ObjectiveTo investigate the antitumor effect and mechanism of Guiqi Yiyuan ointment on Lewis lung cancer mice based on the extracellular regulatory protein kinase （ERK） signaling pathway. MethodsA Lewis lung cancer mouse model was established. Except for the blank group， the model mice were randomly divided into the model group， Guiqi Yiyuan ointment low， medium， and high dose groups， and the extracellular ERK1/2 inhibitor group， with 10 mice per group. The Guiqi Yiyuan ointment was administered by gavage at doses of 1.75， 3.5， 7.0 g·kg^-1·d^-1 for the low， medium， and high dose groups， respectively. The ERK1/2 inhibitor group was given the ERK1/2 inhibitor LY3214996 （100 mg·kg^-1·d^-1） by gavage. The treatment was administered for 14 consecutive days， after which samples were collected. Tumor histopathological changes were observed using hematoxylin-eosin （HE） staining. Transmission electron microscopy was used to observe ultrastructural changes in tumor cells. Immunofluorescence was performed to measure the phosphorylation of ERK1/2 （p-ERK1/2） and the expression of programmed cell death ligand-1 （PD-L1） in tumor tissues. Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of p-ERK1/2， PD-L1， the autophagy marker Beclin-1， the autophagic protein p62， and the microtubule-associated protein light chains LC3Ⅰ and LC3Ⅱ at both the protein and gene levels. ResultsCompared with the model group， the average tumor weight was significantly reduced in the low and medium dose groups of Guiqi Yiyuan ointment （P<0.05）， and markedly reduced in the high dose and inhibitor groups （P<0.01）. Tumor cells in all treatment groups became progressively irregular， with ruptured nuclei and expanded areas of cell disintegration and necrosis. The number of organellar ablations in tumor tissues increased， and the number of autophagic vesicles also increased in all groups. The mean fluorescence intensity of p-ERK1/2 and PD-L1 was reduced in the low and medium dose groups of Guiqi Yiyuan ointment （P<0.05）， and significantly reduced in the high dose and inhibitor groups （P<0.01）. The mRNA expression of ERK1/2， PD-L1， Beclin-1， and p62 was reduced in the medium dose group （P<0.05）， while LC3Ⅰ/Ⅱ mRNA expression was elevated （P<0.05）. In the high dose and inhibitor groups， mRNA expression of ERK1/2， PD-L1， Beclin-1， and p62 was significantly reduced （P<0.01）， while LC3Ⅰ/Ⅱ mRNA expression was significantly increased （P<0.01）. Protein expression of p-ERK1/2， PD-L1， Beclin-1， and p62 was reduced in the medium dose group （P<0.05）， and LC3Ⅰ/Ⅱ protein expression was elevated （P<0.05）. In the high dose and inhibitor groups， protein expression of p-ERK1/2， PD-L1， Beclin-1， and p62 was significantly reduced （P<0.01）， while LC3Ⅰ/Ⅱ protein expression was significantly elevated （P<0.01）. ConclusionGuiqi Yiyuan ointment may inhibit the activation of the ERK signaling pathway， downregulate the expression of p-ERK1/2， promote autophagic flux in tumor cells， and regulate the expression of PD-L1， thereby exerting an inhibitory effect on tumor growth in Lewis lung cancer mice.

Non-small cell lung cancer （NSCLC）， as the most common subtype of lung cancer， has a high incidence and mortality rate among global cancer cases. Although modern medicine has made remarkable progress in the treatment of NSCLC with advances in screening technologies and continuous optimization of therapeutic regimens， current treatments inevitably result in adverse outcomes such as high tumor recurrence rates， significant toxic side effects， and poor quality of life for patients. Traditional Chinese medicine （TCM） holds that the core pathogenesis of lung cancer lies in ''deficiency of healthy Qi and excess of pathogenic factors''. It originates from congenital insufficiency or acquired malnourishment， leading to an imbalance of Yin and Yang， deficiency of healthy Qi， and inability to eliminate pathogenic factors. The interactions among Qi stagnation， phlegm accumulation， blood stasis， and toxins give rise to disease. The root is deficiency， while the manifestation is excess. Therefore， the treatment of lung cancer in TCM is generally guided by the principle of "supporting the healthy Qi and eliminating the pathogens". A large number of clinical and pharmacological studies have shown that TCM and its active components can， through multiple targets and mechanisms， alleviate postoperative and chemoradiotherapy-related adverse reactions， inhibit tumor growth and recurrence， and improve the quality of life of patients with NSCLC. It is worth noting that although extensive studies have been conducted on the therapeutic patterns and pharmacological mechanisms of TCM and its active substances in NSCLC treatment， issues such as the diversity of medicinal materials， the complexity of chemical components， the scientific basis of herbal compatibility， and the flexibility of dosage indicate that there is still considerable room for further clinical and basic research. This review summarizes recent literature on the clinical syndromes， drug selection， medication patterns， and pharmacological mechanisms of TCM and its active components in the treatment of NSCLC， aiming to provide guidance for clinical medication in TCM therapy for NSCLC and to deepen the understanding and research of its therapeutic mechanisms.

Parkinson disease is a progressive neurodegenerative disease whose incidence increases year by year as the population ages.TCM compounds for the treatment of Parkinson disease has the characteristics of multiple components,targets,and pathways.Combined treatment with Western medicine can achieve synergistic effects and reduce adverse drug reactions.This article focused on the mechanism of TCM compounds for the treatment of Parkinson disease,reviewed relevant experimental studies in recent years.TCM compounds may exert therapeutic effects on Parkinson disease by regulating oxidative stress,mitochondrial dysfunction,neurotransmitters,neuroinflammation,abnormal protein aggregation,cell apoptosis,stem cell transplantation,neurotrophic factors,second messengers,and other mechanisms,in order to provide basis for clinical treatment of Parkinson disease.

Parkinson disease is a progressive neurodegenerative disease whose incidence increases year by year as the population ages.TCM compounds for the treatment of Parkinson disease has the characteristics of multiple components,targets,and pathways.Combined treatment with Western medicine can achieve synergistic effects and reduce adverse drug reactions.This article focused on the mechanism of TCM compounds for the treatment of Parkinson disease,reviewed relevant experimental studies in recent years.TCM compounds may exert therapeutic effects on Parkinson disease by regulating oxidative stress,mitochondrial dysfunction,neurotransmitters,neuroinflammation,abnormal protein aggregation,cell apoptosis,stem cell transplantation,neurotrophic factors,second messengers,and other mechanisms,in order to provide basis for clinical treatment of Parkinson disease.

Diabetic kidney disease(DKD)is one of the major complications of diabetes mellitus(DM),which significantly affects the survival and quality of life of DM patients.Currently,existing first-line treatment approaches for DKD are ineffective in effectively preventing the occurrence and progression of DKD.Traditional Chinese medicine(TCM)has the advantages of"ultiple pathways,multiple targets,and multiple mechanisms"in treating DKD,and has a broad prospect in the treatment of DKD.Aquaporin-2(AQP2)is a membrane channel protein widely expressed in the kidneys,and its physiological function is highly similar to the function of kidney filtration and reabsorption.Studies have found that various effective components and related formulae of Chinese medicine can improve symptoms in DKD patients by inhibiting the abnormal expression of AQP2.This article provides a review on the role of AQP2 in DKD and the research progress of TCM intervention,aiming to provide insights and references for the development of drugs related to the prevention and treatment of DKD.

Objective To explore the effects of compound Dihuang Granules on the Parkinson disease(PD)rats with yin deficiency and wind movement syndrome based on PI3K/AKT/mTOR signaling pathway;To explore the mechanism of its mechanism on PD.Methods A rat model of PD with yin deficiency and wind movement syndrome was prepared by injecting 6-OHDA to substantia nigra.The rats were randomly divided into control group,sham-operation group,model group,madopar group,and compound Dihuang Granules low-,medium-,and high-dosage groups,with 10 rats in each group.Each group was treated with corresponding solution by gavage for 28 consecutive days.After treatment,the neurobehavioral changes of rats were detected,HE staining was used to observe the pathological changes in substantia nigra,and RT-qPCR was used to detect the expressions of PI3K,AKT,mTOR,p62 and LC3B mRNA in damaged substantia nigra,immunohistochemistry was used to detect the expressions of p-PI3K,p-AKT and p-mTOR in damaged substantia nigra,Western blot was used to detect the expressions of p-PI3K,PI3K,p-AKT,AKT,p-mTOR,mTOR,p62 and LC3B protein in damaged substantia nigra.Results Compared with the control group and sham-operation group,the model group rats showed an increase in the number of rotations,an extension of pole climbing time,and a decrease in suspension time and number of moving grids(P<0.01),with disordered arrangement of substantia nigra neurons,nuclear pyknosis,and blurred structure,the expressions of PI3K,AKT,mTOR and p62 mRNA in damaged substantia nigra increased,the protein expressions of p-PI3K,p-AKT,p-mTOR and p62 increased,and the expressions of LC3B mRNA and LC3BⅡ/Ⅰ protein decreased(P<0.01).Compared with the model group,the number of rotations and pole climbing time of rats in madopar group and compound Dihuang Granules groups decreased,while the suspension time and number of moving grids increased(P<0.01),with increased number of substantia nigra neurons and improved structural morphology,the expressions of PI3K,AKT,mTOR and p62 mRNA in damaged substantia nigra decreased,the protein expressions of p-PI3K,p-AKT,p-mTOR and p62 decreased,and the expressions of LC3B mRNA and LC3BⅡ/Ⅰ protein increased(P<0.05,P<0.01).The compound Dihuang Granules high-dosage group had the most significant effect(P<0.05,P<0.01),and there was no statistically difference compared with the madopar group(P>0.05).Conclusion Compound Dihuang Granules may enhance damaged substantia nigra autophagy by inhibiting the PI3K/AKT/mTOR signaling pathway,protect dopaminergic neurons,and treat PD.

Objective To explore the inhibitory effect of Guiqi Yiyuan Ointment combined with cisplatin on Lewis lung cancer mice and its mechanism based on the lncRNA H19/miR-19b3p/FTH1 axis.Methods Totally 60 SPF grade male C57BL/6 mice were randomly selected as blank group,and Lewis lung cancer mouse model was replicated in the remaining 50 mice.The modeled mice were randomly divided into model group,cisplatin group,and TCM low-,medium-and high-dosage combined with cisplatin group,with 10 mice in each group.The cisplatin group was given intraperitoneal injection of cisplatin 5 mg/kg,while the TCM low-,medium-and high-dosage combined with cisplatin group were given Guiqi Yiyuan Ointment 1.75,3.5,7.0 g/kg by gavage combined with intraperitoneal injection of cisplatin 5 mg/kg,the blank group and model group were given equal volume of normal saline by gavage for 14 consecutive days.The general condition of mice was observed,the tumor mass of mice was measured,and the tumor inhibition rate,spleen index,and thymus index were calculated,HE staining was used to observe the pathological changes of tumor tissue,and the contents of malondialdehyde(MDA),reduced glutathione(GSH),hydrogen peroxide(H2O2),and ferrous ions(Fe2+)were detected in the tumor tissue,immunohistochemistry and Western blot were used to detect the expression of nuclear factor E2 related factor 2(Nrf2),glutathione peroxidase 4(GPX4),ferritin heavy chain 1(FTH1)and solute carrier family 7 member 11(SLC7A11)protein in tumor tissue,real time fluorescence quantitative PCR was used to detect the expression of lncRNA H19 and miR-19b3p mRNA in tumor tissue.Results Compared with the blank group,the body mass,spleen index and thymus index of mice in the model group were decreased(P<0.05).Compared with the model group,the mental state and tumor histopathological morphology of mice in each administration group were improved to different degrees,the tumor mass of mice was reduced(P<0.05),the spleen index and the thymus index of mice increased(P<0.05),tumor cell lysis,rupture,and decrease in quantity,the contents of MDA,H2O2,Fe2+in tumor tissue increased(P<0.05),while GSH content decreased(P<0.05),the expression of Nrf2,GPX4,FTH1,SLC7A11 protein in tumor tissue decreased(P<0.05),the lncRNA H19 mRNA expression decreased(P<0.05),miR-19b3p mRNA expression increased(P<0.05).Compared with the cisplatin group,the tumor mass of mice in TCM high-dosage combined with cisplatin group reduced(P<0.05),the body mass,spleen index and thymus index increased(P<0.05),the contents of MDA,H2O2,Fe2+in tumor tissue of mice increased(P<0.05),the content of GSH decreased(P<0.05),the expression of Nrf2,FTH1,SLC7A11,GPX4 protein expression decreased(P<0.05),lncRNA H19 mRNA expression decreased(P<0.05),miR-19b3p mRNA expression increased(P<0.05).Conclusion Guiqi Yiyuan Ointment combined with cisplatin can significantly inhibit the tumor of Lewis lung cancer mice,and its mechanism may be related to regulating the expression of ferroptosis molecules related to the lncRNA H19/miR-19b3p/FTH1 axis.

Objective To observe the effects of compound Dihuang Granules on striatum PINK1,Parkin and α-syn in rats with Parkinson disease yin-deficiency and wind movement syndrome;To explore the mechanism of compound Dihuang Granules in the treatment of Parkinson disease yin-deficiency and wind movement syndrome.Methods 6-hydroxydopamine was injected into the substantia nigra of the midbrain to prepare the model of PD yin-deficiency and wind movement syndrome.Totally 65 model rats were randomly divided into model group,Madopar(150 mg/kg)group,and TCM low-,medium-,and high-dosage(1.75,3.5,7 g/kg)groups.Another 26 rats were divided into normal control group and sham-operation group,with 13 rats in each group.Each administration group was given corresponding medication solution by gavage,the normal control group,sham-operation group and the model group were given equivalent volume of normal saline,once a day for 28 consecutive days.The behavioral changes of rats were detected,ELISA and biochemical assay kits were used to detect ATP content and COX Ⅳactivity in striatum,HE staining was used to observe the morphological changes of the striatum,immunohistochemistry staining,Western blot and RT-qPCR were used to detect the expression of PINK1,Parkin,α-syn protein and mRNA in striatal tissue.Results Compared with the normal control group and the sham-operation group,the rats in the model group showed increased number of rotations and pole climbing time,decreased swimming score(P<0.01),the ATP content and COX Ⅳ activity in striatum tissue decreased(P<0.01),with disordered arrangement and reduced number of neurons,cell swelling,partial nuclear shrinkage,formation of vacuoles,and blurred boundaries,the expressions of PINK1,Parkin protein and mRNA in striatal tissue decreased(P<0.01),and the expressions of α-syn protein and mRNA increased(P<0.01).Compared with the model group,the number of rotations and pole climbing time of rats in each medication group decreased,swimming scores increased(P<0.01),ATP content and COX Ⅳ activity in striatal tissue increased(P<0.05,P<0.01),the number of neurons increased,the arrangement tended to be neat,and the morphology improved,the expressions of PINK1,Parkin protein and mRNA in striatal tissue increased(P<0.05,P<0.01),the expressions of α-syn protein and mRNA decreased(P<0.05,P<0.01).The improvement was most significant in the Medopar group and TCM high-dosage group(P<0.05,P<0.01),and there was no significant difference between the two groups(P>0.05),and TCM groups showed dosage dependence(P<0.05,P<0.01).Conclusion Compound Dihuang Granules can improve the behavioral symptoms of Parkinson disease yin-deficiency and wind movement syndrome,possibly by regulating the expressions of PINK1,Parkin and α-syn in the striatum tissue,thereby alleviating mitochondrial dysfunction,protecting dopaminergic neurons,and playing a role in treating Parkinson disease.

Objective To explore the targets and mechanism of Jiegengbai Powder in the treatment of lung adenocarcinoma based on network pharmacology and animal experiments.Methods The targets of effective components of Jiegengbai Powder were obtained from TCMSP,the targets of lung adenocarcinoma were screened from GeneCards,PharmGKB,DrugBank,TTD,OMIM databases,and the intersection targets were obtained.The protein-protein interaction(PPI)network and active components of Chinese materia medica-target network were constructed by using Cytoscape 3.8.0 software,and the key components and core targets were screened out.The intersection targets were analyzed by GO and KEGG enrichment analysis.PyMOL and AutoDockTools 1.5.6 software were used to verify the molecular docking between the key components and core targets.The lung cancer mice model was established.The mice were randomly divided into blank group,model group,cisplatin group,Jiegengbai Powder combined with cisplatin group,Jiegengbai Powder low-,medium-and high-dosage groups.After 14 days of intervention,the tumor inhibition rate was calculated,and the morphology of tumor tissues was observed by HE staining.The gene and protein expressions of PI3K,PTEN,Akt and mTOR in tumor tissues were detected by RT-qPCR and Western blot.Results The core targets of Jiegengbai Powder in the treatment of lung adenocarcinoma such as TP53,CASP3,BCL2L1 and AKT1 were screened by network pharmacology.The key pathways of enrichment were PI3K-Akt signaling pathway and so on.Jiegengbai Powder can inhibit the growth of tumor effectively.Compared with the model group,the mRNA expressions of PI3K,Akt and mTOR decreased in the Jiegengbai Powder medium-and high-dosage groups,and PTEN mRNA expression increased,the ratio of p-PI3K/PI3K,p-Akt/Akt and p-mTOR/mTOR decreased,and the expression of PTEN protein increased(P<0.05,P<0.01).Conclusion Jiegengbai Powder has the characteristics of multi-level and multi-target in the treatment of lung adenocarcinoma.It may promote tumor cell apoptosis and autophagy by regulating PI3K/Akt/mTOR signaling pathway,so as to achieve the anti-tumor effect of inhibiting tumor cell growth.

Objective To observe the anti-tumor effect and mechanism of Guiqi Yiyuan Ointment combined with cisplatin in Lewis lung cancer bearing mice based on AMPK/ULK1 signaling pathway.Methods The mice were inoculated with Lewis lung cancer cells to establish a subcutaneous tumor model in the right axillary subcutaneous area,and were randomly divided into blank group,model group,cisplatin group and Guiqi Yiyuan Ointment high-,medium-and low-dosage+cisplatin groups,with 10 mice in each group.The cisplatin group received intraperitoneal injection of 5 mg/kg(once every 7 days)cisplatin,while the Guiqi Yiyuan Ointment high-,medium-and low-dosage+cisplatin groups received gavage of 7.0,3.5 and 1.75 g/kg Guiqi Yiyuan Ointment on the basis of cisplatin group,once a day,for 14 consecutive days.HE staining was used to observe the morphology of tumor tissue,immunohistochemical method was used to detect the protein expression of p-AMPK and p-ULK1 in tumor tissue,transmission electron microscopy was used to observe the number of autophagosomes,RT-PCR was used to detect the expression of p62,Beclin-1,Atg5 and LC3 mRNA in tumor tissue,Western blot was used to detect the expression of Beclin-1,p62,Atg5,LC3 and AMPK/ULK1 signaling pathway proteins in tumor tissue.Results Compared with the model group,the tumor mass of mice in all administration groups decreased significantly(P<0.05);the tumor tissue showed patchy necrotic areas and an increase in the number of autophagosomes,the mRNA expressions of Beclin-1,Atg5,and LC3 increased,the protein expressions of Beclin-1,Atg5,LC3 Ⅱ/Ⅰ,AMPK,p-AMPK,ULK1 and p-ULK1 increased,and the expression of p62 mRNA and protein decreased(P<0.05).Compared with the cisplatin group,the tumor mass of mice in Guiqi Yiyuan Ointment high-,medium-dosage+cisplatin groups decreased(P<0.05),the tumor inhibition rate increased;the expressions of ULK1 protein and Atg5 mRNA in tumor tissue of Guiqi Yiyuan Ointment high-,medium-and low-dosage+cisplatin groups significantly increased(P<0.05),the expressions of Beclin-1 and LC3 mRNA in Guiqi Yiyuan Ointment high-,medium-dosage+cisplatin groups significantly increased(P<0.05),the expressions of Atg5,LC3 Ⅱ/Ⅰ,AMPK,p-AMPK and p-ULK1 protein significantly increased(P<0.05),and the expression of p62 protein significantly decreased(P<0.05),the expression of p62 mRNA in Guiqi Yiyuan Ointment high-dosage+cisplatin group significantly decreased(P<0.05),the expression of Beclin-1 protein significantly increased(P<0.05).Conclusion Guiqi Yiyuan Ointment combined with cisplatin may activate autophagy and inhibit subcutaneous tumor growth in Lewis lung cancer bearing mice through the AMPK/ULK1 signaling pathway.