Beneficial effect of heat-killed Lactiplantibacillus plantarum L-137 on intestinal barrier function of rat small intestinal epithelial cells.

Heat-killed Lactiplantibacillus plantarum L-137 (HK L-137) has been suggested to enhance the intestinal barrier in obese mice, leading to improvement of metabolic abnormalities and adipose tissue inflammation, and in healthy humans with overweight, leading to improvement of systemic inflammation. However, its detailed mechanism of action has not been clarified. Therefore, this study investigated the effects of HK L-137 on the permeability of rat small intestinal epithelial IEC-6 cells, tight junction-related gene and protein expression and localization, and intracellular signaling pathways involved in barrier function. Treatment of IEC-6 cells with HK L-137 for 26 h significantly reduced the permeability to fluorescein isothiocyanate-dextran (FD-4). HK L-137 also increased gene and protein expression of zonula occludens-1 (ZO-1), an important tight junction protein, without affecting the localization. Furthermore, inhibition of the extracellular signal-regulated kinase (ERK)1/2 pathway in IEC-6 cells canceled the HK L-137-related reduction in permeability to FD-4. Phosphorylation of ERK in IEC-6 cells was induced 15 min after the addition of HK L-137. These results suggest that HK L-137 reduces intestinal permeability partly through activating the ERK pathway and increasing expression of the ZO-1 gene and protein. Enhancement of intestinal barrier function with HK L-137 might be effective in preventing and treating leaky gut, for which no specific therapeutic tool has been established.

Curcuma longa extract reduces serum inflammatory markers and postprandial hyperglycemia in healthy but borderline participants with overweight and glycemia in the normal/prediabetes range: a randomized, double-blind, and placebo-controlled trial.

The spice turmeric, which has the Latin name Curcuma longa (C. longa), has various physiological effects. This study evaluated the effects of a hot water mixture with supercritical carbon dioxide C. longa extracts, CLE, and the potential active components of C. longa, turmeronols A and B and bisacurone on inflammation and glucose metabolism. First, we investigated the effect of CLE and the potential active components of C. longa on lipopolysaccharide-induced inflammation in RAW264.7 macrophages. We found a significant decrease in the production of interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and nitric oxide with CLE, turmeronol A, and bisacurone, Significant inhibition of each of these substances was also observed, except for TNF-α with turmeronol B. The second part of our work was a 12-week randomized, double-blind, placebo-controlled study in healthy but borderline adults aged 40 to 69 years with overweight and normal/prediabetes glycemia. We compared blood inflammatory and glycometabolic markers in the CLE (n = 55) and placebo groups (n = 55). We found significantly lower serum high-sensitivity C-reactive protein and hemoglobin A1c levels in the CLE group. This group also showed significant improvements in postprandial hyperglycemia and insulin sensitivity indices. Our findings indicate that CLE may reduce low-grade inflammation and thus improve insulin sensitivity and postprandial hyperglycemia. Clinical trial registration: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000051492, UMIN-CTR, UMIN000045106.

Turmeronols (A and B) from Curcuma longa have anti-inflammatory effects in lipopolysaccharide-stimulated BV-2 microglial cells by reducing NF-κB signaling.

Turmeronols (A and B), bisabolane-type sesquiterpenoids found in turmeric, reduce inflammation outside the brain in animals; however, their effects on neuroinflammation, a common pathology of various neurodegenerative diseases, are not understood. Inflammatory mediators produced by microglial cells play a key role in neuroinflammation, so this study evaluated the anti-inflammatory effects of turmeronols in BV-2 microglial cells stimulated with lipopolysaccharide (LPS). Pretreatment with turmeronol A or B significantly inhibited LPS-induced nitric oxide (NO) production; mRNA expression of inducible NO synthase; production of interleukin (IL)-1ß, IL-6, and tumor necrosis factor α and upregulation of their mRNA expression; phosphorylation of nuclear factor-κB (NF-κB) p65 proteins and inhibitor of NF-κB kinase (IKK); and nuclear translocation of NF-κB. These results suggest that these turmeronols may prevent the production of inflammatory mediators by inhibiting the IKK/NF-κB signaling pathway in activated microglial cells and can potentially treat neuroinflammation associated with microglial activation.

Corrigendum: Beneficial effect of heat-killed Lactiplantibacillus plantarum L-137 on skin functions in healthy participants: A randomized, placebo-controlled, double-blind study.

[This corrects the article DOI: 10.3389/fmed.2022.912280.].

A Hot Water Extract of Curcuma longa L. Improves Fasting Serum Glucose Levels in Participants with Low-Grade Inflammation: Reanalysis of Data from Two Randomized, Double-Blind, Placebo-Controlled Trials.

The dietary spice Curcuma longa L. (C. longa), also known as turmeric, has various biological effects. A hot water extract of C. longa was shown to have anti-inflammatory activities in preclinical and clinical studies. Chronic low-grade inflammation is associated with the disruption of glucose homeostasis, but the effect of C. longa extract on glucose metabolism in humans is poorly understood. Therefore, we investigated the effect of C. longa extracts on serum glucose levels in the presence of low-grade inflammation. We reanalyzed our published data from two randomized, double-blind, placebo-controlled trials in overweight participants aged 50 to 69 years and performed a stratified analysis using the inflammatory marker high-sensitivity C-reactive protein (hsCRP). In both studies, participants took a test food with a hot water extract of C. longa (C. longa extract group, n = 45 per study) or without C. longa extract (placebo group, n = 45 per study) daily for 12 weeks, and we measured the levels of serum hsCRP and fasting serum glucose. The mean baseline hsCRP value was used to stratify participants into two subgroups: a low-hsCRP subgroup (baseline mean hsCRP < 0.098 mg/dL) and a high-hsCRP subgroup (baseline mean hsCRP ≥ 0.098 mg/dL). In the low-hsCRP subgroup, we found no significant difference in fasting serum glucose levels between the two groups in either study, but in the high-hsCRP subgroup, the C. longa extract group had significantly lower levels of serum hsCRP (p < 0.05) and fasting serum glucose (p < 0.05) than the placebo group in both studies. In conclusion, a hot water extract of C. longa may help to improve systemic glucose metabolism in people with chronic low-grade inflammation.

Beneficial Effect of Heat-Killed Lactiplantibacillus plantarum L-137 on Skin Functions in Healthy Participants: A Randomized, Placebo-Controlled, Double-Blind Study.

To determine whether consuming heat-killed Lactiplantibacillus plantarum L-137 (HK L-137) influences skin functions, we performed a randomized, placebo-controlled, double-blind study in healthy participants who were conscious of dry skin. A total of 80 healthy participants (20 men, 60 women; mean age, 47.3 years) were assigned to receive a tablet containing HK L-137 or a placebo tablet daily for 12 weeks. Every 4 weeks, the skin water content and transepidermal water loss (TEWL) were measured at the forearm and face, and participants completed two skin-related questionnaires, the Dermatology Life Quality Index and a self-evaluation. The HK L-137 group tended to show greater increases from baseline of water content at the forearm and larger decreases of TEWL at the face. The total scores of both questionnaires improved significantly more in the HK L-137 group. Water content and TEWL improved significantly in participants in the HK L-137 group who were above the median age of study participants or had relatively dry skin. These findings suggest that daily HK L-137 intake can improve dry skin, thereby contributing to skin satisfaction.

Curcuma longa extract improves serum inflammatory markers and mental health in healthy participants who are overweight: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: The dietary spice Curcuma longa, also known as turmeric, has various biological effects. Both a water extract and a supercritical carbon dioxide extract of C. longa showed anti-inflammatory activities in animal studies. However, the anti-inflammatory effect in humans of a mixture of these two C. longa extracts (CLE) is poorly understood. Therefore, we investigated the effect of CLE containing anti-inflammatory turmeronols on chronic inflammation and general health. METHODS: We performed a randomized, double-blind, placebo-controlled study in healthy subjects aged 50 to 69 years with overweight. Participants took two capsules containing CLE (CLE group, n = 45) or two placebo capsules (placebo group, n = 45) daily for 12 weeks, and serum inflammatory markers were measured. Participants also completed two questionnaires: the Medical Outcomes Study (MOS) 36-Item Short-Form Health Survey (SF-36) and the Profile of Mood States (POMS) scale. Treatment effects were analyzed by two way analysis of variance followed by a t test (significance level, p <  0.05). RESULTS: After the intervention, the CLE group had a significantly lower body weight (p <  0.05) and body mass index (p < 0.05) than the placebo group and significantly lower serum levels of C-reactive protein (p < 0.05) and complement component 3 (p < 0.05). In addition, the CLE group showed significant improvement of the MOS SF-36 mental health score (p < 0.05) and POMS anger-hostility score (p < 0.05). CONCLUSION: CLE may ameliorate chronic low-grade inflammation and thus help to improve mental health and mood disturbance. TRIAL REGISTRATION: UMIN-CTR, UMIN000037370. Registered 14 July 2019, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000042607.

Safety and efficacy of using heat-killed Lactobacillus plantarum L-137: High-dose and long-term use effects on immune-related safety and intestinal bacterial flora.

Heat-killed Lactobacillus plantarum L-137 (HK L-137) promotes immune function in animals. In healthy people, T-cell proliferation was shown to be enhanced by taking 10 mg HK L-137 daily for 12 weeks. However, the safety and efficacy of higher doses or longer treatments have not yet been investigated in humans. To investigate the high-dose and long-term use effects of HK L-137 on immune-related safety and on host intestinal bacterial flora, 15 healthy volunteers took a daily HK L-137 (50 mg) preparation for 4 weeks. An additional 29 participants who regularly visited a clinic for health care took HK L-137 (10 mg) daily for 12 months. Measures for anthropometrics, hematology, biochemistry, and urinalysis were taken at scheduled timepoints for all participants. Stool and blood samples were also collected and evaluated for microbes and short-chain fatty acids (SCFA); isolated T-cells were assessed for levels of proliferation induced by phytohemagglutinin in the long-term study. Adverse events or shifts in clinical measures from normal ranges due to the dietary intervention were not observed in the high-dose or long-term studies. Long-term intake also did not result in immune exhaustion due to any chronic immunostimulation; ex vivo T-cell proliferation was significantly greater at 12 months than at baseline (p < 0.01). In addition, the Firmicutes/Bacteroidetes ratio in stool samples was significantly lower at 12 months than at baseline (p < 0.05) due to the long-term intake of the HK L-137. Lastly, fecal SCFA concentrations were significantly greater (p < 0.05) at 6 months than at baseline. From these data, it can be concluded that the efficacy of HK L-137 is maintained with no overt adverse effects as a result of high-dose and/or long-term consumption.

Heat-killed Lactobacillus plantarum L-137 attenuates obesity and associated metabolic abnormalities in C57BL/6†J mice on a high-fat diet.

Heat-killed Lactobacillus plantarum L-137 (HK L-137) has anti-allergic, antitumor, and antiviral effects in mice, as well as an anti-inflammatory effect in rats with metabolic syndrome through regulation of immunity. To evaluate the influence of HK L-137 on chronic inflammation in mice with diet-induced obesity, C57BL/6 J mice were fed a normal diet (16% of energy as fat) or a high-fat diet (62% of energy as fat) with or without 0.002% HK L-137 for 4 to 20 weeks. It was found that HK L-137 supplementation alleviated weight gain and elevation of plasma glucose, cholesterol, alanine aminotransferase, and aspartate transaminase levels in mice with diet-induced obesity. Expression of several inflammation-related genes, including F4/80, CD11c, and IL-1ß, in the epididymal adipose tissue of these mice was significantly downregulated by HK L-137. In addition, plasma levels of lipopolysaccharide-binding protein, a marker of endotoxemia, tended to be decreased by administration of HK L-137. These findings suggest that HK L-137 supplementation ameliorates obesity-induced metabolic abnormalities and adipose tissue inflammation, possibly through improvement of intestinal permeability.

Correction: Turmeronol A and turmeronol B from Curcuma longa prevent inflammatory mediator production by lipopolysaccharide-stimulated RAW264.7 macrophages, partially via reduced NF-κB signaling.

Correction for 'Turmeronol A and turmeronol B from Curcuma longa prevent inflammatory mediator production by lipopolysaccharide-stimulated RAW264.7 macrophages, partially via reduced NF-κB signaling' by Chinatsu Okuda-Hanafusa et al., Food Funct., 2019, 10, 5779-5788. DOI: 10.1039/C9FO00336C.

Daily intake of heat-killed Lactobacillus plantarum L-137 improves inflammation and lipid metabolism in overweight healthy adults: a randomized-controlled trial.

PURPOSE: The effects of heat-killed Lactobacillus plantarum L-137 (HK L-137) on inflammation and lipid metabolism were investigated in overweight volunteers. METHODS: One hundred healthy subjects with a body mass index from 23.0 to 29.9 (51 men and 49 women; mean age: 41.4 years) were enrolled in this randomized, double-blind, placebo-controlled, parallel group study. Subjects were randomly assigned to daily administration of a tablet containing HK L-137 (10 mg) or a placebo tablet for 12 weeks. Blood samples were collected every 4 weeks to measure biomarkers of lipid metabolism and inflammatory mediators. RESULTS: The percent change of concanavalin A-induced proliferation of peripheral blood mononuclear cells was significantly larger in the HK L-137 group than in the control group, similar to previous studies. The decreases of aspartate aminotransferase and alanine aminotransferase over time were significantly larger in the HK L-137 group than in the control group, as were the decreases of total cholesterol, low-density lipoprotein cholesterol, and the leukocyte count at one time point. These effects of HK L-137 were stronger in the subjects with higher C-reactive protein levels. CONCLUSIONS: These findings suggest that daily intake of HK L-137 can improve inflammation and lipid metabolism in subjects at risk of inflammation.

High dietary vitamin C intake reduces glucocorticoid-induced immunosuppression and measures of oxidative stress in vitamin C-deficient senescence marker protein 30 knockout mice.

Vitamin C (VC) is a vital micronutrient for humans and some other mammals and also has antioxidant activity. Stress-induced elevation of glucocorticoid production is well known to cause immunosuppression. The present study evaluated the effect of high VC intake on glucocorticoid-induced immune changes in mice. Senescence marker protein 30 knockout mice with genetic VC deficiency were fed a diet containing the recommended VC content (20 mg/kg per d; 0·02 %VC group) or a high VC content (200 mg/kg per d; 0·2 %VC group) for 2 months, then dexamethasone was given by intraperitoneal injection. After administration of dexamethasone, the plasma ascorbic acid concentration decreased significantly in the 0·02 %VC group and was unchanged in wild-type C57BL/6 mice on a VC-deficient diet (wild-type group), while it was significantly higher in the 0·2 %VC group compared with the other two groups. In the 0·02 %VC and wild-type groups, dexamethasone caused a significant decrease in the cluster of differentiation (CD)4+ and CD8+ T cells among splenocytes as well as a significant decrease in IL-2, IL-12p40 and interferon-γ protein production by splenocytes and a significant decrease in T-cell proliferation among splenocytes. In the 0·2 %VC group, these dexamethasone-induced immunosuppression improved when compared with the other two groups. In addition, reduction in the intracellular levels of ascorbic acid, superoxide dismutase and glutathione in splenocytes by dexamethasone as well as elevation in thiobarbituric acid-reactive substances were significantly suppressed in the 0·2 %VC group. These findings suggest that high dietary VC intake reduces glucocorticoid-induced T-cell dysfunction by maintaining intracellular antioxidant activity.

Hot Water Extract of Curcuma longa L. Improves Serum Inflammatory Markers and General Health in Subjects with Overweight or Prehypertension/Mild Hypertension: A Randomized, Double-Blind, Placebo-Controlled Trial.

To investigate the effect of a hot water extract of C. longa L. (WEC) containing anti-inflammatory agents, bisacurone, and turmeronol on chronic inflammation, a randomized double-blind placebo-controlled study was conducted in middle-aged and elderly subjects aged 50-69 years with overweight or prehypertension/mild hypertension. The subjects consumed 900 mg WEC tablets, containing 400 µg bisacurone, 80 µg turmeronol A and 20 µg turmeronol B (WEC group: n = 45), or placebo tablets without WEC (placebo group: n = 45) daily for 12 weeks. Serum inflammatory and metabolic markers were measured. The subjects also completed the MOS 36-item short-form health survey (SF-36) and the Profile of Mood States scale (POMS). In the WEC group, the serum levels of C-reactive protein, tumor necrosis factor-α, interleukin-6, and soluble vascular cell adhesion molecule-1 decreased significantly. Compared with the placebo group, the WEC group had significantly lower serum levels of glucose, hemoglobin A1c, and triglycerides, as well as higher serum levels of high-density lipoprotein cholesterol. The WEC group also showed significant improvement of SF-36 scores (for general health, vitality, mental health, and mental summary component) and POMS scores for positive mood states (vigor-activity and friendliness). In conclusion, WEC may ameliorate chronic low-grade inflammation, thus contributing to the improvement of associated metabolic disorders and general health.

Turmeronol A and turmeronol B from Curcuma longa prevent inflammatory mediator production by lipopolysaccharide-stimulated RAW264.7 macrophages, partially via reduced NF-κB signaling.

Chronic inflammation depends on inflammatory mediators produced by activated macrophages and is the common pathological basis for various diseases. Turmeronol is a sesquiterpenoid found in the spice turmeric (Curcuma longa), which is known to have anti-inflammatory activity. To elucidate the anti-inflammatory mechanism of turmeronol, we investigated the influence of turmeronol A and turmeronol B in mouse macrophages (RAW264.7 cells) stimulated with lipopolysaccharide (LPS). Pretreatment of RAW264.7 cells with either turmeronol A or B significantly inhibited LPS-induced production of prostaglandin E2 and nitric oxide, as well as expression of mRNAs for the corresponding synthetic enzymes. In addition, the turmeronols significantly inhibited LPS-induced upregulation of interleukin-1ß, interleukin-6, and tumor necrosis factor-α at the mRNA and protein levels. Both turmeronols also inhibited nuclear translocation of nuclear factor κB (NF-κB), with a similar time course to the NF-κB inhibitor pyrrolidine dithiocarbamate, but not curcumin (another NF-κB inhibitor). Thus, both turmeronols prevented activation of macrophages and inflammatory mediator production, possibly by suppressing activation of NF-κB, and therefore have potential for use in preventing chronic inflammatory diseases.

Lactobacillus plantarum L-137 upregulates hyaluronic acid production in epidermal cells and fibroblasts in mice.

Heat-killed Lactobacillus plantarum L-137 (HK L-137), an immunobiotic lactic acid bacterium, has been reported to enhance IFN-γ production through induction of IL-12. In this study, we investigated the effects of HK L-137 on skin moisturizing and production of hyaluronic acid (HA), an extracellular matrix associated with the retention of skin moisture. Oral administration of HK L-137 suppressed the loss of water content in the stratum corneum in hairless mice. Treatment of primary epidermal cells with HK L-137 increased HA production. Supernatant from immune cells stimulated by HK L-137, which contained proinflammatory cytokines such as IL-12, TNF-α, and IFN-γ, upregulated HA production and hyaluronan synthase 2 (HAS2) messenger RNA expression by BALB/3T3 fibroblasts via activation of transcription factor nuclear factor κB (NFκB). Although treatment of the supernatant with anti-TNF-α antibody (Ab) alone did not inhibit the HA production, combination of anti-TNF-α Ab with anti-IFN-γ Ab significantly inhibited the HA production. Thus, HK L-137-induced IFN-γ plays a critical role in upregulated HA production in collaboration with TNF-α. HK L-137 may be useful for improvement of skin functions such as moisture retention by inducing HA production.

Effects of hot water extract of Curcuma longa on human epidermal keratinocytes in vitro and skin conditions in healthy participants: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Curcuma longa has been reported to have anti-inflammatory effects. Skin inflammation impairs skin functions. OBJECTIVES: Our aim was to investigate the effect of a hot water extract of C longa (WEC) on skin conditions in cell studies using keratinocytes and in clinical trials. METHODS: We measured proinflammatory cytokine levels in ultraviolet B-irradiated keratinocytes in the presence or absence of WEC. The effects of WEC on hyaluronan production in keratinocytes were also determined. In a randomized, double-blind, placebo-controlled trial, 47 healthy participants were assigned to 8-week intervention groups with daily intakes of WEC with or without curcumin or a placebo. The water content and transepidermal water loss in the face and minimal erythema dose on the back after ultraviolet B irradiation were evaluated every 4 weeks. RESULTS: Hot water extract of C longa significantly inhibited increases in ultraviolet B-induced tumor necrosis factor α and interleukin 1ß at the mRNA and protein levels. WEC also significantly increased hyaluronan production from nonstimulated keratinocytes. In the randomized, double-blind, placebo-controlled trial, increases from baseline in the water content of the face were significantly greater at weeks 4 and 8 in the WEC group, but not in the WEC + curcumin group, than in the placebo group. There were no significant differences in transepidermal water loss and minimal erythema dose among the groups. CONCLUSIONS: The cell studies confirmed that WEC has anti-inflammatory effects and augments hyaluronan production in the skin. The results of clinical trials suggest that WEC may be useful for moisturizing facial skin. TRIAL REGISTRATION: UMIN Clinical Trials Registry 000028510. Retrospectively registered.

Inhibitory effect of the compounds from the water extract of Curcuma longa on the production of PGE2 and NO in a macrophage cell line stimulated by LPS.

We wished to search for the compounds contributing to the anti-inflammatory effects of the water extract of Curcuma longa (WEC). WEC was fractioned and the fractions were evaluated with regard to their inhibitory effect on the production of nitric oxide (NO) from the macrophage cell line stimulated by lipopolysaccharide. Compounds in the active fractions were isolated and identified. One isolated compound was identified as new: (6S)-2-methyl-5-hydroxy-6-(3-hydroxy-4-methylphenyl)-2-heptene-4-one (1). Four isolated compounds were identified as known: (6S)-2-methyl-6-(4-hydroxyphenyl)-2-heptene-4-one (4), bisabolone-4-one (5), curcumenone (6), and turmeronol A (8). Three isolated compounds were not identified their stereostructures but their planar structures: 2-methyl-6-(4-hydroxymethyl-phenyl)-2-heptene-4-one (2), 2-methyl-6-(2,3-epoxy-4-methyl-4-cyclohexene)-2-heptene (3), and 4-methylene-5-hydroxybisabola-2,10-diene-9-one (7). Compounds 1, 4, 7 and 8 inhibited production of prostaglandin E2 and NO. Others inhibited NO production only. These results (at least in part) show the active compounds contributing to the anti-inflammatory effects of WEC, and may be useful for elucidating its various beneficial physiologic effects.

Effect of a water extract of Curcuma longa on emotional states in healthy participants.

Physiological symptoms of mood disturbances, such as fatigue or anxiety, are closely related to inflammation in the central nervous system or the whole body. Curcuma longa is widely used as a dietary spice and has been reported to have anti-inflammatory activity. To investigate the effect of a water extract of C. longa (WEC) on emotional states, a randomized, double-blind, placebo-controlled, parallel-group study was conducted with healthy participants. Forty-eight participants were randomly assigned to receive five tablets containing 150 mg WEC and 0.40 mg bisacurone (L-WEC group), five tablets containing 900 mg WEC and 2.40 mg bisacurone (H-WEC group), or matching placebo tablets (placebo group) daily for 8 weeks. Participant emotional states were measured every 4 weeks using the Profile of Mood States (POMS). The changes from week 0 to week 8 in the fatigue score of the POMS were significantly lower in the L-WEC group than in the placebo group. This result suggests that daily intake of 150 mg WEC may positively influence emotional fatigue, and further investigation focused on emotional fatigue is needed.

Hot water extract of turmeric (Curcuma longa) prevents non-alcoholic steatohepatitis in mice by inhibiting hepatic oxidative stress and inflammation.

Curcuma longa, also known as turmeric, has long been used as a medicinal herb with various biological effects. A hot water extract of C. longa (WEC) has been reported to show antioxidant and anti-inflammatory activity, but its effect on hepatic inflammation is poorly understood. In the present study, to investigate the effect of WEC on non-alcoholic steatohepatitis, C57BL/6J mice were fed a low-methionine, choline-deficient diet with 0·175 % WEC (WEC group) or without WEC (control group) for 6 or 12 weeks. Although hepatic steatosis was similar in the WEC group and the control group, WEC suppressed the elevation of plasma aspartate aminotransferase and alanine aminotransferase, which are markers of hepatocellular damage. Compared with the control group, the WEC group had higher hepatic levels of reduced glutathione and superoxide dismutase, as well as a lower hepatic level of thiobarbituric acid-reactive substances. WEC also reduced hepatic expression of mRNA for inflammatory factors, including TNF-α, IL-1ß, IL-6, monocyte chemoattractant protein-1, vascular cell adhesion molecule-1, F4/80 and CC motif chemokine receptor 2. Histological examination revealed that WEC suppressed hepatic recruitment of F4/80+ monocytes/macrophages and inhibited hepatic fibrosis. Furthermore, WEC inhibited hepatic expression of mRNA for molecules related to fibrosis, such as transforming growth factor-ß, α-smooth muscle actin, type I collagen (α1-chain) and tissue inhibitor of matrix metalloproteinase-1. These findings suggest that dietary intake of WEC prevents the progression of non-alcoholic steatohepatitis by alleviating hepatic oxidative stress and inflammation.

A hot water extract of turmeric (Curcuma longa) suppresses acute ethanol-induced liver injury in mice by inhibiting hepatic oxidative stress and inflammatory cytokine production.

Turmeric (Curcuma longa) is a widely used spice that has various biological effects, and aqueous extracts of turmeric exhibit potent antioxidant activity and anti-inflammatory activity. Bisacurone, a component of turmeric extract, is known to have similar effects. Oxidative stress and inflammatory cytokines play an important role in ethanol-induced liver injury. This study was performed to evaluate the influence of a hot water extract of C. longa (WEC) or bisacurone on acute ethanol-induced liver injury. C57BL/6 mice were orally administered WEC (20 mg/kg body weight; BW) or bisacurone (60 µg/kg BW) at 30 min before a single dose of ethanol was given by oral administration (3·0 g/kg BW). Plasma levels of aspartate aminotransferase and alanine aminotransferase were markedly increased in ethanol-treated mice, while the increase of these enzymes was significantly suppressed by prior administration of WEC. The increase of alanine aminotransferase was also significantly suppressed by pretreatment with bisacurone. Compared with control mice, animals given WEC had higher hepatic tissue levels of superoxide dismutase and glutathione, as well as lower hepatic tissue levels of thiobarbituric acid-reactive substances, TNF-α protein and IL-6 mRNA. These results suggest that oral administration of WEC may have a protective effect against ethanol-induced liver injury by suppressing hepatic oxidation and inflammation, at least partly through the effects of bisacurone.