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1.
Zhongguo Zhong Yao Za Zhi ; 48(18): 4884-4892, 2023 Sep.
Article in Chinese | MEDLINE | ID: mdl-37802830

ABSTRACT

Allergic rhinitis(AR) is a common chronic inflammatory disease of the upper respiratory tract. Due to its high prevalence, high recurrence rate, and lack of a definitive cure, it is considered a global health issue by the World Health Organization. The pathogenesis of AR is complex and mainly involves B cells, helper T cells, eosinophils, basophils, macrophages, as well as the cytokines and inflammatory mediators they secrete. Clinical treatment primarily focuses on inhibiting inflammatory mediators such as histamine and leukotrienes. In recent years, active ingredients of animal-derived traditional Chinese medicine(TCM) have shown unique advantages and potential in AR treatment thanks to their high safety, specificity, selectivity, and biopotency. This study systematically reviewed the therapeutic effects and mechanisms of active ingredients and mixed extracts from animal-derived TCM, such as bovine spleen, honeycomb, bee venom, maggot, and human placenta, which have been shown by modern pharmacological research to regulate the immune function in AR, providing a reference for further exploration and clinical development of active ingredients from animal-derived TCM. Studies have found that the active ingredients from animal-derived TCM can produce definite therapeutic effects in AR by modulating multiple immune balances in the body, with great clinical prospects. However, their mechanisms of action still require further investigation, and the quality control techniques for effective ingredients need to be improved. Currently, the research on active ingredients from animal-derived TCM in China has adopted an interactive system consisting of "traditional medical experience-based research, bioinformatics and artificial intelligence predictions, and validation and development through new experimental techniques". Based on this system, animal-derived TCM can combine modern scientific and technological means to maximize the therapeutic effects of active ingredients and serve the clinical application of AR in a more efficient and innovative manner.


Subject(s)
Drugs, Chinese Herbal , Porifera , Rhinitis, Allergic , Animals , Cattle , Humans , Medicine, Chinese Traditional , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Artificial Intelligence , Rhinitis, Allergic/drug therapy , Inflammation Mediators
2.
Bioengineered ; 13(1): 83-95, 2022 01.
Article in English | MEDLINE | ID: mdl-34951340

ABSTRACT

Dysregulation of microRNAs (miRNAs) is associated with the occurrence and development of breast cancer. In this research, we explored the involvement of miR-181a-5p in the progression of breast cancer and investigated potential molecular mechanisms. Firstly, the miR-181a-5p and N-myc downstream-regulated gene (NDRG) 2 expression was detected by real-time quantitative polymerase chain reaction. Cellular processes were assessed using Cell Counting Kit 8, Bromodeoxyuridine, colony formation and transwell assays. HK2, PKM2 and LDHA activities were assessed by ELISA. The combination between miR-181a-5p was assessed by dual-luciferase reporter assay and RNA pull-down assay. The results indicated that miR-181a-5p levels were upregulated and NDRG2 levels were downregulated in breast cancer, leading to poor prognosis. Silencing of miR-181a-5p inhibited cell proliferation, invasion, glycolysis, and xenograft tumor growth, while enhanced miR-181a-5p got the opposite results. Furthermore, NDRG2 acts as a target of miR-181a-5p. Knockout of NDRG2 facilitated biological behaviors and meanwhile enhanced phosphorylation (p)-PTEN and p-AKT levels. Rescue experiments showed that restoring NDRG2 abolished the effects caused by miR-181a-5p in breast cancer cells. In conclusion, miR-181a-5p facilitated tumor progression through NDRG2-induced activation of PTEN/AKT signaling pathway of breast cancer, suggesting that focusing on miR-181a-5p may provide new insight for breast cancer therapy.Abbreviations Brdu: Bromodeoxyuridine; CCK-8: Cell Counting Kit-8; miRNA: microRNAs; mut: mutant; RT-qPCR: real-time quantitative polymerase chain reaction; UTR: untranslated region; WT: wild-type.


Subject(s)
Breast Neoplasms/pathology , MicroRNAs/genetics , Tumor Suppressor Proteins/genetics , Up-Regulation , Animals , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation , Female , Gene Expression Regulation, Neoplastic , Glycolysis , Humans , Mice , Neoplasm Staging , Neoplasm Transplantation , PTEN Phosphohydrolase/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Tumor Suppressor Proteins/metabolism
3.
Neuroreport ; 30(16): 1121-1128, 2019 11 06.
Article in English | MEDLINE | ID: mdl-31568208

ABSTRACT

Baicalin, an ingredient drawn from Scutellaria amoena Georgi, plays a brain-protective role through anti-inflammatory, antioxidant, and other pathways. The aim of this study was to investigate the possible protective mechanism of baicalin on middle cerebral artery occlusion rats. Rats were divided into 4 groups: sham, middle cerebral artery occlusion, middle cerebral artery occlusion + baicalin, middle cerebral artery occlusion + baicalin treated + inhibitor (bromocriptine, which inhibit progesterone induction). After 7 days treatment, neurological deficits and infarct volume were determined, morphological change of penumbra was examined by (hematoxylin-eosin) staining. The expressions of neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP), and progesterone receptor were also assessed by immunofluorescent staining or immunohistochemistry, progesterone, and adrenocorticotropic hormone in serum were also determinated by ELISA. We found that baicalin could reduce the neurological deficits, infarct volume caused by middle cerebral artery occlusion, increase the expression of NeuN, GFAP, and progesterone receptor in ischemic penumbra and increase the expression of progesterone and adrenocorticotropic hormone level in serum. Those indicated that baicalin plays a protective role in cerebral ischemia rats by improvement of progesterone.


Subject(s)
Brain Ischemia/drug therapy , Brain/drug effects , Flavonoids/pharmacology , Ischemia/drug therapy , Animals , Antioxidants/pharmacology , Apoptosis/drug effects , Brain/metabolism , Brain Ischemia/metabolism , Disease Models, Animal , Glial Fibrillary Acidic Protein/metabolism , Infarction, Middle Cerebral Artery/drug therapy , Male , Neuroprotective Agents/pharmacology , Rats, Sprague-Dawley
4.
J Cancer ; 10(17): 4114-4122, 2019.
Article in English | MEDLINE | ID: mdl-31417656

ABSTRACT

Curcumin, as a high effect and low toxicity anti-cancer drug and photosensitiser, has synergistic and complementary effects with photodynamic therapy (PDT). However, due to its unclear mechanism, PDT's application and efficacy were limited. Notch signaling pathway, which is highly correlates with carcinogenesis and development of cervical cancer, could be a potential therapeutic targets to improve the effectiveness of PDT. Therefore, in this study, we explored the effects of Notch signaling pathway in cervical cancer by curcumin mediated PDT with/without Notch receptor blocker (DAPT), and hope to elucidate its mechanism. Firstly, the effect on the proliferation of cervical cancer Me180 cells were detected with MTT assay, and apoptosis were detected with Annexin V-FITC/PI combined with flow cytometry. Secondly, after establishment of nude mice model, dividing the experimental animals into model group, curcumin PDT group, simple DAPT group, and curcumin-PDT+DAPT group, and analyzing tumor volume changes as well as HE staining in each group. mRNA and protein expression of gene Notch-1 and its downstream NF-κB and VEGF were observed with RT-PCR, immunohistochemical staining and Western-blot with/without inhibition of Notch signaling pathway by DAPT, both in vivo and in vitro experiments. We found both DAPT and curcumin-PDT can inhibit the proliferation and induce apoptosis of cervical cancer cell. The two have synergistic effect in vitro and in vivo. This effect can effectively block the conduction of Notch signaling pathway, which is associated with down-regulation of the expression of Notch1 and NF-κB. Notch signaling pathway could be one of the targets of curcumin-PDT photodynamic therapy.

5.
Biomed Pharmacother ; 111: 485-495, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30594788

ABSTRACT

The pressing need to discover more effective drugs for various CNS disorders has resurrected the idea of investigating the effectiveness of traditional medicines in modern science. Tongluojiunao (TLJN) is an example of revived modern herbal preparation based on traditional Chinese medicine (TCM) with a long history of administration for various types of cerebrovascular injuries and neurodegenerative diseases. TLJN is prepared from the herbal roots of Panax notoginseng (Sanchi) and dried fruits of Gardenia jasminoides (Cape Jasmine), and so far, it has demonstrated promising results in patients with vascular dementia and cerebral ischemic stroke. TLJN has also demonstrated therapeutic ability regarding the slowly-progressed neurodegenerative diseases like Alzheimer's disease. So it tempted us to undertake a thorough review of various features of TLJN therapeutic effects on the mentioned CNS conditions, including the cellular and molecular targets, inflammatory responses, neurogenesis and angiogenesis mediators and cognitive function. For this purpose, multiple global and local databases, including China National Knowledge Infrastructure (CNKI) were checked out and the retrieved information was grouped according to their scope of studies. Among these, TLJN is reported to restore the deregulated cell-cell communication in the neurovascular unit, prevent the stress-related challenges imposed by ischemia/reperfusion insult, help with the cerebral tissue recovery after traumatic brain damage, avoid the epileptic seizure attack and limit the progression of Alzheimer's disease. We hope that the current review provides new insights into TLJN medication as a prospective neuroprotective medication for further more in-depth investigation in the future.


Subject(s)
Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional/methods , Neurodegenerative Diseases/drug therapy , Neuroprotective Agents/therapeutic use , Plant Extracts/therapeutic use , Animals , Brain/drug effects , Brain/pathology , Brain/physiology , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Gardenia , Humans , Medicine, Chinese Traditional/trends , Neurodegenerative Diseases/pathology , Neurons/drug effects , Neurons/pathology , Neurons/physiology , Neuroprotective Agents/chemistry , Neuroprotective Agents/pharmacology , Panax notoginseng , Plant Extracts/chemistry , Plant Extracts/pharmacology , Treatment Outcome
6.
Mol Med Rep ; 12(4): 5328-34, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26238400

ABSTRACT

The synergistic mechanism underlying the effects of multi­component combined drug use for complex diseases remains to be fully elucidated. Microglial activation following ischemia can either affect neural survival or cause neuronal injury. The aim of the present study was to determine the synergistic effect of geniposide and ginsenoside Rg1, based on microglial­neuronal communication. N2a neuronal cells were divided into the following seven groups: Control group; normal cultured microglial cells in conditioned medium (N­MG­CM) group; oxygen­glucose deprivation (OGD) model group; OGD­injured MG­CM (I­MG­CM) group; geniposide­treated MG­CM (G­MG­CM) group; ginsenoside Rg1­treated MG­CM (R­MG­CM) group; and combination­treated MG­CM (C­MG­CM) group. A series of assays were used to detect the effects of the different MG­CM on neurons in terms of: (i) cell viability, determined using a Cell Counting Kit­8; (ii) lactate dehydrogenase (LDH) leakage rate; (iii) expression of NMDAR1 and activated caspase­3, detected using western blotting; (iv) mitochondrial transmembrane potential, determined by JC­1; and (v) mitochondrial ultrastructural features, determined using electron microscopy. The experimental results demonstrated that MG­CM including the integrated use of geniposide and ginsenoside Rg1 significantly protected neuronal cell viability and inhibited LDH leakage, suppressed the expression of N­methyl­D­aspartate receptor subunit 1 and activated caspase­3, increased the mitochondrial transmembrane potential and improved the mitochondrial ultrastructure. MG­CM from separately used geniposide or ginsenoside Rg1 demonstrated differential neuroprotection at different levels. These findings revealed that the synergistic drug combination of geniposide and ginsenoside Rg1 in the treatment of stroke is a feasible approach for use.


Subject(s)
Culture Media, Conditioned/pharmacology , Ginsenosides/pharmacology , Microglia/metabolism , Neurons/drug effects , Neurons/metabolism , Neuroprotective Agents/pharmacology , Animals , Caspase 3/metabolism , Cell Line , Cell Survival/drug effects , Drug Synergism , Ginsenosides/chemistry , L-Lactate Dehydrogenase/metabolism , Membrane Potential, Mitochondrial/drug effects , Mice , Molecular Structure , Neurons/pathology , Receptors, N-Methyl-D-Aspartate/metabolism
7.
Neural Regen Res ; 10(3): 445-50, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25878594

ABSTRACT

The Chinese herbal formula Tongluo Jiunao, containing the active components Panax notoginseng and Gardenia jasminoides, has recently been patented and is in use clinically. It is known to be neuroprotective in cerebral ischemia, but the underlying pathway remains poorly understood. In the present study, we established a rat model of cerebral ischemia by occlusion of the middle cerebral artery, and administered Tongluo Jiunao, a positive control (Xuesai Tong, containing Panax notoginseng) or saline intraperitoneally to investigate the pathway involved in the action of Tongluo Jiunao injection. 2,3,5-Triphenyltetrazolium chloride (TTC) staining showed that the cerebral infarct area was significantly smaller in model rats that received Tongluo Jiunao than in those that received saline. Enzyme-linked immunosorbent assay revealed significantly greater expression of neurotrophin 3 and growth-associated protein 43 in ischemic cerebral tissue, and serum levels of neurotrophin 3, in the Tongluo Jiunao group than in the saline group. The reverse transcription polymerase chain reaction and immunohistochemical staining showed that after treatment with Tongluo Jiunao or Xuesai Tong, tropomyosin-related kinase C gene expression and immunoreactivity were significantly elevated compared with saline, with the greatest expression observed after Tongluo Jiunao treatment. These findings suggest that Tongluo Jiunao injection exerts a neuroprotective effect in rats with cerebral ischemia by activating the neurotrophin 3/tropomyosin-related kinase C pathway.

8.
Zhongguo Zhong Yao Za Zhi ; 39(8): 1516-24, 2014 Apr.
Article in Chinese | MEDLINE | ID: mdl-25039193

ABSTRACT

In view of the effective traditional Chinese medicine (TCM) in the treatment of clinical depression, the mechanism is not clear, this study attempts to research the cause of depression in a complex situation to lay the foundation for the next step of TCM curative effect evaluation. Based on the brain wave of 120 depression patients and 40 ordinary person, the change regulation of acetylcholine, dopamine, norepinephrine, depression neurotransmitters and excited neurotransmitters in the whole and various encephalic regions' multi-neurotransmitters of depression patients-serotonin are analysed by search of encephalo-telex (SET) system, which lays the foundation for the diagnosis of depression. The result showed that: contrased with the normal person group, the mean value of the six neurotransmitters in depression patients group are: (1) in the whole encephalic region of depression patients group the dopamine fall (P < 0.05), and in the double centralregions, right temporal region and right parietal region distinct fall (P < 0.01); (2) in the right temporal region of depression patients group the serotonin rise (P < 0.05); (3) in the right central region, left parietal region of depression patients group the acetylcholine fall (P < 0.05), left rear temporal region fall obviously (P < 0.01). The correlation research between antagonizing pairs of neurotransmitters and neurotransmitters: (1) the three antagonizing pairs of neurotransmitters-serotonin and dopamine, acetylcholine and norepinephrine, depression neurotransmitters and excited neurotransmitters, in ordinary person group and depression patients group are characterizeed by middle or strong negative correlation. Serotonin and dopamine, which are characterized by weak negative correlation in the right rear temporal region of ordinary person group, are characterized by strong negative correlation in the other encephalic regions and the whole encephalic (ordinary person group except the right rear temporal region: the range of [r] is [0.82, 0.92], P < 0.01)/(depression patients group:the range of [r] is [0.88, 0.94], P < 0.01); acetylcholine and norepinephrine, in the whole and various encephalic region are characterized by middle negative correlation(ordinary person group:the range of [r] is [0.39, 0.76], P < 0.01 or P < 0.05)/(depression patients group: the range of [Ir] is [0.56, 0.64], P < 0.01); depression neurotransmitters and excited neurotransmitters are characterized by middle strong negative correlation (ordinary person group: the range of [r] is [0.57, 0.80], P < 0.01)/(depression patients group: the range of [r] is [0.68, 0.78], P < 0.01). (2) The two neurotransmitters which are not antagonizing pairs of neurotransmitters, serotonin and excited neurotransmitters, or acetylcholine and depression neurotra-nsmitters, or dopamine and depression neurotransmitters in the various encephalic regions are characterized by weak negative correlation. Serotonin and excited neurotransmitters are characterizeed by weak negative correlation (ordinary person group: in the right central region, left parietal region, double front temporal regions, right rear temporal region, the range of [r] is [0.25, 0.50], P < 0.01 or P < 0.05)/(depression patients group: in the whole encephalic regions, double parietal regions, double occipital regions, right front temporal region, left central region, left frontal region, the range of [r] is [0.18, 0.37], P < 0.01 or P < 0.05); acetylcholine and depression, neurotransmitters are characterized by weak negative correlation (ordinary person group: in the double frontal regions, left parietal region, left front temporal region, right rear temporal region, the range of [r] is [0.31, 0.46], P < 0.01 or P < 0.05)/(depression patients group: in double rear temporal regions, right front temporal region, double occipital regions, left central region, the range of [r] is [0.20, 0.32] , P < 0.01 or P < 0.05); do-pamine and depression neurotransmitters are characterized by weak middle negative correlation (ordinary person group: in left parietal region, right central region, left frontal region, left occipital region, double front temporal regions, the range of [r] is [0.33, 0.68], P < 0.01 or P < 0.05)/(depression patients group: in the whole region and other various regions except the left frontal region, right central region, the range of Irl is [0.21, 0.34], P < 0.01 or P < 0.05). Dopamine and acetylcholine or norepinephrine and serotonin are characterized by weak positive correlation in all encephalic regions. Dopamine and acetylcholine are characterized by weak positive correlation (ordinary person group: in left frontal region, right parietal region, left front temporal region and left rear temporal region, the range of [r] is [0.37, 0.46], P < 0.01)/(depression patients group: in the whole region and the orther various regions except the double central regions, the range of [r] is [0.23, 0.5], P < 0.01 or P < 0.05); norepinephrine and serotonin are characterized by weak positive correlation (ordinary person group: in double front temporal regions, double rear temporal regions, right frontal region and left parietal region, the range of [r] is [0.34, 0.48], P < 0.01 or P < 0.05)/(depression patients group: in the whole and various regions, the range of [r] is [0.18, 0.42], P < 0.01). The main differences between the depression patients group and ordinary person group are: (1) In the whole regin, left frontal region and right central region of depression patients group, the six neurotransmitters all fall normally (P < 0.05). (2) The percent of dopamine falling or including dopamine falling, or including dopamine falling and serotonin rising in depression patients group increases. The percent of dopamine falling or including dopamine falling in the whole region, right frontal region, right central region increases (P < 0.01), such as dopamine decreasing, serotonin increasing dopamine decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing, dopamine decreasing norepinephrine increasing depression neurotransmitters decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing neurotransmitters increasing and so on. (3) The percent of acetylcholine falling, or including acetylcholine falling, or including acetylcholine falling and neurotransmitters (beta)-receptor)rising in depression patients group increases. The percent of acetylcholine falling, or including acetylcholine falling in the right temporal region, double central regions increases (P < 0.05 or P < 0.01), such as acetylcholine decreasing, acetylcholine decreasing neurotransmitters increaseng, acetylcholine decreasing neurotransmitters increasing depression neurotransmitters decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing neurotransmitters increasing and so on. It's showed in research that depression patients' brain are characterized by multi-neurotransmitters abnormal, the synchronous change of multi-neurotransmitters has some certain regularities, which are not the simple linear relation. It's conformed that the three antagonizing pairs, neurotransmitters-serotonin and dopamine, acetylcholine and norepinephrine, depression eurotransmitters and excited neurotransmitters of ordinary person group and depression patients group, are both characterized by strong antagonizing relation, that the two neurotransmitters which are not antagonizing pairs of neurotransmitters are characterized by weak positive correlation or negative correlation, prompt maybe has the indirect causal relationship. And the change of six neurotransmitters in depression patients' various encephalic regions is rather complex. It's conformed preliminarily that the right frontal region and right central region are characterized by dopamine decreasing, acetylcholine decreasing, serotonin increasing dopamine decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing, dopamine decreasing norepinephrine increasing excited neurotransmitters decreasing, serotonin increasing acetylcholine decreasing dopamine decreasing neurotransmitters increasing, acetylchoine decreasing neurotransmitters increasing, acetylcholine decreasing neurotransmitters increasing excited neurotransmitters decreasing and so on. Contrasted with the ordinary person group, the depression patients group have the notable difference.


Subject(s)
Brain/metabolism , Depression/metabolism , Neurotransmitter Agents/metabolism , Acetylcholine/metabolism , Adolescent , Adult , Aged , Case-Control Studies , Dopamine/metabolism , Female , Humans , Male , Middle Aged , Norepinephrine/metabolism , Serotonin/metabolism , Young Adult
9.
Neural Regen Res ; 8(18): 1644-54, 2013 Jun 25.
Article in English | MEDLINE | ID: mdl-25206461

ABSTRACT

Kidney-tonifying recipe can reduce the accumulation of advanced glycation end products, prevent neuronal degeneration and improve cognitive functions in ovariectomized rats. Radix Achyranthis Bidentatae alcohol extracts may dose-dependently inhibit non-enzymatic saccharification in vitro. This study aimed to examine the effect of Radix Achyranthis Bidentatae on advanced glycation end products and on learning and memory capabilities in ovariectomized rats. Ovariectomized rats were treated with Radix Achyranthis Bidentatae alcohol extracts (containing 1.5 g/kg crude drug) or 0.1% aminoguanidine for 12 weeks and behavioral testing was performed with the Y-electrical maze. This test revealed that Radix Achyranthis Bidentatae and aminoguanidine could improve the learning and memory capabilities of ovariectomized rats. Results of competitive enzyme-linked immunosorbent assay showed that treatment with Radix Achyranthis Bidentatae or aminoguanidine reduced the accumulation of advanced glycation end products in the frontal cortex of ovariectomized rats, while increasing content in the blood and urine. Biochemical tests showed that treatment with Radix Achyranthis Bidentatae or aminoguanidine decreased superoxide dismutase activity in the serum and frontal cortex, and increased serum levels of glutathione peroxidase in ovariectomized rats. In addition, there was no apparent effect on malondialdehyde levels. These experimental findings indicate that Radix Achyranthis Bidentatae inhibits production of advanced glycation end products and its accumulation in brain tissue, and improves learning and memory capabilities in ovariectomized rats. These effects may be associated with an anti-oxidative action of the extract.

10.
J Ethnopharmacol ; 141(1): 151-7, 2012 May 07.
Article in English | MEDLINE | ID: mdl-22366434

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Tong Luo Jiu Nao injection (TLJN), a modern Chinese formula based on Traditional Chinese Medicine theory, has been used to treat ischemic stroke and vascular dementia. TLJN belongs to the ethnopharmacological family of medicines. AIM OF THE STUDY: To investigate the protective effect of TLJN on oxygen-glucose deprivation (OGD) induced-injury of brain microvascular endothelial cells (BMECs). MATERIALS AND METHODS: The model of OGD was established in the primarily cultured BMECs. TLJN was added to the OGD-injured BMECs for 6h. A series of assays were used to detect the effects of TLJN on: (i) MIP-1ß content in BMECs conditioned media (CM) by ELISA; (ii) MIP-1ß protein expression in BMECs by western blotting and immunocytochemistry; (iii) the expression of CCR5, receptor of MIP-1ß, in BMECs by western blotting; (iv) the proliferative activity of microglial cells via the Cell Counting Kit-8 (CCK-8). RESULTS: Our results showed that the OGD-injured BMECs presented with large amounts of secretion and expression of MIP-1ß and up-regulation of CCR5. Also, the CM of OGD-injured BMECs remarkably increased the proliferative activity of microglial cells. The TLJN-treated BMECs exhibited a reduction of MIP-1ß content in BMECs-CM and a down-regulation of MIP-1ß and CCR5 expression. In addition, an inhibitory effect of CM of OGD-injured plus TLJN injection-treated BMECs on microglial proliferation was also found. CONCLUSION: TLJN reduced the expression of MIP-1ß and CCR5 in OGD-injured BMECs, and the CM of OGD-injured plus TLJN injection-treated BMECs inhibited the proliferative activity of microglial cells, suggesting the therapeutic potential of TLJN on ischemic cerebral vascular disease.


Subject(s)
Brain/blood supply , Chemokine CCL4/metabolism , Drugs, Chinese Herbal/pharmacology , Endothelial Cells/drug effects , Glucose/deficiency , Microvessels/drug effects , Neuroprotective Agents/pharmacology , Animals , Blotting, Western , Cell Hypoxia , Cell Proliferation/drug effects , Cells, Cultured , Culture Media, Conditioned/metabolism , Down-Regulation , Drugs, Chinese Herbal/administration & dosage , Endothelial Cells/metabolism , Endothelial Cells/pathology , Enzyme-Linked Immunosorbent Assay , Immunohistochemistry , Injections , Microglia/drug effects , Microglia/pathology , Microvessels/metabolism , Microvessels/pathology , Neuroprotective Agents/administration & dosage , Phytotherapy , Plants, Medicinal , Rats , Rats, Sprague-Dawley , Receptors, CCR5/metabolism , Time Factors
11.
Brain Res Bull ; 86(1-2): 53-9, 2011 Aug 10.
Article in English | MEDLINE | ID: mdl-21756984

ABSTRACT

Neuronal survival can be influenced by activated microglia, but limited evidence exists on the effects of paracrine signaling from brain microvascular endothelial cells (BMECs) on microglial action. Therefore, we examined the effects of normal BMECs conditioned medium (BMECs-CM) on activated microglia induced by pro-inflammatory cytokine macrophage inflammatory protein-1beta (MIP-1ß), a chemokine that released from ischemic BMECs and has been proved to stimulate microglial proliferation. Our results showed that BMECs-CM inhibited the proliferation and transmigration of microglia induced by MIP-1ß. Moreover, BMECs-CM significantly suppressed the expression of the MIP-1ß receptor, CCR5, and the phosphorylation of p38 and JNK (P<0.05). These findings suggest that BMECs-CM could inhibit MIP-1ß-induced microglial activation. Future therapeutic strategies that prioritize the early recovery of BMECs could be beneficial for microglial inhibition and further increase neuronal survival.


Subject(s)
Brain/blood supply , Brain/cytology , Chemokine CCL4/pharmacology , Endothelial Cells/metabolism , Microglia/drug effects , Microglia/physiology , Paracrine Communication/physiology , Animals , Brain/physiology , Cell Movement/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Cerebrovascular Circulation/physiology , Culture Media, Conditioned/chemistry , Endothelial Cells/cytology , JNK Mitogen-Activated Protein Kinases/metabolism , Microcirculation , Microglia/cytology , Rats , Rats, Sprague-Dawley , Receptors, CCR5/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism
12.
Brain Res ; 1357: 1-8, 2010 Oct 21.
Article in English | MEDLINE | ID: mdl-20637183

ABSTRACT

Placental growth factor (PlGF) is involved in the angiopoiesis of the placental chorion and the maintenance of the placenta. Some additional roles of PlGF in other tissues have recently been described. Relatively little is known about PlGF expression in the CNS and the involvement of PlGF in cerebral ischemia injury. We examined the expression of PlGF in cerebral ischemia, utilizing a permanent middle cerebral artery occlusion (MCAO) model in the rat. PlGF expression and release from brain microvascular endothelial cells (BMECs) in response to oxygen and glucose deprivation (OGD) were examined in primary culture. To elucidate the effects of PlGF in cerebral ischemic injury, we investigated the effects of varying concentrations of PlGF upon neurons in an in vitro model of OGD. The effects of PlGF upon neuronal vascular endothelial growth factor receptor-1 (VEGFR-1) and vascular endothelial growth factor receptor-2 (VEGFR-2) expression were examined. We detected PlGF immunoreactivity mainly in the microvessels and interstitum of rat brain cortex after cerebral ischemic injury. In primary BMECs, PlGF expression and release were significantly higher under OGD conditions in culture. In primary cultures of rat cortical neurons, PlGF administration reduced cell death in an in vitro model of OGD. VEGFR-1 and VEGFR-2 were expressed in primary cortical neurons as measured by Western blotting. VEGFR-2 expression in primary neurons was significantly higher following PlGF administration. These data demonstrate that VEGFR-2 signaling may play a role in PlGF-mediated neuroprotection, and that PlGF may be a promising target for therapeutic intervention in ischemic injury.


Subject(s)
Cerebral Cortex/metabolism , Infarction, Middle Cerebral Artery/metabolism , Neurons/metabolism , Pregnancy Proteins/metabolism , Vascular Endothelial Growth Factor A/metabolism , Analysis of Variance , Animals , Blotting, Western , Cell Death/drug effects , Cells, Cultured , Cerebral Cortex/cytology , Cerebral Cortex/drug effects , Enzyme-Linked Immunosorbent Assay , Glucose/metabolism , Hypoxia/metabolism , Immunohistochemistry , Male , Neurons/cytology , Neurons/drug effects , Neuroprotective Agents/metabolism , Neuroprotective Agents/pharmacology , Placenta Growth Factor , Pregnancy Proteins/pharmacology , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects , Signal Transduction/physiology , Vascular Endothelial Growth Factor Receptor-1/metabolism , Vascular Endothelial Growth Factor Receptor-2/metabolism
13.
Biosci Biotechnol Biochem ; 74(7): 1350-4, 2010.
Article in English | MEDLINE | ID: mdl-20622443

ABSTRACT

This work evaluates the protective effects of Chinese herbs against ONOO(-)-induced biomolecule damage. Thirty-two Chinese traditional herbs were preliminarily screened for their ONOO(-)-scavenging activity by the fluorometric method. The potency of scavenging activity was in the following order: Apis cerana Fabricius (Propolis) > Rosmarinus officinalis L (Rosemary) > Pseudolarix amabilis (Nelson) Rehd. (Pine Bark PE) > Echinacea Moenck. (Echinacea); the remaining twenty-eight herbs performed unsatisfactorily for their scavenging activity. The four extracts with high ONOO(-) scavenging activity were selected for further characterization of their inhibiting effects on DNA single breaks, tyrosine nitration and LDL oxidation. A further study of the origin of this scavenging activity on the major active components showed cichoric acid and rosemary acid to both have strong ability to scavenge ONOO(-). These scavengers might be developed as therapeutic drugs for preventing ONOO(-)-involved diseases.


Subject(s)
Drugs, Chinese Herbal/pharmacology , Free Radical Scavengers/pharmacology , Peroxynitrous Acid/toxicity , DNA Breaks/drug effects , Drug Evaluation, Preclinical , Fluorescein/metabolism , Fluorometry , Humans , Lipoproteins, LDL/metabolism , Oxidation-Reduction/drug effects , Tyrosine/metabolism
14.
Article in English | MEDLINE | ID: mdl-16750434

ABSTRACT

A simple, rapid, and specific analytical method for simultaneous determination of geniposide, baicalin, cholic acid and hyodeoxycholic acid in 50 microL samples of rat serum was developed by high performance liquid chromatography-tandem mass spectrometry. The quantification of the target compounds was determined by multiple reaction monitoring (MRM) mode using electrospray ionization (ESI). The correlation coefficients of the calibration curves were better than 0.997. The intra- and inter-day accuracy, precision, and linear range had been investigated in detail. This method was subsequently applied to pharmacokinetic studies of geniposide, baicalin, cholic acid and hyodeoxycholic acid in rats successfully.


Subject(s)
Cholic Acid/blood , Chromatography, High Pressure Liquid/methods , Deoxycholic Acid/blood , Flavonoids/blood , Iridoids/blood , Pyrans/blood , Spectrometry, Mass, Electrospray Ionization/methods , Animals , Calibration , Cholic Acid/pharmacokinetics , Deoxycholic Acid/pharmacokinetics , Flavonoids/pharmacokinetics , Iridoids/pharmacokinetics , Male , Pyrans/pharmacokinetics , Rats , Rats, Wistar , Reference Standards
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