ABSTRACT
This study aims to explore the mechanism of Yanghe Decoction(YHD) against subcutaneous tumor in pulmonary metastasis from breast cancer, which is expected to lay a basis for the treatment of breast carcinoma with YHD. The chemical components of medicinals in YHD, and the targets of the components were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The disease-related targets were searched from GeneCards and Online Mendelian Inheritance in Man(OMIM). Excel was employed to screen the common targets and plot the Venn diagram. The protein-protein interaction network was constructed. R language was used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. A total of 53 female SPF Bablc/6 mice were randomized into normal group(same volume of normal saline, ig), model group(same volume of normal saline, ig), and low-dose and high-dose YHD groups(YHD, ig, 30 days), with 8 mice in normal group and 15 mice in each of the other groups. Body weight and tumor size was measured every day. Curves for body weight variation and growth of tumor in situ were plotted. In the end, the subcutaneous tumor sample was collected and observed based on hematoxylin and eosin(HE) staining. The mRNA and protein levels of hypoxia inducible factor-1α(HIF-1α), pyruvate kinase M2(PKM2), lactate dehydrogenase A(LDHA), and glucose transporter type 1(GLUT1) were detected by PCR and Western blot. A total of 213 active components of YHD and 185 targets against the disease were screened out. The hypothesis that YHD may regulate glycolysis through HIF-1α signaling pathway to intervene in breast cancer was proposed. Animal experiment confirmed that the mRNA and protein levels of HIF-1α, PKM2, LDHA, and GLUT1 in the high-and low-dose YHD groups were lower than those in the model group. YHD has certain inhibitory effect on subcutaneous tumor in pulmonary metastasis from breast cancer in the early stage, which may intervene pulmonary metastasis from breast cancer by regulating glycolysis through HIF-1α signaling pathway.
Subject(s)
Female , Mice , Animals , Glucose Transporter Type 1/genetics , Network Pharmacology , Animal Experimentation , Saline Solution , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional , Signal Transduction , Glycolysis , RNA, Messenger , Neoplasms/drug therapy , Molecular Docking SimulationABSTRACT
Objective:To investigate the therapeutic effect of Yanghe decoction combined with Tounongpowder on patients with acute plasma cell mastitis and its influence on inflammatory factors.Methods:A total of 120 patients with acute plasma cell mastitis admitted to Yantai Affiliated Hospital of Binzhou Medical College from May 2019 to May 2020 were selected, and divided into control group (60 cases) and combination group (60 cases). The control group was treated with western medicine, and the combination group was treated with Yanghe decoction and Tounongpowder on the basis of the control group. Seven days was 1 course and a total of 4 courses were continued. The scores of symptoms and signs and clinical effects of the two groups before treatment and 1 month after treatment were compared. The serum interleukin(IL)-1β and IL-6 were measured by radioimmunoassay, and tumor necrosis factor-α(TNF-α) was measured by enzyme-linked immunosorbent assay.Results:After 1 month of treatment, the scores of breast swelling, breast lumps, breast pain, breast fistula symptoms and signs in the two groups were significantly decreased, the scores of above index in the combination group were significantly lower than those in the control group, and the differences were statistically significant ( P<0.05). The total effective rate in the combined group was higher than that in control group: 91.7%(55/60) vs. 76.7% (46/60), and the difference was statistically significant ( χ2 = 8.456, P<0.05). After 1 month of treatment, the serum levels of IL-1β, IL-6 and TNF-α in the two groups were significantly reduced, and the serum levels of above 3 index in the combination group were significantly lower than those in the control group: (3.24 ± 0.92) ng/L vs. (3.81 ± 1.02) ng/L, (1.12 ± 0.42) ng/L vs. (1.41 ± 0.35) ng/L, (32.27 ± 19.03) ng/L vs. (43.04 ± 21.58) ng/L, and the differences were statistically significant ( P<0.05). After treatment, the liver and kidney functions of the two groups were not abnormal, and the differences in adverse reactions such as headache, dizziness, nausea and vomiting were not statistically significant ( P>0.05). Conclusions:Yanghe decoction combined with Tounongpowder can significantly improve the clinical symptoms of patients with acute plasma cell mastitis, with a definite clinical effect. Its mechanism of action may be related to reducing the levels of IL-1β, IL-6, and TNF-α and reducing the inflammatory response.
ABSTRACT
Objective To investigate the effect of Yanghe decoction serum on the proliferation of breast cancer stem cells MDA-MB-231 and the expression of Smad3 and NF-κB. Methods According to the random number table method, 20 female SD rats were divided into blank control group and Yanghe decoction high, medium and low dose group. Drug serum were given gastric gavage of Yanghe decoction 28, 14, 7 g/kg, and control group were given gastric gavage of same volume saline. Each group of rats was given orally for 3 days to prepare 10% Yanghe decoction serum and blank serum. MDA-MB-231 cells were divided into blank control group and Yanghe decoction low, medium and high dose group according to random number table method. Low, medium and high dose Yanghe decoction groups were cultured with medium containing 10% Yanghe decoction high, medium and low dose drug serum, and the blank control group was cultured with medium containing 10% control serum. After drug intervention, the effects of each group on the proliferation of MDA-MB-231 cells at 24 h, 48 h, and 72 h were detected by MTT assay. The expression of Smad3 and NF-κB protein in each group was detected by Western blot. The expression of Smad3 and NF-κB mRNA in each group were detected by real-time fluorescence quantitative PCR. Results Compared to the control group, Yanghe decoction low, medium and high dose group of cells for 24 h (1.143 ± 0.093, 0.953 ± 0.069, 0.874 ± 0.041 vs. 1.239 ± 0.160), 48 h (1.223 ± 0.129, 0.989 ± 0.093, 0.864 ± 0.105 vs. 1.389 ± 0.095), 72 h (1.092 ± 0.147, 0.881 ± 0.095, 0.719 ± 0.086 vs. 1.353 ± 0.150) proliferation activity were significantly lower (P<0.05 or P<0.01). After 48 h of drug intervention, the expression of Smad3 protein (0.974 ± 0.098, 0.844 ± 0.084, 0.789 ± 0.105 vs. 1.214 ± 0.012), NF-κB p50 protein (0.994 ± 0.047, 0.911 ± 0.015, 0.765 ± 0.084 vs. 1.147 ± 0.103) in the low, medium and high dose Yanghe decoction group were significantly lower than those in the control group (P<0.05 or P<0.01). The expression of Smad3 mRNA (1.223 ± 0.129, 0.989 ± 0.093, 0.864 ± 0.105 vs.1.389 ± 0.095), NF-κB mRNA (1.092 ± 0.147, 0.881 ± 0.095, 0.719 ± 0.086 vs. 1.353 ± 0.150) significantly decreased in the Yanghe decoction group (P<0.05 or P<0.01). Conclusions Yanghe decoction can inhibit the proliferation of breast cancer stem cell MDA-MB-231, and lower the expression of Smad3 and NF-κB.
ABSTRACT
Objective@#To investigate the effect of Yanghe decoction serum on the proliferation of breast cancer stem cells MDA-MB-231 and the expression of Smad3 and NF-κB.@*Methods@#According to the random number table method, 20 female SD rats were divided into blank control group and Yanghe decoction high, medium and low dose group. Drug serum were given gastric gavage of Yanghe decoction 28, 14, 7 g/kg, and control group were given gastric gavage of same volume saline. Each group of rats was given orally for 3 days to prepare 10% Yanghe decoction serum and blank serum. MDA-MB-231 cells were divided into blank control group and Yanghe decoction low, medium and high dose group according to random number table method. Low, medium and high dose Yanghe decoction groups were cultured with medium containing 10% Yanghe decoction high, medium and low dose drug serum, and the blank control group was cultured with medium containing 10% control serum. After drug intervention, the effects of each group on the proliferation of MDA-MB-231 cells at 24 h, 48 h, and 72 h were detected by MTT assay. The expression of Smad3 and NF-κB protein in each group was detected by Western blot. The expression of Smad3 and NF-κB mRNA in each group were detected by real-time fluorescence quantitative PCR.@*Results@#Compared to the control group, Yanghe decoction low, medium and high dose group of cells for 24 h (1.143 ± 0.093, 0.953 ± 0.069, 0.874 ± 0.041 vs. 1.239 ± 0.160), 48 h (1.223 ± 0.129, 0.989 ± 0.093, 0.864 ± 0.105 vs. 1.389 ± 0.095), 72 h (1.092 ± 0.147, 0.881 ± 0.095, 0.719 ± 0.086 vs. 1.353 ± 0.150) proliferation activity were significantly lower (P<0.05 or P<0.01). After 48 h of drug intervention, the expression of Smad3 protein (0.974 ± 0.098, 0.844 ± 0.084, 0.789 ± 0.105 vs. 1.214 ± 0.012), NF- κB p50 protein (0.994 ± 0.047, 0.911 ± 0.015, 0.765 ± 0.084 vs. 1.147 ± 0.103) in the low, medium and high dose Yanghe decoction group were significantly lower than those in the control group (P<0.05 or P<0.01). The expression of Smad3 mRNA (1.223 ± 0.129, 0.989 ± 0.093, 0.864 ± 0.105 vs.1.389 ± 0.095), NF-κB mRNA (1.092 ± 0.147, 0.881 ± 0.095, 0.719 ± 0.086 vs. 1.353 ± 0.150) significantly decreased in the Yanghe decoction group (P<0.05 or P<0.01).@*Conclusions@#Yanghe decoction can inhibit the proliferation of breast cancer stem cell MDA-MB-231, and lower the expression of Smad3 and NF-κB.
ABSTRACT
Objective To investigate the effect of Yanghe decoction serum on the proliferation of breast cancer stem cells HMLER90hi and its mechanism. Methods Twenty female Sprague-Dawley rats were randomly divided into low,medium and high dose groups containing drug serum and control group, in order to prepare the Yanghe decoction serum and blank serum. After 24 hours of drug intervention,the effects of each group on the proliferation of HMLER90hi cells at 24 h,48 h,and 72 h were detected by MTT assay. The expression of EphA4 and p50 mRNA in each group were detected by real-time fluorescence quantitative PCR. Results Compared with the blank control group,the cell proliferation activity of each dose group of Yanghe decoction significantly decreased at 24 h (0.818 ± 0.061, 0.706 ± 0.073, 0.587 ± 0.052 vs. 0.928 ± 0.075), 48h (0.760 ± 0.047, 0.638 ± 0.056, 0.510 ± 0.059 vs. 0.973 ± 0.095), and 72 h (0.672 ± 0.102, 0.508 ± 0.092, 0.448 ± 0.048vs.1.023 ± 0.099) (P<0.05 orP<0.01), respectively. After 24 h of drug intervention, compared with the control group, the expression of EphA4 mRNA (0.54 ± 0.07, 0.54 ± 0.07, 0.33 ± 0.04 vs.0.68 ± 0.09) significantly decreased, and p50 mRNA (0.69 ± 0.10, 0.54 ± 0.08, 0.41 ± 0.06vs. 0.85 ± 0.13) significantly decreased in each dose group of Yanghe decoction (P<0.05 orP<0.01).ConclusionsTheYanghe decoction can inhibit the proliferation of breast cancer stem cell HMLER90hi,and its mechanism may be related to its inhibition of the conduction of the juxtacrine pathway of monocyte macrophage.
ABSTRACT
Objective To observe the changes of iNOS, COX-2 and NF-κB in breast cancer MCF-7 cells treated with Yanghe decoction containing serum. Methods The MCF-7 human breast cancer cells were divided into blank group, low dose group, middle dose group and high dose group (4.5, 9, 18 g/kg, respectively). Real-time RT-PCR was used to detect the mRNA expression of iNOS and COX-2 at 24, 48, 72 and 96 hours, and Western-blot was used to detect the expression of NF-κB protein. Results Compared with the blank group, the expression of iNOS and COX-2 mRNA in the low dose group, middle dose group and high dose group decreased significantly at 24, 48, 72 and 96 hours(P<0.05), the the expression of NF-κB protein in the low dose group, middle dose group and high dose group decreased significantly at 24, 48, 72 and 96 hours (P<0.05). So it reduced with the increase of drug concentration and time. There was no significant difference in 72 hours after intervention. Conclusions The Yanghe decoction could reduce the expression of NF-κB, and then reducing the related inflammatory factors COX-2 and iNOS.
ABSTRACT
Objective To observe the therapeutic effect of modified Yanghe Decoction combined with analgesic western medicine on relieving cancerous pain and constipation and on improving the quality of life ( QOL) of osseous metastasis patients. Methods A total of 200 patients with cancerous pain were evenly randomized into treatment group and control group in the admission order. The control group was given oral use of oxycodone hydrochloride controlled-release tablets, and the treatment group was given modified Yanghe Decoction on the basis of treatment for the control group. Twenty-one days constituted one treatment course. After one treatment course, the effect on relieving pain and constipation and on improving QOL were evaluated in both groups. Results (1) The analgesic efficiency was 95.0 % in the treatment group, and was 81.0 % in the control group, the analgesic efficiency of the treatment group was better than that of the control group ( P<0.05) . ( 2) Constipation occurred in 92 cases of the treatment group and was relieved to various degrees in 88 cases after treatment, with an efficiency of 95.7%. In the control group, constipation occurred in 91 cases, but was not relieved after treatment. The treatment group had better effect on relieving constipation than the control group (P<0.05) . (3) The total effective rate on improving QOL was 89.0% in the treatment group and was 71.0% in the control group, the difference being significant (P<0.05) . (4) Both groups had 2 cases of drug-induced mild hepatic damage, and the damage disappeared after symptomatic treatment . Conclusion Modified Yanghe Decoction combined with analgesic western medicine shows good toxicity-reducing and efficiency-enhancing effect for the treatment of cancerous pain.
ABSTRACT
Objective To investigate the curative effect of modified Yanghe decoction on pulmonary interstitial fibrosis.Methods In this study,62 patients suffering fiom pulmonary interstitial fibrosis were randomly divided into 2 groups with the use of the Random Number Table method.31 cases in the treatment group were treated with modified Yanghe decoction,while 31 cases in the control group were treated with prednisone,40 mg/d (produced by Zhejiang Xianju Pharmaceutical Factory).The dosages of prednisone were gradually reduced a month later.The changes and improvement in symptoms,pulmonary function,chest CT,etc were observed and analyzed after three month.Results The study showed that the total?effective?rates of the treatment group and control group were 83.9％ (26/31) and 58.1％ (18/31) respectively,and the difference had statistical significance (P=0.031,P＜0.05).The integrals of gasping,breathlessness,cough and Velcros Rale of the treatment group before the treatment were (3.1 ± 2.61),(4.1 ± 1.53),(1.38 ± 1.02),(1.56 ±2.34)respectively while those of the control group were (2.83±2.34),(3.90±1.67),(1.28±1.24),(1.61±2.14) respectively.The after-treatment integrals of the treatment group were (1.1 ± 1.06),(1.52± 1.40),(0.36±0.71),(0.65±0.67)respectively while those of the control group were(1.2± 1.33),(2.15±1.31),(0.41±0.70),(0.78 ± 0.30)respectively.Compwered with their symptoms before the treatment,there was obviousimprovement in the symptoms of both groups after the treatment,(P＜0.05),but the difference in these aspects between the two groups had no statistical significance (P＞0.05).Before the treatment,the total lung capacity,vital capacity,diffusion function,arterial oxygen pressure of the treatment group were (69.80±21.7) ％,(73.16±16.38) ％,(51.46± 16.42) ％,(69.70± 10.74) mm Hg (1 mm Hg=0.133 kPa) respectively while those of the control group were(77.52 ± 15.96)％,(74.57 ± 20.73)％,(55.68 ± 17.27)％,(64.86 ± 11.40)mm Hg respectively.After the treatment,the total lung capacity,vital capacity,mass function,arterial oxygen pressure of the treatment group were (82.31±21.65)％,(83.66±17.32)％,(62.34±17.96)％,(83.51±9.37)mm Hg respectively while those of the control group were (85.06± 16.10) ％,(85.72± 20.40) ％,(68.32± 20.16) ％,(79.61 ±9.41)mm Hg respectively.Compwered with their symptoms before the treatment,there was obvious improvement in the symptoms of both groups after the treatment (P＜0.05),but the difference in these aspects between the two groups had no statistical significance (P＞0.05).Conclusion Modified Yanghe decoction can be effectively applied in the prevention and treatment of pulmonary interstitial fibrosis.