Journal of Medicinal Food

Cerebral ischemia, a condition with insufficient blood flow in the brain, is associated with cognitive and behavioral changes. The underlying cellular mechanisms of ischemia-induced brain damage include oxidative stress and inflammation. Cerebral ischemia is a major cause of death and long-term disability; thus, investigating novel dietary sources and their therapeutic potentials have gained interest. Seaweed contains various functional phytochemicals with antioxidant and anti-inflammatory effects. Studies have reported that consumption of seaweed is negatively associated with the risk of cardiovascular disease and stroke in humans, but the cellular mechanisms of seaweed's effects are less known. In this review, we discuss the neuroprotective roles of seaweed phytochemicals in various models of cerebral ischemia. We further describe the potential cellular mechanisms such as the effect of seaweed phytochemicals in ischemia-mediated oxidative stress and inflammation. Additional preclinical studies are needed to develop effective dietary interventions for the prevention of ischemia-associated brain damage in humans.

Obesity is currently regarded as a global concern, and the key objectives of the global health strategy include its prevention and control. Probiotic supplementation can help achieve these objectives. This study aimed to assess whether a probiotic strain Lactobacillus paracasei ssp. paracasei, Lactobacillus casei 431 (henceforth, L. casei 431) possesses antiobesogenic properties. High-fat diet-induced obese Sprague-Dawley rats were treated with L. casei 431 for 10 weeks, and the outcomes were compared with those of rats treated with the antiobesity medication orlistat. Body weights, epididymal fat, and tissues from mice were assessed. Furthermore, serological and histological analyses were performed. Epididymal fat accumulation was significantly reduced in groups administered L. casei 431 and orlistat. Furthermore, L. casei 431 and orlistat treatments lowered serum alanine transaminase, aspartate aminotransferase, and triglyceride (TG) levels. Hematoxylin and eosin staining of the liver and epididymal adipose tissues showed that the L. casei 431-treated groups exhibited reduced lipid buildup and adipocyte size. Furthermore, sterol regulatory element-binding protein 1c, adipose TG lipase, and lipoprotein lipase messenger RNA (mRNA) levels were upregulated, leading to lipid oxidation and degradation, in L. casei 431-supplemented groups. Furthermore, carnitine palmitoyltransferase 1, a major factor in lipolysis, was consistently upregulated at the protein level after L. casei 431 administration. Collectively, these results demonstrate the potential of L. casei 431 in alleviating obesity in rats through optimizing lipid metabolism and some related biomarkers.

Good immunity is highly valued in modern society. Although yuja's efficacy in immunity enhancement has been elucidated, there have been few studies on its role. In this study, we investigate the immune enhancement activity of yuja juice extracts (YJEs) and yuja concentrate extracts (YCEs). The immunoregulatory potencies of YJE and YCE were examined by determining cell viability and the expression of cytokines and immune-related molecules in RAW264.7 cells and mouse primary splenocytes. YJE and YCE induced the production of inducible nitric oxide synthase and cytokines (IL-10, IL-4, IL-6, and IFN-γ) at 1000 μg/mL concentration in RAW 264.7 cells. In addition, in mice that were orally administered 3000 or 2000 mg/kg concentrations of YJE or YCE, immune-related cytokines in splenocytes were boosted to levels higher than those in control mice. Importantly, no liver toxicity was observed at all doses. Thus, our results suggest that compounds present in YJEs and YCEs represent novel natural immune-modulatory substances.

Diabetes is highly linked to the occurrence of Alzheimer disease (AD), which is characterized by beta amyloid peptide (Aβ) and hyperphosphorylation of tau (p-tau), and neuron damage particularly in hippocampus. Type 2 diabetes (T2D) is featured by insulin resistance, and phosphorylation of Ser³⁰⁷-IRS-1 is regarded as a resistance marker. Inhibitors of dipeptidyl peptidase-4 (DPP-4) are effective tools for treating T2D. Previously, we reported subfractions of Abelmoschus esculentus (AE, okra) (F1 rich in quercetin glycosides; F2 composed of polysaccharide) attenuated DPP-4 and its downstream signals of insulin resistance, thus preventing Aβ-induced neuron damage. Since autophagy could be protective, we now explore if AE works to modulate neuron autophagy by regulating DPP-4 and insulin resistance and, thus, improves the hippocampal function and behavior. We demonstrated that AE subfractions attenuate Aβ-induced insulin resistance and the expression of p-tau and normalize the autophagy and survival of hippocampal neurons. The action of AE may be attributed to the downregulation of DPP-4, which plays a critical role in mediating insulin resistance and hinders neuron autophagy. The in vivo findings reveal that the hippocampal insulin resistance appears to link with loss of memory, reduction of curiosity, and depression, whereas treatment with AE significantly improves the insulin sensitivity and hippocampal function. Noteworthy, even at only 5 μg/mL, F2 seems to exhibit a meaningful effect. In conclusion, we suggest that AE attenuates insulin resistance and recovers neuron autophagy which are regulated by DPP-4, thus preventing the damage to the hippocampus, improving recognition and emotion. AE may be an effective adjuvant or supplement to prevent insulin resistance-associated pathogenesis of AD if these results can be confirmed in human clinical trials.

Diabetes mellitus (DM) is a chronic disease and one of the oldest known disorders. It is characterized by dysglycemia, dyslipidemia, insulin resistance (IR), and pancreatic cell dysfunction. Although different drugs, metformin (MET), glipizide, glimepiride, etc., have been introduced to treat type 2 DM (T2DM), these drugs are not without side effects. Scientists are now seeking natural treatments such as lifestyle modification and organic products known with limited side effects. Thirty-six male Wistar rats were randomized into six groups (n = 6 per group): control, DM untreated rats, DM+orange peel extract (OPE), DM+exercise (EX), DM+OPE +EX, and DM+MET. The administration was once daily through the oral route and lasted for 28 days. EX and OPE synergistically ameliorated the diabetic-induced increase in fasting blood sugar, homeostatic model assessment for insulin resistance (HOMA IR), total cholesterol (TC) and triglyceride (TG), TC/high-density lipoprotein (HDL), TG/HDL, triglyceride glucose (TyG) index, and hepatic lactate dehydrogenase, alanine transaminase, malondialdehyde, c-reactive protein, and tumour necrosis factor α when compared with the diabetic untreated group. Also, EX+OPE blunted DM-induced decrease in serum insulin, homeostasis model assessment of β-cell function (HOMA-B), homeostasis model assessment of insulin sensitivity (HOMA S), quantitative insulin-sensitivity check index (QUICK 1), HDL, total antioxidant capacity, superoxide dismutase, and hepatic glycogen. Furthermore, EX+OPE ameliorated the observed DM-induced decrease in glucose transporter type 4 (GLUT 4), expression. This study showed that OPE and EX synergistically ameliorate T2DM-induced dysglycaemia, dyslipidaemia, and down-regulation of GLUT4 expression.

The maintenance of bone is dependent on both osteoclasts, which break down bone, and osteoblasts, which build new bone. Various bone-related disorders, including osteoporosis, can occur as a result of an imbalance between these two cell types. Prolonged use of currently available bone resorption inhibitors may show side effects. Therefore, developing a novel preventive material which effectively inhibits osteoclast differentiation could be beneficial. This study planned to investigate the inhibitory effect of wheat sprout ethanolic extracts (Saegeumgang [SGG] and Arriheuk [ARH]) on the differentiation of osteoclasts induced by RANKL, as well as the mechanisms why fundamental to these effects. The effects of SGG and ARH on bone resorption and osteoclast differentiation were evaluated using RAW 264.7 cells and assessed through TRAP cell count, pit formation, and activity. The expressions of mRNA and protein were accomplished using western blotting, and reverse transcription quantitative polymerase chain reaction analyses were conducted. SGG and ARH were found to suppress osteoclast differentiation in RANKL-stimulated RAW264.7 cells without causing cytotoxic effects. In addition, treatment with SGG and ARH led to a reduction in the number of cells with positive staining for TRAP and TRAP activity. SGG and ARH treatment dose-dependently decreased the pit area in pit formation assays, showing a notable reduction compared to the pit area created by mature osteoclasts. SGG and ARH inhibited osteoclast activity by 84.9% and 95.7% at 200 μg/mL, respectively. In addition, SGG and ARH suppressed the transcriptional activation of various osteoclast-related genes, such as RANK, NFATc1, cathepsin K, c-Fos, TRAP, matrix metallopeptidase-9, dendritic cell-specific transmembrane protein, ATPase H+ transporting v0 subunit d2, and osteoclast-associated receptor in RAW264.7 cells treated with RANKL. SGG and ARH extracts were found to affect the expression of NFATc1 and genes that are specific to osteoclasts during osteoclast differentiation, suggesting their potential use as functional foods or as therapeutic interventions targeting bone health.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated and unbalanced immune response to microbial infection. Restoring immune homeostasis and infection control are considered the primary strategies to manage sepsis. Natural bioactives such as polysaccharide and polyphenols from botanicals are known for their immune modulation activity. In this study, we evaluated a standardized aloe-based composition, UP360 (constitute of polysaccharides from Aloe barbadense and Poria cocos and polyphenols from Rosemary officinalis) in lipopolysaccharide (LPS)-induced sepsis and acute inflammatory lung injury murine models. Prophylactic oral administration of UP360 for 7 days at an oral dose of 500 mg/kg improved the survival rate of mice by 62.5%, whereas all mice in the vehicle control group were deceased 82 h after LPS injection. The merit of combining these traditional herbs to yield the standardized composition UP360 was also demonstrated in this model with a mortality rate of only 30.8%, whereas 76.9%, 53.9%, and 61.5% were recorded for each individual constituents A. barbadense, P. cocos, and R. officinalis, respectively. Dose-correlated statistically significant reductions in proinflammatory cytokines and chemokine tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-6, and cytokine-induced neutrophil chemoattractant (CINC)-3 were observed for UP360 when administered at 250 and 500 mg/kg orally for 7 days before induction of acute lung injury (ALI) model in rats. The histopathology data from lung showed statistically significant 37.9% and 37% reductions in the overall lung damage severity and pulmonary edema, respectively, for UP360-treated rats. The aloe-based composition UP360 effectively improved the survival rate of septic animals and mitigated the severity of LPS-induced ALI in vivo. These data warrant further investigation of the composition for a potential application in human as an adjunct supplement in respiratory distress and sepsis.

The present study investigated the impact of aspartame (ASP) on biochemical and histological profiles and the therapeutic potential of aqueous extract of Phyllanthus niruri (PN) in female Swiss albino mice (20 ± 2 g b. w.). ASP (40 mg/kg b. w.) and PN (100 mg/kg b. w.) were fed to the mice for a period of 30 and 60 days. A significant (P ≤ .01) decrease was observed in body weight and relative organ weight in ASP-treated mice. ASP induced a significant (P ≤ .01) increase in lipid profile, bilirubin, creatinine, and enzyme activity. Furthermore, histomorphological changes in the liver and kidney, including atrophy, lesions, and derangement of cellular structure, were observed in ASP-treated animals. However, animals treated with ASP and supplemented with aqueous extract of PN showed significant (P ≤ .01) improvements in enzyme activity and histomorphological changes in the liver and kidney. Aqueous extract of PN mitigates ASP-induced physiological effects, including liver and kidney function markers and histomorphological changes. The study suggests a need for identification of mechanisms of interaction of ASP and its breakdown products once ingested and the bioactive compounds of PN responsible for its therapeutic potential.

In solid tumors, such as breast cancer, hypoxic microenvironment worsens patient prognoses. We have previously reported in MCF-7 breast cancer cells that, under hypoxic conditions, hydroxytyrosol (HT) downregulates the level of reactive oxygen species, reduces the expression of hypoxia inducible factor-1α (HIF-1α), and, at high concentrations, can bind to the aryl hydrocarbon receptor (AhR). With this background, the present study investigated whether the most abundant extra virgin olive oil (EVOO) phenolic compound tyrosol (TYR), with a chemical structure similar to HT but with only one hydroxyl group, exerts comparable effects. Our results revealed that, although TYR did not show any antioxidant activity in hypoxic MCF-7 cells, it inhibited the PI3K/Akt/mTOR/S6 kinase (S6K) pathway and reduced the expression of HIF-1α and some of its target genes. Besides, TYR showed a lower binding affinity with the cytosolic transcription factor AhR, and even reduced its transcriptional activity. Some of these results are positive to control tumor progression in a hypoxic environment; however, they are observed at doses unachievable with diet intake or nutraceutical presentations. Considering that EVOO phenols can have synergistic effects, a mixture of low doses of TYR and other phenols could be useful to achieve these beneficial effects.

The aim of this study was to evaluate the effect of fucoxanthin on metabolic syndrome (MetS), insulin sensitivity, and insulin secretion. A randomized, double-blind, placebo-controlled clinical trial was conducted in 28 patients diagnosed with MetS. Patients were randomly assigned to receive 12 mg of fucoxanthin or placebo once a day for 12 weeks. Before and after the intervention, the components of MetS, insulin sensitivity (Matsuda index), first phase of insulin secretion (Stumvoll index), and total insulin secretion were evaluated during a 2-h oral glucose tolerance test. After fucoxanthin administration, significant differences were observed in body weight (BW) (80.6 ± 11.2 vs. 79.16 ± 12.3 kg, P < .01), body mass index (BMI) (31.1 ± 3.6 vs. 30.3 ± 3.7 kg/m², P < .01), waist circumference (WC) (101.2 ± 9.1 vs. 98.9 ± 9.3 cm, P < .01), systolic blood pressure (SBP) (126.1 ± 10.3 vs. 120.8 ± 9.7 mmHg, P < .01), diastolic blood pressure (DBP) (81.5 ± 6.5 vs. 78.6 ± 6.3 mmHg, P < .01), triglycerides (TG) (2.2 ± 0.7 vs. 2.1 ± 0.7 mmol/L, P < .01), Stumvoll index (2403 ± 621 vs. 2907 ± 732, P < .05), and total insulin secretion (0.84 ± 0.31 vs. 1.02 ± 0.32, P < .05). In conclusion, fucoxanthin administration leads to a decrease in BW, BMI, WC, SBP, DBP, TG, as well as increase in the first phase of insulin secretion and total insulin secretion in patients with MetS.

Clinical Trial Registration number: NCT03613740.