1.Patterns and Mechanisms of Traditional Chinese Medicine in Treating Non-small Cell Lung Cancer Based on Theory of ''Supporting Healthy Qi and Eliminating Pathogens''
Pengfei ZHANG ; Huijuan ZHANG ; Jianqing LIANG ; Jinhua WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):228-237
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.
2.Effect of Guiqi Yiyuan Ointment on Lewis Lung Cancer Mice by Increasing Autophagic Flux and Stabilizing PD-L1 Expression Through Regulation of ERK Signaling Pathway
Nan YANG ; Qiangping MA ; Jianqing LIANG ; Kejun MIAO ; Shang LI ; Jintian LI ; Juan LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):107-114
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.
3.Molecular Mechanism Study of Compound Dihuang Granule in Treating PD Rats with Yin-Deficiency and Dynamic Wind Syndrome by Ubiquitin-Proteasome System
Ziwei LYU ; Jianqing LIANG ; Xingling WANG ; Guangjie SUN ; Jiancheng HE ; Yongqiang KANG
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(6):608-617
OBJECTIVE To explore the molecular mechanism of Compound Dihuang Granule in treating Parkinson's disease(PD)with yin-deficiency and dynamic wind syndrome by regulating the changes of ubiquitin-proteasome system-related proteins.METHODS SPF male SD rats were randomly selected as normal control group and sham operation group,13 rats in each group.The remaining rats were treated with 6-hydroxydopamine lateral brain injection to damage the substantia nigra to establish PD yin-deficien-cy and dynamic wind syndrome rat model.The established rats were randomly divided into model group,madopar group(150 mg·kg-1),low,medium and high dose groups of Compound Dihuang Granule(1.75,3.5,7 g·kg-1),13 rats in each group.Each group was given drugs by intragastric gavage for 28 d.The general conditions and neurobehavioral manifestations of the rats were observed;the expression of ubiquitin(UB),ubiquitin activating enzyme(UBE1),ubiquitin conjugating enzyme(UBE2A)and ubiquitin carboxyl terminal hydrolase(UCH-L1)positive cells,protein and mRNA expression levels in the damaged lateral stria-tum of the brain of rats were detected by immunohistochemistry,Western blot and qPCR methods;changes of dopamine(DA)content in the damaged lateral striatum of the brain of rats were detected by ELISA.RESULTS There was no significant difference in general conditions between the normal control group and the sham operation group,and there was no significant difference in the number of ro-tations,suspension time and number of moving grids.Compared to the sham-op group,the model group rats showed poor spirit,irrita-bility,limb tremor,slow movement,dark yellow fur,less food intake,reduced body weight;the modeling increased number of rota-tions,decreased hanging time and number of moving grids(P<0.01),significantly decreased expression of UB,UBE1,UBE2A,and UCH-L1 positive cells,mRNA and protein expression levels in the damaged lateral striatum(P<0.01),and significantly decreased DA content(P<0.01).Compared with the model group,the general condition of the rats in the madopar group and Compound Di-huang Granule groups was improved,the number of rotations was reduced,the hanging time and number of moving grids were increased(P<0.05,P<0.01),the expression of UB,UBE1,UBE2A,and UCH-L1 positive cells,mRNA and protein expression levels were increased(P<0.05,P<0.01),and the DA content was increased(P<0.01);behavioral tests and the expression levels of various in-dicators were most significantly improved in the madopar group and the high-dose Compound Dihuang Granule group(P<0.05,P<0.01),and there was no statistical significance between the two groups.CONCLUSION Compound Dihuang Granule may play a role in treating PD yin-deficiency and dynamic wind syndrome by regulating the expression of ubiquitin-proteasome system-related proteins,reducing abnormal protein aggregation,and thus alleviating DA content deficiency,and the high-dose Compound Dihuang Granule has the best effect.
4.Exploration on the Effects of Compound Dihuang Granules on Parkinson Disease Rats with Yin Deficiency and Wind Movement Syndrome Based on PI3K/AKT/mTOR Signaling Pathway
Zhijing ZHANG ; Jianqing LIANG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(7):83-90
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.
5.Exploration on the Intervention Effect and Mechanism of Guiqi Yiyuan Ointment Combined with Cisplatin on Lewis Lung Cancer Mice Based on lncRNA H19/miR-19b3p/FTH1 Axis
Chunxia XUE ; Jianqing LIANG ; Yuanyuan ZHANG ; Yinxia JIN ; Shang LI ; Pu ZHANG ; Nan YANG ; Jintian LI ; Juan LI
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(8):90-96
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.
6.Effects of Compound Dihuang Granules on the Expressions of PINK1,Parkin and α-syn in Striatum of Rats with Parkinson Disease Yin-deficiency and Wind Movement Syndrome
Ziwei LYU ; Jianqing LIANG ; Yongqiang KANG ; Guangjie SUN ; Xingling WANG ; Jiancheng HE
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(8):117-125
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.
7.Exploration on the Mechanism of Jiegengbai Powder in the Treatment of Lung Adenocarcinoma Based on Network Pharmacology and Animal Experiments
Chao YUAN ; Jiachen JIANG ; Siqi KONG ; Jianqing LIANG ; Yi ZHANG ; Yue ZHANG ; Yu LIU ; Jintian LI
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(9):33-40
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.
8.Effects of Guiqi Yiyuan Ointment Combined with Cisplatin on Regulating the AMPK/ULK1 Signaling Pathway in Tumor Tissue of Lewis Lung Cancer Bearing Mice
Shang LI ; Jianqing LIANG ; Yinxia JIN ; Nan YANG ; Chunxia XUE ; Juan LI ; Jintian LI
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(9):110-116
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.
9.Exploration on the Mechanism of Shenqi Yiliu Prescription in a Rat Model of Precancerous Lesions of Gastric Carcinoma Based on Transcriptomics
Yue PENG ; Jianqing LIANG ; Yongqiang DUAN ; Min BAI ; Yanying ZHANG ; Junrui HU ; Bing SONG ; Xiaomei YUAN ; Ziyou LIU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(9):131-138
Objective To investigate the intervention mechanism of Shenqi Yiliu Prescription in a rat model of precancerous lesions of gastric carcinoma(PLGC)based on transcriptomics.Methods A PLGC rat model was constructed using composite factor modeling method.Rats were randomly divided into blank group,model group,folic acid group(0.002 g/kg),and Shenqi Yiliu Prescription high-,medium-and low-dosage groups(39.6,19.8 and 9.9 g/kg),with 10 rats in each group.They were given corresponding solutions for gavage for 90 consecutive days.The general condition of rats was observed,HE staining was used to observe the morphology gastric mucosa,immunofluorescence staining was used to detect the expression of PCNA protein in gastric tissue,transcriptomics obtains differentially expressed mRNA in gastric tissue and enriches differentially expressed pathways,ELISA was used to detect the contents of Bcl-xL,C-myc and Cyclin D1 in gastric tissue,RT-qPCR was used to detect the expression of Bcl-xL,C-myc and Cyclin D1 mRNA in gastric tissue,Western blot was used to detect the expressions of IL-6,JAK2,STAT3,p-JAK2 and p-STAT3 protein in gastric tissue.Results Compared with the blank group,rats in the model group showed decreased body mass(P<0.05),with structural disorders of the gastric mucosa,the expression of PCNA protein in gastric tissue increased(P<0.05),the contents and mRNA expression Bcl-xL,C-myc and Cyclin D1 in gastric tissue significantly increased(P<0.05),the expression of IL-6,JAK2,STAT3,p-JAK2,p-STAT3 protein significantly increased(P<0.05).Compared with the model group,the body mass of rats in Shenqi Yiliu Prescription high-and medium-dosage groups increased to varying degrees(P<0.05),the abnormal morphology of the gastric mucosa were improved to different degrees,and the expression of PCNA protein in Shenqi Yiliu Prescription high-,medium-and low-dosage groups significantly decreased(P<0.05).The results of transcriptomics experiments confirmed that the JAK-STAT signalling pathway showed significant differences between the blank group and model group,as well as the model group and Shenqi Yiliu Prescription high-dosage group.The content and mRNA expression of Bcl-xL,C-myc and Cyclin D1 in gastric tissue of Shenqi Yiliu Prescription high-and medium-dosage groups significantly decreased(P<0.05),and the protein expression of IL-6,JAK2,STAT3,p-JAK2 and p-STAT3 significantly decreased(P<0.05).Conclusion Shenqi Yiliu Prescription can improve the abnormal morphology of gastric mucosa in PLGC model rats,and its mechanism is related to regulating the IL-6/JAK2/STAT3 signaling pathway,thereby inhibiting cell proliferation.
10.Effects of Compound Dihuang Granules on the Expressions of DJ-1,IP3R,GRP75 and VDAC1 in Gut-Liver-Brain Axis in Rats with Parkinson Disease with Yin Deficiency and Wind Movement Syndrome
Xingling WANG ; Guangjie SUN ; Ziwei LYU ; Jiancheng HE ; Jianqing LIANG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(10):121-128
Objective To observe the effect of compound Dihuang Granules on the expressions of DJ-1,IP3R,GRP75 and VDAC1 in liver and colonic tissue of Parkinson disease(PD)rats with yin deficiency and wind movement syndrome.Methods 6-Hydroxydopamine was used to inject into the right substantia nigra to prepare PD with yin deficiency and wind movement syndrome rats model.65 rats that successfully modeled were randomly divided into model group,madopar group(madopar 150 mg/kg)and TCM low-,medium-and high-dosage groups(compound Dihuang Granules 1.75,3.5,7 g/kg),with 13 rats in each group;another 13 rats without intervention were selected as the normal control group,and 13 rats were only injected with ascorbic acid solution as sham-operation group.The administration groups were given corresponding drugs by gavage,and the normal control group,sham-operation group and model group were given normal saline by gavage,once a day for 28 consecutive days.The neurobehavioral changes of rats were observed,and the morphology of liver tissue and colonic tissue were observed by HE staining,the protein and mRNA expressions of DJ-1,IP3R,GRP75 and VDAC1 in liver and colonic tissue were detected by immunohistochemical staining,Western blot and RT-PCR,respectively.Results Compared with the normal control group and the sham-operation group,the number of rotation circles of rats in the model group increased,with granular degeneration of liver tissue,loose cytoplasm of cells,slight hepatic steatosis,edema of colonic mucosal and submucosal layers,loose connective tissue,infiltration of a small number of lymphocytes,and significant vascular dilation,the expressions of DJ-1,IP3R,GRP75 and VDAC1 protein and mRNA in liver and colonic tissue were significantly decreased(P<0.01).Compared with the model group,the number of rotation circles of rats in madopar group and TCM groups were significantly decreased,with mild granular degeneration of liver cells,loose cytoplasm,orderly arrangement of hepatic cords,mild edema of the colon,a small amount of lymphocyte and granulocyte infiltration,and a small amount of vascular dilation,the protein and mRNA expressions of DJ-1,IP3R,GRP75 and VDAC1 in liver and colonic tissue significantly increased(P<0.05).The TCM high-dosage group showing the most obvious changes,there was no statistical significance with the madopar group(P>0.05).Conclusion Compound Dihuang Granules may restore endoplasmic reticulum-mitochondria homeostasis,improve gut-liver-brain axis mitochondrial function,protect dopamine neurons,and delay PD by regulating the expressions of DJ-1,IP3R,GRP75 and VDAC1 in liver tissue and colonic tissue.

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