Astragali Radix (AR), a traditional Chinese medicine (TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use. While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy (DIC); however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action. Through network medicine analysis, astragaloside IV (AsIV) and formononetin (FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsIV-FMT combination (AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsIV and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.
Animals ; Doxorubicin/adverse effects* ; Saponins/administration & dosage* ; Isoflavones/pharmacology* ; Rats ; Cardiomyopathies/prevention & control* ; Mice ; Fatty Acids/metabolism* ; Myocytes, Cardiac/metabolism* ; Triterpenes/administration & dosage* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Cardiotonic Agents/administration & dosage* ; Mice, Inbred C57BL ; Cell Line ; Astragalus Plant/chemistry* ; Astragalus propinquus

Objective To investigate the impact of different kinds of laparoscopic surgery including conventional blunt elimination and modified acute elimination on sex hormone, antral follicle count and ovarian volume of patients with endometriosis (EMs). Methods 100 patients with EMs were chosen from January 2013 to April 2016 and randomly divided into control group (50 patients) with conventional blunt elimination and observation group (50 patients) with modified acute elimination; and the thickness of elimination lesion, the removal rate of ovary cortex, the thickness of ovarian cortex, the level of serum sex hormones, the AFC number of affected side and the volume of ovary before and after operation of the two groups were compared. Results There was no significant difference in the thickness of lesion elimination, the removal rate and removed thickness of ovarian cortical between the two groups (P > 0.05). The thickness of lesion elimination and the thickness of ovarian cortex in middle position of observation group were significantly lower than that in control group (P < 0.05). The thickness of lesion elimination, removed thickness of ovarian cortical and the removal rate of ovary cortex in hilus ovarii in observation group were significantly lower than that in control group (P < 0.05). There was no significant difference in the levels of serum sex hormones before and after treatment between the two groups (P > 0.05). There was no significant difference in the levels of AFC number of affected side before and after treatment (P > 0.05). The levels of AFC number of affected side in hilus ovarii of control group after treatment were significantly lower than that before treatment (P < 0.05). The volume of ovary of both groups after treatment were significantly lower than that before treatment (P < 0.05). The volume of ovary of observation group after treatment were significantly higher than that in control group (P < 0.05). Conclusion Compared with conventional blunt elimination, modified acute elimination in the treatment of patients with EMs can efficiently shorten the operation time, reduce the surgical trauma degree, speed up the recovery process after operation, regulate the level of FSH and AMH and be helpful to protect the ovarian reserve function.

OBJECTIVEThe chemopreventive activity and mechanism of dehydroepiandrosterone (DHEA) were studied.

METHODSModel of 7, 12-dimethylbenz (alpha) anthracene (DMBA) induced breast carcinoma in Sprague-Dawley rats, uitra-violet (UV)-induced DNA damage and Salmonella mutation assay were used.

RESULTSIn DMBA-induced rat mammary tumor model, the rats were orally given daily DHEA for 2 weeks before DMBA and continued for 10 weeks after DMBA administration. The results showed significant inhibition of tumor development by DHEA. The incidence of mammary carcinoma also decreased significantly on daily dose of oral 25 mg/kg DHEA with the mean tumor volume per rat also remarkably reduced by 92%. Moreover, 25 mg/kg DHEA treatment could significantly increase the carcinoma latency for about 3.5 weeks as compared with the control. Using polymerase chain reaction (PCR) assay, in vitro 10(-9) mol/L DHEA showed significant inhibitory effect on UV-induced DNA damage by 90%. In Ames test, DHEA was found to decrease DMBA and benzo (alpha) pyrene-induced TA98 and TA100 His(+) revertants markedly and the number of Salmonella clones were significantly reduced by 53.2% and 73.0% on dose of 5 microgram DHEA/plate. It was also shown that in vitro 10(-7) mol/L DHEA could also effectively inhibit the G-6-PDH activity, which might play an important role in its chemoprophylaxis activities.

CONCLUSIONThe results strongly prove that DHEA is a potent cancer chemoprophylaxis agent, which exhibits inhibitory potential on mutation and chemical carcinogen in vivo and in vitro.

9,10-Dimethyl-1,2-benzanthracene ; administration & dosage ; Adjuvants, Immunologic ; pharmacology ; Animals ; Antimutagenic Agents ; pharmacology ; DNA Damage ; drug effects ; Dehydroepiandrosterone ; pharmacology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Glucosephosphate Dehydrogenase ; antagonists & inhibitors ; metabolism ; Mammary Neoplasms, Experimental ; chemically induced ; prevention & control ; Mutagenicity Tests ; Rats ; Rats, Sprague-Dawley ; Salmonella ; drug effects ; genetics ; Time Factors ; Tumor Cells, Cultured