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1.
Article in Chinese | WPRIM | ID: wpr-905890

ABSTRACT

Objective:To observe the effect of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma, and Chuanxiong Rhizoma extract (GNC) on mitochondrial oxidative stress in hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)-induced aging of human umbilical vein endothelial cells (HUVECs), and explore the therapeutic mechanism of GNC on aging HUVECs. Method:The HUVECs were classified into the control group (control), H<sub>2</sub>O<sub>2</sub> model group (H<sub>2</sub>O<sub>2</sub>), H<sub>2</sub>O<sub>2</sub> + DMSO group (DMSO, 1 mL·L<sup>-1</sup>), resveratrol group (Resv, 8 μmol·L<sup>-1</sup>), and low- (200 mg·L<sup>-1</sup>), medium- (300 mg·L<sup>-1</sup>), and high-dose (400 mg·L<sup>-1</sup>) GNC (GNC-L, GNC-M, and GNC-H) groups. Except control group and H<sub>2</sub>O<sub>2</sub> group, the other groups were intervened with corresponding agents. Subsequently, 300 μmol·L<sup>-1</sup> H<sub>2</sub>O<sub>2</sub> was given to other groups except the control group for 4 h to induce aging, and then the cells were cultured in normal media for 24 h. The aging degree, cell cycle, and mitochondrial reactive oxygen species (mtROS) level were determined by SA-<italic>β</italic>-galactosidase (SA-<italic>β</italic>-Gal) staining, flow cytometry, and MitoSox red fluorescence staining, respectively. JC-10 was used as a fluorescent probe to detect the changes in mitochondrial membrane potential, and Western blot was performed to detect the expression of manganese superoxide dismutase (MnSOD) and p-p66 proteins. Result:The SA-<italic>β</italic>-gal staining results showed that H<sub>2</sub>O<sub>2</sub> group had increased blue-stained cells compared with other groups (<italic>P</italic><0.01). Compared with those in the control group, the ratio of G<sub>0</sub>/G<sub>1</sub> phase cells significantly increased (<italic>P</italic><0.05) and that of G<sub>2</sub>/M phase cells decreased (<italic>P</italic><0.05) in the H<sub>2</sub>O<sub>2</sub> group. Compared with those in the H<sub>2</sub>O<sub>2</sub> group, the proportion of G<sub>0</sub>/G<sub>1</sub> cells decreased (<italic>P</italic><0.05) while that of G<sub>2</sub>/M cells increased (<italic>P</italic><0.05) in GNC-H groups and Resv group. The fluorescence staining for determining mitochondrial ROS level showed that the H<sub>2</sub>O<sub>2</sub> group had weakened fluorescence intensity than the control, GNC-H, and GNC-M groups (<italic>P</italic><0.05). The mitochondrial membrane potential fluorescence intensity of the H<sub>2</sub>O<sub>2</sub> group was weaker than that of the control, GNC-H, GNC-M, and GNC-L groups (<italic>P</italic><0.01), as well as the Resv group (<italic>P</italic><0.05). Western blot showed that the protein level of MnSOD was significantly lower in the H<sub>2</sub>O<sub>2</sub> group than in the control, GNS-H, and GNS-M groups (<italic>P</italic><0.05), whereas the protein level of p-p66 showed an opposite trend (<italic>P</italic><0.01), indicating that the medication can alleviate the intracellular mitochondrial oxidative stress. Conclusion:GNC can delay the H<sub>2</sub>O<sub>2</sub>-induced aging of vascular endothelial cells. The GNC intervention significantly regulated the mitochondrial ROS, mitochondrial membrane potential, and related proteins MnSOD and p-p66 to alleviate oxidative stress. Chinese medicinal materials may delay the aging of vascular endothelial cells by inhibiting mitochondrial oxidative stress.

2.
Article in Chinese | WPRIM | ID: wpr-909612

ABSTRACT

Chuanxiong Rhizoma is the dry rhizome of Ligusticum chuanxiong in the umbelliferae family. Chuanxiong Rhizoma pungent, warm, go to liver, gallbladder and pericardium. Effective in promoting blood circulation, promoting Qi, dispelling wind and relieving pain, it could treat chest pain, tingling pain in chest and flank, lump, irregular menstruation, amenorrhea, symptomatic abdominal pain, headache and rheumatic pain. Neurovascular headache is a primary disease caused by dysregulation of intracranial vascular movement and nerve function. It has the characteristics of long course, intermittent recurrent attacks, lingering and difficult to heal. Attacks are often accompanied by many plant nervous sys?tem symptoms, such as rapid breathing, accelerated heart rate, vomiting, and gastrointestinal dysfunction. Vascular nerve headache is a common clinical disease, frequently bidity. Studies have shown that Chuanxiong Rhizoma has good pharmacological effects in the treatment of vascular neuropathic headache.① The action of Qi and blood circula?tion: vascular and neurovascular headache is caused by the evil of external wind and cold and damp heat, which leads to the disconnection of the veins, the disorder of Qi and blood, the obstruction of Qi and blood channels, the loss of brain collateral, and finally causes migraine. Modern Chinese medicine points out that"wind, blood stasis, deficiency, phlegm"are the key factors of the disease. Chuanxiong Rhizoma is the medicine of Qi in the blood. It is pungent and warm. It is good at activating blood and promoting Qi, dispelling wind, relieving pain and dispelling cold, so as to achieve the effect of treating vascular headaches. ② Improve brain circulation: angioneurotic headache is caused by dysfunction of the central nervous system related to the regulation of vascular movement, which causes vasospasm or extreme vasodi?lation, and the decrease of intracranial blood flow causes cerebral ischemia and hypoxia. Sodium ferulate is a chemical component in Chuanxiong Rhizoma. It has a relatively good inhibitory effect on platelet aggregation and the release of 5-HT from platelets. It can ensure the normal contraction of intracranial and extracranial blood vessels, improve the patient's brain circulation and nerve function, so as to achieve the effect of treating angioneurotic headaches.③Sedative and analgesic effect:the volatile oil and water decoction of Chuanxiong Rhizoma have sedative and analgesic effects, and the water decoction can counteract the excitatory effect of caffeine. Studies have shown that the ATP activa?tion current of rat dorsal root ganglion neurons can be inhibited by ligustrazine in a non-competitive way, which also indi?cates that Chuanxiong Rhizoma has a good analgesic effect. In this study, the effects of Chuanxiong Rhizoma on angoneeurotic headache were reviewed, and the pharmacological effects of Chuanxiong Rhizoma were further elucidated, providing basis for clinical application and new drug development of Chuanxiong Rhizoma in the treatment of angoneeu?rotic headache.

3.
Article in Chinese | WPRIM | ID: wpr-907701

ABSTRACT

Objective:To optimize the preparation technic of Chuanxiong Rhizoma with vacuum steam method, and to investigate the anti-inflammatory and analgesic activity of Chuanxiong Rhizoma decoction pieces with Central Composite Design-Response Surface Method. Methods:Taking the content of ferulic acid as the evaluation index and the moistening temperature, moistening time and vacuum time as the observation indexes, the moistening technic of Chuanxiong Rhizoma was optimized by Response Surface Method, and selected the optimized plan. The anti-inflammatory and analgesic activities of Chuanxiong Rhizoma were investigated by auricle swelling induced by xylene and writhing induced by glacial acetic acid. Results:The optimum vacuum moistening technic was that the softening temperature was 80 ℃, the softening time was 50 min and the vacuum time was 45 min. The content of ferulic acid in Chuanxiong Rhizoma produced by this technic is highand could decreased the times of wrinkle reaction induced by acetic acid in mice, prolonged the latent period, and obviously or partially inhibitied the ear swelling degree induced byxylene in rats. Conclusions:The Response Surface Method technic of Chuanxiong Rhizoma is easy to operate with high accuracy. The vacuum steam treatment was more obvious than traditional technology group. It provides reference for the subsequent production of Chuanxiong Rhizoma decoction pieces and have the certain value for its promotion and application.

4.
Article in Chinese | WPRIM | ID: wpr-906528

ABSTRACT

Objective:To explore the reasonable combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma in treatment of cerebral malaria and investigate its mechanism based on network pharmacology. Method:The traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and SymMap were used to obtain all the chemical components of Artemisiae Annuae Herba and Chuanxiong Rhizoma and the action targets were screened to construct a component target protein-protein interaction (PPI) network. Target genes related to cerebral malaria were collected with use of GeneCards and DisGeNET databases. Common targets were screened by overlapping drug targets and disease targets, and protein-protein interaction network analysis was performed to get key targets. Gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out to get main signaling pathways. Furthermore, the classical experimental cerebral malaria mouse model was used to detect survival curve, protozoanemia level, survival rate, experimental cerebral malaria (ECM) coma and behavior scores. RayBio<sup>®</sup> cytokine antibody array was used to detect the expression level of cytokines in tissues and experiment was conducted for verification. Result:After combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma, 23 active ingredients, 179 drug targets, and a total of 100 common targets of the drug and disease were obtained. GO functional analysis identified 59 items (<italic>P</italic><0.05), involving cytokine activity, growth factor activity, immune response, etc. KEGG pathway analysis revealed 51 related signaling pathways. The experimental results showed that the combined use of Artemisiae Annuae Herba and Chuanxiong Rhizoma could significantly improve the clinical signs of ECM mice, such as survival state, coma and behavioral scores. In the detection of expression levels of related cytokines in mice, the expression levels of <italic>γ-</italic>interferon (IFN-<italic>γ)</italic>, interleukin-10 (IL-10), IL-4, and IL-1<italic>β</italic> in the compatible drug combination drug were significantly higher than those in the model group (<italic>P</italic><0.05), which was consistent with the overlapping core targets predicted by network pharmacology. Conclusion:Based on the network pharmacology analysis and<italic> in vivo</italic> experiment verification, this study confirmed the synergistic effect of the combination of Artemisiae Annuae Herba and Chuanxiong Rhizoma in the treatment of cerebral malaria, providing clear direction for further mechanism research, and a new possibility for the clinical intervention of cerebral malaria.

5.
Article in Chinese | WPRIM | ID: wpr-906174

ABSTRACT

Objective:To investigate the effect of Ginseng Radix et Rhizoma-Notoginseng Radix et Rhizoma-Chuanxiong Rhizoma extract on endothelial microparticles (EMPs)-induced vascular endothelial cell senescence, and explore the possible mechanism. Method:Human umbilical vein endothelial cells (HUVECs) were used as the research objects, and the aged model was established with 10-12 passages of replicative senescence cells. The experimental cells were divided into young group (2-4 passage cells), aged group (10-12 passage cells), only EMPs intervention group (extract EMPs produced by aged cells to intervene young cells) and low dose, middle dose and high dose drug intervention groups (200, 300, 400 mg·L<sup>-1</sup>). Senescence related <italic>β</italic>-galactosidase (SA-<italic>β</italic>-gal) staining and cell cycle propidium iodide (PI) staining were used to determine cell senescence. Cell counting kit-8 (CCK-8) assay was used to screen the drug concentration. EMPs were extracted by two-step centrifugation, EMPs labeled with phycoerythrin (PE) anti-human CD31 antibody or fluorescein isothiocyanate (FITC) annexin V were detected by flow cytometry, intracellular reactive oxygen species (ROS) were detected by 2',7'- dichlorofluorescein diacetate (DCFDA) staining. Result:After treatment with the drug, SA-<italic>β</italic>-gal activity of the aged cells significantly decreased (<italic>P</italic><0.01), the S phase arrest was restored (<italic>P</italic><0.01), and the number of CD31<sup>+</sup> EMPs and annexin V<sup>+</sup> EMPs secreted by aged cells decreased (<italic>P</italic><0.05). Compared with the young group, only EMPs intervention group could induce increased SA-<italic>β</italic>-gal activity and S phase arrest in young cells (<italic>P</italic><0.05,<italic>P</italic><0.01). However, after intervention of EMPs and the drug, EMPs-mediated increase of SA-<italic>β</italic>-gal activity was significantly inhibited and S phase arrest was restored (<italic>P</italic><0.05). The increase of intracellular ROS induced by EMPs was also significantly inhibited by the drug (<italic>P</italic><0.05,<italic>P</italic><0.01). Conclusion:Ginseng Radix et Rhizoma-Notoginseng Radix et Rhizoma-Chuanxiong Rhizoma extract can delay the senescence of vascular endothelial cells by influencing EMPs, and the mechanism may be related to the inhibition of increased intracellular ROS induced by EMPs.

6.
Article in Chinese | WPRIM | ID: wpr-906145

ABSTRACT

Objective:To investigate the protective effect and molecular mechanism of Angelicae Sinensis Radix-Chuanxiong Rhizoma medicated serum (ASRCRS) against oxidative damage of PC12 cells induced by H<sub>2</sub>O<sub>2</sub>. Method:Oxidative damage of PC12 cells was induced by H<sub>2</sub>O<sub>2</sub><italic> in vitro</italic>, and intervention was performed in the low-, medium-, and high-dose ASRCRS groups with a final volume fraction of 15%. The cell viability was determined by methyl thiazolyl tetrazolium (MTT) assay. Cell morphology was observed by an inverted fluorescence microscope. The content of lactate dehydrogenase (LDH) and malondialdehyde (MDA), the activity of superoxide dismutase (SOD), and the distribution of reactive oxygen species (ROS) in the cell supernatant were detected by the kits. Cell apoptosis was detected by Annexin V-FITC/PI double staining. The protein expression levels of nuclear factor E<sub>2</sub>-related factor 2 (Nrf2), Kelch-like epichlorohydrin associated protein-1 (Keap1), heme oxygenase-1 (HO-1), and SOD1 were detected by Western blot. Result:Oxidative damage was induced by 300 μmol·L<sup>-1</sup> H<sub>2</sub>O<sub>2</sub> for 24 hours. Compared with the normal group, the model group showed abnormal cell morphology, reduced cell viability (<italic>P</italic><0.01), increased LDH and MDA (<italic>P</italic><0.01), blunted SOD activity, elevated intracellular distribution of ROS, down-regulated protein expression of Nrf2, HO-1, and SOD1 (<italic>P</italic><0.05, <italic>P</italic><0.05), and up-regulated protein expression of Keap1 (<italic>P</italic><0.01). Compared with the model group, ASRCRS groups displayed improved cell morphology, increased cell viability, inhibited cell apoptosis, potentiated SOD activity (<italic>P</italic><0.01), suppressed release of LDH (<italic>P</italic><0.01) and generation of ROS, decreased content of MDA (<italic>P</italic><0.01), up-regulated protein expression of Nrf2, HO-1 and SOD1 (<italic>P</italic><0.05, <italic>P</italic><0.01), and down-regulated protein expression of Keap1 (<italic>P</italic><0.01). Conclusion:ASRCRS could protect PC12 cells from oxidative damage induced by H<sub>2</sub>O<sub>2</sub> by up-regulating the expression of Nrf2 to activate the Nrf2/antioxidant response element (ARE) signaling pathway, enhancing the ability to resist oxidative damage, and inhibiting cell apoptosis.

7.
Article in Chinese | WPRIM | ID: wpr-921779

ABSTRACT

This study aims to explore the effect of extract of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma, and Chuanxiong Rhizoma(hereinafter referred to as GNS) on the SIRT1-autophagy pathway of endothelial cell senescence induced by hydrogen peroxide(H_2O_2). To be specific, vascular endothelial cells were classified into the blank control group(control), model group(model), model + DMSO group(DMSO), resveratrol group(RESV), and GNS low-dose(GNS-L), medium-dose(GNS-M), and high-dose(GNS-H) groups. They were treated with H_2O_2 for senescence induction except the control. After intervention of cells in each group with corresponding drugs for 24 h, cell growth status was observed under an inverted microscope, and the formation of autophagosome under the transmission electron microscope. In addition, the changes of microtubule-associated protein 1 light chain 3β(LC3 B) were detected by immunofluorescence staining. The autophagy flux was tracked with the autophagy double-labeled adenovirus(mRFP-GFP-LC3) fusion protein. Dansylcadaverine(MDC) staining was employed to determine the autophagic vesicles, and Western blot the expression of sirtuin 1(SIRT1), ubiquitin-binding protein p62, and LC3Ⅱ. After H_2O_2 induction, cells demonstrated slow growth, decreased adhesion ability, raised number of SA-β-gal-stained blue ones, a certain number of autophagosomes with bilayer membrane and secondary lysosomes in the cytoplasm, and slight rise of autophagy flux level. Compared with the model group, GNS groups showed improved morphology, moderate adhesion ability, complete and smooth membrane, decreased SA-β-gal-stained blue cells, many autophagosomes, autophagic vesicles, and secondary lysosomes in the cytoplasm, increased autophagolysosomes, autophagy flux level, and fluorescence intensity of LC3 B and MDC, up-regulated expression of SIRT1 and LC3Ⅱ, and down-regulated expression of p62, suggesting the improvement of autophagy level. GNS can delay the senescence of vascular endothelial cells. After the intervention, the autophagy flux and related proteins SIRT1, LC3Ⅱand p62 changed significantly, and the autophagy level increased significantly. However, EX527 weakened the effect of Chinese medicine in delaying vascular senescence. GNS may delay the senescence of vascular endothelial cells through the SIRT1 autophagy pathway.


Subject(s)
Autophagy , Cells, Cultured , Cellular Senescence , Drugs, Chinese Herbal/pharmacology , Endothelial Cells/drug effects , Hydrogen Peroxide , Panax/chemistry , Sirtuin 1/genetics
8.
Article in Chinese | WPRIM | ID: wpr-888140

ABSTRACT

This study was mainly based on the compatibility of Puerariae Lobatae Radix and Chuanxiong Rhizoma to prepare submicron emulsion and evaluated its physical and pharmaceutical properties. Firstly, pseudo-ternary phase diagrams were drawn by dripping method which took Chuanxiong oil as the oil phase and the area of microemulsion region as the index. On this basis, suitable emulsifier and co-emulsifier were screened for the preparation of Chuanxiong oil submicron emulsion. Then, the formula realizing the largest oil loading was selected. Finally, puerarin substituted part of emulsifier and co-emulsifier to lower their content, so as to form puerarin-Chuanxiong oil submicron emulsion featuring the combination of medicine and adjuvant. Its particle size, zeta potential, centrifugal stability and storage stability were determined, and the in vitro drug release behavior was investigated by dialysis bag method, based on which the quality of the as-prepared submicron emulsion was evaluated comprehensively. The proposed method was proved feasible for the preparation of Chuanxiong oil submicron emulsion, which adopted polyoxyethylene castor oil(EL-40) as the emulsifier and was free from co-emulsifier. The formula of the maximum oil loading was found as Chuanxiong oil∶EL-40∶water 3∶7∶90. Further, puera-rin successfully replaced up to 10% of the emulsifier in submicron emulsion. Eventually, the optimal drug-loading formula was determined as puerarin∶Chuanxiong oil∶EL-40∶water 7∶30∶63∶900. The quality evaluation results of the as-prepared submicron emulsion demonstrated that the average emulsion droplet size was 333.9 nm, the PDI 0.26, and the zeta potential-10.12 mV. The submicron emulsion had a good centrifugal stability and did not present any instable phenomena such as delamination and precipitation during its standing still for 50 days. The evaluation of in vitro drug release behavior indicated that the submicron emulsion was capable of releasing the drug completely. The puerarin-chuanxiong oil submicron emulsion prepared in this study possessed a stable quality and to some extent increased the solubility of puerarin along with a sustained-release effect. This study provided ideas for the clinical application of puerarin.


Subject(s)
Emulsions , Isoflavones , Particle Size , Solubility
9.
Article in Chinese | WPRIM | ID: wpr-888092

ABSTRACT

Fourteen classical prescriptions in the Catalog of 100 Ancient Classical Prescriptions(First Batch) promulgated in 2018 contain Chuanxiong Rhizoma, which reveals the high medicinal value and wide application of Chuanxiong Rhizoma. This paper systematically reviews the ancient herbal books and modern literature to explore the name, origin, genuine producing area, medicinal part, harvesting, and processing of Chuanxiong Rhizoma, thus facilitating the development of classical prescriptions containing Chuan-xiong Rhizoma. It is confirmed that Chuanxiong Rhizoma, formerly known as "Xiongqiong" in Chinese, was first called "Chuanxiong" in late Tang Dynasty, which has been gradually accepted as its official name due to the rise of the status of Chuanxiong Rhizoma produced in Sichuan. The main original plant of Chuanxiong Rhizoma in past dynasties has always been deemed to be Ligusticum chuan-xiong(Umbellifera), whose rhizome serves as the medicinal part. In general, it is best harvested in summer but the harvesting time can vary with different growth environments. Since the Song Dynasty, Sichuan province has been recognized as the genuine producing area of Chuanxiong Rhizoma in light of the high yield and good quality. It is suggested that Chuanxiong Rhizoma from Sichuan be used preferentially in the development of classical prescriptions. There are multiple processing methods of Chuanxiong Rhizoma recorded in ancient medical classics, and the raw(after purifying and slicing) or wine-processed or stir-fried Chuanxiong Rhizoma is still in use today. In the development of classical prescriptions containing Chuanxiong Rhizoma, Chuanxiong Rhizoma is advised to be processed in accordance with current processing standards if the specific processing method is described in the medical classics. If not, the raw Chuanxiong Rhizoma is preferred and then processed following the processing standards of Chuanxiong Rhizoma decoction pieces in Chinese Pharmacopoeia.


Subject(s)
China , Drugs, Chinese Herbal , Medicine, Chinese Traditional , Prescriptions , Rhizome
10.
Article in Chinese | WPRIM | ID: wpr-888078

ABSTRACT

Excitatory toxicity(ET) is an important factor of neuropathic pain(NPP) induced by central sensitization(CS), and the association of pannexin-1(Panx1)-Src-N-methyl-D-aspartate receptor subunit 2 B(NMDAR-2 B) is an important new pathway for ET to initiate CS. The present study confirmed whether the central analgesic effect of Chuanxiong Rhizoma extract(CRE) was achieved through the synchronous regulation of the brain and spinal pathways of Panx1-Src-NMDAR-2 B. In this study, dynamic and simulta-neo-us microdialysis of the brain and spinal cord in vivo combined with behavioristics, high performance liquid chromatography(HPLC)-fluorescence detection, microdialysis analysis(ISCUS~(flex)), ultrasensitive multifactorial electrochemiluminescence immunoassay, ELISA, and Western blot was employed to investigate the protein expression of NMDAR-2 B, Src, and Panx1, extracellular excitatory amino acids, cytokines, energy metabolites, and substance P in spinal dorsal horn(SDH) and anterior cingulate cortex(ACC) after CRE intervention with the rat model of spared sciatic nerve injury(SNI) as the experimental tool. Compared with the sham group, the SNI group exhibited diminished mechanical withdrawal threshold(MWT)(P<0.01), increased cold spray scores(P<0.01), glutamate(Glu), D-serine(D-Ser), and glycine(Gly) in extracellular fluids of ACC, and Glu, D-Ser, interleukin-1β(IL-1β), and lactic acid(Lac) in extracellular fluids of SDH(P<0.05), dwindled tumor necrosis factor(TNF-α)(P<0.05), and elevated protein levels of NMDAR-2 B, Src, and Panx1 in ACC(P<0.05). Compared with the SNI model rats, high-and medium-dose CRE(CRE-H/M) could potentiate the analgesic activity as revealed by the MWT test(P<0.05) and CRE-M enabled the decrease in cold spray scores(P<0.05). CRE-H/M could inhibit the levels of Glu, D-Ser and Gly in the extracellular fluids of ACC(P<0.05), and the levels of Glu in the extracellular fluids of SDH(P<0.05) in SNI rats. CRE-M significantly increased the levels of glucose(Gluc), Lac, interferon-gamma(IFN-γ), keratinocyte chemoattractant/human growth-regulated oncogenes(KC/GRO), and IL-4 in extracellular fluids of SDH in SNI rats(P<0.05). CRE-H/M/L could also inhibit the levels of NMDAR-2 B, Src and Panx1 in ACC and SDH in SNI rats(P<0.05). The central analgesic effect of CRE is presumedly related to the inhibited release of excitatory amino acid transmitters(Glu, D-Ser and Gly) in ACC and SDH of SNI rats, decreased protein expression of NMDAR-2 B, Src and Panx1 in the two regions, and the regulation of the Panx1-Src-NMDAR-2 B pathway in the spinal cord and brain. The above findings partially clarified the scientific basis of clinical analgesic effect of Chuanxiong Rhizoma.


Subject(s)
Animals , Central Nervous System Sensitization , Neuralgia/drug therapy , Rats , Rats, Sprague-Dawley , Receptors, N-Methyl-D-Aspartate/metabolism , Signal Transduction , Spinal Cord/metabolism
11.
Article in Chinese | WPRIM | ID: wpr-888038

ABSTRACT

Cerebral ischemia is one of the most common diseases in China, and the drug pair of Chuanxiong Rhizoma and Paeoniae Radix Rubra can intervene in cerebral ischemia to reduce the inflammatory response of cerebral ischemia and apoptosis. To reveal the intervention mechanism of Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair on cerebral ischemia systematically, computer network pharmacology technology was used in this paper to predict the target and signaling pathway of the drug pair on the intervention of cerebral ischemia, and then the molecular docking technology was used to further analyze the mechanism of the intervention. The target results were then verified by the rat cerebral ischemia model. The target network results showed that the active compounds of Chuanxiong Rhizoma-Paeoniae Radix Rubra for cerebral ischemic disease contained 30 compounds, 38 targets and 9 pathways. The main compounds included phenolic acids in Chuanxiong Rhizoma and monoterpene glycosides in Paeoniae Radix Rubra. The key targets involved mitogen-activated protein kinase 1(MAPK1), steroid receptor coactivator(SRC), epidermal growth factor receptor(EGFR), mitogen-activated protein kinase 14(MAPK14), caspase-3(CASP3), caspase-7(CASP7), estrogen receptor 1(ESR1), and mitogen-activated protein kinase 8(MAPK8), etc. The target gene functions were biased towards protein kinase activity, protein autophosphorylation, peptidyl-serine phosphorylation and protein serine/threonine kinase activity, etc. The important KEGG pathways involved Ras signaling pathway, ErbB signaling pathway and VEGF signaling pathway. Molecular docking results showed that catechin, oxypaeoniflorin, albiflorin, paeoniflorin and benzoylpaeoniflorin had strong binding ability with MAPK1, SRC, EGFR, MAPK14 and CASP7. MCAO rat experimental results showed that Chuanxiong Rhizoma-Paeoniae Radix Rubra significantly improved the cerebral ischemia injury and interstitial edema, and significantly reduced the activation of caspase-7 and the phosphorylation of ERK1/2. The Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair alleviated cerebral ischemia injury through a network model of multi-phenotype intervention by promoting cell proliferation and differentiation, reducing inflammatory factor expression, protecting nerve cells from death and figh-ting against neuronal cell apoptosis, with its action signaling pathway most related to Ras signaling pathway, ErbB signaling pathway and VEGF signaling pathway. This study provides the basis for clinical intervention of Chuanxiong Rhizoma-Paeoniae Radix Rubra drug pair on cerebral ischemia, and also provides ideas for the modernization of drug pairs.


Subject(s)
Animals , Brain Ischemia/genetics , Cerebral Infarction , Drugs, Chinese Herbal , Molecular Docking Simulation , Paeonia , Rats , Rhizome
12.
Acta Pharmaceutica Sinica ; (12): 1804-1810, 2021.
Article in Chinese | WPRIM | ID: wpr-887025

ABSTRACT

To study the changes in the pharmacokinetic behavior of four coumarins (bergapten, oxypeucedanin, imperatorin and isoimperatorin) in rats before and after combinating Angelicae Dahuricae Radix with Chuanxiong Rhizoma. The plasma concentrations of the drugs were determined by ultra performance liquid chromatography-fluorescence detection (UPLC-FLD) for dose response and time dependent curves. The pharmacokinetic parameters were calculated by DAS 3.2.8, and SPSS 20.0 was used to analyze the differences of main pharmacokinetic parameters between the two groups. The result showed: comparing with Angelicae Dahuricae Radix group, the area under drug time curve (AUC0-24 h) of bergapten, oxypeucedanin and imperatorin increased by 177.2%, 97.14% and 54.43% respectively, AUC0-∞ increased by 282.3%, 104.2%, and 75.40% respectively, and clearance rate (CLZ/F) decreased by 68.26%, 51.08% and 43.98% respectively; the peak drug concentration (Cmax) of four coumarins was significantly increased; the distribution volume (VZ/F) of bergapten was significantly decreased. These data indicated that Chuanxiong Rhizoma can promote the absorption of coumarins in Angelicae Dahuricae Radix, slow down the elimination of coumarins, and increase their bioavailability in vivo. The animal experiment scheme in this study has been approved by the Experimental Animal Ethics Committee of Beijing University of Chinese Medicine (approval number: BUCM-4-2020083105-3072).

13.
Article in Chinese | WPRIM | ID: wpr-879129

ABSTRACT

Nanocrystals self-stabilized Pickering emulsion(NSSPE) is a new kind of emulsion where only nanocrystals of poorly soluble drugs are used as stabilizers. Our previous study showed that NSSPE with Ligusticum chuanxiong oil as the main oil phase can significantly promote oral absorption of puerarin. The present study aimed to explore its absorption mechanism in oral administration. The in vitro dissolution test was carried out to study the effect of NSSPE on release of puerarin. The effects and mechanism of NSSPE on uptake and transport of puerarin across Caco-2 cell were investigated. The results showed that the drug release rate of NSSPE was similar to that of nanocrystals, with their cumulative dissolution of puerarin not affected by pH of releasing mediums, both significantly higher than that of crude material. The uptake of puerarin in NSSPE was concentration-dependent and significantly higher than that of solution or surfactant stabilized emulsion. Genistein and indomethacin, inhibitors of lipid rafts/caveolin, could significantly reduce the uptake of puerarin in NSSPE. Compared with solution, NSSPE and surfactants stabilized emulsion obviously increased transport rate K_a and apparent permeability coefficient P_(app) of puerarin in AP → BL direction, but there was no significant difference in BL → AP direction. It could be inferred that there were both passive and active transport mechanisms, as well as lipid raft/caveolin mediated endocytosis for absorption of NSSPE. The promoted oral absorption of puerarin in NSSPE was mainly related to the existing nanocrystal form which could promote dissolution, puerarin as well as Ligusticum chuanxiong oil which could promote drug transmembrane transport and inhibit drug efflux. It is the unique structure and composition of the compound NSSPE that promoted the oral absorption of puerarin.


Subject(s)
Caco-2 Cells , Drugs, Chinese Herbal , Emulsions , Humans , Isoflavones , Nanoparticles
14.
Article in Chinese | WPRIM | ID: wpr-878983

ABSTRACT

To determine the content of extracts in different processed products of Chuanxiong Rhizoma and the content of chlorogenic acid, ferulic acid, senkyunolide Ⅰ, coniferyl ferulate, senkyunolide A and ligustilide, in order to study the effect of different proces-sing methods on the alcohol-soluble extract and the content of six ingredients of Chuanxiong Rhizoma. The extract was determined according to the alcohol-soluble extract determination method set forth in item 2201 of the 2020 Chinese Pharmacopoeia Ⅳ; the content was determined by using Agilent TC-C_(18) column(4.6 mm×250 mm, 5 μm) for gradient elution, with acetonitrile(A)-0.5% acetic acid solution(B) as the mobile phase; the column temperature was at 30 ℃; the flow rate was 1.0 mL·min~(-1), the detection wavelength was 285 nm; and the injection volume was 10 μL. Compared with Chuanxiong Rhizoma, the extracts of processed products all increased significantly; by the degree of increase, the order was stir-frying Chuanxiong Rhizoma with honey>stir-frying Chuanxiong Rhizoma with rice wine>stir-frying Chuanxiong Rhizoma with Angelicae Dahuricae Radix decoction>stir-frying Chuanxiong Rhizoma with tea decoction; the HPLC method was convenient and reliable, with a high linear relationship of chlorogenic acid, ferulic acid, senkyunolide Ⅰ, coniferyl ferulate, senkyunolide A and ligustilide, and a high precision, repeatability, stability and the sample recovery rate in Chuanxiong Rhizoma and its processed products. There were 15 chromatographic peaks before and after processing, eight of them were identified. Compared with the pre-processing, two chromatographic peaks were added after the stir-frying with honey and rice wine; and four chromatographic peaks were added after the processing with Angelicae Dahuricae Radix decoction; the contents of chlorogenic acid, ferulic acid, senkyunolide Ⅰ, coniferyl ferulate, senkyunolide A, and ligustilide in stir-frying Chuanxiong Rhizoma with rice wine were all reduced. Except for the content of ferulic acid that increased, the content of the other five components decreased in stir-frying Chuanxiong Rhizoma with honey, stir-frying Chuanxiong Rhizoma with tea decoction, and stir-frying Chuanxiong Rhizoma with Angelicae Dahuricae Radix decoction. Rice wine, honey, decoction of tea and Angelicae Dahuricae Radix could all promote the dissolution of chemical components in Chuanxiong Rhizoma, and increase the content of extract; the changes in the contents of six components of different processed products could provide a certain basis for studying chemical composition and efficacy of different processed products of Chuanxiong Rhizoma.


Subject(s)
Chlorogenic Acid , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/analysis , Rhizome/chemistry , Wine
15.
Article in English | WPRIM | ID: wpr-881068

ABSTRACT

Angelicae Sinensis Radix (Danggui) and Ligusticum Chuanxiong Rhizoma (Chuan Xiong) herb-pair (DC) have been frequently used in Traditional Chinese medicine (TCM) prescriptions for hundreds of years to prevent vascular diseases and alleviate pain. However, the mechanism of DC herb-pair in the prevention of liver fibrosis development was still unclear. In the present study, the effects and mechanisms of DC herb-pair on liver fibrosis were examined using network pharmacology and mouse fibrotic model. Based on the network pharmacological analysis of 13 bioactive ingredients found in DC, a total of 46 targets and 71 pathways related to anti-fibrosis effects were obtained, which was associated with mitogen-activated protein kinase (MAPK) signal pathway, hepatic inflammation and fibrotic response. Furthermore, this hypothesis was verified using carbon tetrachloride (CCl

16.
Article in Chinese | WPRIM | ID: wpr-873278

ABSTRACT

Objective::To explore the protective mechanism of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma (GNC) extracts on cardiac aging in diabetic mice by observing the activation of AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, changes of cardiac pathomorphological and related senescent proteins. Method::C57BL/6 male mice, SPF level, were randomly divided into normal control group and high-glucose group. The mice in high-glucose group were intraperitoneally injected with streptozotocin (STZ) and fed with high-fat diet. After successful modeling, they were randomly divided into model group, low-dose GNC group (0.819 g·kg-1), high-dose GNC group (1.638 g·kg-1) and metformin group (150 mg·kg-1). The drug was administered by gavage once a day for a continuous period of 9 weeks. 4-week-old male C57BL/6 mice were normally fed for 1 week as a youth group. General conditions of mice were observed. Hematoxylin-eosin (HE) staining combined with transmission electron microscope (TEM) was used to observe the cardiac pathomorphology in mice. Von Kossa staining was used to determine the degree of calcium salt deposition in cardiac micro vessels. Western blot was used to detect the activation of signaling pathways in myocardial tissue of mice, as well as the expression levels of matrix metalloproteinases-2 (MMP-2), tumor suppressor p53 (p53), and phospho-tumor suppressor p53 (p-p53). Result::As compared with the normal group, the blood glucose in the model group increased (P<0.01), as compared with the model group, the blood glucose in each administration group decreased significantly (P<0.05, P<0.01). The results of three pathological morphology experiments (HE, TEM, and Von Kossa) showed that as compared with the normal control group, the mice in model group showed cardiomyocytes hypertrophy, disordered arrangement of myocardial fibers, focal dissolving and necrosis, mitochondria swelling, degeneration, crest fracture, vacuolar alteration, disordered microvascular structure of the heart, uneven staining, and a large amount of calcium deposition in tunica media and intima. As compared with the model group, the pathomorphological changes of mice in each administration group were improved in varying degrees. Compared with the normal group, the expression levels of MMP-2, p53 and p-p53 protein in the model group were significantly increased (P<0.05, P<0.01), the protein ratios of p-liver kinase B2(LKB1)/LKB1, p-AMPK/AMPK were significantly decreased (P<0.05, P<0.01), and the average gray level of p-mTOR/mTOR and p-p70S6 kinase(p70S6k)/p70S6k protein was significantly increased (P<0.05, P<0.01), while the protein ratios of p-mTOR/mTOR, p-p70S6k/p70S6k were increased (P<0.01). As compared with the model group, the expression levels of MMP-2, p53 and p-p53 protein in each administration group were significantly decreased (P<0.05, P<0.01), the protein ratios of p-LKB1/ LKB1, p-AMPK/AMPK were significantly increased (P<0.05, P<0.01), while the protein ratios of p-mTOR/mTOR and p-p70S6k/p70S6k were decreased (P<0.05, P<0.01). Conclusion::STZ combined with high-fat diet can induce cardiac aging in mice, and GNC can improve cardiac aging in diabetic mice, which may be related to the inhibition of AMPK/mTOR pathway related protein expression.

17.
Article in Chinese | WPRIM | ID: wpr-873277

ABSTRACT

Objective::To investigate the protective effect of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma (GNC) extracts on myocardial fibrosis in diabetic mice by observing the degree of myocardial fibrosis and collagen types I (Collagen Ⅰ), collagen types Ⅲ (Collagen Ⅲ) and transforming growth factor-β1 (TGF-β1) protein expression in myocardial tissues. Method::A diabetic mice model was induced by streptozotocin (STZ) and high-fat diet. A normal control group was established. According to random number table method, diabetic mice were divided into model group, GNC low-dose and high-dose groups (0.819, 1.638 g·kg-1), and metformin group (150 mg·kg-1). Intragastrical administration was given in all groups, and the mice in normal control group received an equal dose of deionized water once a day for 9 weeks. The myocardial interstitial fibrosis in mice was observed by Masson trichromatic staining. Image-pro plus 6.0 analysis software was used to calculate the ratio of collagen area to total area. Immunohistochemistry was used to detect Collagen I, Collagen Ⅲ and TGF-β1 protein expression in myocardial tissues. The protein expression electrophoresis and gray value levels of Collagen I, Collagen Ⅲ and TGF-β1 in the myocardial tissues were detected by Western blot. Result::The results of Masson staining showed that as compared with the normal control group, the myocardial cells of diabetic mice were hypertrophic and disordered, and the myocardial stroma, especially the blue-stained collagenous fibers around the blood vessels, were heavily deposited and connected to each other in a network (P<0.01). As compared with the model group, the arrangement of myocardial cells was significantly improved in GNC low-dose and high-dose groups and metformin group, and the collagenous fibers in the myocardial stroma were significantly decreased (P<0.05). Immunohistochemistry and Western blot results showed positive expression of Collagen Ⅰ, Collagen Ⅲ and TGF-β1 in myocardial tissues, with significantly increased content of protein expression in diabetic mice (P<0.05, P<0.01). As compared with the model group, the positive protein expression decreased and the protein content tended to be normal in each administration group (P<0.05, P<0.01). Conclusion::High-fat diet combined with STZ can induce myocardial fibrosis in diabetic mice, and increase Collagen I, Collagen Ⅲ and TGF-β1 protein expression. Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma extracts can improve myocardial fibrosis in diabetic mice by regulating the expression of Collagen I, Collagen Ⅲ and TGF-β1 protein.

18.
Article in Chinese | WPRIM | ID: wpr-873276

ABSTRACT

Objective::To investigate the effects of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma extracts (GNC) on the protein expression of α-smooth muscle actin (α-SMA) and runt-related transcription factor2(Runx2) after high glucose-induced vascular aging in mice, and elucidate the protective mechanism of GNC in delaying vascular aging. Method::Totally 130 male C57BL/6 mice were randomly divided into normal control group and high glucose group. The mice in high glucose group were intraperitoneally injected with streptozotocin (STZ). After successful modeling, the mice received high-fat diet for 7 months, and then they were randomly divided into model group, GNC low-dose and high-dose groups (0.819, 1.638 g·kg-1), and metformin group (150 mg·kg-1). The drug was given by intragastric administration once a day for 9 weeks. Seven days before tissues collection, a new batch of 4-week-old male C57BL/6 mice were purchased and fed normally for 1 week as a youth group. The general condition of the mice was observed. Morphological changes of the common carotid artery in mice were determined by hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). Masson trichromatic staining was used to observe the fibrosis of common carotid artery in mice. The expression levels of matrix metalloproteinases-2 (MMP-2), cyclin-dependent kinase inhibitor 2A (p16), cyclic-dependent kinase inhibitor 1A (p21), α-SMA and Runx2 in the common carotid arteries of mice were detected by immunohistochemistry. Result::The results of HE, TEM and Masson showed that there was almost no change in the inimal and adventitial thickness, ultrastructure and relative contents of collagen and elastic fibers in the common carotid arteries of mice between the youth group and normal control group. As compared with the normal control group, the intima of the common carotid artery in the model group was not smooth, the endothelial cells were almost completely detached, the cytoplasm was lysed, the inner elastic membrane became thinner, fractured, or even detached, and the proliferating collagen fibers sneaked into the tunica media. The hyperplasia of tunica media and tunica adventitia was obvious and disordered (P<0.01). The vascular smooth muscle cells showed deformations, protuberances, bifurcations, and even fragmentation, and focal necrosis was observed. There were significantly more vacuoles, lysosomes, and obvious autophagy vesicles. The relative content of collagen and elastic fibers in vascular walls increased significantly (P<0.01). Compared with the model group, the above situation was relieved in each administration group (P<0.01). The results of immunohistochemistry showed that high glucose induced high expression of MMP-2, p16, p21 and Runx2 in the common carotid arteries(P<0.01), low expression of α-SMA(P<0.01), and the protein expression tended to be normal after drug intervention(P<0.05, P<0.01). Conclusion::High glucose can induce the aging of common carotid artery in mice and change the expression of α-SMA and Runx2 proteins. The Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma extracts can delay vascular aging by regulating the protein expression of α-SMA and Runx2.

19.
Article in Chinese | WPRIM | ID: wpr-873275

ABSTRACT

Objective::To investigate the protective effect of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma extracts on vascular calcification induced by high glucose in mice by observing the expression of osteopontin (OPN) and smooth muscle 22α (SM22α) as well as vascular calcium deposition in the common carotid artery and thoracic aorta of mice. Method::Totally 130 male C57BL/6 mice were randomly divided into normal control group and high glucose group. The mice in high glucose group were intraperitoneally injected with streptozotocin(STZ), and fed on a high-fat diet for 7 months. Then, the mice were randomly divided into model group, low-dose and high-dose Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma extracts groups (0.819, 1.638 g·kg-1), and metformin group (150 mg·kg-1). Each group was intragastrically administered once a day for 9 weeks. The changes in blood glucose were measured. Seven days before the end of the administration, a group of 4-week old male C57BL/6 mice were purchased and fed normally for one week as a youth group. At the end of the administration, the common carotid artery and thoracic aorta tissues of the mice were collected. Von Kossa staining was used to determine the degree of calcium deposition in the common carotid artery and thoracic aorta. The expression levels of OPN and SM22α protein in the common carotid artery and thoracic aorta were detected by immunohistochemistry. The expression of OPN and SM22α protein in the common carotid artery of mice was determined by Western blot. Result::As compared with the young group, the blood glucose of the normal control group was slightly increased without statistical difference, the common carotid artery and thoracic aorta were uniformly stained, and no black granular precipitate was observed. As compared with the normal control group, the blood glucose of the model group was increased (P<0.01), with a large amount of brown-black particles deposited in the intimal elastic fibers, showing obvious calcium salt deposition. As compared with the model group, blood glucose was significantly decreased in each administration group (P<0.05, P<0.01), and the degree of vascular calcium salt deposition was significantly reduced. There were no significant changes in expression levels of OPN protein and SM22α protein in the common carotid artery and thoracic aorta between the youth group and normal control group. As compared with the normal control group, the expression of intimal OPN protein in the common carotid artery and thoracic aorta of the model group was positive, SM22α protein expression was weakly positive, and the gray value of OPN protein expression in the common carotid artery was significantly increased (P<0.01), while the gray value of SM22α protein was decreased significantly (P<0.01). As compared with the model group, the expression levels of intimal OPN protein and SM22α protein in the common carotid artery and thoracic aorta of each administration group were significantly improved, and the gray value of OPN protein expression in the common carotid artery was reduced (P<0.05, P<0.01), while SM22α protein expression was significantly increased (P<0.01). Conclusion::High glucose can induce calcification of common carotid artery and thoracic aorta in mice and accelerate vascular aging. This formation process may be related to the expression of OPN and SM22α. Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma extracts can reduce vascular calcification and delay vascular aging by regulating the expression of OPN and SM22α.

20.
Article in Chinese | WPRIM | ID: wpr-873209

ABSTRACT

Chuanxiong Chatiaosan was first recorded in Taiping Huimin Heji Jufang, which was made up of 8 herbs, including Chuanxiong Rhizoma, Menthae Haplocalycis Herba, Asari Radix et Rhizoma, Schizonepetae Herba, Saposhnikoviae Radix, Angelicae Dahuricae Radix, Notopterygii Rhizoma et Radix and Glycyrrhizae Radix et Rhizoma. This prescription mainly contains a variety of alkaloids, flavonoids, phenylpropanoids, volatile oils and other compounds, which play the biological activity of promoting blood circulation and relieving pain. Modern pharmacological studies have confirmed that Chuanxiong Chatiaosan can reduce blood viscosity, improve cerebral circulation, and has central analgesic effect to treat migraine effectively. However, the mechanism for treating migraine of this prescription is still unclear. The author elaborated the research status of Chuanxiong Chatiaosan from four aspects, including quality control method, chemical composition, preparation technology and pharmacological research, hoping to provide references for rational clinical application and explanation of pharmacological mechanism of this prescription.

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