Showing papers in "Journal of Medicinal Food in 2023"

The Effect of Apple-Derived Nanovesicles on the Osteoblastogenesis of Osteoblastic MC3T3-E1 Cells

Abstract: Osteoporosis is characterized by low bone mass and elevated structural deterioration of the bone tissue, resulting in bone weakness with an increased risk of fracture. Considering biological activities of various phytochemicals extracted from apples, we herein demonstrated the potential antiosteoporotic effects of apple-derived nanovesicles (apple NVs) using osteoblastic MC3T3-E1 cells. Apple NVs significantly stimulated the growth of MC3T3-E1 cells. The cellular alkaline phosphatase (ALP) activity was significantly upregulated in the 5 μg/mL apple NVs-treated group. In addition, the concentrarion of mineralized nodules was significantly increased in the apple NVs-treated groups. Furthermore, apple NVs increased the expression of the genes and proteins associated with osteoblast growth and differentiation, such as Runx2, ALP, OPN, and BMP2/4, which further activated ERK- and JNK-related mitogen-activated protein kinase signaling. These results demonstrate that apple NVs have a potential to prevent osteoporosis by promoting osteoblastogenesis in osteoblastic MC3T3-E1 cells through regulating the BMP2/Smad1 pathways.

Potential Mechanisms of <i>Perillae folium</i> Against COVID-19: A Network Pharmacology Approach

Abstract: In China, Perillae folium is widely used to treat colds, especially in the early stages of cold; the effect of taking P. folium is readily noticeable at that time. The active compounds and targets of P. folium were screened from Traditional Chinese Medicine Systems Pharmacology, Chinese Pharmacopoeia, and UniProt. Targets related to the initiation and progression of 2019 Coronavirus Disease (COVID-19) were retrieved from Online Mendelian Inheritance in Man and GeneCards. The potential therapeutic targets of P. folium on COVID-19 were the cross targets between them. Enrichment analysis of Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were conducted by using the Database for Annotation, Visualization and Integrated Discovery website. Molecular docking between key compounds and core targets was performed with AutoDock. The effects of P. folium extract and rosmarinic acid on inflammatory cytokines were tested by a cellular inflammatory model. The “Perillae folium-compound-target-COVID-19” network contained 11 kinds of compounds and 33 matching targets. There were 261 items in the GO functions (P < .05) and 67 items linked to the KEGG signaling pathways (P < .05). Luteolin and rosmarinic acid were key compounds of P. folium. Their docking with the core targets mitogen-activated protein kinase 1 (MAPK1) and chemokine (C-C motif) ligand 2 (CCL2), respectively, showed that they had good affinity with each other. Cell experiments demonstrated that P. folium extract had inhibitory effects on interleukin-6 and tumor necrosis factor (TNF)-α in cells, and was better than rosmarinic acid. Luteolin, rosmarinic acid, and other individual active compounds in P. folium, which may participate in PI3K-Akt, TNF, Jak-STAT, COVID-19, and other multisignaling pathways through multiple targets such as MAPK1 and CCL2, and play a therapeutic role in COVID-19.

Dietary Intervention with Quercetin Attenuates Diesel Exhaust Particle-Instilled Pulmonary Inflammation and Behavioral Abnormalities in Mice

Abstract: Exposure to diesel exhaust particles (DEPs) is inevitable and closely linked with increased health hazards, causing pulmonary abnormalities by increasing inflammation, hypoxia, and so on. Moreover, long-term exposure to DEPs may trigger whole-body toxicity with behavioral alterations. Therefore, nutritional intervention with natural components may be desirable to prevent and/or ameliorate DEP-inducible pathophysiology in mammals. Quercetin has been demonstrated to reduce metabolic complications by possessing antioxidative, anti-inflammatory, and antimutagenic effects. In this study, we investigated the effects of quercetin on pulmonary inflammation and behavioral alteration in male C57BL/6 mice against DEP instillation. The experimental mice were separated into four treatment groups (n = 8 per group), which include: vehicle control, DEP instillation, dietary intervention with a low dose of quercetin (20 mg/kg) for 14 days with DEP instillation for 7 days, or dietary intervention with a high dose of quercetin (100 mg/kg) for 14 days with DEP instillation for 7 days. Compared with the DEP-instilled group, dietary intervention with quercetin significantly attenuated eosinophils in the bronchoalveolar lavage fluid analysis, pulmonary cytokine, and hypoxic mRNA expressions regardless of quercetin concentrations. DEP instillation triggered hyperactivities in the experimental mice, while quercetin pretreatment successfully normalized DEP-inducible abnormalities regardless of the dosage. Therefore, dietary intervention with quercetin may be an applicable means to prevent DEP-triggered pulmonary and behavioral abnormalities.

Dietary Intervention with Quercetin Attenuates Diesel Exhaust Particle-Instilled Pulmonary Inflammation and Behavioral Abnormalities in Mice.

Abstract: Exposure to diesel exhaust particles (DEPs) is inevitable and closely linked with increased health hazards, causing pulmonary abnormalities by increasing inflammation, hypoxia, and so on. Moreover, long-term exposure to DEPs may trigger whole-body toxicity with behavioral alterations. Therefore, nutritional intervention with natural components may be desirable to prevent and/or ameliorate DEP-inducible pathophysiology in mammals. Quercetin has been demonstrated to reduce metabolic complications by possessing antioxidative, anti-inflammatory, and antimutagenic effects. In this study, we investigated the effects of quercetin on pulmonary inflammation and behavioral alteration in male C57BL/6 mice against DEP instillation. The experimental mice were separated into four treatment groups (n = 8 per group), which include: vehicle control, DEP instillation, dietary intervention with a low dose of quercetin (20 mg/kg) for 14 days with DEP instillation for 7 days, or dietary intervention with a high dose of quercetin (100 mg/kg) for 14 days with DEP instillation for 7 days. Compared with the DEP-instilled group, dietary intervention with quercetin significantly attenuated eosinophils in the bronchoalveolar lavage fluid analysis, pulmonary cytokine, and hypoxic mRNA expressions regardless of quercetin concentrations. DEP instillation triggered hyperactivities in the experimental mice, while quercetin pretreatment successfully normalized DEP-inducible abnormalities regardless of the dosage. Therefore, dietary intervention with quercetin may be an applicable means to prevent DEP-triggered pulmonary and behavioral abnormalities.

Potential Mechanisms of Perillae folium Against COVID-19: A Network Pharmacology Approach.

Abstract: In China, Perillae folium is widely used to treat colds, especially in the early stages of cold; the effect of taking P. folium is readily noticeable at that time. The active compounds and targets of P. folium were screened from Traditional Chinese Medicine Systems Pharmacology, Chinese Pharmacopoeia, and UniProt. Targets related to the initiation and progression of 2019 Coronavirus Disease (COVID-19) were retrieved from Online Mendelian Inheritance in Man and GeneCards. The potential therapeutic targets of P. folium on COVID-19 were the cross targets between them. Enrichment analysis of Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were conducted by using the Database for Annotation, Visualization and Integrated Discovery website. Molecular docking between key compounds and core targets was performed with AutoDock. The effects of P. folium extract and rosmarinic acid on inflammatory cytokines were tested by a cellular inflammatory model. The "Perillae folium-compound-target-COVID-19" network contained 11 kinds of compounds and 33 matching targets. There were 261 items in the GO functions (P < .05) and 67 items linked to the KEGG signaling pathways (P < .05). Luteolin and rosmarinic acid were key compounds of P. folium. Their docking with the core targets mitogen-activated protein kinase 1 (MAPK1) and chemokine (C-C motif) ligand 2 (CCL2), respectively, showed that they had good affinity with each other. Cell experiments demonstrated that P. folium extract had inhibitory effects on interleukin-6 and tumor necrosis factor (TNF)-α in cells, and was better than rosmarinic acid. Luteolin, rosmarinic acid, and other individual active compounds in P. folium, which may participate in PI3K-Akt, TNF, Jak-STAT, COVID-19, and other multisignaling pathways through multiple targets such as MAPK1 and CCL2, and play a therapeutic role in COVID-19.

Effect of Panax ginseng and Fructus Mume on Intestinal Barrier and Gut Microbiota in Rats with Diarrhea.

Abstract: Panax ginseng and Fructus mume (Renshen Wumei in Chinese, RW) are natural medicines with high nutritional and pharmacological value. They have been widely used together in China to treat gastrointestinal diseases, especially persistent diarrhea, but the potential mechanisms remain elusive. In this study, a diarrhea model was established in rats using a 30% aqueous extract of senna. The therapeutic effects of RW were evaluated by recording the prevalence of loose stools, the diarrhea index, and histopathological changes in colon tissue. The levels of mucins, tight junction (TJ) proteins, inflammatory cytokines, and phosphoinositide 3-kinase/Akt/nuclear factor-κB (PI3K/Akt/NF-κB) signaling pathway proteins were measured. Metagenomic sequencing was used to analyze the gut microbiota. Treatment with RW alleviated injury to the intestinal barrier in rats with diarrhea and also upregulated levels of Muc2 and TJ proteins, such as occludin, zonula occludens-1, and claudin-1. Administration of RW regulated the structure of the gut microbiota in diarrheal rats. Furthermore, RW suppressed levels of interleukin (IL), tumor necrosis factor (TNF)-α, IL-1, PI3K, Akt, and p-NF-κB p65 and also increased IL-4 levels. Our study indicates that P. ginseng and Fructus mume help improve the symptoms of diarrhea, possibly by alleviating the intestinal barrier injury, regulating intestinal flora composition, and inhibiting the PI3K/Akt/NF-κB signaling pathway.

Anti-Inflammatory Activity of Phenylethanoids from <i>Acanthus ilicifolius</i> var. <i>xiamenensis</i>

Abstract: Acanthus ilicifolius var. xiamenensis is a traditional herbal medicine in China. In this study, the anti-inflammatory activities of active ingredients of A. ilicifolius var. xiamenensis were investigated in RAW 264.7 cells and Freund's complete adjuvant-induced arthritic rats. Results showed that n-butanol extract exerted antiarthritic potential by reducing paw edema, arthritis score, and altered hematological and biochemical parameters in experimental rats. Phytochemical studies on n-butanol extract resulted in the isolation of five alkaloids (1–5) and five phenylethanoids (6–10). The anti-inflammatory assay of compounds 1–10 on lipopolysaccharide (LPS)-treated RAW 264.7 cells indicated that phenylethanoids 9 and 10 exhibited notable inhibitory activities. The result indicated that compounds 9 and 10 attenuated inflammation by decreasing the production of nuclear factor kappa-B (NF-κB) p65, inhibitory subunit of NF kappa B alpha, Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), and inducible nitric oxide synthase in LPS-mediated RAW 264.7 macrophages. Phenylethanoids 9 and 10 increased the expression of interleukin-10 and endothelial nitric oxide synthase. Therefore, compounds 9 and 10 showed anti-inflammatory activity by regulation of NF-κB and JAK/STAT signaling pathways.

Effect of Fucoxanthin on Metabolic Syndrome, Insulin Sensitivity, and Insulin Secretion.

Abstract: 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.

Effect of <i>Panax ginseng</i> and <i>Fructus Mume</i> on Intestinal Barrier and Gut Microbiota in Rats with Diarrhea

Abstract: Panax ginseng and Fructus mume (Renshen Wumei in Chinese, RW) are natural medicines with high nutritional and pharmacological value. They have been widely used together in China to treat gastrointestinal diseases, especially persistent diarrhea, but the potential mechanisms remain elusive. In this study, a diarrhea model was established in rats using a 30% aqueous extract of senna. The therapeutic effects of RW were evaluated by recording the prevalence of loose stools, the diarrhea index, and histopathological changes in colon tissue. The levels of mucins, tight junction (TJ) proteins, inflammatory cytokines, and phosphoinositide 3-kinase/Akt/nuclear factor-κB (PI3K/Akt/NF-κB) signaling pathway proteins were measured. Metagenomic sequencing was used to analyze the gut microbiota. Treatment with RW alleviated injury to the intestinal barrier in rats with diarrhea and also upregulated levels of Muc2 and TJ proteins, such as occludin, zonula occludens-1, and claudin-1. Administration of RW regulated the structure of the gut microbiota in diarrheal rats. Furthermore, RW suppressed levels of interleukin (IL), tumor necrosis factor (TNF)-α, IL-1, PI3K, Akt, and p-NF-κB p65 and also increased IL-4 levels. Our study indicates that P. ginseng and Fructus mume help improve the symptoms of diarrhea, possibly by alleviating the intestinal barrier injury, regulating intestinal flora composition, and inhibiting the PI3K/Akt/NF-κB signaling pathway.

Effects of Mixed Nut Consumption on Blood Glucose, Insulin, Satiety, and the Microbiome in a Healthy Population: A Pilot Study

Abstract: Nuts contain many health-promoting nutrients, fiber, and phytochemicals. Nut consumption has been reported to improve several chronic disease risk factors. Most studies to date have investigated single variety nut consumption. A nut mixture may offer a more diverse array of nutrients over single variety nuts. The primary outcome of this study was to examine the effects of mixed nut consumption on postprandial glucose, insulin, and satiety in healthy young adults. Exploratory outcomes include the effects of daily nut consumption on stool microbiome and bowel movement patterns. Twenty participants were randomized to consume either 42 g of mixed nuts or 46 g of potato chips daily for 3 weeks. Mixed nut consumption did not alter postprandial blood glucose and insulin, while potato chip consumption increased glucose and insulin (P < .05). There were no significant differences in fasting blood glucose or insulin for either snack after 3 weeks of daily consumption. Both snacks increased satiety while there were no significant differences in body weight, body fat, blood pressure, waist-to-hip ratio, or anxiety. After 3 weeks of snack consumption, both groups significantly reduced straining during bowel movements while the mixed nut group slightly increased stool amount. There were no significant changes in microbiome composition for either group; however, there was a nonsignificant trend toward increased Firmicutes to Bacteroidetes ratio in the potato chip group and an opposite trend in the mixed nut group. The results of this study suggest that mixed nuts are a healthy alternative for blood sugar control. The study was registered at ClinicalTrials.gov, Number: NCT03375866.

Gochujang Consumption Prevents Metabolic Syndrome in a High-Fat Diet Induced Obese Mouse Model

Abstract: High-fat and high-salt diets are risk factors for metabolic syndrome development. However, gochujang, which has a high salt content, possesses antiobesity properties in cell and animal models. We aimed to evaluate the effects of Sunchang traditional and modern factory produced gochujang on metabolic syndrome factors in high-fat diet (HFD)-induced obese mice. For 14 weeks, 4-week-old C57BL/6J male mice were separated into five groups and fed a normal diet (ND), a high-fat diet only (HD), a HD with salt (SALT), a HD with traditional Sunchang gochujang (TS), and HD with modern factory made Sunchang gochujang (FS). Compared to HD and SALT groups, the gochujang groups had lower body weight, blood leptin, and insulin levels with reduced Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index and improved serum and liver lipid profiles. In addition, gochujang supplemented groups exhibited a significant reduction in mRNA expression of anabolic lipid metabolism related factors; PPARγ, CEBPα, and FABP4, and a significant increase in mRNA expression of energy expenditure-related factors; PPARα and CPT1. Protein expressions of SREBP1 were downregulated in the gochujang fed groups. TS and FS intakes improved obesity in HFD-induced obese mice. Compared to the gochujang groups, the SALT group did not exhibit any of those benefits suggesting that the high salt content of gochujang has different effects compared with added salt alone. Our findings provide evidence that gochujang could be a functional food to attenuate metabolic syndrome.

Sesamin Attenuates Obesity-Associated Nonalcoholic Steatohepatitis in High-Fat and High-Fructose Diet-Fed Mice

Abstract: This study explored the effects of sesamin on nonalcoholic steatohepatitis (NASH). High-fat and high-fructose diet-fed mice supplemented with or without sesamin. The results suggested that sesamin-treated mice lost body weight and fat tissue weight, had lower levels of serum metabolic parameters, and insulin resistance was mitigated. Histological examinations showed that sesamin treatment mitigated the progression of hepatic steatosis, and inflammation. In addition, sesamin enhanced hepatic antioxidant capacity, and decreased the activations of hepatic c-jun N-terminal kinase, inhibitor of kappa B kinase α, and insulin receptor substrate 1 as well as hepatic interleukin-6 and tumor necrosis factor-alpha levels. Further experiments indicated that sesamin treatment downregulated GRP78 and phospho-inositol-requiring enzyme 1 (IRE1) expression, and upregulated x-box binding protein 1 (XBP1) expression in hepatic tissue. The aforementioned results suggest that sesamin alleviates obesity-associated NASH, which might be linked to the effect of sesamin on the regulation of the hepatic endoplasmic reticulum stress-IRE1/XBP1 pathway. Thus, sesamin may be a good food functional ingredient in the treatment of obesity-associated NASH.

Antiobesity Effect of N-Acetylneuraminic Acid by Enhancing Antioxidative Capacity in Mice Fed a High-Fat Diet.

Abstract: The sialic acid N-acetylneuraminic acid (NANA), an essential factor in bioregulation, is a functional food component that is known to have beneficial health effects, but its antiobesity effect has not been clearly understood. Adipocyte dysfunction in obesity involves a decrease in the level of NANA sialylation. In this study, we investigated the antiobesity effect of NANA in mice fed a high-fat diet (HFD) and in 3T3-L1 adipocytes. Male C57BL/6J mice were randomly divided into three groups and administered the following diets: a normal diet, an HFD, and an HFD with 1% NANA supplementation for 12 weeks. NANA supplementation significantly reduced body weight gain; epididymal adipose tissue hypertrophy; and serum lipid, fasting glucose, and aspartate transaminase levels compared with those in HFD mice. The percentage of lipid droplets in hepatic tissue was also decreased by NANA supplementation in HFD mice. The downregulation of Adipoq expression and upregulation of Fabp4 expression induced by HFD in epididymal adipocytes were improved by NANA supplementation. The downregulation of Sod1 expression and increase in malondialdehyde level were induced by HFD, and they were significantly improved in the liver by NANA supplementation, but not in epididymal adipocytes. However, NANA supplementation had no effect on sialylation and antioxidant enzyme levels in mouse epididymal adipocytes and 3T3-L1 adipocytes. Overall, NANA exerts antiobesity and antihypolipidemic effects and may be beneficial in suppressing obesity-related diseases.

Myo-Inositol Attenuates Renal Interstitial Fibrosis in Obstructive Nephropathy by Inhibiting PI3K/AKT Activation.

Abstract: Emerging evidence suggests that myo-inositol (MI) has a critical role in reducing renal inflammatory processes and improving podocyte function and preventing diabetes-related renal damage. We aimed to explore the function and underlying workings of MI in renal interstitial fibrosis (RIF). Based on a mouse model, we explored the effect of MI in unilateral ureteral obstruction (UUO) and in transforming growth factor-β1 (TGF-β1)-treated HK-2 cells. Pathological changes of the kidney tissues were examined following staining of the tissues with hematoxylin, eosin, and Masson's trichrome. The mRNA quantities of fibrosis markers, fibronectin, α-smooth muscle actin (α-SMA), and collagen I, were analyzed by means of real-time polymerase chain reaction, whereas those of protein levels were assessed with Western blotting. We also determined the expression of collagen I by immunofluorescence, and the levels of phosphorylated phosphotidylinositol-3-kinase and protein kinase B (PI3K/AKT) by Western blot. In vivo, histopathological examination in the UUO mice revealed renal tubular epithelial cell necrosis, inflammatory cell infiltration, and RIF. UUO mice showed higher expression levels of collagen I, fibronectin, α-SMA, pPI3K, and pAKT compared with sham-operated mice. However, MI treatment diminished the pathological alterations of RIF in UUO mice and downregulated the expression of fibrosis markers and phosphorylated PI3K/AKT. In vitro, TGF-β1 positively influenced the propagation and differentiation of HK-2 cells and upregulated the levels of α-SMA, fibronectin, collagen I, pPI3K, and pAKT, but these became significantly reversed by MI treatment. In conclusion, MI ameliorates RIF, possibly by negatively regulating TGF-β1-induced epithelial transdifferentiation and PI3K/AKT activation.

Gochujang Consumption Prevents Metabolic Syndrome in a High-Fat Diet Induced Obese Mouse Model.

Abstract: High-fat and high-salt diets are risk factors for metabolic syndrome development. However, gochujang, which has a high salt content, possesses antiobesity properties in cell and animal models. We aimed to evaluate the effects of Sunchang traditional and modern factory produced gochujang on metabolic syndrome factors in high-fat diet (HFD)-induced obese mice. For 14 weeks, 4-week-old C57BL/6J male mice were separated into five groups and fed a normal diet (ND), a high-fat diet only (HD), a HD with salt (SALT), a HD with traditional Sunchang gochujang (TS), and HD with modern factory made Sunchang gochujang (FS). Compared to HD and SALT groups, the gochujang groups had lower body weight, blood leptin, and insulin levels with reduced Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index and improved serum and liver lipid profiles. In addition, gochujang supplemented groups exhibited a significant reduction in mRNA expression of anabolic lipid metabolism related factors; PPARγ, CEBPα, and FABP4, and a significant increase in mRNA expression of energy expenditure-related factors; PPARα and CPT1. Protein expressions of SREBP1 were downregulated in the gochujang fed groups. TS and FS intakes improved obesity in HFD-induced obese mice. Compared to the gochujang groups, the SALT group did not exhibit any of those benefits suggesting that the high salt content of gochujang has different effects compared with added salt alone. Our findings provide evidence that gochujang could be a functional food to attenuate metabolic syndrome.

Radical Scavenging-Linked Anti-Obesity Effect of Standardized <i>Ecklonia stolonifera</i> Extract on 3T3-L1 Preadipocytes and High-Fat Diet-Fed ICR Mice

Abstract: Ecklonia stolonifera, belonging to the Laminariaceae family, is an edible widely distributed perennial brown marine alga that is rich in polyphenols. Dieckol, a bioactive component of the E. stolonifera extract (ESE), is a major phlorotannin compound found only in brown algae. This study aimed to evaluate the ability of ESE to inhibit lipid accumulation caused by oxidative stress in 3T3-L1 adipocytes and high-fat diet-fed obese ICR mice. We report that ESE-treated obese ICR mice, which were fed a high-fat diet, showed reduced whole-body and adipose tissue weights with improved plasma lipid profiles. In vitro and in vivo studies have indicated that ESE inhibited the expression of adipogenesis-related genes associated with fat accumulation through AMP-activated protein kinase activity and increased the expression of lipolysis-related genes. In addition, ESE reduced the expression of enzymes involved in reactive oxygen species (ROS) production and increased the expression of antioxidant enzymes, thereby reducing ROS levels. These findings suggest that ESE possesses strong antioxidant properties and inhibits oxidative stress-induced lipid accumulation by reducing ROS production during adipocyte generation.

Efficacy of Veronica incana for Treating Osteoarthritis Induced by Monosodium Iodoacetate in Rats.

Abstract: The aim of this study is to investigate the efficacy and the underlying mechanism of Veronica incana in osteoarthritis (OA) induced by intraarticular injection of monosodium iodoacetate (MIA). The selected major four compounds (A-D) of V. incana were found from fractions 3 and 4. Its structure elucidation was determined by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) data analysis and nuclear magnetic resonance (NMR) data comparison with literature. MIA (50 μL with 80 mg/mL) for the animal experiment was injected into the right knee joint. The V. incana was administered orally every day to rats for 14 days from 7 days after MIA treatment. Finally, we confirmed the four compounds: (A) verproside; (B) catalposide; (C) 6-vanilloylcatapol; and (D) 6-isovanilloylcatapol. When we evaluated the effect of V. incana on the MIA injection-induced knee OA model, there were a noticeable initial decreased in hind paw weight-bearing distribution compared to the Normal group (P < .001), but V. incana supplementation resulted in a significant increase in the weight-bearing distribution to the treated knee (P < .001). Moreover, the V. incana treatment led to a decrease in the levels of liver function enzymes and tissue malondialdehyde (P < .05 and .01). The V. incana significantly suppressed the inflammatory factors through the nuclear factor-kappa B signaling pathway and downregulated the expression of matrix metalloproteinases, which are involved in the degradation of the extracellular matrix (P < .01 and .001). In addition, we confirmed the alleviation of cartilage degeneration through tissue stains. In conclusion, this study confirmed the major four compounds of V. incana and suggested that V. incana could serve as an anti-inflammatory candidate agent for patients with OA.

Orange Peel Extract and Physical Exercise Synergistically Ameliorate Type 2 Diabetes Mellitus-Induced Dysmetabolism by Upregulating GLUT4 Concentration in Male Wistar Rats.

Abstract: 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.

Preventive Activity of Patchouli Alcohol Against Colorectal Cancer and Diabetes.

Abstract: Patchouli alcohol (PA) is a tricyclic sesquiterpene and the dominant bioactive component in oil extracted from the aerial parts of Pogostemon cablin (patchouli). It has been reported to possess diverse health-beneficial activities, including anti-inflammatory, antiobese, and anticancer activities. However, preclinical studies are required to explore the possibility of developing PA as a promising functional and promising drug for the prevention and treatment of human diseases. In this study, we used animal models to examine whether PA shows benefits in inflammation-induced colorectal cancer and obesity-induced diabetes. ApcMin/+ mice for colorectal cancer model were treated PA 0, 25 and 50 mg/kg body weight three times a week for 6 weeks along with 2% dextran sulfate sodium (DSS) in drinking water for 1 week. High-fat diet (HFD)-induced obesity mice were treated with PA 0, 25, and 50 mg/kg bodyweight three times a week for 8 weeks. Oral administration of PA to ApcMin/+ mice treated with DSS significantly suppressed formation and development of tumors in both small and large intestines. In cell culture using Caco-2 human colorectal cancer cells, treatment of culture media with PA suppressed proliferation and induced G1-phase growth arrest. In a mouse model of HFD-induced obesity, glucose tolerance tests indicated the same orally administered dose of PA to significantly reduce blood glucose. In vitro assays in differentiated C2C12 myocytes further demonstrated PA to significantly enhance glucose uptake and increase phosphorylation of 5' adenosine monophosphate-activated protein kinase and protein kinase B. This study demonstrates that PA might possess health beneficial effects on colorectal cancer and obesity-induced diabetes.

Neuroprotective Potential of Brown Seaweed Phytochemicals in Rodent Models of Cerebral Ischemia.

Abstract: 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.

Scopoletin Improves Glucose Homeostasis in the High-Fructose High-Fat Diet-Induced Diabetes Model in Wistar Rats.

Abstract: Antihyperglycemic action of scopoletin needs to be validated before considering it for clinical trials. The present study explored antihyperglycemic action of scopoletin in high-fructose high-fat diet (HFHFD)-induced diabetes in rats. The animal study was performed using 48 rats, 6 in each group. HFHFD was administered for model induction for 74 days. Rats in Group I (normal control [NC]) and group II (experimental control [EC]) received normal saline and HFHFD, respectively, throughout the study. Groups III, IV, V, and VI received oral scopoletin (1 mg/kg [low dose, LD], 5 mg/kg [medium dose, MD], 10 mg/kg [high dose, HD]), and metformin (250 mg/kg; positive control [PC] for efficacy), respectively, once daily from day 60 to 74, in addition to HFHFD. Group VII (10 mg/kg oral scopoletin safety group) and VIII (0.1 mg/kg oral warfarin; PC for safety) were separately used for bleeding time-clotting time (BTCT) assessment on days 60, 68, and 74. Groups I, VII, and VIII rats were studied for safety assessment. Later, animals were sacrificed for histological examination. Scopoletin-treated groups showed a significant decline in glucose levels, especially in the MD (5.18 ± 0.12) and HD group (5.271 ± 0.11) in comparison to the EC (6.37 ± 0.05) on day 74 (P < .05). Two weeks after scopoletin treatment, β-cell function significantly improved (53.073 ± 4.67) in the MD group versus 29.323 ± 8.505 in the NC group (P < .05). A statistically significant difference was observed when the MD group (53.07 ± 4.67) was compared to the metformin-treated group (24.80 ± 3.24; P < .05). The safety assessment in the form of BTCT findings did not observe a difference among groups I, VII, and VIII (P > .05). The study showed that scopoletin dose-independently reversed insulin resistance. Consequently, scopoletin can be a potential candidate for antidiabetic drug development.

<i>Abelmoschus esculentus</i> (Okra) Prevents Insulin Resistance and Restores Neuron Autophagy by Regulating Dipeptidyl Peptidase-4 and Thus Improving Hippocampal Function

Abstract: 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.

Hovenia dulcis Thunb. Fruit Extract Attenuates Psoriatic Skin Inflammation in Tumor Necrosis Factor-α-Stimulated Human Keratinocyte HaCaT Cells In Vitro.

Abstract: Hovenia dulcis Thunb. fruit (HDF) is traditionally used for treating liver diseases and alcohol poisoning. The purpose of this study was to explore the effects of HDF on hyperproliferation, levels of inflammatory cytokines, and signaling mechanisms in human psoriatic keratinocyte HaCaT cells. HDF showed a preventive effect on tumor necrosis factor-α (TNF-α)-induced abnormal proliferation of psoriatic keratinocytes. Furthermore, real-time reverse transcription-PCR analysis showed that HDF suppressed the expressions of inflammatory cytokines; interleukin (IL)-1α and IL-1β and chemokines; CCL-20 and CXCL-8 in TNF-α-induced HaCaT cells. Western blotting revealed that HDF suppressed the levels of phosphorylated IκB and STAT3 together with a decline in the levels of phosphorylated mitogen-activated protein kinases (MAPKs). These outcomes indicate that HDF prevents the abnormal proliferation of keratinocytes and modulates inflammatory responses by suppressing nuclear factor-κB (NF-κB) and STAT3 activation through downregulation of the MAPK signaling pathway in TNF-α-induced psoriatic keratinocytes. Our study demonstrates that HDF is prospective and beneficial for psoriatic skin inflammation.

Efficacy of <i>Veronica incana</i> for Treating Osteoarthritis Induced by Monosodium Iodoacetate in Rats

Abstract: The aim of this study is to investigate the efficacy and the underlying mechanism of Veronica incana in osteoarthritis (OA) induced by intraarticular injection of monosodium iodoacetate (MIA). The selected major four compounds (A–D) of V. incana were found from fractions 3 and 4. Its structure elucidation was determined by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) data analysis and nuclear magnetic resonance (NMR) data comparison with literature. MIA (50 μL with 80 mg/mL) for the animal experiment was injected into the right knee joint. The V. incana was administered orally every day to rats for 14 days from 7 days after MIA treatment. Finally, we confirmed the four compounds: (A) verproside; (B) catalposide; (C) 6-vanilloylcatapol; and (D) 6-isovanilloylcatapol. When we evaluated the effect of V. incana on the MIA injection-induced knee OA model, there were a noticeable initial decreased in hind paw weight-bearing distribution compared to the Normal group (P < .001), but V. incana supplementation resulted in a significant increase in the weight-bearing distribution to the treated knee (P < .001). Moreover, the V. incana treatment led to a decrease in the levels of liver function enzymes and tissue malondialdehyde (P < .05 and .01). The V. incana significantly suppressed the inflammatory factors through the nuclear factor-kappa B signaling pathway and downregulated the expression of matrix metalloproteinases, which are involved in the degradation of the extracellular matrix (P < .01 and .001). In addition, we confirmed the alleviation of cartilage degeneration through tissue stains. In conclusion, this study confirmed the major four compounds of V. incana and suggested that V. incana could serve as an anti-inflammatory candidate agent for patients with OA.

Sesamin Attenuates Obesity-Associated Nonalcoholic Steatohepatitis in High-Fat and High-Fructose Diet-Fed Mice.

Abstract: This study explored the effects of sesamin on nonalcoholic steatohepatitis (NASH). High-fat and high-fructose diet-fed mice supplemented with or without sesamin. The results suggested that sesamin-treated mice lost body weight and fat tissue weight, had lower levels of serum metabolic parameters, and insulin resistance was mitigated. Histological examinations showed that sesamin treatment mitigated the progression of hepatic steatosis, and inflammation. In addition, sesamin enhanced hepatic antioxidant capacity, and decreased the activations of hepatic c-jun N-terminal kinase, inhibitor of kappa B kinase α, and insulin receptor substrate 1 as well as hepatic interleukin-6 and tumor necrosis factor-alpha levels. Further experiments indicated that sesamin treatment downregulated GRP78 and phospho-inositol-requiring enzyme 1 (IRE1) expression, and upregulated x-box binding protein 1 (XBP1) expression in hepatic tissue. The aforementioned results suggest that sesamin alleviates obesity-associated NASH, which might be linked to the effect of sesamin on the regulation of the hepatic endoplasmic reticulum stress-IRE1/XBP1 pathway. Thus, sesamin may be a good food functional ingredient in the treatment of obesity-associated NASH.

Feeding Soy Protein Concentrates with Low and High Isoflavones Alters 9 and 18 Weeks Serum Isoflavones and Inflammatory Protein Levels in Lean and Obese Zucker Rats.

Abstract: Soy's anti-inflammatory properties contribute to the health benefits of soy foods. This study was designed to investigate the bioavailability of soy isoflavones and whether the isoflavone content of soy protein concentrate diet would affect serum inflammatory proteins in an obese (fa/fa) Zucker rat model. Six-week-old male lean (L) and obese (O) Zucker rats were fed a casein control diet (C), soy protein concentrate with low isoflavones (SPC-LIF), or soy protein concentrate with high isoflavones (SPC-HIF) (7 rats/dietary group) before being killed at 9 and 18 weeks. Serum samples were analyzed for isoflavones and inflammatory proteins. At both time points, serum total (aglycone + conjugates) genistein, daidzein, and equol concentrations were significantly higher in L-SPC-HIF and O-SPC-HIF groups compared with L-SPC-LIF and O-SPC-LIF groups, respectively, and were not detectable in either L-C or O-C groups. At week 9, serum C-reactive protein (CRP) concentration was significantly lower in O-SPC-HIF group compared with O-C and O-SPC-LIF group, whereas proteins tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels did not differ between any groups. At week 18, serum CRP levels in both O-SPC-HIF and O-SPC-LIF groups were significantly lower compared with the O-C group. TNF-α level was higher in the O-SPC-LIF group compared with both O-C and O-SPC-HIF groups, whereas IL-6 levels were not different between any groups. Taken together, feeding Zucker rats SPC-LIF and SPC-HIF diets led to different serum isoflavone concentrations in both L and O Zucker rats and altered CRP and TNF-α levels in obese Zucker rats compared with controls.

Natural Products as Modulators of Mitochondrial Dysfunctions Associated with Cardiovascular Diseases: Advances and Opportunities.

Abstract: The mitochondria have an important role in modulating cell cycle progression, cell survival, and apoptosis. In the adult heart, the cardiac mitochondria have a unique spatial arrangement and occupy nearly one-third the volume of a cardiomyocyte, being highly efficient for converting the products of glucose or fatty acid metabolism into adenosine triphosphate (ATP). In cardiomyocytes, the decline of mitochondrial function reduces ATP generation and increases the production of reactive oxygen species, which generates impaired heart function. This is because mitochondria play a key role in maintaining cytosolic calcium concentration and modulation of muscle contraction, as ATP is required to dissociate actin from myosin. Beyond that, mitochondria have a significant role in cardiomyocyte apoptosis because it is evident that patients who have cardiovascular diseases (CVDs) have increased mitochondrial DNA damage to the heart and aorta. Many studies have shown that natural products have mitochondria-modulating effects in cardiac diseases, determining them as potential candidates for new medicines. This review outlines the leading plant secondary metabolites and natural compounds derived from microorganisms as modulators of mitochondrial dysfunctions associated with CVDs.

UP360, a Standardized Composition from Extracts of Aloe barbadense, Poria cocos, and Rosemary officinalis Protected Against Sepsis and Mitigated Acute Lung Injury in Murine Models.

Abstract: 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 Effect of Mastic Chios Supplementation in Inflammatory Bowel Disease: A Systematic Literature Review.

Abstract: Mastic Chios is a natural treasure of Greece that offers many potential benefits in various disorders due its antioxidant and anti-inflammatory properties. This systematic review aimed to investigate the effect of Mastic Chios supplementation in inflammatory bowel disease (IBD). A systematic search was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines across PubMed/Medline and EBSCO databases until February 2023. Clinical studies that examined individuals of any age being diagnosed with IBD as well as preclinical studies using animals with experimental colitis were considered eligible for inclusion. Studies included were assessed for methodological quality. Eight articles were eligible for inclusion, with seven conducted in Greece and one study in Iran. Most of the studies were randomized controlled trials (RCTs) and one was a pilot study. The intervention period varied between 3 and 7 days for animal studies and 4 weeks to 6 months for human studies. Mastic Chios supplementation varied between 2.2 and 2.8 g/day for clinical studies. The majority of studies concluded that Mastic Chios has significant antioxidant and inflammatory effects in IBD. This systematic review suggests that Mastic Chios may have a positive effect on the regulation and management of IBD. However, more high-quality clinical trials are needed to provide reliable and concrete conclusions about the effectiveness of Mastic Chios in this population. Such studies will further support the use of Mastic Chios as a reliable therapeutic option for IBD.