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1.
Int J Mol Sci ; 25(2)2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38255916

ABSTRACT

Chicoric acid (CA) has been reported to exhibit biological activities; it remains unclear, however, whether CA could regulate colitis via modulation of the gut microbiota and metabolites. This study aimed to assess CA's impact on dextran sulfate sodium (DSS)-induced colitis, the gut microbiota, and metabolites. Mice were induced with 2.5% DSS to develop colitis over a 7-day period. CA was administered intragastrically one week prior to DSS treatment and continued for 14 days. The microbial composition in the stool was determined using 16S rRNA sequencing, while non-targeted metabolomics was employed to analyze the metabolic profiles of each mouse group. The results show that CA effectively alleviated colitis, as evidenced by an increased colon length, lowered disease activity index (DAI) and histological scores, and decreased tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression levels. CA intervention restored the structure of gut microbiota. Specifically, it decreased the abundance of Bacteroidetes and Cyanobacteria at the phylum level and Bacteroides, Rosiarcus, and unclassified Xanthobacteraceae at the genus level, and increased the abundance of unclassified Lachnospiraceae at the genus level. Metabolomic analysis revealed that CA supplementation reversed the up-regulation of asymmetric dimethylarginine, N-glycolylneuraminic acid, and N-acetylneuraminic acid, as well as the down-regulation of phloroglucinol, thiamine, 4-methyl-5-thiazoleethanol, lithocholic acid, and oxymatrine induced by DSS. Our current research provides scientific evidence for developing CA into an anti-colitis functional food ingredient. Further clinical trials are warranted to elucidate the efficacy and mechanism of CA in treating human inflammatory bowel disease (IBD).


Subject(s)
Caffeic Acids , Colitis , Gastrointestinal Microbiome , Succinates , Humans , Animals , Mice , Mice, Inbred BALB C , Dextran Sulfate/toxicity , RNA, Ribosomal, 16S/genetics , Colitis/chemically induced , Colitis/drug therapy
2.
Zhen Ci Yan Jiu ; 48(5): 475-80, 2023 May 25.
Article in Chinese | MEDLINE | ID: mdl-37247861

ABSTRACT

OBJECTIVE: To observe the effect of electroacupuncture (EA) on neurological function, the expressions of phosphorylated c-Jun amino terminal kinase (p-JNK) and Beclin-1 in rats with traumatic brain injury (TBI), so as to explore the underlying mechanism of EA in the treatment of TBI. METHODS: A total of 64 SD rats were randomly divided into blank, sham, modeling groups, with 8 rats in the blank group and the sham group and 48 rats in the modeling group. The modified Feeney free-fall impact method was used to establish the TBI rat model. After modeling, rats of the modeling group were randomly divided into model and EA groups, which were further divided into 3 d, 7 d and 14 d subgroups with 8 rats in each group. Rats in the EA group were treated with acupuncture at "Baihui" (GV20, retained for 15 min), "Shuigou" (GV26, stabbed for 20 s), "Neiguan" (PC6) and "Zusanli" (ST36) of the right side. EA (2 Hz, 1 mA) was applied to PC6 and ST36 for 15 min. The above treatments were performed once a day, and different subgroups were continuously stimulated for 3, 7 and 14 days, respectively. The neurological impairment was evaluated by modified neurological severity score(mNSS). The pathological morphological changes and the protein expressions of p-JNK and Beclin-1 in the injured area of the brain were detected by Nissl staining and immunohistochemistry, separately. RESULTS: After modeling, the mNSS and the protein expressions of p-JNK and Beclin-1 were increased (P< 0.05) on day 3, 7 and 14 in the model group relative to the sham group. The Nissl bodies were reduced or even dissolved and neurons were seriously damaged in the model group on the 3rd day, which were mildly repaired on day 7 and 14. Following acupuncture interventions, compared with the model group, the mNSS on day 7 and 14 and the protein expressions of p-JNK and Beclin-1 on day 3, 7 and 14 were decreased (P< 0.05)in the EA group. The status of Nissl bodies and neurons in the EA group was better at all time points than that in the model group. There were no significant differences in the above indicators between the blank group and the sham group. CONCLUSION: EA can significantly improve the neurological function of TBI model rats, which may be related to its effects in down-regulating the protein expressions of p-JNK and Beclin-1 in the injured area of the brain.


Subject(s)
Brain Injuries, Traumatic , Electroacupuncture , Rats , Animals , Rats, Sprague-Dawley , Beclin-1/genetics , Brain Injuries, Traumatic/genetics , Brain Injuries, Traumatic/therapy , Brain
3.
Brain Res Bull ; 193: 27-36, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36470555

ABSTRACT

The mechanism of electroacupuncture (EA) pretreatment-induced neuroprotection remains unclear. In this study, we found that neuronal Triggering receptor expressed on myeloid cells 2 (TREM2) expression was increased and peaked at 48 h and 72 h after ischemia/reperfusion. After specific knockdown of TREM2 in excitatory neurons, neurological function was damaged, and the infarct volume was enlarged. Furthermore, the expression of LC3II/LC3I and Beclin1 was decreased, while the expression of p62 was increased. EA pretreatment enhanced TREM2, LC3II/LC3I and Beclin1 expression while reducing p62 in the ischemic penumbra area. The EA-induced neuroprotective effects and improvements in autophagic flux were abolished by specific knockdown of TREM2 in excitatory neurons. Taken together, our findings provide novel mechanistic insight into EA-induced ischemic tolerance and suggest a promising therapeutic strategy of targeting neuronal TREM2 to treat brain ischemia.


Subject(s)
Brain Ischemia , Electroacupuncture , Membrane Glycoproteins , Receptors, Immunologic , Reperfusion Injury , Beclin-1/metabolism , Brain Ischemia/metabolism , Ischemia/metabolism , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Neurons/metabolism , Receptors, Immunologic/metabolism , Reperfusion Injury/metabolism , Animals
4.
Biomed Pharmacother ; 151: 113170, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35676782

ABSTRACT

Mesenchymal stem cells (MSCs) are promising candidates for regenerative therapy. However, the research and clinical application of MSCs are greatly hindered by the limited cells proliferation and replicative senescence. Therapeutic agents that can both enhance the proliferative ability and decrease the replicative senescence of MSCs are greatly needed, however, not been reported yet. Herein, for the first time, we identified 11 natural compounds from medicinal plants with both excellent proliferative and anti-senescence abilities in MSCs. The qPCR analysis indicated underlying mechanisms associated with fibroblast growth factor, transforming growth factor, Wnt/ß-catenin and leukemia-induced factor in proliferation; the reactive oxygen species production, mitochondrial dysfunction autophagy and proteostasis are involved in cells senescence-related mechanism. Phytochemicals are demonstrated as novel therapeutic candidates with promising effects in both stimulating proliferation and retarding replicative senescence of stem cells with high safety.


Subject(s)
Cellular Senescence , Mesenchymal Stem Cells , Cell Proliferation , Cells, Cultured , Mesenchymal Stem Cells/metabolism , Phytochemicals/metabolism , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , Stem Cells
5.
Zhongguo Zhen Jiu ; 40(8): 851-6, 2020 Aug 12.
Article in Chinese | MEDLINE | ID: mdl-32869594

ABSTRACT

OBJECTIVE: To observe the effect of electroacupuncture (EA) on neuronal apoptosis in rats with traumatic brain injury (TBI), and to explore the action mechanism of EA on improving the brain nerve function of TBI. METHODS: A total of 88 6-week-old SD rats were randomly divided into a sham operation group, a model group, an EA group and a LY294002+EA group, 22 rats in each group. The TBI model on the left side was established by the improved Feeney's free fall method. After modeling for 24 h, the rats in the EA group and LY294002+EA group were treated with acupuncture at "Baihui" (GV 20) for 10 min and pricking acupuncture at "Shuigou" (GV 26) for 20 s; EA was applied at "Neiguan" (PC 6) and "Zusanli" (ST 36) on the right side (discontinuous wave, 2 Hz of frequency, 1 mA of intensity) for 10 min, once a day for 3 days. After 3 days of intervention, the TUNEL method was used to detect the level of neuron apoptosis in left cerebral cortex; the Western blot method was used to detect the expression of Akt, p-Akt, Bcl-2, Bax, Cyt-C and Caspase-9 in the left cerebral cortex. RESULTS: After 3-day treatment, compared with the sham group, the number of neuronal apoptosis in the left cortex was increased in the model group (P<0.01), and the expression of Bax, Cyt-C and Caspase-9 protein was increased (P<0.01), and the expression of p-Akt/Akt, Bcl-2 was decreased (P<0.01). Compared with the model group, the number of neuronal apoptosis in the left cortex was decreased in the EA group (P<0.01), and the expression of Bax, Cyt-C and Caspase-9 was decreased (P<0.01), and the expression of p-Akt/Akt and Bcl-2 was increased (P<0.01). Compared with the LY294002+EA group, the number of neuronal apoptosis in the left cortex was decreased in the EA group (P<0.01), and the expression of Bax, Caspase-9 and Cyt-C was decreased (P<0.01, P<0.05), and the expression of p-Akt/Akt and Bcl-2 was increased (P<0.01). CONCLUSION: EA could significantly reduce the neuronal apoptosis in rats with TBI, and its mechanism may be related to the activation of PI3K/Akt signaling pathway.


Subject(s)
Acupuncture Points , Apoptosis , Brain Injuries, Traumatic , Electroacupuncture , Animals , Brain Injuries, Traumatic/therapy , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction
6.
Zhongguo Zhen Jiu ; 40(7): 749-55, 2020 Jul 12.
Article in Chinese | MEDLINE | ID: mdl-32648400

ABSTRACT

OBJECTIVE: To observe the impacts of electroacupuncture (EA) on neurological function, the pathological morphology in brain tissue, apoptosis level and the protein expressions of apoptosis-related cytochrome C (Cyt-C) and cysteine aspartic acid protease-9 (Caspase-9) in the rats with traumatic brain injury (TBI) and explore the potential mechanism of EA in treatment of TBI. METHODS: A total of 70 clean-grade SD mice were randomized into a blank group (8 rats), a sham-operation group (8 rats), a model group (27 rats) and an EA group (27 rats). In terms of interventions of 3, 7 and 14 days, 3 subgroups were divided in the model group and the EA group successively, 9 rats in each subgroup. The modified Feeney free-fall percussion method was adopted to establish TBI models of rats. In the sham-operation group, only the skull was exposed and drilled and no free-fall percussion was exerted. One day after modeling, EA was given in the rats of EA group at "Shuigou" (GV 26), "Baihui" (GV 20) and "Neiguan" (PC 6) and "Zusanli" (ST 36) on the affected side, with intermittent wave, 2 Hz in frequency, once daily, 10 min each time, for 3, 7 and 14 days successively. Separately, on the day 3, 7 and 14 of intervention, the modified neurological severity scale (mNSS) was used to evaluate the degree of neurological function injury in the rats, HE staining and Nissl staining were to observe the pathological and morphological changes in brain tissue, TUNEL method was to observe the level of apoptosis in brain tissue and immunohistochemistry (IHC) method and Western blot were to determine the protein expressions of Cyt-C and Caspase-9 in brain tissue. RESULTS: Compared with the sham-operation group, on the day 3, 7 and 14 of intervention, mNSS scores were increased obviously in the rats of the model group respectively (P<0.01). Compared with the model group, on the day 3, 7 and 14 of intervention, mNSS scores were reduced in the rats of the EA group respectively (P<0.05). On day 3 of intervention, in brain injury region of the rats in the model group and the EA group, gross tissue necrosis, nuclear fragmentation, consolidation and obvious vacuolar changes, reduced Nissl bodies and scattered arrangement were found. On day 7 and 14 of intervention, in the model group and the EA group, the new connective tissue filling and normal cells were visible and Nissl bodies increased. The overall repair and Nissl body quantity in the EA group were better than the model group. Compared with the sham-operation group, on day 3, 7 and 14 of intervention, the numbers of apoptotic cells were increased obviously in the model group (P<0.01) and they were reduced in the EA group as compared with the model group (P<0.05). Compared with the sham-operation group, on day 3, 7 and 14 of intervention, the protein expressions of Cyt-C and Caspase-9 in damaged brain tissue were all increased obviously in the model group (P<0.01) and they were all reduced in the EA group as compared with the model group successively (P<0.05). CONCLUSION: Electroacupuncture remarkably improves the condition in the neurological function injury and reduces apoptosis degree in TBI model rats, which is likely related to the down-regulation of the protein expressions of Cyt-C and Caspase-9 in damaged brain tissue and further to bring the impacts on mitochondria mediated apoptosis process.


Subject(s)
Apoptosis , Brain Injuries, Traumatic/therapy , Electroacupuncture , Animals , Caspase 9/metabolism , Cytochromes c/metabolism , Random Allocation , Rats , Rats, Sprague-Dawley
7.
Zhen Ci Yan Jiu ; 45(7): 524-8, 2020 Jul 25.
Article in Chinese | MEDLINE | ID: mdl-32705824

ABSTRACT

OBJECTIVE: To observe the effect of electroacupuncture on the expression of phosphorylated adenosine 5'-monophosphate-activated protein kinase(p-AMPK), phosphorylated mammalian target of rapamycin(p-mTOR) and phosphorylated Ulk1(p-Ulk1) proteins in the cortex of traumatic brain injury (TBI) rats, so as to explore its mechanisms underlying treatment of TBI. METHODS: Male SD rats were randomly divided into sham operation (sham), model, electroacupuncture Ⅰ (EA Ⅰ), electroacupuncture Ⅱ (EA Ⅱ) groups (n=10 in each group). TBI model was established by using a free fall brain injury striking device after exposing the local cranial bone (to induce the left parietal cerebral contusion). Rats in EA Ⅰ group were treated by electroacupuncture at "Neiguan" (SP6) and "Zusanli" (ST36) combined with acupuncture at "Shuigou" (GV26) and "Baihui"(GV20) on the 7thday after modeling, once a day for 7 consecutive days. Rats in EA Ⅱ group received the treatments as those in EA Ⅰ group on 24 h after modeling, once a day for 14 d. After the treatment, histopathological changes of the injured cerebral cortex were observed by HE staining and Nissl staining. Western blot was used to detect the expression of AMPK, p-AMPK, mTOR, p-mTOR, Ulk1, p-Ulk1 proteins in the injured cerebral cortex tissue. RESULTS: After modeling and compared with the sham group, a large number of tissue necrosis, scattered arrangement of nerve fibers, vacuolar changes of cells, nuclear fragmentation, consolidation and hyperplastic scar tissue were found in the brain trauma area of rats in the model group. Nissl corpuscles were obviously absent. The ratio of p-AMPK/AMPK was up-regulated in the cortex of the wound region (P<0.01), and the ratio of p-mTOR/mTOR, p-Ulk1/Ulk1 were down-regulated (P<0.01). Compared with the model group, the pathological changes in brain injury area of rats in both EA groups were alleviated, the number of Nissl corpuscles increased, the ratio of p-AMPK/ AMPK was down-regulated in cortex of the injury area (P<0.01), and the ratios of p-mTOR/mTOR and p-Ulk1/Ulk1 were up-regulated (P<0.01). Compared with EA Ⅰ group, the pathological changes in the brain injury area in EA Ⅱ group showed obvious improvement, with down-regulation of p-AMPK/AMPK (P<0.05), and up-regulation of p-mTOR/mTOR and p-Ulk1/Ulk1 (P<0.05). CONCLUSION: Electroacupuncture may inhibit the over-activation of autophagy of cranial neurons by regulating the activation of AMPK, mTOR and Ulk1, thus exerting brain protection effect on TBI rats, and early electroacupuncture intervention is more effective in acute phase of TBI.


Subject(s)
Brain Injuries, Traumatic , Electroacupuncture , Animals , Autophagy-Related Proteins , Cerebral Cortex , Male , Rats , Rats, Sprague-Dawley
8.
Zhongguo Zhen Jiu ; 40(3): 267-71, 2020 Mar 12.
Article in Chinese | MEDLINE | ID: mdl-32270639

ABSTRACT

OBJECTIVE: To compare the clinical therapeutic effect on perimenopausal depression between the combined treatment with acupuncture at the "thirteen ghost points" and kaixin powder and the single application of kaixin powder. METHODS: A total of 60 patients with mild perimenopausal depression were randomized into a Chinese medication group (30 cases, 2 cases dropped off) and a combined treatment group (acupuncture and Chinese medication, 30 cases). In the Chinese medication group, the modified kaixin powder was administered, one dose a day, taking in the morning and the evening separately. In the combined treatment group, on the base of the treatment as the Chinese medication group, acupuncture was applied to the "thirteen ghost points" invented by SUN Si-miao, e.g. Shuigou (GV 26), Shaoshang (LU 11), Yinbai (SP 1), Daling (PC 7), Shenmai (BL 62), Jiache (ST 6), Chengjiang (CV 24), Laogong (PC 8), Shangxing (GV 23), etc. The needles were withdrawed after the qi was acquired, and acupuncture was given once every two days, 3 times a week. In both of the groups, the consecutive treatment for 12 weeks was required. Separately, before treatment, after treatment and in 1-month follow-up visit, the score of the Hamilton depression scale (HAMD), the score of the self-rating depression scale (SDS) and the score of the perimenopausal Kupperman were observed in the two groups. In 12 weeks of treatment, the clinical therapeutic effect was compared between the two groups. RESULTS: After treatment and during the follow-up, HAMD, SDS and Kupperman scores were all reduced obviously as compared with those before treatment in the two groups (P<0.05). These scores in the combined treatment group were all lower than those in the Chinese medication group (P<0.05). The total effective rate was 90.0% (27/30) in the combined treatment group, better than 78.6% (22/28) in the Chinese medication group (P<0.05). CONCLUSION: Either the combined treatment with acupuncture at the "thirteen ghost points" and kaixin powder or the single application of kaixin powder is effective on perimenopausal depression. The therapeutic effect of the combined treatment of acupuncture and Chinese medication is superior to the simple application of kaixin powder.


Subject(s)
Acupuncture Therapy , Depression/therapy , Drugs, Chinese Herbal/therapeutic use , Acupuncture Points , Female , Humans , Perimenopause , Treatment Outcome
9.
Anim Reprod Sci ; 196: 211-218, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30115522

ABSTRACT

The extremely low full-term developmental efficiency of cloned pig embryos limits the practical application of pig cloning techniques. Maternal dietary supplementation of the nutritionally important amino acid, arginine, can enhance prenatal developmental rate of in vivo fertilization-derived pig embryos. It was hypothesized that maternal dietary addition of arginine can also improve the developmental capacity of cloned pig embryos. To test this hypothesis, there was a comparison of the reproductive performance between recipient sows fed an L-arginine-supplemented diet (L-Arg group) and those fed the control diet (control group). There was a subsequent comparison of the developmental indexes of cloned piglets farrowed in the L-Arg and control groups of surrogate sows. Dietary supplementation of L-arginine during gestation days 14-75 increased the plasma concentrations of arginine and arginine metabolites, including nitric oxide, spermidine, and putrescine in recipient sows of transferred cloned pig embryos. Although maternal arginine addition did not affect the birth weight and placental development indexes of newborn cloned piglets, it significantly increased the ratio of total cloned piglets born to total transferred cloned pig embryos by increasing the pregnancy rate of recipient sows. The results of this study suggest that nutritional management of recipient sows is an effective approach to improve the developmental rate of cloned pig embryos.


Subject(s)
Animal Nutritional Physiological Phenomena/physiology , Arginine/administration & dosage , Cloning, Organism , Pregnancy Rate , Swine/physiology , Animal Feed , Animals , Birth Weight , Cloning, Organism/veterinary , Dietary Supplements , Female , Litter Size , Parturition , Pregnancy
10.
Zhongguo Zhong Yao Za Zhi ; 42(5): 989-997, 2017 Mar.
Article in Chinese | MEDLINE | ID: mdl-28994545

ABSTRACT

The study aims to analyze the varieties and standards of compositae medicinal plants used in Dai medicine. The results showed that there were 78 species (including varieties) compositae plants recorded in literatures, which belongs to 63 medicinal materials varieties. And 47 original plants (60.25%) were recorded in Chinese medicinal material standards. In those standards and literatures of Dai medicine, there are great differences in translated Chinese names, original plants, medicinal parts, and efficacy of medicinal plants. Therefore, the variety systematization and the quality standards of Dai medicine should be strengthened.


Subject(s)
Asteraceae/classification , Drugs, Chinese Herbal/standards , Plants, Medicinal/classification , Medicine, Chinese Traditional , Phytotherapy , Reference Standards
11.
Pharm Biol ; 54(10): 2158-67, 2016 Oct.
Article in English | MEDLINE | ID: mdl-26955854

ABSTRACT

Context Scutellarin (1) has been widely used in China to treat acute cerebral infarction and paralysis induced by cerebrovascular diseases. However, scutellarin (1) has unstable metabolic characteristics. Objective The metabolic profile of 6-O-scutellarein was studied to determine its metabolic stability in vivo. Materials and methods In this study, a method of UFLC/Q-TOF MS was used to study the 6-O-methyl-scutellarein metabolites in rat plasma, urine, bile and faeces after oral administration of 6-O-methyl-scutellarein (3). One hour after oral administration of 6-O-methyl-scutellarein (3) (34 mg/kg), approximately 1 mL blood samples were collected in EP tubes from all groups. Bile, urine and faeces samples were collected from eight SD rats during 0-24 h after oral administration. The mass defect filtering, dynamic background subtraction and information dependent acquisition techniques were also used to identify the 6-O-methyl-scutellarein metabolites. Results The parent compound 6-O-methyl-scutellarein (3) was found in rat urine, plasma, bile and faeces. The glucuronide conjugate of 6-O-methyl-scutellarein (M1, M2), diglucuronide conjugate of 6-O-methyl-scutellarein (M3), sulphate conjugate of 6-O-methyl-scutellarein (M4), glucuronide and sulphate conjugate of 6-O-methyl-scutellarein (M5), methylated conjugate of 6-O-methyl-scutellarein (M6) were detected in rat urine. M1, M2 and M3 were detected in rat bile. M1 was found in rat plasma and M7 was detected in faeces. Discussion and conclusion Because the parent compound 6-O-methyl-scutellarein (3) was found in rat urine, plasma, bile and faeces, we speculate that 6-O-methyl-scutellarein (3) had good metabolic stability in vivo. This warrants further study to develop it as a promising candidate for the treatment of ischemic cerebrovascular disease.


Subject(s)
Chromatography, Liquid/methods , Drugs, Chinese Herbal/metabolism , Flavones/metabolism , Tandem Mass Spectrometry , Administration, Oral , Animals , Bile/metabolism , Drug Stability , Drugs, Chinese Herbal/administration & dosage , Feces/chemistry , Flavones/administration & dosage , Flavones/blood , Flavones/urine , Glucuronides/metabolism , Male , Metabolic Detoxication, Phase II , Rats, Sprague-Dawley , Sulfates/metabolism
12.
Chem Biol Drug Des ; 87(6): 946-57, 2016 06.
Article in English | MEDLINE | ID: mdl-26808289

ABSTRACT

Three series of scutellarein derivatives have been designed and synthesized based on metabolic mechanism of scutellarin (1) in vivo. Their thrombin inhibition activities were tested through the analyzation of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB). The antioxidant activities of these target products were assessed by 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay and the ability to protect PC12 cells against H2 O2 -induced cytotoxicity, and their solubilities were evaluated by ultraviolet (UV) spectrophotometer. The results showed that the two isopropyl groups substituted derivative (18c) demonstrated stronger anticoagulant activity, better water solubility, and good antioxidant activity compared with scutellarein (2), which warrants further development of 18c as a promising agent for ischemic cerebrovascular disease treatment.


Subject(s)
Anticoagulants , Antioxidants , Apigenin , Brain Ischemia , Drug Design , Neuroprotective Agents , Animals , Anticoagulants/chemical synthesis , Anticoagulants/chemistry , Anticoagulants/pharmacokinetics , Anticoagulants/pharmacology , Antioxidants/chemical synthesis , Antioxidants/chemistry , Antioxidants/pharmacokinetics , Antioxidants/pharmacology , Apigenin/chemical synthesis , Apigenin/chemistry , Apigenin/pharmacokinetics , Apigenin/pharmacology , Brain Ischemia/drug therapy , Brain Ischemia/metabolism , Drug Evaluation, Preclinical , Neuroprotective Agents/chemical synthesis , Neuroprotective Agents/chemistry , Neuroprotective Agents/pharmacokinetics , Neuroprotective Agents/pharmacology , PC12 Cells , Rats
13.
PLoS One ; 10(7): e0131569, 2015.
Article in English | MEDLINE | ID: mdl-26147971

ABSTRACT

For more than thirty years, scutellarin (Scu) has been used in China to clinically treat acute cerebral infarction and paralysis. Scutellarein (Scue), the major Scu metabolite in vivo, exhibits heightened neuroprotective effects when compared to Scu. To explore the neuroprotective role of these compounds, we performed ultra-high-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UHPLC-QTOF/MS) coupled with a pattern recognition approach to investigate metabolomic differences in a rat model of ischemia after treatment with each compound. We examined metabolites in urine, hippocampal tissue, and plasma, and we tentatively identified 23 endogenous metabolites whose levels differed significantly between sham-operated and model groups. Upon pathway analysis, we found an additional 11 metabolic pathways in urine, 14 metabolic pathways in the hippocampal tissue, and 3 metabolic pathways in plasma. These endogenous metabolites were mainly involved in sphingolipid metabolism, lysine biosynthesis, and alanine, aspartate, and glutamate metabolism. We found that metabolic changes after ischemic injury returned to near-normal levels after Scue intervention, unlike Scu treatment, further validating the heightened protective effects exerted by Scue compared to Scu. These results demonstrate that Scue is a potential drug for treatment of ischemic insult.


Subject(s)
Apigenin/pharmacology , Brain Ischemia/drug therapy , Brain Ischemia/metabolism , Glucuronates/pharmacology , Metabolome/drug effects , Neuroprotective Agents/pharmacology , Animals , Drugs, Chinese Herbal/pharmacology , Male , Metabolomics/methods , Rats , Rats, Wistar
15.
Br J Pharmacol ; 169(6): 1352-71, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23647015

ABSTRACT

BACKGROUND AND PURPOSE: Thioredoxin-interacting protein (TXNIP), a regulator of cellular oxidative stress, has been associated with activation of NOD-like receptor 3 (NLRP3) inflammasome, inflammation and lipid metabolism, suggesting it has a role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) in diabetes. In this study we investigated whether TXNIP is involved in type 1 diabetes-associated NAFLD and whether antioxidants, quercetin and allopurinol, alleviate NAFLD by targeting TXNIP. EXPERIMENTAL APPROACH: Diabetes was induced in male Sprague-Dawley rats by a single i.p. injection of 55 mg · kg⁻¹ streptozotocin. Quercetin and allopurinol were given p.o. to diabetic rats for 7 weeks. Hepatic function, oxidative stress, inflammation and lipid levels were determined. Rat BRL-3A and human HepG2 cells were exposed to high glucose (30 mM) in the presence and absence of antioxidants, TXNIP siRNA transfection or caspase-1 inhibitor, Ac-YVAD-CMK. KEY RESULTS: Quercetin and allopurinol significantly inhibited the TXNIP overexpression, activation of NLRP3 inflammasome, down-regulation of PPARα and up-regulation of sterol regulatory element binding protein-1c (SREBP-1c), SREBP-2, fatty acid synthase and liver X receptor α, as well as elevation of ROS and IL-1ß in diabetic rat liver. These effects were confirmed in hepatocytes in vitro and it was further shown that TXNIP down-regulation contributed to the suppression of NLRP3 inflammasome activation, inflammation and changes in PPARα and SREBPs. CONCLUSIONS AND IMPLICATIONS: Inhibition of hepatic TXNIP by quercetin and allopurinol contributes to the reduction in liver inflammation and lipid accumulation under hyperglycaemic conditions. The targeting of hepatic TXNIP by quercetin and allopurinol may have therapeutic implications for prevention of type 1 diabetes-associated NAFLD.


Subject(s)
Allopurinol/therapeutic use , Antioxidants/therapeutic use , Carrier Proteins/antagonists & inhibitors , Diabetes Mellitus, Type 1/complications , Fatty Liver/prevention & control , Liver/drug effects , Quercetin/therapeutic use , Allopurinol/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antioxidants/administration & dosage , Antioxidants/metabolism , Antioxidants/pharmacology , Carrier Proteins/genetics , Carrier Proteins/metabolism , Cell Cycle Proteins , Cell Line , Dietary Supplements , Fatty Liver/complications , Fatty Liver/metabolism , Fatty Liver/pathology , Gene Silencing , Humans , Inflammasomes/drug effects , Inflammasomes/metabolism , Lipid Metabolism/drug effects , Liver/immunology , Liver/metabolism , Liver/pathology , Male , Molecular Targeted Therapy , Non-alcoholic Fatty Liver Disease , Oxidative Stress/drug effects , Quercetin/administration & dosage , Quercetin/metabolism , Random Allocation , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/antagonists & inhibitors , Reactive Oxygen Species/metabolism
16.
Zhongguo Zhen Jiu ; 33(11): 993-5, 2013 Nov.
Article in Chinese | MEDLINE | ID: mdl-24494286

ABSTRACT

OBJECTIVE: To observe the difference in the efficacy on traumatic nerve injury among electroacupuncture, warm needling therapy and electroacupuncture plus warm needling therapy and explore the better therapeutic method. METHODS: The electromyography (EMG) and electroneurography (ENG) of 93 cases showed traumatic nerve injury of moderate damage. According to the single blind randomization principle, they were divided into an electroacupuncture (EA) group, a warm needling therapy (WN) group and an EA plus WN group, 31 cases in each one. The main acupoints were selected from Yangming Meridian and Shaoyang Meridian corresponding to the distribution of damaged nerves. EA, WN and EA plus WN were applied separately. The treatment was given once every day, 15 treatments made one session. After 3 sessions of treatment (45 treatments in total), EMG and ENG were re-checked and the results were analyzed statistically. RESULTS: Regarding the total effective rate and effective rate, it was 96. 8% (30/31) in the EA plus WN group, which was better than 74.2% (23/31) in the EA group and 77. 4% (24/31) in the WN group (P<0. 05). Concerning to the improvements of EMG, the result in the EA plus WN group was 96.8% (30/31), which was better than the other two groups [74. 2%(23/31),74. 2%(23/31)] (P<0. 05). In terms of the recovery of nerve conduction and amplitude, the results in EA plus WN group [(50.9+/-4. 6)m/s,(8. 8+/-2. 9),microVx1 000] were better than the other two groups [(43.7+/-3.1)m/s,(4. 2+/-1. 9)microV X 1 000,(43. 8+/-3. 3)m/s,(4. 5+/-2. 2)microV X 1 000] (P<0. 05). CONCLUSION: EA combined with WN is a better therapy of acupuncture and moxibustion in the treatment of traumatic nerve injury.


Subject(s)
Acupuncture Therapy , Peripheral Nerve Injuries/therapy , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Treatment Outcome , Young Adult
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