Lipid accumulation in renal cells has been implicated in the pathogenesis of obesity-related kidney disease, and lipotoxicity in the kidney can be a surrogate marker for renal failure or renal fibrosis. Fatty acid oxidation provides energy to renal tubular cells. Ca²⁺ is required for mitochondrial ATP production and to decrease reactive oxygen species (ROS). However, how nifedipine (a calcium channel blocker) affects lipogenesis is unknown. We utilized rat NRK52E cells pre-treated with varying concentrations of nifedipine to examine the activity of lipogenesis enzymes and lipotoxicity. A positive control exposed to oleic acid was used for comparison. Nifedipine was found to activate acetyl Coenzyme A (CoA) synthetase, acetyl CoA carboxylase, long chain fatty acyl CoA elongase, ATP-citrate lyase, and 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase, suggesting elevated production of cholesterol and phospholipids. Nifedipine exposure induced a vast accumulation of cytosolic free fatty acids (FFA) and stimulated the production of reactive oxygen species, upregulated CD36 and KIM-1 (kidney injury molecule-1) expression, inhibited p-AMPK activity, and triggered the expression of SREBP-1/2 and lipin-1, underscoring the potential of nifedipine to induce lipotoxicity with renal damage. To our knowledge, this is the first report demonstrating nifedipine-induced lipid accumulation in the kidney.

Memory impairment has been shown to be associated with glutamate (Glu) excitotoxicity, homocysteine (Hcy) accumulation, and oxidative stress. We hypothesize that Glu and Hcy could damage neuronal cells, while astaxanthin (ATX) could be beneficial to alleviate the adverse effects. Using PC12 cell model, we showed that Glu and Hcy provoked a huge amount of reactive oxygen species (ROS) production, causing mitochondrial damage at EC₅₀ 20 and 10 mm, respectively. The mechanisms of action include: (1) increasing calcium influx; (2) producing ROS; (3) initiating lipid peroxidation; (4) causing imbalance of the Bcl-2/Bax homeostasis; and (5) activating cascade of caspases involving caspases 12 and 3. Conclusively, the damages caused by Glu and Hcy to PC12 cells can be alleviated by the potent antioxidant ATX.

Metastasis of hepatocellular carcinoma (HCC) is usually unrecognized before any pathological examination, resulting in time-taking treatment and poor prognosis. As a consequence, HCC patients usually show symptoms of depression. In order to suppress such psychiatric disorders and to facilitate better treatment outcome, antidepressants are prescribed. Up to present, information about the effect of antidepressants on HCC is still lacking. Therefore, we chose fluoxetine (FXT), one of the top five psychiatric prescriptions in the United States, together with the HepG2 cell model to explore its effect on HCC. Our study found that FXT (5 µM) increased the migratory distance of HepG2 cells by a factor of nearly 1.7 compared to control. In addition, our study also investigated the effect of genipin (GNP), which is an active compound from Gardenia jasminoides Ellis fruit (family Rubiaceae), on the FXT-induced HepG2 cells. Our study found that 30 and 60 µM GNP reduced the migratory distance by 42% and 74% respectively, compared to FXT treatment alone. Furthermore, we also found that FXT upregulated matrix metalloproteinases (MMPs) genes, increased the protein expression of MMPs, urokinase-type plasminogen activator (uPA), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), activator protein 1 (AP-1), phosphorylated mitogen-activated protein kinase (P-p38), phosphorylated protein kinase B (P-Akt), downregulated tissue inhibitor metalloproteinases (TIMPs) genes and decreased the TIMPs proteins expression whereas, GNP fully counteracted the action of FXT. Conclusively, this study has provided valuable information regarding the possible molecular mechanisms through which FXT affects the metastatic invasiveness of HepG2 cells and evidences to support that GNP counteracts such effect via the same molecular mechanisms.

Grapefruit (G) parts contain abundant phenolic acids and flavonoids (PPNs and FLVs). The wastes created from exocarps, mesocarps (G wastes, GW) and waste blanching water (WBW) lead to a considerable loss of PPNs and FLVs. Here, we assessed Buntan (CB), Buntan Hayata (CBH), and Peiyu (CP) cultivars and observed considerable amounts of PPNs and FLVs. The ethanolic extracts of GW (GWE) and WBW contained gallic acid, protocatechuic acid, chlorogenic acid, caffeic acid, ferulic acid, coumaric acid, naringin, hesperidin, diosmin, quercetin, hesperetin, nobiletin, and tangeretin (GWC). GWE has previously been reported to be a relatively active antioxidant, anti-inflammatory (based on the expression of TNF-α in Raw264.7 cells), antihypertensive, and anti-hyperglycemic compound. The IC₅₀ values for antihyperglycemic activity with WBW for α-amylase were as follows: CB (27.96 ± 0.03 mg/mL) < CP (28.13 ± 0.19 mg/mL) < CBH (41.60 ± 0.16 mg/mL), and those for α-glucosidase were CB (1.80 ± 0.03 mg/mL) < CP (2.97 ± 0.29 mg/mL) < CBH (9.10 ± 0.51 mg/mL). GWC upregulated Glut4 in HepG2 cells, as well as the insulin secretion capability, and intracellular levels in RIN-m5F cells, and it downregulated DPP4 in HepG2 cells. The IC₅₀ values for the angiotensin-converting enzyme activity were: CBP (5.10 ± 0.02 mg/mL) < CB (7.24 ± 0.65 mg/mL) < CP (8.60 ± 2.03 mg/mL). Our results indicate that PPNs and FLVs present in GW are worth reclaiming.

Changes in human life style have increased the incidence of obesity which has become a risk factor to human health. In Taiwan, the annual production of Citrus grandis [L.] reaches 75 000 tons, while the amount of waste fruits could reach 5%. We propose that abundant phytochemicals present in the wastes can be beneficial to attenuate obesity with hyperlipidemia. An animal Wistar rat model showed that pomelo flesh, peels, carpel (the segmental membrane), as well as the essential oil attenuated obesity as well as hyperlipidemia, and the AMPK–SREBP–PPARS pathway was involved. To further verify the mechanism, a HepG2 cell model was used to test some representative pomelo phytonutrients including limonene (Ln), γ-terpinene (γT), p-synephrine (SP), β-sitosterol (βS), and hesperidin (Hn). Data interestingly revealed it to be a multiple mechanism of anti-lipogenic bioactivity via downregulating the enzymes involved in both the cholesterol and triacylglyceride de novo biosynthesis (in the order of decreasing bioactivity): acetyl CoA carboxylase (Hn, SP, βS, Ln = γT), fatty acid synthase (Ln, γT, SP, βS, Hn), HMG-CoA synthase (Ln, Hn, SP, βS, γT), and HMG-CoA reductase (Hn, Ln, βS, γT, SP), and via upregulation of cholesterol-7α-monooxygenase (CYP7A1) (Hn, βS). In addition, all pomelo fruit parts enhanced the fecal crude lipid and sterol excretion capability. Thus, fruits of C. grandis can serve as a rather promising integrative antihyperlipidemic agent.

The effect of dyslipidemia on peritoneal dialysis (PD) patients based on the presence of residual renal function (RRF; renal creatinine clearance >2 mL/min/1.73 m²) is unknown. Data from the Taiwan Renal Registry Data System between 2005 and 2012 were analyzed to estimate the association between dyslipidemia and mortality in PD patients. Long-term PD patients (n = 8032) were divided into groups with (RRF; n = 2691, 33.5%) and without RRF (non-RRF; n = 5341, 66.5%). The primary outcome was three-year mortality, and multivariate Cox regression was used for survival analysis. After stratifying the total cholesterol (TC) level between the first and third years, the hazard ratio for mortality was estimated. In the non-RRF group, TC < 120 mg/dL was associated with independently increased risk of mortality. In the RRF group, low TC was not independently correlated with increased mortality, but TC > 285 mg/dL was associated with increased risk. PD patients with higher level of TC (>200 mg/dL) in both first and third years of dialysis had significantly lower risk of mortality. In this nationwide cohort study, PD patients without RRF who had low TC level had the highest mortality, in contrast to those with RRF. Malnutrition in long-term PD patients without RRF is an important issue to be monitored.