Cardioprotective effect of Chinese herbal medicine for anthracycline-induced cardiotoxicity in cancer patients: A meta-analysis of prospective studies.

BACKGROUND: To assess the benefits and harmful effects of Chinese herbal medicine (CHM) formulations in preventing anthracyclines (ANT)-induced cardiotoxicity. METHOD: The Cochrane Library, Pubmed and EMBASE databases were electronically searched for relevant randomized controlled trials (RCTs) published till December 2021 in English or Chinese-language, in addition to manual searches through the reference lists of the selected papers, and the Chinese Conference Papers Database. Data was extracted by 2 investigators independently. RESULT: Seventeen RCTs reporting 11 different CHMs were included in this meta-analysis. The use of CHM reduced the occurrence of clinical heart failure (RR 0.48, 95% CI 0.39 to 0.60, P < .01) compared to the control group. Data on subclinical heart failure in terms of LVEF values showed that CHM reduced the occurrence of subclinical heart failure (RR 0.47, 95% CI 0.35 to 0.62, P < .01) as well. CONCLUSION: CHM is an effective and safe cardioprotective intervention that can potentially prevent ANT-induced cardiotoxicity. However, due to the insufficient quality of the included trials, our results should be interpreted with cautious.

Juniperus communis extract induces cell cycle arrest and apoptosis of colorectal adenocarcinoma in vitro and in vivo.

Juniperus communis (JCo) is a well-known traditional Chinese medicinal plant that has been used to treat wounds, fever, swelling, and rheumatism. However, the mechanism underlying the anticancer effect of JCo extract on colorectal cancer (CRC) has not yet been elucidated. This study investigated the anticancer effects of JCo extract in vitro and in vivo as well as the precise molecular mechanisms. Cell viability was evaluated using the MTT assay. Cell cycle distribution was examined by flow cytometry analysis, and cell apoptosis was determined by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Protein expression was analyzed using western blotting. The in vivo activity of the JCo extract was evaluated using a xenograft BALB/c mouse model. The tumors and organs were examined through hematoxylin-eosin (HE) staining and immunohistochemistry. The results showed that JCo extract exhibited higher cytotoxicity against CRC cells than against normal cells and showed synergistic effects when combined with 5-fluorouracil. JCo extract induced cell cycle arrest at the G0/G1 phase via regulation of p53/p21 and CDK4/cyclin D1 and induced cell apoptosis via the extrinsic (FasL/Fas/caspase-8) and intrinsic (Bax/Bcl-2/caspase-9) apoptotic pathways. In vivo studies revealed that JCo extract suppressed tumor growth through the inhibition of proliferation and induction of apoptosis. In addition, there was no obvious change in body weight or histological morphology of normal organs after treatment. JCo extract suppressed CRC progression by inducing cell cycle arrest and apoptosis in vitro and in vivo, suggesting the potential application of JCo extract in the treatment of CRC.

[Ruyiping Inhibited Pulmonary Metastasis of Breast Cancer by Regulating the Formation of Pre-metastasis Microenvironment].

Objective To observe the effect of Ruyiping (RYP, a recipe for fighting against re- currence and metastasis of breast cancer) on pre-metastatic microenvironment, and to study its possi- ble mechanism. Methods The experiment was divided into two parts. The 1st part lies in setting the pre- cancerous transfer, and the 2nd part lies in the effect of RYP on pre-metastatic microenvironment. There were 24 BALB/c mice in the 1st part. Logarithmic phase 4T1 cells were dispensed into cell suspension. Blood cells were counted by blood cell counter. Then they were injected into the 4th mammary fat pad of the 24 BALB/c mice under aseptic condition (1 x 106 cells/mL, 0.1 mL for each mouse). There were 60 BALB/c mice in the 2nd part. They were divided into the blank group, the model group, low, middle, high dose RYP groups by random digit table, 12 in each group. The modeling method was the same as men- tioned above. Medication was started from the 2nd day of inoculation. Mice in low, middle, high dose RYP groups were administered with 5. 13, 10. 26, 20. 52 g/kg RYP crude drugs per day by gastrogavage, once per day for 14 successive days. Equal volume of normal saline was administered by gastrogavage to mice in the blank group and the model group. Six mice were sacrificed at day 10, 14, 18, and 22, respectively in the 1 st part of the experiment. The pulmonary metastasis was observed. The histology and mi- cromorphology of lung tissues were observed under light microscope and electron microscope/transmission electron microscopy (TEM) in the 2nd part of the experiment. The relative pulmonary vascular per- meability was determined by Evans blue. The effect of RYP on the formation of pre-metastatic microenvironment was observed. The levels of angiogenin2 (Angpt2), vascular endothelial growth factor (VEGF) , IL6 and IL1 ß were detected by Western blot and Real time PCR. Results The period from day 0 to day 14 was considered to be the pre-metastatic phase. Compared with the model group, significant inhibition on the tumor weight and tumor volume were shown in middle and high dose RYP groups (P <0. 05,P <0. 01). RYP dose-dependently inhibited the tumor weight and tumor volume (P <0. 05,P <0. 01). Infiltration of lymphocytes occurred in the model group and the low dose RYP group. But there was no statistical difference in the morphology of lung tissue in light microscopic results between middle/high dose RYP groups and the blank group. The pulmonary blood vessel net was consisted of continuously densely capillaries. The structure of pulmonary capillaries was normal in the blank group. The blood vessel walls were not regular and even in the model group, with obviously distended capillaries. After treated by RYP, the injury was improved, with normal basic morphology of blood vessels. Compared with the blank group, the exudate in Evans blue was obviously increased, protein and mRNA expressions of Angpt2, VEGF, IL6, and IL1ß were increased in the model group (P <0. 05,P <0. 01). Compared with the model group, the exu- date in Evans blue was obviously decreased in each YRP group. The reduction of the exudate was dose- dependently with the dose of YRP (P <0. 01). Protein and mRNA expressions of VEGF in the middle dose RYP group, protein and mRNA expressions of Angpt2, VEGF, IL6, and ILI1ß were decreased in middle and high dose RYP groups (P <0. 05,P <0. 01). Protein expressions of IL6 were decreased in the middle dose RYP group (P <0. 01). Conclusions RYP had favorable regulation in the tumor growth and the formation of pre-metastatic microenvironment. It could protect the integrity of vascular system, inhibit the formation of pre-metastatic microenvironment possibly through inhibiting the expressions of Angpt2, VEGF, IL6, and IL11ß, and finally inhibiting the occurrence of pulmonary metastasis of breast cancer.

[Inhibitory acting mechanism of psoralen-osthole on bone metastasis of breast cancer--an expatiation viewing from OPG/RANKL/RANK system].

OBJECTIVE: To find the optimal proportion of Composite Fructus Psoralea and Fructus Cnidii (CFPC) for inhibiting the bone metastasis of breast cancer by way of exploring its acting mechanism viewing from OPG/RANKL/RANK system. METHODS: The human bone metastasis of breast cancer model was established by injecting tumor cells of MDA-MB-231BO cell line into the left cardiac ventricle of nude mice. The modeled mice were randomly divided into seven groups: the blank group administered with normal saline by gastrogavage, the positive control group with zoledronic acid via peritoneal injection, and the 5 tested group with CFPC in different proportions of Fructus Psoralea and Fructus Cnidii, i.e., (A, 4:0; B, 3:1; C, 1:1; D, 1:3, and E 0:4), given by gastric infusion. The treatment started from 1 week after modeling and lasted for six weeks. By the end of the experiment, the metastatic foci in bone were imaged by radionuclide tracing method and X-ray photograph, and separated for detecting gene and protein expressions of osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB ligand (RANKL), interleukin-8 (IL-8), parathyroid hormone-related protein (PTHrP), macrophage colony stimulating factor (MCSF) by Real-time PCR and Western blot respectively. RESULTS: Inhibition of bone metastasis gene was displayed to some extent in all the tested groups treated with CFPC, showing an increased level of OPG mRNA expression (It was 60.343 +/- 6.274 in the tested group C), and decreased mRNA expressions of IL-8, PTHrP, MCSF, RANKL (218.010 +/- 12.802, 232.399 +/- 14.354, 319.831 +/- 5.322, and 195.701 +/- 4. 862, respectively in the tested group C). The optimal effect was shown in the tested group C, showing significant difference to that in the blank group (P < 0.01). Meanwhile, the OPG in the bone metastatic foci could be up-regulated and protein expressions of RANKL/IL-8/PTHrP/MCSF down-regulated in all the tested groups. The optimal effect was shown in the tested group C, with significant difference from those of the normal saline group. CONCLUSION: CFPC could inhibit the bone metastasis of breast cancer through activating OPG/RANKL/RANK pathway. Among different proportions of Fructus Psoralea and Fructus Cnidii, 1:1 was the best one.

[Effects of serum containing Fructus Cnidii and Psoralea corylifolia on highly metastatic human breast cancer cell line MDA-MB-231BO and bone marrow stromal cell line ST-2].

OBJECTIVE: To explore the effects of different proportions of Fructus Cnidii (Shechuangzi) and Psoralea corylifolia (Buguzhi) on highly metastatic human breast cancer cell line MDA-MB-231BO and bone marrow stromal cell line ST-2 in vitro. METHODS: Thirty-six female SD rats were randomly divided into 6 groups to prepare the drug-medicated sera by administering with different proportions of Fructus Cnidii and Psoralea corylifolia, including 4:0 group, 3:1 group, 1:1 group, 1:3 group, 0:4 group and control group. MDA-MB-231BO cells and ST-2 cells were cultured in Dulbecco's modified Eagle's medium containing drug-medicated serum. Inhibition rates of MDA-MB-231BO cells and ST-2 cells were measured by methyl thiazolyl tetrazolium (MTT) method; migration ability of MDA-MB-231BO cells was tested by a cell migration experiment; alkaline phosphatase activity (ALP) of ST-2 cells was measured by using 4-nitrophenyl phosphate disodium salt, and mineralized nodule formation of ST-2 cells was measured by alizarin red staining. RESULTS: Sera contaning different proportions of Fructus Cnidii and Psoralea corylifolia inhibited the migration activity of MDA-MB-231BO cells as compared with the blank serum, and serum contaning Fructus Cnidii and Psoralea Corylifolia at proportion of 1:1 had the best function (P<0.01). Fructus Cnidii and Psoralea corylifolia at ratio of 1:1 also enhanced the ALP activity of ST2 cells (P<0.05) and increased the number of mineralized nodules of ST2 cells (P<0.01). CONCLUSION: Kidney-warming recipe of Fructus Cnidii and Psoralea corylifolia can inhibit proliferation and migration of MDA-MB-231BO cells and increase the activity of ST-2 cells.