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BACKGROUND:Endogenous neurogenesis and exogenous stem cell transplantation in the brain show great therapeutic potential for neurological diseases including ischemic stroke,repairing and replacing lost neurons,promoting synaptic remodeling,and inhibiting apoptosis.Traditional Chinese medicine and compound therapy for supplementing qi,activating blood circulation and inducing resuscitation for the treatment of neurological dysfunction after ischemia have certain advantages,targeting nerve repair through a variety of ways,including promoting endogenous neurogenesis and exogenous stem cell survival,proliferation,homing,and inducing neuronal differentiation. OBJECTIVE:To summarize the mechanism of traditional Chinese medicine and compound for supplementing qi,activating blood circulation and inducing resuscitation to promote nerve repair in the acute phase of ischemic stroke,in order to provide a reference for the research and treatment of new drugs in ischemic stroke. METHODS:The articles from CNKI and PubMed databases about traditional Chinese medicine and compound for supplementing qi,activating blood circulation and inducing resuscitation in promotion of nerve repair in the acute phase of ischemic stroke from 2010 to 2022 were searched,with"supplementing qi and activating blood circulation;inducing resuscitation;traditional Chinese medicine(TCM);compounds;ischemic stroke;nerve repair;stem cells"as Chinese and English search terms.After excluding old and duplicate views,the retrieved literature was analyzed and collated,and a total of 124 articles were included for analysis. RESULTS AND CONCLUSION:(1)The definition of stem cells,ischemic stroke and the nerve repair pathway in the acute phase of ischemic stroke were sorted out.(2)The mechanism of action of traditional Chinese medicine and compound for supplementing qi,activating blood circulation and inducing resuscitation to promote nerve repair in the acute phase of ischemic stroke was summarized,mainly including promoting stem cell proliferation,improving stem cell viability and survival rate,promoting nerve cell homing,inducing stem cell differentiation to neurons,inhibiting apoptosis of nerve cells,promoting axon regeneration,regulating angiogenesis and remodeling,improving the level of neurotrophic factors and repairing the integrity of the blood-brain barrier.(3)Through the existing research,the relevant factors and signaling pathways of traditional Chinese medicines and compounds for supplementing qi,activating blood circulation and inducing resuscitation to promote nerve repair in the acute phase of ischemic stroke were summarized,such as Nestin protein expression,DCX protein expression,brain-derived neurotrophic factor,vascular endothelial growth factor and Wnt/β-catenin signaling pathway,Notch signaling pathway,PI3k/Akt signaling pathway,BDNF/TrkB signaling pathway and ERK/MAPK signaling pathway.It provides a relevant reference for future research on ischemic stroke-specific drugs and new clinical treatment methods.
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BACKGROUND:The aging of mesenchymal stem cells is one of the main causes of aging-related diseases,and seriously affects its clinical application.Traditional Chinese medicine has a good anti-aging effect,and it can inhibit the aging of mesenchymal stem cells to promote its application in tissue engineering and prevent and treat aging-related diseases. OBJECTIVE:To review the effect and mechanism of traditional Chinese medicine on inhibiting the aging of mesenchymal stem cells. METHODS:We searched CNKI and PubMed for the literature on inhibiting mesenchymal stem cell aging with traditional Chinese medicine from 2012 to 2022.The keywords were"traditional Chinese medicine,mesenchymal stem cells(MSCs),aging"in Chinese and English,respectively.Finally,92 articles were included for further review. RESULTS AND CONCLUSION:(1)We summarized five main mechanisms of the aging of mesenchymal stem cells:DNA damage,telomere shortening,oxidative stress,autophagy disorder and mitochondrial dysfunction.(2)This paper reviewed the phenotypic characteristics of senescent mesenchymal stem cells,including increases in cell volume,decreases in proliferation and multi-directional differentiation,increases in β-galactosidase activity,and activation of p21 and p16 pathways,and so on.(3)We summarized the main mechanisms of Chinese medicine inhibiting the senescence of mesenchymal stem cells at present,including inhibiting the activation of the Wnt pathway,inhibiting the production of mitochondrial reactive oxygen species,promoting the silencing of information regulator factor 2 homolog 1,phosphatidylinositol 3-kinase/protein kinase B,adenosine 5'-monophosphate-activated protein kinase and nuclear factor E2 related factor 2 pathway activation,and promoting the expression of telomerase reverse transcriptase.(4)At present,bone marrow mesenchymal stem cells are the most widely studied in the research of traditional Chinese medicine to inhibit the aging of bone marrow mesenchymal stem cells,and the effect is better.(5)Zuogui Wan,Bushen Tiaogan Formula,resveratrol,Astragalus membranaceus and other traditional Chinese medicines can prevent and treat osteoporosis by promoting the proliferation and osteogenic differentiation of aging mesenchymal stem cells.However,the mechanism of Chinese medicine in improving the paracrine function of mesenchymal stem cells and preventing other aging-related diseases by inhibiting the aging of mesenchymal stem cells needs to be further explored.
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BACKGROUND:Amyotrophic lateral sclerosis is a progressive neurodegenerative disease,which often leads to the death of neurons in the brain and spinal cord.The pathogenesis of amyotrophic lateral sclerosis is extremely complex,with high refractory rate and mortality rate.There are only two kinds of drugs for its treatment,so it is urgent to develop new treatment methods to improve the prognosis of patients. OBJECTIVE:To review the mechanism of Chinese medicine and mesenchymal stem cells regulating the immune response in the treatment of amyotrophic lateral sclerosis. METHODS:"Traditional Chinese medicine,medical stem cells,ALS,immune response"were Chinese and English search terms.Articles were retrieved from WanFang,CNKI,PubMed,Web of Science and other databases from 2010 to 2023.Finally,69 articles were included for review. RESULTS AND CONCLUSION:(1)The article summarizes in detail the five mechanisms of traditional Chinese medicine regulating the immune response in the treatment of amyotrophic lateral sclerosis:mainly including the promotion of expression of closed zone protein-1 and closed protein-5 by traditional Chinese medicine such as borneol and astragaloside IV to rebuild the integrity of the blood central nervous system barrier.Fufangteng Mixture can regulate the receptor molecules on the surface of the natural killer cells to inhibit their autotoxicity.The complement system factors such as Scutellaria barbata and patchouli can inhibit their abnormal activation.Tripterygium wilfordii and Uncaria rhynchophylla inhibit the activation of microglia by mediating the production of extracellular signal-regulated kinase 1/2 attenuated inducible nitric oxide synthase.Zuogui Pill and Trichosanthes kirilowii Root promote the expression of interleukin-10 and regulate T cells to improve the immune environment.(2)Through existing research,five mechanisms of mesenchymal stem cells regulating the immune response in the treatment of amyotrophic lateral sclerosis have been summarized,mainly including reducing the expression of aquaporin 4 and reducing endothelial nitric oxide synthase signal transduction to repair the integrity of the immune barrier;releasing indoleamine 2,3-dioxygenase,prostaglandin E2 and other factors to resist natural killer cell toxicity;secretion factor H interferes with the activity of invertase and inhibits abnormal activation of the complement system;regulating the CX3CL1/CX3CR1 system axis or secreting transforming growth factors β,which can change the phenotype of microglia and inhibit its activity by other ways;increasing the expression of interleukin-10 or activating the STATS phosphorylation pathway to restore T cell function.(3)At present,there are few studies on the combination of traditional Chinese medicine and mesenchymal stem cells in the treatment of amyotrophic lateral sclerosis.Relevant research reports have shown that Jiweiling Injection can promote stem cell proliferation and differentiation and that Buyang Huanwu decoction combined with bone marrow mesenchymal stem cells can significantly improve the integrity of the blood-brain barrier.In the future,further exploration is needed to explore the synergistic treatment effect of both on refractory amyotrophic lateral sclerosis.
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ObjectiveTo investigate the interventional effects of Shugan Jianpi Yangxin prescription on the expression of orexin-A （OXA）， orexin-1 receptor （OX1R）， and orexin-2 receptor （OX2R） in the mouse model of insomnia. MethodThe mouse model of insomnia was established by intraperitoneal injection of DL-4-chlorophenylalanine （PCPA）. Fifty BALB/c mice were randomized into a blank group， a model group， an eszopiclone （0.13 mg·kg-1） group， and low- and high-dose （8.4 and 33.6 g·kg-1， respectively） Shugan Jianpi Yangxin prescription groups and treated with the corresponding drugs for 14 consecutive days. The weight changes of mice were monitored， and Morris water maze and pentobarbital-induced sleep tests were conducted. Immunohistochemistry （IHC） was employed to examine the expression of OXA in the hypothalamus. Enzyme-linked immunosorbent assay was used to measure the levels of OXA and 5-hydroxytryptamine （5-HT） in the hypothalamus， serum， and spleen. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of OXA， OX1R， and OX2R in the hypothalamus. ResultCompared with the blank group， the model group had decreased body weight （P<0.01）， increased escape latency （P<0.01）， increased sleep latency （P<0.01）， shortened sleep duration （P<0.01）， elevated OXA level and lowered 5-HT level in the hypothalamus， serum， and spleen （P<0.05）， and up-regulated mRNA levels of OXA， OX1R， and OX2R in the hypothalamus （P<0.01）. Compared with the model group， the low- and high-dose groups of Shugan Jianpi Yangxin prescription showed increased body weight （P<0.05， P<0.01）， shortened escape latency （P<0.05）， shortened sleep latency and prolonged sleep duration （P<0.01）， and lowered OXA level and elevated 5-HT level in the hypothalamus， serum， and spleen （P<0.05， P<0.01）. Moreover， the two doses of Shugan Jianpi Yangxin prescription down-regulated the mRNA levels of OXA， OX1R， and OX2R in the hypothalamus （P<0.01）. ConclusionShugan Jianpi Yangxin prescription exerts sedative and hypnotic effects in mice by increasing the content of 5-HT in the brain and inhibiting the expression of OXA and its receptors in the hypothalamus.
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Parkinson's disease （PD） is a common neurological degenerative disease in the middle-aged and elderly， characterized by pathological changes of progressive degeneration of dopaminergic neurons in the substantia nigra and Lewy body formation， with high prevalence and long course of disease. The drug is mainly used to treat PD in western medicine， and the early curative effect is remarkable. However， with the progression of the disease and the long-term use of the drug， the efficacy will be significantly reduced， or there may be sports complications， and the long-term efficacy is not good. As a traditional medical system， traditional Chinese medicine has a unique understanding of PD. Traditional Chinese medicine plays an important role in the treatment of PD， which is natural， mild， safe， and effective， and it can cooperate with western medicine to enhance its efficacy and reduce the adverse reactions of western medicine. The pathogenesis of PD is complex， involving multiple levels such as mitochondrial dysfunction and apoptosis. Neuroinflammation is also involved in the progressive degeneration of dopaminergic neurons in PD. The Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway is a classic inflammatory pathway， and its expression changes play an important role in the occurrence and development of inflammatory response in the body. In recent years， the research on this pathway in TCM is increasing. This paper summarized the literature of traditional Chinese and western medicine in the past 10 years and reviewed the relevant mechanism of TCM regulation of TLR4/NF-κB pathway in the treatment of PD from the aspects of TCM monomer， compound， and other TCM therapies， so as to provide some references for the search for new targets of drug therapy and gene therapy and the in-depth study of TCM prevention and treatment of PD.
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Cerebral ischemia/reperfusion injury （CIRI） is a complex cascade reaction process in which the blood flow and oxygen supply of brain tissue in the infarcted area recover after cerebral ischemia， resulting in secondary injury of ischemic brain tissue. At present， thrombolysis as soon as possible and restoration of cerebral blood supply are still the only strategies for the treatment of stroke， but a considerable number of patients' symptoms will be more serious after reperfusion， making patients face adverse outcomes such as neurological function injury and even death and seriously affecting the quality of life and safety of patients. Therefore， an in-depth exploration of the mechanism and treatment strategy of CIRI has important clinical significance. The phosphatidylinositol 3- kinase （PI3K）/protein kinase B （Akt） signaling pathway is one of the classic anti-apoptosis/reproductive-promoting signal transduction pathways， which is responsible for cell proliferation， growth， and differentiation. It is the key cascade signaling pathway of CIRI， located at the core site in many mechanisms such as mitochondrial disorder， apoptosis， autophagy， oxidative stress， and inflammation. It is closely related to the occurrence and development of CIRI. Traditional Chinese medicine has been used in the clinical treatment of stroke and its complications for thousands of years， and the clinical effect of traditional Chinese medicine in the prevention and treatment of CIRI has been affirmed by a large number of research results in recent years. It is further clarified that the monomers， active components， and their compound prescriptions of traditional Chinese medicine can directly or indirectly regulate the PI3K/Akt signaling pathway by virtue of the biological advantages of multi-targets， multi-components， and multi-pathways and play an overall protective role in CIRI. By analyzing the related research progress of traditional Chinese medicine in China and abroad in recent years， the authors summarized the role and mechanism of regulating the PI3K/Akt signaling pathway in the prevention and treatment of CIRI， so as to provide further theoretical basis for the study of the mechanism of clinical prevention and treatment of CIRI.
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ObjectiveTo establish a mouse model of basilar artery dolichoectasia （BAD） and explore the mechanism of modified Tongqiao Huoxuetang （JTQHX） in regulating BAD via phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） pathway. MethodSixty C57/BL6 female mice were randomized into sham operation （injected with 10 U·mL-1 inactivate elastase）， model， atorvastatin calcium tablets （2.6 mg·kg·d-1）， and low- and high-dose （crude drug 3.4， 17 g·kg-1·d-1， respectively） JTQHX groups. The mouse model of BAD was established by injection with 10 U·mL-1 elastase. After 14 days of modeling， the sham operation group and model group were administrated with equal volumes of pure water by gavage， and other groups with corresponding drugs for 2 months. The levels of interleukin-6 （IL-6） and calpain （LpA） in the serum were measured by enzyme-linked immunosorbent assay （ELISA）. Verhoeff 's Van Gieson （EVG） staining was employed to observe the pathological changes of blood vessels. Terminal-deoxynucleotidyl transferase mediated nick end labeling （TUNEL） was employed to examine the apoptosis rate of vascular smooth muscle cells （VSMCs）. Image Pro Plus was used to observe and calculate the curvature index， elongation length， percentage increase in vessel diameter， and curvature angle of the basilar artery vessels in mice. Western blot was employed to determine the expression levels of PI3K and Akt in the vascular tissue. ResultCompared with the sham operation group， the model group showed lowered IL-6 level （P<0.01）， no significant change in LpA level， increased apoptosis of VSMCs （P<0.01）， and increased curvature index， elongation length， percentage increase in vessel diameter， and curvature angle （P<0.01）. Furthermore， the modeling up-regulated the protein levels of PI3K and Akt in blood vessels （P<0.01） and aggravated the destruction of the inner elastic layer， atrophy of the muscular layer， and hyaline changes in the connective tissue of the medial membrane of the basilar artery wall. Compared with the model group， 2 months of treatment with JTQHX elevated the IL-6 level （P<0.01）， reduced the apoptosis of VSMCs （P<0.01）， decreased the curvature index， elongation length， percentage increase in vessel diameter， and curvature angle （P<0.05， P<0.01）， and down-regulated the protein levels of PI3K and Akt in blood vessels （P<0.01）. In addition， the treatment alleviated the destruction of the inner elastic layer， atrophy of the muscular layer， and hyaline changes in the connective tissue of the medial membrane of the basilar artery wall. ConclusionJTQHX inhibits the elongation， expansion， and curvature of basilar artery vessels and alleviates the pathological changes by reducing the apoptosis of VSMCs and down-regulating the expression of PI3K/Akt pathway.
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Alzheimer's disease （AD） is a neurodegenerative disease associated with aging and age-related cognitive decline. It is characterized by insidious onset and progressive development， and has become a major global health and socioeconomic issue. The exact mechanisms underlying AD have not been fully elucidated， and various hypotheses have been proposed by researchers based on different etiologies， including the amyloid β （Aβ） cascade hypothesis， Tau protein hyperphosphorylation hypothesis， mitochondrial dysfunction and oxidative stress hypothesis， and neurotransmitter hypothesis. Therefore， there is an urgent need for comprehensive interventions targeting multiple pathways， links， and targets. Based on traditional Chinese medicine （TCM） theory and modern research findings， kidney-tonifying and anti-aging Chinese medicines have unique advantages of toxicity reduction， long-lasting effects， and treating both the root cause and the symptoms. They have been shown to counteract immune-inflammatory responses， clear reactive oxygen species， exhibit antioxidant properties， inhibit abnormal aggregation of Aβ and Tau proteins， reduce neuronal apoptosis， regulate central neurotransmitters， and modulate gut microbiota in AD. In recent years， stem cell therapy has been explored for the treatment of AD through two strategies： endogenous activation and exogenous transplantation， thereby replenishing and replacing damaged neurons. However， factors such as blood-brain barrier permeability， targeted delivery to the affected area， immune rejection， and cell survival rate can affect the efficacy of stem cell transplantation. Therefore， combining stem cell therapy with medication and other methods can further enhance the effectiveness of stem cell transplantation. Kidney-tonifying and anti-aging Chinese medicines can activate dormant neural stem cells（NSCs） in the body， promote neuroregeneration， and facilitate tissue and organ repair and reconstruction in AD. The combined treatment of these Chinese medicines and stem cell transplantation has shown more significant efficacy compared to either treatment alone. This combination therapy provides a new integration point for the modernization of TCM and offers new ideas and approaches for the prevention and treatment of AD， as well as improving the effectiveness of stem cell transplantation.
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Stroke is one of the major diseases threatening human health， with ischemic stroke accounting for about 70%. Ischemic stroke is characterized by complex pathological mechanism and high incidence， mobility and mortality. At present， the effective clinical treatment measures for ischemic stroke are limited， and it is urgent to develop new and effective treatment measures to improve the prognosis of patients. In recent years， bone marrow mesenchymal stem cells （BMSCs） transplantation has shown great therapeutic potential for a variety of diseases， including ischemic stroke， and has become a new research hotspot. However， due to the low homing and survival rate of BMSCs in human body after transplantation， their clinical effect on ischemic stroke needs to be further improved. With the characteristics of multi-components， multi-channels and multi-targets， Chinese medicine displays desirable curative effect on ischemic stroke， which has been widely concerned. Both Chinese medicine and BMSCs transplantation have good overall brain protection， and their combined effect on ischemic stroke is significantly better than that of single application. The mechanisms include improving the transplantation efficiency of BMSCs， promoting angiogenesis， enhancing neuroplasticity， ameliorating neuroinflammation， enhancing neuroprotection， and regulating the blood-brain barrier and exosomes. The combination of Chinese medicine and modern cutting-edge cell therapy reflects the advantages of integrative medicine， providing a new model and idea for preventing and treating ischemic stroke and improving the efficacy of BMSCs transplantation.
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Objective:To investigate the effect of magnetic resonance angiography (MRA) in evaluating the mouse model of vertebrobasilar dolichoectasia (VBD) induced by injection of elastase into cerebellomedullary cistern.Methods:Twenty-four male C57/BL6 mice were selected. The mice in the elastase group ( n=12) were injected in the cerebellomedullary cistern with 2.5 μl of phosphate buffer containing 25 mU elastase, and the mice in the saline control group ( n=12) were injected with the same volume of normal saline. MRA examination of the brains of living mice was performed 2 weeks after modeling. Successful modeling was defined as the basilar artery bending angle ≤170°, or the basilar artery bending length accounts for ≥10%, or the basilar artery deviated from the midline by more than 1 grade, or the percentage increase in artery diameter was ≥25%. Results:In the elastase group and the saline control group, 2 mice and 1 mouse did not wake up normally or died, respectively. The 11 surviving mice in the saline control group had no obvious vertebral artery and basilar artery abnormalities. The success rate of modeling in the 10 surviving mice in the elastase group was 80%, and the difference in the success rate between the two groups was statistically significant ( P<0.05). There were significant differences in mean basilar artery diameter (0.30 mm vs. 0.22 mm; P<0.05), mean basilar artery bending angle (115° vs. 170°; P<0.05), and proportion of mean basilar artery bending length (31% vs. 5%; P<0.05) of the surviving mice between the elastase group and the saline control group. Conclusion:MRA can better evaluate the mouse VBD model induced by elastase injection in the cerebellomedullary cistern.
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Posterior circulation ischemic stroke can be manifested as isolated vertigo, and the posterior circulation small infarcts often show early negative diffusion-weighted imaging, which is likely to cause misdiagnosis and missed diagnosis. Summarizing the characteristics and screening strategies of these patients can provide help for timely diagnosis and selection of effective treatment strategies.
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Objective To observe the clinical effect of Xiaoke-Yuzu decoction on diabetic peripheral neuropathy (DPN). Methods A total of 100 DPN inpatients were recruited and randomly divided into the treatment and control groups. The two groups were both received basic therapy, while the treatment group additionally received Xiaoke-Yuzu decoction. Toronto clinical scores and Chinese medicine symptom scores of both groups were collected to evaluate the clinical effect before and after the therapy. Results The Toronto scores of treatment group were significantly lower than control group after treatment (symptoms score 1.50 ± 0.94 vs. 2.23 ± 1.01, reflection score 3.60 ± 1.77 vs. 4.27 ± 1.72, feeling test score 1.53 ± 0.63 vs. 2.10 ± 0.84,all P<0.05). Meanwhile, the Chinese medicine symptom scores of treatment group were also significantly lower than the control group (main symptom score 1.77 ± 1.17 vs. 3.17 ± 1.82, posterior symptom score 2.23 ± 1.59 vs. 4.27 ± 1.57, the tongue and pulse score 1.83 ± 0.65 vs. 2.47 ± 0.51, all P<0.05). Conclusion Xiaoke-Yuzu decoction plus basic therpy could improve the clinical symptoms of DPN patients.