Poncirus trifoliata Aqueous Extract Protects Cardiomyocytes against Doxorubicin-Induced Toxicity through Upregulation of NAD(P)H Dehydrogenase Quinone Acceptor Oxidoreductase 1.

Doxorubicin (DOX), an anthracycline-based chemotherapeutic agent, is widely used to treat various types of cancer; however, prolonged treatment induces cardiomyotoxicity. Although studies have been performed to overcome DOX-induced cardiotoxicity (DICT), no effective method is currently available. This study investigated the effects and potential mechanisms of Poncirus trifoliata aqueous extract (PTA) in DICT. Changes in cell survival were assessed in H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells. The C57BL/6 mice were treated with DOX to induce DICT in vivo, and alterations in electrophysiological characteristics, serum biomarkers, and histological features were examined. The PTA treatment inhibited DOX-induced decrease in H9c2 cell viability but did not affect the MDA-MB-231 cell viability. Additionally, the PTA restored the abnormal heart rate, R-R interval, QT interval, and ST segment and inhibited the decrease in serum cardiac and hepatic toxicity indicators in the DICT model. Moreover, the PTA administration protected against myocardial fibrosis and apoptosis in the heart tissue of mice with DICT. PTA treatment restored DOX-induced decrease in the expression of NAD(P)H dehydrogenase quinone acceptor oxidoreductase 1 in a PTA concentration-dependent manner. In conclusion, the PTA inhibitory effect on DICT is attributable to its antioxidant properties, suggesting the potential of PTA as a phytotherapeutic agent for DICT.

Cycling of phosphorus from wastewater to fertilizer using wood ash after energy production.

Quercus wood was used for thermal energy production, and wood bottom ash (WDBA) was used as a medium for water purification and soil fertilizer in accordance with the recently proposed food-water-energy nexus concept. The wood contained a gross calorific value of 14.83 MJ kg-1, and the gas generated during thermal energy production has the advantage of not requiring a desulfurization unit due to its low sulfur content. Wood-fired boilers emit less CO2 and SOX than coal boilers. The WDBA had a Ca content of 66.0%, and Ca existed in the forms of CaCO3 and Ca(OH)2. WDBA absorbed P by reacting with Ca in the form of Ca5(PO4)3OH. Kinetic and isotherm models revealed that the results of the experimental work were in good agreement with the pseudo-second-order and Langmuir models, respectively. The maximum P adsorption capacity of WDBA was 76.8 mg g-1, and 6.67 g L-1 of WDBA dose could completely remove P in water. The toxic units of WDBA tested using Daphnia magna were 6.1, and P adsorbed WDBA (P-WDBA) showed no toxicity. P-WDBA was used as an alternative P fertilizer for rice growth. P-WDBA application resulted in significantly greater rice growth in terms of all agronomic values compared to N and K treatments without P. This study proposed the utilization of WDBA, obtained from thermal energy production, to remove P from wastewater and replenish P in the soil for rice growth.

Value-added application of cattle manure bottom ash for phosphorus recovery from water and replenishment in soil.

This study addresses ways to circulate the flow of phosphorus (P) from water to soil to improve water quality and provide a sustainable supply of P into soil. Here, bottom ash (BA_CCM), the byproduct of the combustion of cattle manure, which is performed for obtaining energy, was used to remove P in wastewater. Next, the P-captured BA_CCM was used as P fertilizer for rice growth. BA_CCM was primarily composed of Ca (49.4%), C (24.0%), and P (9.9%), and the crystalline phases of Ca were calcium carbonate (CaCO3) and hydroxyapatite (Ca5(PO4)3OH). The mechanism of P removal by BA_CCM involves the formation of hydroxyapatite by reacting Ca2+ with PO43-. A reaction time of 3 h was required to achieve P adsorption to BA_CCM, and the maximum P adsorption capacity of BA_CCM was 45.46 mg/g. The increase in solution pH reduced P adsorption. However, at pH > 5, the P adsorption amount was maintained regardless of the pH increase. The presence of 10 mM SO42- and CO32- reduced P adsorption by 28.4% and 21.5%, respectively, and the impact of the presence of Cl- and NO3- was less than 10%. The feasibility of BA_CCM was tested using real wastewater, and 3.33 g/L of BA_CCM dose achieved a P removal ratio of 99.8% and a residual concentration of <0.02 mg/L. The toxicity unit of BA_CCM determined for Daphnia magna (D. magna) was 5.1; however, the BA_CCM after P adsorption (P-BA_CCM) did not show any toxicity to D. magna. BA_CCM after P adsorption was used as an alternative to commercial P fertilizer. Rice fertilized with a medium level of P-BA_CCM showed better agronomic values for most agronomic traits, except root length, than that seen with the commercial P fertilizer. This study suggests that BA_CCM can be used as a value-added product to address environmental issues.

Restoring phosphorus from water to soil: Using calcined eggshells for P adsorption and subsequent application of the adsorbent as a P fertilizer.

This study investigated the solution for two environmental issues: excess of P in water and its deficiency in soil, which is restored by transferring the adsorbed P from water into the soil using eggshell as an adsorbent. The eggshells were calcined at different temperatures to improve their adsorption capacity, and evaluated for their physical/chemical properties and P adsorption capacity. The eggshells calcined at 800 °C (CES-800) had the highest P adsorption; CaCO3 decomposed into 23.6% of CaO and 40.8% of Ca(OH)2, eluting more Ca that reacted with soluble P in water. X-ray diffraction analysis confirmed that CES-800 removed P as hydroxylapatite by reacting with Ca. Pseudo-first-order and Langmuir models suitably described the kinetic and equilibrium of P adsorption by CES-800, respectively. The maximum adsorption capacity of CES-800 was 108.2 mg g-1. As the solution pH increased from 3 to 11, the adsorption amount decreased from 99.8 mg g-1 to 62.3 mg g-1. The feasibility of CES-800 as a filter medium was assessed using real lake water under dynamic flow conditions; > 90% of P removal was achieved at 158 h, and the P adsorbed was 11.5 mg g-1. When CES-800 and P adsorbed CES-800 (P-CES-800) were applied to the soil at the studied rates, the earthworms were unaffected by toxicity, suggesting the use of both adsorbents in soil without adverse effects. The shoot fresh weight, tiller number, and total dry weight significantly increased in P-CES-800 applied rice plants compared to the control plants, indicating that P-CES-800 can be a good alternative to conventional P-fertilizer in rice cultivation.

Inhibition of melanogenesis by Aster yomena callus pellet extract in melanoma cells and patients with skin pigmentation.

Plant tissue culture holds immense potential for the production of secondary metabolites with various physiological functions. We recently established a plant tissue culture system capable of producing secondary metabolites from Aster yomena. This study aimed to uncover the mechanisms underlying the potential therapeutic effects of Aster yomena callus pellet extract (AYC-P-E) on photoaging-induced skin pigmentation. Excessive melanogenesis was induced in B16F10 melanoma cells using α-melanocyte stimulating hormone (α-MSH). The effects of AYC-P-E treatment on melanin biosynthesis inducers and melanin synthesis inhibition were assessed. Based on the results, a clinical study was conducted in subjects with skin pigmentation. AYC-P-E inhibited melanogenesis in α-MSH-treated B16F10 cells, accompanied by decreased mRNA and protein expression of melanin biosynthesis inducers, including cyclic AMP response element-binding protein (CREB), tyrosinase, microphthalmia-associated transcription factor (MITF), tyrosinase related protein-1 (TRP-1), and TRP-2. This anti-melanogenic effect was mediated by mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) phosphorylation. Treatment of subjects with skin pigmentation with AYC-P-E-containing cream formulations resulted in 3.33%, 7.06%, and 8.68% improvement in the melanin levels at 2, 4, and 8 weeks, respectively. Our findings suggest that AYC-P-E inhibits excessive melanogenesis by activating MEK/ERK and AKT signaling, potentiating its cosmetic applications in hyperpigmentation treatment.

Comparative Analysis of Metabolite Profiling of Momordica charantia Leaf and the Anti-Obesity Effect through Regulating Lipid Metabolism.

This study investigated the effects of Momordica charantia (M. charantia) extract in obesity and abnormal lipid metabolism in mice fed high fat diet (HFD). Fruit, root, stem, and leaf extracts of M. charantia were obtained using distilled water, 70% ethanol and 95% hexane. M. charantia leaf distilled water extract (MCLW) showed the highest antioxidant activity in both 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity tests and reducing power. Metabolite profiles of M. charantia leaf extracts were analyzed for identification of bioactive compounds. HFD-fed mice were treated with MCLW (oral dose of 200 mg/kg/d) for 4 weeks. MCLW reduced lipid accumulation, body weight, organ weight, and adipose tissue volume and significantly improved glucose tolerance and insulin resistance in HFD mice. Furthermore, MCLW administration reduced serum total cholesterol and low-density lipoprotein cholesterol, and increased serum high-density lipoprotein cholesterol compared with HFD mice. Moreover, MCLW significantly reduced the levels of serum urea nitrogen, alanine aminotransferase, alkaline phosphatase, and aspartate aminotransferase; alleviated liver and kidney injury. MCLW decreases expression of genes that fatty acid synthesis; increase the expression of catabolic-related genes. These results indicate that MCLW has an inhibitory effect on obese induced by high fat diet intake, and the mechanism may be related to the regulation of abnormal lipid metabolism in liver and adipose tissue, suggesting that MCLW may be a suitable candidate for the treatment of obesity.

Metabolomic Analysis of Morus Cultivar Root Extracts and Their Ameliorative Effect on Testosterone-Induced Prostate Enlargement in Sprague-Dawley Rats.

We investigated the metabolite changes of Morus roots (MRs) according to different cultivar families (Simheung, Daesim, Cheong-il, Sangchon, Daeseong, Suhong, Suwon, and Igsu) using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) to understand the relationship between different cultivars and metabolite changes. Data were analyzed by partial least squares discriminant analysis (PLS-DA), and samples were successfully separated in PLS-DA scores. Eight metabolites in the electrospray ionization (ESI)-positive mode and 16 metabolites in the ESI-negative mode contributed to the separation in PLS-DA. Our data suggest that comparative analysis of MR metabolites according to different cultivars is useful to better understand the relationship between the different cultivars and metabolite changes. Furthermore, we analyzed the MRs for their ability to improve benign prostatic hyperplasia (BPH). LNCaP cells were used to evaluate the prostate-specific antigen (PSA) inhibitory activity of MRs, and, amongst them, the extract with the highest activity was selected. Igsu demonstrated the highest inhibition effect of prostate-specific antigen (PSA) expression among the MR cultivars. Igsu was also evaluated by administration in a testosterone-induced benign prostatic hyperplasia model in Sprague-Dawley rats. Igsu was shown to ameliorate BPH as evidenced by the prostate index, expression of androgen receptor (AR) signaling-related protein, growth factors, cell proliferation-related proteins, apoptosis-related proteins, mitogen-activated protein kinase (MAPK) signaling proteins, and histological analysis. Hence, this study strongly suggests that Igsu may have a beneficial effect of on BPH.

Anticancer effects of O-desmethylangolensin are mediated through cell cycle arrest at the G2/M phase and mitochondrial-dependent apoptosis in Hep3B human hepatocellular carcinoma cells.

In the present study, in order to investigate the anticancer effects of O-desmethylangolensin (O-DMA) on human hepatocellular carcinoma Hep3B cells, we first examined the antiproliferative effect of O-DMA. When Hep3B cells were treated with O-DMA at various concentrations (5-200 µM) for 24, 48 or 72 h, cell proliferation decreased significantly in a dose- and time-dependent manner. Moreover, O-DMA exposure at the IC50 concentration for 72 h arrested cells at the G2/M phase, which was accompanied by a reduction in CDK1, and an increase in cyclin A and B. Under the same conditions, O-DMA significantly increased the number of sub-G1 phase cells. Additionally, an Annexin V assay revealed that exposure to O-DMA affected the rate of cell apoptosis. O-DMA caused the downregulation of Bcl-2 and upregulation of Bax, which led to cytochrome c release from the mitochondria and activation of caspase-3. Taken together, these data suggest that O-DMA exhibits anticancer activity by arresting the cell cycle at G2/M phase and causing mitochondrial-dependent apoptosis in Hep3B cells.