Ischemic stroke （IS） is an acute cerebrovascular disease caused by insufficient blood supply to the brain， resulting in brain tissue necrosis and neurological dysfunction. It is characterized by impaired motor， language， sensory， cognitive， and other functions. The pathogenesis involves inflammatory responses， excitotoxicity of excitatory amino acids， and mitochondrial dysfunction. IS with a high incidence， high mortality， high disability， and a high recurrence rate is the leading cause of death in China. At present， Western medical therapies mainly focus on vascular recanalization， including thrombolysis and mechanical thrombectomy. However， due to the possibility of cerebral hemorrhage and edema， narrow time windows， and contraindications associated with intravascular therapy， only a few patients can benefit from these therapies， which greatly limit their clinical application. IS belongs to the categories such as stroke， hem iplegia， and major syncope in traditional Chinese medicine （TCM）. It is mainly caused caused by wind， fire， phlegm， and stasis， which lead to imbalance of Yin and Yang， disorder of Qi and blood， and invasion of clear orifices. The common treatment methods include calming the liver and dispelling wind， resolving phlegm and unblocking meridians， and activating blood and resolving stasis. TCM acting on multiple pathways and targets with low toxicity and side effects has definite effects in improving the prognosis and reducing the recurrence rate， being worthy of promotion and research. Brain-derived neurotrophic factor （BDNF） plays a key role in promoting neurogenesis and increasing synaptic plasticity. During the progression of IS， BDNF binds to tyrosine kinase receptor B （TrkB） to initiate intracellular signaling cascades， thus exerting neuroprotective effects. Studies have shown that TCM can regulate the BDNF/TrkB signaling pathway， treating IS by regulating synaptic plasticity and promoting neural repair. This paper summarizes and generalizes the mechanisms of active components， single herbs， and compound prescriptions of TCM in regulating the BDNF/TrkB signaling pathway in the treatment of IS through the review of domestic and foreign literature in recent years， aiming to provide a theoretical basis and treatment reference for the treatment of IS with TCM.

OBJECTIVE To identify tortoiseshell glue and antler glue in Qichong zuogui granules， and determine the contents of 12 chemical components. METHODS Identification and content determination were performed by using liquid chromatography- tandem mass spectrometry （LC-MS/MS） method. The identification was performed on Hypersil GOLD column with a mobile phase consisted of acetonitrile-0.1% formic acid solution （gradient elution）； the electrospray ion source was used to scan in the positive ion multi-reaction detection mode. The mass charge ratio （m/z） 631.3→546.4， 631.3→921.4 was the detection ion pair for tortoiseshell glue， and the m/z 765.4→554.0， 765.4→733.0 was the detection ion pair for antler glue. The determination method for 12 chemical components was as follows： Accucore C18 column， methanol-0.1% formic acid as mobile phase （gradient elution）； scanning range of positive and negative ions was m/z 100→1 000 with the electric spray ion source and single ion detection scanning mode. RESULTS Average retention times of the molecular ion peaks for characteristic peptide segments of tortoiseshell glue and antler glue were 6.28 and 6.77 min， respectively； the linear relationship of 12 chemical components was good within their respective concentration ranges， such as astragaloside Ⅳ， calycosin-7-O-β-D-glucoside， calycosin， chlorogenic acid， ferulic acid， betaine， amygdalin， rutin， hydroxysafflor yellow A， hyperoside， loganin， cyasterone （r＞0.999）； RSDs for precision， stability （24 h） and reproducibility tests were all less than 5%. The average sample recovery rates ranged from 98.04% to 101.08%. The average contents of 12 components were 1.83， 25.73， 13.76，56.71， 23.80， 49.82， 807.49， 15.01， 317.02， 60.21， 202.71 and 17.70 μg/g， respectively. CONCLUSIONS In this study， tortoiseshell glue and antler glue in Qixiong zuogui granules are identified， and the contents of 12 chemical components therein are determined. This provides a reference for the quality control of this granule.

BACKGROUND:Studies have shown that mitochondrial apoptosis of alveolar epithelial cells plays an important role in the pathogenesis of pulmonary fibrosis,and Feibi prescription can attenuate pulmonary fibrosis and inhibit the transformation of extracellular mechanisms in mice with pulmonary fibrosis. OBJECTIVE:To investigate the mechanism of Feibi prescription on mitochondrial apoptpsis of alveolar epithelial cells in bleomycin induced pulmonary fibrosis mice. METHODS:Forty male C57BL/6 mice were randomly divided into blank control group,model group,pirfenidone group,and Feibi prescription group.There were 10 mice in each group.Except for the blank control group,the other three groups were intraperitoneally injected with bleomycin(7.5 mg/kg per day)for 10 continuous days to establish the model of pulmonary fibrosis.On day 1 after modeling,the mice in corresponding drug groups were intragastrically administered with pirfenidone(51.43 mg/kg per day)or Feibi prescription(12.86 mg/kg per day).Drug administration lasted for 28 days.Then,morphological changes of lung tissue in mice were observed by hematoxylin-eosin staining and Masson staining.The levels of interleukin-1,interleukin-6,interleukin-17,and interleukin-37 in the serum were detected by ELISA,and the expression of Bax,Bcl-2,Beclin-1,and Caspase3 in the lung tissue was detected by western blot assay. RESULTS AND CONCLUSION:Morphological observation of lung tissue showed that in the model group,the alveolar septum and alveolar lumen were infiltrated with a large number of inflammatory cells,and there were large clusters of fibrous foci;in the pirfenidone group,alveolar septa were thickened,with a small infiltration of inflammatory cells and the appearance of pulmonary fibrous foci;in the Feibi prescription group,the alveolar structure was widened,with a small amount of inflammatory cell infiltration,and the alveolar structure was almost not obviously damaged,with a small number of lung fibrous foci.Compared with the blank control group,the mass concentrations of interleukin-1,interleukin-6,interleukin-17,and interleukin-37 were significantly higher in the model group(P<0.01),while the levels were significantly lower in the two drug groups than the model group(P<0.01).Moreover,the mass concentrations of interleukin-1,interleukin-6,interleukin-17,and interleukin-37 in the Feibi prescription group were lower than those in the pirfenidone group.Compared with the blank control group,the expression of Bax and Caspase3 proteins in the lung tissue of mice was significantly higher in the model group,while the expression of Bax and Caspase3 proteins was significantly lower in the two drug groups than the model group.Compared with the blank control group,the expression of Bcl-2 and Beclin-1 proteins in the lung tissue of mice was significantly lower in the model group,while the expression of Bcl-2 and Beclin-1 proteins was significantly higher in the two drug groups than the model group.To conclude,Feibi prescription can reduce pulmonary fibrosis and its mechanism may be related to the downregulation of interleukin-1,interleukin-6,interleukin-17,and interleukin-37 levels.This prescription can also reduce the apoptosis of alveolar epithelial cells by regulating mitochondrial apoptosis-related proteins,Bax,Bcl-2,Beclin-1 and Caspase3.

Glioblastoma (GBM) is a highly aggressive primary brain tumor characterized by poor prognosis. Conventional chemo-radiotherapy demonstrates limited therapeutic efficacy and is often accompanied by significant side effects, largely due to factors such as drug resistance, radiation resistance, the presence of the blood-brain barrier (BBB), and the activation of DNA damage repair mechanisms. There is a pressing need to enhance treatment efficacy, with BRD4 identified as a promising target for increasing GBM sensitivity to therapy. Lacking small molecule inhibitors, BRD4 can be degraded using PROteolysis Targeting Chimera (PROTAC), thereby inhibiting DNA damage repair. To deliver PROTAC, SIAIS171142 (SIS) effectively, we designed a responsive nanocapsule, MPL_(SS)P@SIS, featuring GBM-targeting and GSH-responsive drug release. Modified with 1-methyl-l-tryptophan (MLT), nanocapsules facilitate targeted delivery of SIS, downregulating BRD4 and sensitizing GBM cells to radiotherapy and chemotherapy. After intravenous administration, MPL_(SS)P@SIS selectively accumulates in tumor tissue, enhancing the effects of radiotherapy and temozolomide (TMZ) by increasing DNA damage and oxidative stress. GSH activates the nanocapsules, triggering BRD4 degradation and hindering DNA repair. In mouse models, the nanosensitizer, combined with TMZ and X-ray irradiation, efficiently inhibited the growth of GBM. These findings demonstrate a novel PROTAC-based sensitization strategy targeting BRD4, offering a promising approach for effective GBM therapy.

OBJECTIVES: To exple the mechanism of Qixiong Zuogui Granules (QXZG) for enhancing synaptic plasticity in aging rats. METHODS: Forty SD rats were randomized into control group, aging model group, donepezil treatment group, and QXZG treatment group (n=10). Except for the control rats, all the rats were subjected to daily intraperitoneal injection of D-galactose for 8 consecutive weeks to induce brain aging, and donepezil hydrochloride and QXZG suspension were administered by gavage during modeling. After the interventions, the rats were evaluated for general conditions, behavioral changes, oxidative stress indicators, hippocampal pathologies, and expressions of the brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) pathway, p16, and synaptic plasticity-associated proteins. RESULTS: The rats in the model group exhibited obvious aging phenotypes such as yellowing of the teeth and hair, body weight loss, and impaired learning and memory abilities, with decreased serum SOD and GSH-Px activities and increased serum MDA level. The rat models also showed obvious pathological changes, reduced Nissl bodies, and elevated p16 protein expression in the hippocampal CA1 region, with significantly decreased expression levels of BDNF, TrkB, CREB and synaptic plasticity proteins SYN, GAP43, and PSD95. Treatment with QXZG alleviated the aging phenotypes in the rat models, improved their learning and memory abilities and pathological changes in the hippocampal CA1 region, reduced oxidative stress and p16 protein expression, and promoted the expressions of the BDNF/TrkB pathway proteins and synaptic plasticity proteins. CONCLUSIONS QXZG enhances synaptic plasticity and reduces oxidative stress in aging rats possibly by upregulating the BDNF/TrkB signaling pathway proteins, thereby delaying brain aging and improving learning and memory abilities of the rats.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; Neuronal Plasticity/drug effects* ; Signal Transduction/drug effects* ; Rats, Sprague-Dawley ; Receptor, trkB/metabolism* ; Rats ; Aging ; Drugs, Chinese Herbal/pharmacology* ; Male ; Oxidative Stress ; Hippocampus/metabolism*

Nigella sativa L. seeds have been traditionally utilized in Chinese folk medicine for centuries to treat vitiligo. This study revealed that the ethanolic extract of Nigella sativa L. (HZC) enhances melanogenesis and mitigates oxidative stress-induced cellular senescence and dysfunction in melanocytes. In accordance with established protocols, the ethanol fraction from Nigella sativa L. seeds was extracted, concentrated, and lyophilized to evaluate its herbal effects via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, tyrosinase activity evaluation, measurement of cellular melanin contents, scratch assays, senescence-associated β-galactosidase (SA-β-gal) staining, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis for expression profiling of experimentally relevant proteins. The results indicated that HZC significantly enhanced tyrosinase activity and melanin content while notably increasing the protein expression levels of Tyr, Mitf, and gp100 in B16F10 cells. Furthermore, HZC effectively mitigated oxidative stress-induced cellular senescence, improved melanocyte condition, and rectified various functional impairments associated with melanocyte dysfunction. These findings suggest that HZC increases melanin synthesis in melanocytes through the activation of the MAPK, PKA, and Wnt signaling pathways. In addition, HZC attenuates oxidative damage induced by H₂O₂ therapy by activating the nuclear factor E2-related factor 2-antioxidant response element (Nrf2-ARE) pathway and enhancing the activity of downstream antioxidant enzymes, thus preventing premature senescence and dysfunction in melanocytes.
Oxidative Stress/drug effects* ; Melanocytes/cytology* ; Cellular Senescence/drug effects* ; Nigella sativa/chemistry* ; Plant Extracts/pharmacology* ; Seeds/chemistry* ; Mice ; Animals ; Melanins/metabolism* ; Monophenol Monooxygenase/metabolism* ; Humans

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.

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.

Objective:To explore the effects of Zishui Qinggan Decoction on the PTEN-induced putative kinase protein 1 (PINK1)/Parkin and cyclic GMP-AMP (cGAS)/ stimulator of interferon genes (STING) signaling pathways; To reveal the anti-inflammatory mechanism of Zishui Qinggan Decoction in treating depression.Methods:Totally 60 rats were randomly divided into control group, model group, and Zishui Qinggan Decoction low-, medium-, and high-dosage groups using a random number table method ( n=12 in each group) . All rats except for the rats in control group were prepared with CUMS induced depression models. The rats in the Zishui Qinggan Decoction low-, medium-, and high-dosage groups were orally administered with 12, 24, and 48 g/kg of Zishui Qinggan Decoction for gavage, respectively. The control group and model group were orally administered with distilled water of equal volume for gavage, once a day for 4 weeks. Forced swimming test (FST), the open field test (OFT) and the sucrose preference test (SPT) were used to detect behavioral changes in rats in each group. Hematoxylin eosin (HE) staining was used to observe the cell structure of the medial prefrontal cortex. The levels of IL-1 β, IL-6, TNF-α and Interferon-γ (IFN-γ) were detected using ELISA. Western blot was used to detect the expressions of Pink1, Parkin, cGAS and STING. Results:Behavioral testing results showed that, compared with the model group, the incubation period for rats in Zishui Qinggan Decoction low-, medium-, and high-dosage groups to enter the first immobility state in FST was significantly prolonged ( P<0.05), and the immobility time was significantly shortened ( P<0.05); the time spent in the central area was significantly increased ( P<0.05), and the incubation period for entering the central area was significantly shortened in ( P<0.05); the percentage of sugar water consumption significantly increased in ( P<0.05). HE staining revealed that the aggregation of prefrontal cortex nuclei decreased, the number of neurons increased, and the distribution of neurons was uniform in Zishui Qinggan Decoction low-, medium-, and high-dosage groups. Compared with the model group, the levels of IL-1β, IL-6, TNF-α and IFN-γ in the Zishui Qinggan Decoction groups significantly decreased ( P<0.05). The protein expressions of PINK1 and Parkin in the prefrontal cortex in Zishui Qinggan Decoction groups significantly increased ( P<0.05), while the protein expression levels of cGAS and STING significantly decreased ( P<0.05). Conclusion:Zishui Qinggan Decoction can significantly improve the depressive behavior, neuronal damage, and neuroinflammatory response in CUMS rats. Its mechanism may be related to up-regulating the PINK1/Parkin signaling pathway and inhibiting the cGAS/STING signaling pathway.

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.