Doxorubicin is a widely used and promising anticancer drug; however, a severe dose-dependent cardiotoxicity hampers its therapeutic value. Doxorubicin may cause acute and chronic issues, depending on the duration of toxicity. In clinical practice, the accumulative toxic dose is up to 400 mg/m² and increasing the dose will increase the probability of cardiac toxicity. Several molecular mechanisms underlying the pathogenesis of doxorubicin cardiotoxicity have been proposed, including oxidative stress, topoisomerase beta II inhibition, mitochondrial dysfunction, Ca²⁺ homeostasis dysregulation, intracellular iron accumulation, ensuing cell death (apoptosis and necrosis), autophagy, and myofibrillar disarray and loss. Natural products including flavonoids have been widely studied both in cell, animal, and human models which proves that flavonoids alleviate cardiac toxicity caused by doxorubicin. This review comprehensively summarizes cardioprotective activity flavonoids including quercetin, luteolin, rutin, apigenin, naringenin, and hesperidin against doxorubicin, both in in vitro and in vivo models.

Doxorubicin has been used as an anticancer drug and has already indicated effective in the treatment of cancer. The incidence of cardiotoxicity due to doxorubicin was approximately 11%, resulting in the limited use of doxorubicin. Cardiac protection during doxorubicin therapy is needed because it can reduce the incidence of heart failure. Vernonia amygdalina (VA) is traditionally used by Indonesians as a traditional medicine and contains many secondary metabolites, including vernolide, vernodalol, vernoamygdalin, vernolepin, luteolin, luteolin 7-O-beta-glucoronoside and luteolin 7-O-glucoside. The pharmacological activity of VA has been widely studied, including its antimalarial, antidiabetic, anticancer, hepatoprotective, nephroprotective, and antioxidant activities. This research aimed to determine the antioxidant 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity, total phenol, total flavonoid, and cardioprotective effects of Vernonia Amygdalina.

Nasri, Harahap U, Silalahi J, Satria D. 2021. Antibacterial activity of lactic acid bacteria isolated from Dengke Naniura of Carp (Cyprinus carpio) against diarrhea-causing pathogenic bacteria. Biodiversitas 22: 3098-3104. Diarrhea is the discharge of liquid or watery stools 3 to 4 times a day caused by a bacterial infection. Treatments for diarrhea are probiotics, which have a beneficial effect on the health of the host such as antibacterial. Traditional Batak Toba fermented food, Dengke Naniura, is a source of probiotics. This study aimed to determine the minimum inhibitory concentration, minimum bactericidal concentration, and leakage of DNA and protein from lactic acid bacteria against pathogens. Isolation of LAB was obtained from Dengke Naniura by pour plate method on deMann Rogosa and Sharpe Agar + CaCO3 1%. In this study, Characterization and analysis of bacterial sequencing used Polymerase Chain Reaction. Determination of MIC used the agar diffusion method. The MBC test used the streaking method which was a stroke from the inhibition zone formed. DNA and protein leakage was measured using spectrophotometry UV-VIS (260nm and 280nm). The isolation results obtained were Lactobacillus fermentum, the characterization showed that the bacteria were Gram-positive, bacilli, non-sporing, catalase-negative, and able to ferment sugar. The MIC determination was obtained at a concentration of 10%v/v with a clear zone diameter. Determination of MBC against pathogens was obtained at different concentrations. The results of DNA and protein leakage showed an increased absorption (260nm and 280nm).

Doxorubicin (DOX) has been extensively utilized in cancer treatment. However, DOX administration has adverse effects, such as cardiac injury. This study intends to analyze the expression of TGF, cytochrome c, and apoptosis on the cardiac histology of rats induced with doxorubicin, since the prevalence of cardiotoxicity remains an unpreventable problem due to a lack of understanding of the mechanism underlying the cardiotoxicity result. Vernonia amygdalina ethanol extract (VAEE) was produced by soaking dried Vernonia amygdalina leaves in ethanol. Rats were randomly divided into seven groups: K- (only given doxorubicin 15 mg/kgbw), KN (water saline), P100, P200, P400, P4600, and P800 (DOX 15 mg/kgbw + 100, 200, 400, 600, and 800 mg/kgbw extract); at the end of the study, rats were scarified, and blood was taken directly from the heart; the heart was then removed. TGF, cytochrome c, and apoptosis were stained using immunohistochemistry, whereas SOD, MDA, and GR concentration were evaluated using an ELISA kit. In conclusion, ethanol extract might protect the cardiotoxicity produced by doxorubicin by significantly reducing the expression of TGF, cytochrome c, and apoptosis in P600 and P800 compared to untreated control K- (p < 0.001). These findings suggest that Vernonia amygdalina may protect cardiac rats by reducing the apoptosis, TGF, and cytochrome c expression while not producing the doxorubicinol as doxorubicin metabolite. In the future, Vernonia amygdalina could be used as herbal preventive therapy for patient administered doxorubicin to reduce the incidence of cardiotoxicity.

Objective: This study was carried out to investigate the antimigration activity of Zanthoxylum acanthopodium DC. in the 4T1 breast cancer cell line. Methods: Zanthoxylum acanthopodium DC. fruit powder was extracted by maceration method with n-hexane and ethylacetate solvents. Cytotoxicity and proliferation were assessed using the MTT method and the cell cycle by flow cytometry. In addition, wound healing assays were conducted by a microscopic method, and expression of COX-2 and VEGFR-2 were determined using qRT-PCR. Results: The IC50 of the ethylacetate fraction (EAF) was 48.1 ± 1.06 μg/mL. The EAE at a concentration 10 μg/mL with viable cells was 62.3 ± 0.28% after 72 h incubation, with accumulation in the G2-M phase, inhibition of cell migration in the wound healing assay, and decrease in expression of COX-2 (0.62 ± 0.01) and VEGFR-2 (0.39 ± 0.003). Conclusion: The results reveal that an ethylacetate fraction of Zanthoxylum acanthopodium DC. fruits provides effective antimigration effects. Further studies are now planned to assess the potential of the ethylacetate fraction to inhibit angiogenesis in breast cancer and determine underlying mechanisms.

Andaliman (Zanthoxylum acanthopodium DC.) fruit is a spice plant widely used in North Sumatra. The chemical content in the Andaliman plant has a cardioprotective effect, with antioxidant properties that inhibit oxidative stress and free radicals. SOD (superoxide dismutase), BNP (Brain Natriuretic Peptide), and cTnT (troponin T) are measured as markers of heart damage, and histopathology is to see heart damage. Quercetin administration was used as a comparison. The hydroalcoholic extract’s phytochemical content and chemical elements were analyzed using LC-HRMS and GC-MS. The findings showed that the hydroalcohol extract of Andaliman fruits affected the blood levels of SOD, BNP, and cTnT in the blood of doxorubicin-induced rats. SOD levels increased, and BNP decreased; the 300 mg/kg BW group was not significantly different from the 50 mg/kg BW quercetin group. cTnT levels also decreased; the 150 mg/kg BW and 300 mg/kg BW groups were not significantly different, and both were better than the 50 mg/kg BW quercetin group. EAF with 150 mg/kg BW and 300 mg/kg BW can also repair damage to rat heart tissue caused by doxorubicin. Andaliman fruit extract has cardioprotective effects and anti-free radical activity due to its content and potential to be developed.