Thyme Extract Alleviates High-Fat Diet-Induced Obesity and Gut Dysfunction.

Prolonged intake of a high-fat diet (HFD) disturbs the composition of gut microbiota, contributing to the development of metabolic diseases, notably obesity and increased intestinal permeability. Thyme (Thymus vulgaris L.), an aromatic plant, is known for its several therapeutic properties. In this study, we explored the potential of thyme extract (TLE) to mitigate HFD-induced metabolic derangements and improve the gut environment. Eight-week-old C57BL/6 mice were administered 50 or 100 mg/kg TLE for eight weeks. Administration of 100 mg/kg TLE resulted in decreased weight gain and body fat percentage, alongside the regulation of serum biomarkers linked to obesity induced by a HFD. Moreover, TLE enhanced intestinal barrier function by increasing the expression of tight junction proteins and ameliorated colon shortening. TLE also altered the levels of various metabolites. Especially, when compared with a HFD, it was confirmed that 2-hydroxypalmitic acid and 3-indoleacrylic acid returned to normal levels after TLE treatment. Additionally, we investigated the correlation between fecal metabolites and metabolic parameters; deoxycholic acid displayed a positive correlation with most parameters, except for colon length. In contrast, hypoxanthine was negatively correlated with most parameters. These results suggest a promising role for thyme in ameliorating obesity and related gut conditions associated with a HFD.

Hippophae rhamnoides L. leaf extracts alleviate diabetic nephropathy via attenuation of advanced glycation end product-induced oxidative stress in db/db mice.

Diabetes mellitus leads to chronic complications, such as nephropathy. Diabetic complications are closely related to advanced glycation end products (AGEs). Excessive formation and accumulation of AGEs in diabetic renal diseases lead to excessive oxidative stress, resulting in chronic renal failure. The leaves of Hippophae rhamnoides L. (sea buckthorn leaves; SBL) show biological benefits, including antioxidant effects. This study aimed to evaluate the effect of SBL on kidney damage in db/db mice. The SBL extract was orally administered at 100 and 200 mg kg-1 for 12 weeks to db/db mice. Histological changes and the urine albumin/creatinine ratio were relieved, and the accumulation of AGEs in kidney glomeruli decreased following SBL treatment. Moreover, the SBL extract reduced the expression of AGEs, the receptor for AGEs, and NADPH oxidase 4, but upregulated glyoxalase 1 in the diabetic renal tissue. Urinary excretion levels and expression of 8-hydroxy-2'-deoxyguanosine as a biomarker of oxidative stress decreased after SBL treatment in the renal tissue. Furthermore, SBL attenuated oxidative stress in diabetic kidneys by reducing AGE accumulation, thereby ameliorating renal damage. Therefore, from these results, we infer that the SBL extract can act as a potential therapeutic agent for diabetic renal complications caused by AGEs.

Lactococcus lactis KF140 Reduces Dietary Absorption of Nε - (Carboxymethyl)lysine in Rats and Humans via ß-Galactosidase Activity.

Background and Aims: Excessive intake of advanced glycation end products (AGEs), which are formed in foods cooked at high temperatures for long periods of time, has negative health effects, such as inflammatory responses and oxidative stress. Nε-(Carboxymethyl)lysine (CML) is one of the major dietary AGEs. Given their generally recognized as safe status and probiotic functionalities, lactic acid bacteria may be ideal supplements for blocking intestinal absorption of food toxicants. However, the protective effects of lactic acid bacteria against dietary AGEs have not been fully elucidated. Materials and Methods: We investigated the effect of treatment with Lactococcus lactis KF140 (LL-KF140), which was isolated from kimchi, on the levels and toxicokinetics of CML. The CML reduction efficacies of the Lactococcus lactis KF140 (LL-KF140), which was isolated from kimchi, were conducted by in vitro test for reducing CML concentration of the casein-lactose reaction product (CLRP) and in vivo test for reducing serum CML level of LL-KF140 administered rats at 2.0 × 108 CFU/kg for14 days. In addition, 12 volunteers consuming LL-KF140 at 2.0 × 109 CFU/1.5 g for 26 days were determined blood CML concentration and compared with that before intake a Parmesan cheese. Results: Administration of LL-KF140 reduced serum CML levels and hepatic CML absorption in rats that were fed a CML-enriched product. In a human trial, the intake of LL-KF140 prevented increases in the serum levels of CML and alanine aminotransferase after consumption of a CML-rich cheese. LL-KF140 was determined to presence in feces through metagenome analysis. Furthermore, ß-galactosidase, one of the L. lactis-produced enzymes, inhibited the absorption of CML and reduced the levels of this AGE, which suggests an indirect inhibitory effect of LL-KF140. This study is the first to demonstrate that an L. lactis strain and its related enzyme contribute to the reduction of dietary absorption of CML.

Inhibitory effect of sea buckthorn extracts on advanced glycation endproduct formation.

This study shows the inhibitory effect of sea buckthorn (Hippophae rhamnoides L.) extracts, sea buckthorn leaf (HRL) and berry (HRB), on the formation of advanced glycation endproducts (AGEs), closely linked to diverse disease. In vitro assay revealed the superior inhibitory effect of HRL on the AGEs formation and AGEs-induced collagen crosslinking compared with that of HRB. Ultra-performance liquid chromatography-mass spectrometry results revealed that HRL displays a higher inhibition efficiency on the AGEs formation at 30 AGEs binding sites in bovine serum albumin than HRB. The high concentration of 3-sophoroside-7-rhamnoside in HRL compared with that in HRB may result in the strong inhibitory effect of HRL compared with that of HRB. HRL also exhibited significantly higher ABTS and DPPH radical scavenging activities than HRB. Overall, this study demonstrated that HRL has excellent potential as a dietary agent for controlling various diseases mediated by AGEs and oxidative stress.

Syzygium aromaticum Reduces Diabetes-induced Glucotoxicity via the NRF2/Glo1 Pathway.

Advanced glycation end products and methylglyoxal are known to show increased levels in diabetic conditions and induce diverse metabolic disorders. However, the antiglycation ability of the bark of Syzygium aromaticum is not yet studied. In this study, we determined the inhibitory effects of S. aromaticum on AGE formation. Moreover, S. aromaticum showed breakage and inhibitory ability against the formation of AGE-collagen crosslinks. In SV40 MES13 cells, treatment with the S. aromaticum extract significantly ameliorated MG-induced oxidative stress as well as cytotoxicity. Furthermore, in the S. aromaticum extract-treated group, there was a reduction in levels of several diabetic markers, such as blood glucose, kidney weight, and urinary albumin to creatinine ratio in streptozotocin-induced diabetic rats. Treatment with the S. aromaticum extract significantly increased the expression of nuclear factor erythroid 2-related factor 2, a transcription factor involved in the expression of antioxidant enzymes. Moreover, the treatment significantly upregulated the expression of glyoxalase 1 and downregulated the expression of receptor for AGEs. These results suggest that the S. aromaticum extract might ameliorate diabetes-induced renal damage by inhibiting the AGE-induced glucotoxicity and oxidative stress through the Nrf2/Glo1 pathway.

Synergistic antimicrobial activity of oregano and thyme thymol essential oils against Leuconostoc citreum in a laboratory medium and tomato juice.

This study was done to identify combinations of essential oils (EOs) that elicit synergistic antimicrobial effects against Leuconostoc citreum, a spoilage bacterium in vegetable and fruit juices. Twenty-four EOs were tested for antimicrobial activity against L. citreum using an agar well diffusion assay. Ten EOs showed relatively strong antimicrobial activity. Among those, cinnamon bark, oregano, and thyme thymol EOs showed the strongest activity (minimal inhibitory concentration = 1.25 µL/mL). It was confirmed that a combination of oregano and thyme thymol EOs had a synergistic antimicrobial activity (fractional inhibitory concentration index = 0.3750) using a checkerboard assay. This combination also had a synergistic antimicrobial activity against L. citreum in tomato juice. An initial population of L. citreum in tomato juice (5.3 log CFU/mL) increased to ≥ 8.6 log CFU/mL within 48 h at 15 °C and 24 h at 25 °C. Populations reached 6.8-7.2 log CFU/mL in tomato juice containing either 0.156 mL/mL oregano or thyme thymol. However, in the presence of both EOs (0.156 µL/mL in total), populations of L. citreum were significantly lower (5.7-6.5 log CFU/mL) (P ≤ 0.05). Findings will be useful when developing non-thermal food preservation technologies to increase the shelf-life of juices and other foods not containing synthetic preservatives.

Development of a senior-specific, citizen-oriented healthcare service system in South Korea based on the Canadian 48/6 model of care.

BACKGROUND: In the age of aging, Korea's current medical delivery system threatens to increase the number of medical and caring refugees. This study attempts to develop an integrated senior citizen-oriented healthcare service system in which daily care, professional care, and rehabilitation are organically organized between medical institutions and local communities, thereby meeting the daily life needs of the elderly and inducing well-being, wellness, and well-dying. METHODS: To develop the integrated healthcare system, data collection and analyses were conducted through a systematic review, literature review, benchmarking, focus group interviews, and expert consultation. RESULTS: The senior-specific, citizen-oriented healthcare service system developed in this study is designed to screen patients aged 65 or older within 24 h of being admitted, using the Geriatric Screening for Care-10. If there is reason for concern as a result of the screening, further evaluation is performed through assessment. Doctors and nurses create a care plan and a discharge plan based on the results from the screening and assessment. The nurse further uses the screening to monitor the patient's condition before discharge. Based on the screening results at the time of discharge, a transitional care plan is prepared and provided to elderly patients and/or their families. This process enables a systematic link between medical institutions and community resources, aiming for the continuous management of health issues. It also establishes a multidisciplinary treatment plan that considers patients and their families so that diseases common to the elderly are diagnosed and treated promptly. CONCLUSIONS: The most important issue for the elderly is to be able to live healthily and independently for the rest of their lives through well-being, wellness, and well-dying. The senior-specific, citizen-oriented healthcare service proposed in this study is an integrated medical treatment system for elderly users the implementation of which requires the daily care, professional care, and rehabilitation of elderly members of society to be organically organized according to the role of the patients, their families, and the caregiver.

Spatholobus suberectus Ameliorates Diabetes-Induced Renal Damage by Suppressing Advanced Glycation End Products in db/db Mice.

Spatholobus suberectus (SS) is a medicinal herb commonly used in Asia to treat anemia, menoxenia and rheumatism. However, its effect of diabetes-induced renal damage and mechanisms of action against advanced glycation end-products (AGEs) are unclear. In this study, we evaluated the effects of SS on diabetes-induced renal damage and explored the possible underlying mechanisms using db/db type 2 diabetes mice. db/db mice were administered SS extract (50 mg/kg) orally for 6 weeks. SS-treated group did not change body weight, blood glucose and glycated hemoglobin (HbA1c) levels. However, SS treatment reversed diabetes-induced dyslipidemia and urinary albumin/creatinine ratio in db/db mice. Moreover, SS administration showed significantly increased protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), which is a transcription factor for antioxidant enzyme. SS significantly upregulated glyoxalase 1 (Glo1) and NADPH quinine oxidoreductase 1 (NQO1) expression but reduced CML accumulation and downregulated receptor for AGEs (RAGE). Furthermore, SS showed significant decrease of periodic acid⁻Schiff (PAS)-positive staining and AGEs accumulation in histological and immunohistochemical analyses of kidney tissues. Taken together, we concluded that SS ameliorated the renal damage by inhibiting diabetes-induced glucotoxicity, dyslipidemia and oxidative stress, through the Nrf2/antioxidant responsive element (ARE) stress-response system.

Eucommia ulmoides Ameliorates Glucotoxicity by Suppressing Advanced Glycation End-Products in Diabetic Mice Kidney.

Eucommia ulmoides Oliv. (EU), also known as Du-Zhong, is a medicinal herb commonly used in Asia to treat hypertension and diabetes. Despite evidence of the protective effects of EU against diabetes, its precise effects and mechanisms of action against advanced glycation end-products (AGEs) are unclear. In this study, we evaluated the effects of EU on AGEs-induced renal disease and explored the possible underlying mechanisms using streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice received EU extract (200 mg/kg) orally for 6 weeks. EU treatment did not change blood glucose and glycated hemoglobin (HbA1c) levels in diabetic mice. However, the EU-treated group showed a significant increase in the protein expression and activity of glyoxalase 1 (Glo1), which detoxifies the AGE precursor, methylglyoxal (MGO). EU significantly upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression but downregulated that of receptor for AGE (RAGE). Furthermore, histological and immunohistochemical analyses of kidney tissue showed that EU reduced periodic acid-Schiff (PAS)-positive staining, AGEs, and MGO accumulation in diabetic mice. Based on these findings, we concluded that EU ameliorated the renal damage in diabetic mice by inhibiting AGEs formation and RAGE expression and reducing oxidative stress, through the Glo1 and Nrf2 pathways.

Plantamajoside from Plantago asiatica modulates human umbilical vein endothelial cell dysfunction by glyceraldehyde-induced AGEs via MAPK/NF-κB.

BACKGROUND: Plantago asiatica has been traditionally used for traditional medicine around East Asia. Plantamajoside (PM), which is isolated from this plant, is known for biological properties including anti-inflammation and antioxidant activity. To demonstrate the biological activity of PM against endothelial dysfunction induced by advanced glycation end-products (AGEs), a cellular inflammatory mechanism system was evaluated in human umbilical vein endothelial cells (HUVECs). METHODS: We obtained PM through previous research in our laboratory. We formed the AGEs from bovine serum albumin with glyceraldehyde in the dark for seven days. To confirm the modulation of the inflammatory mechanism in endothelial dysfunction, we quantified the various pro-inflammatory cytokines and endothelial dysfunction-related proteins in the HUVECs with Western blotting and with real-time and quantitative real-time polymerase chain reactions. RESULTS: Co-treatment with PM and AGEs significantly suppressed inflammatory cytokines and adhesion molecule expression. Moreover, the PM treatment for down-regulated inflammatory signals and blocked monocyte adhesion on the HUVECs. CONCLUSIONS: Theses results demonstrated that PM, as a potential natural compound, protects AGE-induced endothelial cells against inflammatory cellular dysfunction.

Endothelium-Dependent Vasorelaxant Effects of Dealcoholized Wine Powder of Wild Grape (Vitis coignetiae) in the Rat Thoracic Aorta.

The vasorelaxant effects of dealcoholized wild grape (Vitis coignetiae) wine were investigated with isolated rat thoracic aorta. In our present study, we demonstrate that wild grape wine powder (WGWP) induced relaxation of aortic rings preconstricted with norepinephrine in a dose-dependent manner (at concentrations ranging from 0.1 to 1 mg/mL). The vasorelaxant effect of WGWP was dependent on intact endothelia, which was attenuated by incubation with inhibitors of endothelium-derived relaxing factors, such as NG-nitro-L-arginine (nitric oxide synthase inhibitor), methylene blue (guanylate cyclase inhibitor), and indomethacin (cyclooxygenase inhibitor). Moreover, treatment with WGWP and atropine (muscarinic receptor antagonist) or diphenylhydramine (histamine receptor antagonist) significantly inhibited endothelium-dependent vasorelaxation. Our results suggest that WGWP induces relaxation in rat aortic rings in an endothelium-dependent manner. Results further indicate that this effect occurs via nitric oxide-cGMP pathway and prostacyclin-cAMP pathway through a muscarinic receptor and histamine receptor.

Narirutin fraction from citrus peels attenuates LPS-stimulated inflammatory response through inhibition of NF-κB and MAPKs activation.

In this study, we examined the regulatory activity of narirutin fraction from citrus peels on the production of inflammatory mediators managing acute or chronic inflammatory diseases in macrophages. Narirutin fraction inhibited the release, by lipopolysaccharide (LPS)-stimulated macrophages, of nitric oxide (NO) and prostaglandin E2 (PGE2) through suppressing the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively. The release, by LPS stimulated macrophages, of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) was also reduced by narirutin fraction in a dose-dependent manner. Furthermore, narirutin fraction inhibited the LPS-mediated activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs), which are signaling molecules involved in production of pro-inflammatory factors. As a result of these properties, narirutin fraction has the potential to be used as a functional dietary supplement and effective anti-inflammatory agent.

A comparison between high hydrostatic pressure extraction and heat extraction of ginsenosides from ginseng (Panax ginseng CA Meyer).

BACKGROUND: To determine biomaterial components, the components must first be transferred into solution; thus extraction is the first step in biomaterial analysis. High hydrostatic pressure technology was used for ginsenoside extraction from ginseng roots. In the extraction of fresh and red ginseng, high hydrostatic pressure extraction (HHPE) was found to be more effective than heat extraction (HE). RESULTS: In fresh ginseng extraction under HHPE, total ginsenosides (1602.2 µg mL⁻¹) and ginsenoside metabolite (132.6 µg mL⁻¹) levels were slightly higher than those under HE (1259.0 and 78.7 µg mL⁻¹), respectively. In red ginseng, similar results indicated total ginsenoside and ginsenoside metabolite amounts according to the extraction methods. Most volatile compounds by HHPE were higher than by HE treatment. HHPE of red ginseng was conducted under four pressures: 0.1 MPa (1 atm), 30, 50, and 80 MPa. Total sugar, uronic acid, and polyphenol amounts increased until 30 MPa of pressure and then showed decreasing tendencies. Total ginsenoside and ginsenoside metabolite contents linearly increased with increasing pressure, and a maximum was reached at 80 MPa for the metabolites. CONCLUSION: HHPE used for red ginseng processing contributes to enhanced extraction efficiencies of functional materials such as ginsenosides through cell structure modification.