmídeos , Genética , Regiões Promotoras Genéticas , GenéticaRESUMO
<p><b>OBJECTIVE</b>To optimize the manufacturing process of the total flavonoid from Chrysanthemum morifolium and Sophora japonica, and establish the quality control methods for total flavonoid and its indicative constituents.</p><p><b>METHOD</b>The solvent for extraction was investigated and L9 (3(4)) orthogonal experiment was used to optimize the extraction process of the total flavonoid. Colorimetric method was used to determine the content of total flavonoid, and HPLC was used to determine the content of the indicative constituents.</p><p><b>RESULT</b>The optimized manufacturing process of the total flavonoid was that the prescribed crude drugs were extracted by using 70% ethanol for 3 times, 1 h each time. The extract was concentrated to the final concentration of 0.5 g x mL(-1), and was subjected to HPD-600 macroporous resin column chromatography at the weight ratio 1 : 0. 5 of crude drugs to macroporous resin. The sample was eluted with water in the volume of 10 times of the resin's, and then was desorpted with 85% ethanol in the volume of 5 times of the resin's. The content of total flavonoid was determined as 64.98%-66.79%, and the content of indicative constituents was determined as 5.87% - 6.93% for luteolin-7-O-glucoside and 14.09%-16.62% for rutin.</p><p><b>CONCLUSION</b>Extracting with aqueous alcohol in combination with purifying with macroporous resin column chromatography is an efficient way to prepare the total flavonoid from Ch. morifolium and S. japonica, and the colorimetric and the HPLC methods are useful for its quality control.</p>
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Fracionamento Químico , Métodos , Cromatografia Líquida , Métodos , Chrysanthemum , Química , Medicamentos de Ervas Chinesas , Padrões de Referência , Flavonoides , Padrões de Referência , Controle de Qualidade , Sophora , QuímicaRESUMO
<p><b>OBJECTIVE</b>To screen the active component of Wuzhuyutang (WZYT, Evodiae prescription) and investigate the regulatory effects of the components in WZYT on the TPH2 promoter, and to explore the possible molecular mechanism of WZYT on migraine.</p><p><b>METHOD</b>By transfecting a TPH2 promoter regulating Red Fluorescent Protein expressing plasmid into PC12 cell, the global fluorescence intensities and calculations of fluorescent cells after components treatment were statistically evaluated.</p><p><b>RESULT</b>Different regulatory effects of different components in WZYT with different concentrations on TPH2 promoter were observed.</p><p><b>CONCLUSION</b>TPH2 promoter drove Red Fluorescent Protein expressing cell line can be used as system screening components targeting TPH2 promoter activity. The possible mechanism of WZYT on migraine may due to its stimulating effects on TPH2 promoter, and promote the synthesis and release of 5-HT in cerebral.</p>
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Animais , Humanos , Ratos , Medicamentos de Ervas Chinesas , Química , Farmacologia , Evodia , Química , Transtornos de Enxaqueca , Tratamento Farmacológico , Genética , Células PC12 , Regiões Promotoras Genéticas , Triptofano Hidroxilase , Genética , MetabolismoRESUMO
AIM To explore pharmacokinetics of Berberine in YL2000 in normal and febrile rats. METHODS The levels of Berberine in plasma were measured through HPLC and secondary parameters were obtained by fitting the dose time data of Berberine making use of 3P87 programme. RESULTS In normal and febrile rats, the plasma concentration of Berberine was peaked at (3 4?0 3) h vs (0 3?2 1) h( P
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AIM To determine the dynamic changes of monoamine neurotransmitters and their metabolites in various brain regions of cerebral ischemia reperfusion mice. METHODS Concentrations of monoamine neurotransmitters such as norepinephrine (NE), dopamine (DA), serotonin (5-HT) and metabolites were determined by HPLC-ECD on d 0,1,3,5 and d 20 after cerebral ischemia reperfusion by common carotid artery occlusion. RESULTS The cerebral ischemia reperfusion mice showed decreased concentrations of NE, MHPG, DA, DOPAC, 5-HT and 5-HIAA in various brain regions, especially in hippocampus. CONCLUSION Several neuron systems play an important role in neurons damage of cerebral ischemia reperfusion, especially the NE and DA in hippocampus which is sensitive to the ischemia damage. The data offer useful guides for clinical treatments of cerebral ischemia diseases.