Radioprotective effect of mistletoe extract on intestinal toxicity: in vivo study using adult zebrafish.

PURPOSE: The intestine is a dose-limiting organ in the treatment of intra-abdominal cancer. We previously reported that the extract of mistletoe parasites on Quercus had a more potent radioprotective effect than amifostine in reducing the developmental toxicities of zebrafish embryos. In this study, radioprotection against intestinal toxicity was investigated in adult zebrafish. METHODS: Wild-type adult AB zebrafish were exposed to 45-50 Gy of photon beam irradiation and/or treated with mistletoe extract orally 1 h before. The main endpoints of the study were survival and degree of deformation of the intestinal villi. RESULTS: The median follow-up period was 10 d post-irradiation (range: 7-11 d). A total of 105 zebrafish were used, including 42 in the radiation alone, 42 in the radiation and mistletoe arms, and 21 control subjects (mistletoe alone, mock-irradiated arm). The rate of both significant deformity and death was 53% in the radiation-alone arm, whereas the corresponding rate was 30% in the radiation and mistletoe arms. Significant deformity-free survival rates at 10 d post-irradiation in the radiation alone, and radiation and mistletoe arms were 44.7% (95% confidence interval [CI]:20-54.3) and 68.4% (95% CI:53.8-86.8), respectively (p=.046). The radiation and mistletoe arms showed decreased expression of two of three inflammatory genes (IL-1ß and IL-6) compared to the radiation alone group (p<.05). CONCLUSION: The radioprotective effect against intestinal toxicity was successfully shown in an adult zebrafish model. This result suggests the possibility of clinical use of mistletoe extract for the treatment of abdominal cancers.

Beneficial Effect of Gastrodia elata Blume and Poria cocos Wolf Administration on Acute UVB Irradiation by Alleviating Inflammation through Promoting the Gut-Skin Axis.

Bioactive compounds in some herbs can, directly and indirectly, protect against photoaging. We evaluated the effects of Gastrodia elata Blume (GE) and Poria cocos Wolf (PC) water extracts on ultraviolet (UV) B-induced skin lesions by acute UVB exposure in ICR mice and explored their mechanism of action. After removing the hair on the back of the mice, UVB (280-310 nm) was exposed to the back for 30 min to induce skin damage. Four UVB exposure groups were divided into the following according to the local application (1,3-butanediol extract) on the dorsal skin and oral intake (0.3 g water extract/kg body weight/day): 1,3-butanediol and cellulose(control; UV-Con), retinoic acid (positive-control; UV-Positive), PC extracts (UV-PC), and GE extracts (UV-GE). The fifth group had no UVB exposure with the same treatment as the UV-Con (Normal-control). The erythema, burns, erosion, and wounds of the UV-PC and UV-PC groups were alleviated, and the most significant improvements occurred in the UV-PC group. PC and GE reduced the thickness of the dorsal skin tissue, the penetration of mast cells, and malondialdehyde contents. The mRNA expression of TNF-α, IL-13, and IL-4, inflammatory factors, were also reduced significantly in the dorsal skin of the UV-PC and UV-GE groups. UV-PC, UV-GE, and UV-Positive showed improvements in UV-induced intestinal tissue inflammation. UV-Con deteriorated the intestinal morphology, and PC and GE alleviated it. The α-diversity of the fecal microbiota decreased in the UV-control, and UV-PC and UV-GE prevented the decrease. Fecal metagenome analysis revealed increased propionate biosynthesis in the UV-PC group but decreased lipopolysaccharide biosynthesis in the UV-PC and UV-GE groups compared to UV-Con. In conclusion, the local application and intake of PC and GE had significant therapeutic effects on acute UV-induced skin damage by reducing oxidative stress and proinflammatory cytokines, potentially promoting the gut-microbiota-gut-skin axis.

Mitigation of Memory Impairment with Fermented Fucoidan and λ-Carrageenan Supplementation through Modulating the Gut Microbiota and Their Metagenome Function in Hippocampal Amyloid-ß Infused Rats.

Attenuating acetylcholinesterase and insulin/insulin-like growth factor-1 signaling in the hippocampus is associated with Alzheimer's disease (AD) development. Fucoidan and carrageenan are brown and red algae, respectively, with potent antibacterial, anti-inflammatory, antioxidant and antiviral activities. This study examined how low-molecular-weight (MW) and high-MW fucoidan and λ-carrageenan would improve memory impairment in Alzheimer's disease-induced rats caused by an infusion of toxic amyloid-ß(Aß). Fucoidan and λ-carrageenan were dissected into low-MW by Luteolibacter algae and Pseudoalteromonas carrageenovora. Rats receiving an Aß(25-35) infusion in the CA1 region of the hippocampus were fed dextrin (AD-Con), 1% high-MW fucoidan (AD-F-H), 1% low-MW fucoidan (AD-F-L), 1% high-MW λ-carrageenan (AD-C-H), and 1% low-MW λ-carrageenan (AD-C-L) for six weeks. Rats to receive saline infusion (Normal-Con) had an AD-Con diet. The AD-F-L group showed an improved memory function, which manifested as an enhanced Y-maze spontaneous alternation test, water maze, and passive avoidance tests, similar to the Normal-Con group. AD-F-L also potentiated hippocampal insulin signaling and increased the expression of ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in the hippocampus. AD-C-L improved the memory function mainly by increasing the BDNF content. AD-F-H and AD-C-H did not improve the memory function. Compared to AD-Con, the ascending order of AD-C-H, AD-F-H, AD-C-L, and AD-F-L increased insulin signaling by enhancing the pSTAT3®pAkt®pGSK-3ß pathway. AD-F-L improved glucose tolerance the most. Compared to AD-CON, the AD-F-L treatment increased the serum acetate concentrations and compensated for the defect of cerebral glucose metabolism. AD-Con increased Clostridium, Terrisporobacter and Sporofaciens compared to Normal-Con, and AD-F-L and AD-C-L increased Akkermentia. In conclusion, AD-F-L and AD-C-L alleviated the memory function in the rats with induced AD symptoms by modulating.

A Causal Relationship between Vitamin C Intake with Hyperglycemia and Metabolic Syndrome Risk: A Two-Sample Mendelian Randomization Study.

Excessive oxidative stress can contribute to metabolic syndrome (MetS), and antioxidants can protect against its development. Vitamin C (VC) is a well-known antioxidant, and observational studies have associated a deficiency with an increased MetS risk. This study tested the hypothesis that dietary VC intake caused an inverse relation of MetS and its components risk using a two-sample Mendelian randomization (MR) method in adults ≥40 years in a city hospital-based (n = 58,701) and Ansan/Ansung plus rural (n = 13,598) cohorts. Independent genetic variants associated with dietary VC intake were explored using a genome-wide association study (GWAS) with significance levels of p < 5 × 10−5 and linkage disequilibrium (r2 threshold of 0.001), after adjusting for the covariates related to MetS, in a city hospital-based cohort (n = 52,676) excluding the participants having vitamin supplementation. MR methods, including inverse-variance weighting (IVW), weighted median, MR-Egger, and weighted model, were used to determine the causal relationship between the dietary VC intake and the risk of MetS and its components in Ansan/Ansung plus rural cohorts (n = 11,733). Heterogeneity and leave-one-out sensitivity analyses were conducted. Energy intake, as well as other nutrient intakes, were significantly lower in the low VC intake group than in the high VC intake group, but the incidence of MetS and its components, including hyperglycemia, hypertriglyceridemia, and hypertension, was observationally higher in inadequate low VC intake in the combined cohorts. In MR analysis, insufficient dietary VC intake increased the risk of MetS, hyperglycemia, hypertriglyceridemia, and hypertension in an IVW (p < 0.05). In contrast, only the serum fasting blood glucose concentration was significantly associated with VC intake in weight median analysis (p < 0.05), but there was no significant association of low dietary VC with MetS and its components in MR-Egger. There was no likelihood of heterogeneity and horizontal pleiotropy in MetS and its components. A single genetic variant did not affect their association in the leave-one-out sensitivity analysis. In conclusion, insufficient dietary VC intake potentially increased the MetS and hyperglycemia risk in Asian adults. Low VC intake can contribute to increasing type 2 diabetes incidence in Asians.

Bioactive Components of Houttuynia cordata Thunb and Their Potential Mechanisms Against COVID-19 Using Network Pharmacology and Molecular Docking Approaches.

We investigated the molecular mechanism by which Houttuynia cordata Thunb (HCT) may intervene in coronavirus disease 2019 (COVID-19) and COVID-19-induced cytokine storms using network pharmacology and molecular docking approaches. Using the Traditional Chinese medicine Systems Pharmacology Database and Analysis Platform (TCMSP), a "component-target-pathway" topology map of HCT for COVID-19 treatment was constructed using Cytoscape. Core target genes were analyzed using the STRING database, and the signal pathway map and biological mechanism of COVID-19 therapy were obtained using cluster profilers. Active components of HCT were docked with severe respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like protease (3CLpro) and RNA-dependent RNA polymerase (RdRp) using AutoDockTools. Data visualization and statistical analysis were conducted using the R program. A molecular dynamic simulation was carried out with the Groningen Machine for Chemical Simulation program. HCT had six active anti-COVID-19 ingredients and 45 molecular targets. Their crucial target proteins for COVID-19 treatment were the RELA (nuclear factor kappa B [NF-κB] p65 subunit), interleukin 6, and mitogen-activated protein kinase 1. In functional enrichment analysis, the potential molecular targets of active components of HCT for COVID-19 treatment belonged to 18 signaling pathways (adjusted P = 2.12E-11). Gene ontology obtained by Kyoto Encyclopedia of Genes and Genome enrichment screening showed that the primary mechanism of COVID-19 treatment was upregulation of protein kinase C followed by downregulations of T cell differentiation and proliferation and NF-κB signaling. Molecular docking showed that the active components of HCT (quercetin and kaempferol) had similar binding affinities for SARS-CoV-2 3CLpro and SARS-CoV-2 RdRp, primary COVID-19 target proteins as did clinically used drugs. These results were confirmed with molecular dynamics simulation. In conclusion, multiple components of HCT, especially quercetin and kaempferol, have the potential to treat COVID-19 infection and COVID-19-induced cytokine storm by targeting multiple proteins.

Pinus koraiensis needle or cone extracts alleviate atopic dermatitis symptoms by regulating immunity and suppressing inflammation in HaCaT cells and Nc/Nga mice.

Pinus koraiensis needles (PKN) and cones (PKC) have been shown to protect against inflammation and pathogenic bacteria. We investigated the efficacies and action mechanisms of topical applications of 1,3-butylene glycol (BG) extracts and oral administration of their water extracts on atopic dermatitis (AD) symptoms. After exposing HaCaT cells and Nc/Nga mice dorsal skins to 2,4-dinitrochlorobenzene (DNCB) to induce atopic dermatitis models, they were topically applied BG (AD-control), 30% PKNX, or 30% PKCX to the skin lesions and fed water extracts (0.5%) in high-fat diets for 5 weeks. Normal-control mice had no DNCB exposure. Serum immunoglobulin E (IgE), IL-4, and TNF-α levels and gene expressions of TNF-α, IL-4, IL-6, and IFN-γ in the dorsal skin and HaCaT cells were measured. The AD-control mice elevated TNF-α and IL-6 mRNA levels in HaCaT cells. Both extracts attenuated clinical AD symptoms in AD-induced Nc/Nga mice: PKNX improved hemorrhage, erythema, and lichenification of dorsal skin better than PKCX while both similarly alleviated erythema, edema, excoriation, and itching behavior. PKCX reduced IgE contents and increased filaggrin mRNA expression better than PKNX, but PKNX reduced lipid peroxides and mRNA levels of TNF-α and IL-4 in the dorsal skin. In the histological analysis of the dorsal skin, the administration of both extracts significantly decreased mast cell numbers, immune cell infiltration, gaps between the epidermis and dermis, and abnormal cell and nucleus shapes. In conclusion, both PKCX and PKNX treatment alleviated the DNCB-induced clinical symptoms of AD by alleviating immune-related symptoms and inflammation in partially different pathways. Therefore, PKNX and PKCX may be effective for AD therapy. PRACTICAL APPLICATIONS: Atopic dermatitis (AD) is related to an overly activated immune response, and it has steadily increased last 3 decades. However, no optimal sustainable treatments are available. Pinus koraiensis needles and cones extracts have been used for anti-inflammatory and antimicrobial treatment. The present study demonstrated that their intake and topical administration onto the AD lesion alleviated clinical AD symptoms associated with reduced proinflammatory cytokines, mast cell numbers, and immune cell infiltrates to maintain dermal structure with maintaining filaggrin expression in AD-induced HaCaT cells and Nc/Nga mice. These results suggested that Pinus koraiensis needles and cones extracts can be developed and applied as beneficial alternative therapies for AD.

Alleviation of Dyslipidemia via a Traditional Balanced Korean Diet Represented by a Low Glycemic and Low Cholesterol Diet in Obese Women in a Randomized Controlled Trial.

A traditional balanced Korean diet (K-diet) may improve energy, glucose, and lipid metabolism. To evaluate this, we conducted a randomized crossover clinical trial, involving participants aged 30-40 years, who were randomly assigned to two groups-a K-diet or westernized Korean control diet daily, with an estimated energy requirement (EER) of 1900 kcal. After a 4-week washout period, they switched the diet and followed it for 4 weeks. The carbohydrate, protein, and fat ratios based on energy intake were close to the target values for the K-diet (65:15:20) and control diet (60:15:25). The glycemic index of the control diet and the K-diet was 50.3 ± 3.6 and 68.1 ± 2.9, respectively, and daily cholesterol contents in the control diet and K-diet were 280 and 150 mg, respectively. Anthropometric and biochemical parameters involved in energy, glucose, and lipid metabolism were measured while plasma metabolites were determined using UPLC-QTOF-MS before and after the 4-week intervention. After the four-week intervention, both diets improved anthropometric and biochemical variables, but the K-diet significantly reduced them compared to the control diet. Serum total cholesterol, non-high-density lipoprotein cholesterol, and triglyceride concentrations were significantly lower in the K-diet group than in the control diet group. The waist circumference (p = 0.108) and insulin resistance index (QUICKI, p = 0.089) tended to be lower in the K-diet group than in the control diet group. Plasma metabolites indicated that participants in the K-diet group tended to reduce insulin resistance compared to those in the control diet group. Amino acids, especially branched-chain amino acids, tyrosine, tryptophan, and glutamate, and L-homocysteine concentrations were considerably lower in the K-diet group than in the control diet group (p < 0.05). Plasma glutathione concentrations, an index of antioxidant status, and 3-hydroxybutyric acid concentrations, were higher in the K-diet group than in the control diet group. In conclusion, a K-diet with adequate calories to meet EER alleviated dyslipidemia by decreasing insulin resistance-related amino acids and increasing ketones in the circulation of obese women.

Protective effects of Forsythiae fructus and Cassiae semen water extract against memory deficits through the gut-microbiome-brain axis in an Alzheimer's disease model.

CONTEXT: Fruits of Forsythia suspensa Vahl (Oleaceae) and seeds of Cassia obtusifolia Linne (Caesalpinaceae) have been used to treat inflammation in Asia. OBJECTIVE: We examined the alleviation of memory function in Alzheimer's disease (AD) rats fed Forsythiae Fructus (FF) and Cassiae Semen water extracts (CS) and investigated the mechanisms responsible for the effects. MATERIALS AND METHODS: Thirty Sprague-Dawley male rats had hippocampal infusions of amyloid-ß(25-35) (AD rats; memory deficit), and ten rats were infused with amyloid-ß(35-25) (non-AD rats; no memory deficit). For eight weeks, all rats freely consumed high-fat diets (43% lard) incorporated with 200 mg/kg body weight assigned aqueous herbal extracts: AD-FF, AD-CS, or without extracts AD-CON (control), non-AD (normal-control). RESULTS: Memory impairment was prevented in the AD-FF (0.54 ± 0.06-fold) and the AD-CS rats (0.33 ± 0.04-fold) compared to the AD-CON by inhibiting amyloid-ß deposition to the levels less than one-fourth of the AD-CON group. The hippocampal pAkt→pGSK-3ß→pFOXO1 pathway was attenuated by approximately 3.25-fold in the AD-CON, while AD-FF prevented the attenuation better than AD-CS. The relative intensity of hippocampal tau protein based on ß-actin was suppressed with AD-FF (0.68 ± 0.09) and AD-CS (0.96 ± 0.81), compared to AD-CON (1.19 ± 0.13). AD decreased the abundance of Bacteroidales by 34.2% and Lactobacillales by 23.8% and increased Clostridiales by 181% while the AD-FF, but not the AD-CS, normalised the gut microbiota changes to be similar to the non-AD. DISCUSSION AND CONCLUSIONS: FF improved memory deficits better than CS in an AD-induced rat model. The potential neuroprotective benefits of FF against AD may be applicable to human AD therapy with additional clinical research.

Coffee Intake Interacted with the Bcl-2 rs1944420, rs7236090, and rs2849382 Haplotype to Influence Breast Cancer Risk in Middle-Aged Women.

We hypothesized that the haplotype of Bcl-2 genetic variants increases breast cancer risk and interacts with lifestyles in Korean women. We identified single nucleotide polymorphism (SNPs) of Bcl-2 associated with breast cancer risk after adjusting for covariates in 390 breast cancer patients and 36,726 women without any cancer that participated in the Korean Genomic Epidemiology Study (KoGES). An allelic genetic model showed that three SNPs (rs1944420, rs7236090, and rs2849382) in the Bcl-2 gene were significantly associated with breast cancer (ORs = 1.28, 0.84, and 0.79, respectively). The participants with the minor allele of the haplotype with three SNPs had 1.65-fold higher breast cancer risk than those with the major allele, after adjusting for covariates. Serum C-reactive protein concentration had a positive association with breast cancer risk. A significant interaction was also observed between the minor allele of the Bcl-2 haplotype and coffee intake (P = 0.03). A low coffee intake in women with the minor allele presented a higher breast cancer risk than a low coffee intake in those with the major allele. In conclusion, the risk of breast cancer risk was higher in post-menopausal women with the minor allele of the Bcl-2 haplotype, and consuming more than 1 cup of coffee per day reduced the risk. The results of this study could be applied to reduce the risk of breast cancer.

Efficacy and safety of Di-Tan Decoction for treating post-stroke neurological disorders: a systematic review and Meta-analysis of randomized clinical trials.

The management of post-stroke complications plays an important role in the quality of life. Di-Tan Decoction (DTD; ) is a widely used traditional Chinese medicine. This study incorporated systematic review and meta-analysis to evaluate the efficacy of DTD in post-stroke neurological disorders. Randomized clinical trials (RCTs) were searched from English, Chinese and Korean electronic medical databases, by including the keywords "Di-Tan Tang", "Di-Tan Decoction", "Scour Phlegm Decoction", "stroke", and "RCT. Each RCT included control (placebo, conventional therapy, or Western medicine) and experimental (DTD treatment) groups. For patients inflicted with stroke for 1-6 weeks, the outcomes of post-stroke neurological disorders were measured by scales for post-stroke symptoms and were classified as "completely healed", "markedly effective", "effective" and "ineffective". Totally, 11 RCTs (n = 490 controls and n = 502 DTD subjects) were selected from 210 articles identified in the initial search. A meta-analysis of evaluation criteria in post-stroke symptoms revealed that the overall odds ratio (ORs) for alleviating post-stroke neurological disorders were 0.30-fold lower (95% CI = 0.21-0.43) in the DTD group than the control (Western medicine) group (P < 0.000 01). Moreover, regardless of the type of stroke diagnostic scale applied (including NFA, HDS, and NIHSS), the overall post-stroke symptoms determined were less severe in the DTD group (n = 219) than the control group (n = 217). No adverse effects of DTD were observed in the 11 RCTs reviewed. All 11 studies used an appropriate method for randomization of subjects to evaluate the risk of bias (ROB), and 7 studies included allocation concealment as well as blinding of patients and practitioners. High-risk ROB was included in 6 RCTs. No significant publication bias was derived from the funnel plot. Our results indicate that the administration of DTD alone, and DTD in combination with Western medicine, exert greater efficacy for post-stroke complication therapy, than Western medicine administered alone. More rigorous and regulated studies are required to confirm the therapeutic efficacy of DTD for post-stroke neurological disorders. disorders.

Menopause, Ultraviolet Exposure, and Low Water Intake Potentially Interact with the Genetic Variants Related to Collagen Metabolism Involved in Skin Wrinkle Risk in Middle-Aged Women.

Genetic and environmental factors influence wrinkle development. We evaluated the polygenetic risk score (PRS) by pooling the selected single nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS) for wrinkles and the interaction of PRS with lifestyle factors in middle-aged women. Under the supervision of a dermatologist, the skin status of 128 women aged over 40 years old was evaluated with Mark-Vu, a skin diagnosis system. PRS was generated from the selected SNPs for wrinkle risk from the genome-wide association study. Lifestyle interactions with PRS were also evaluated for wrinkle risk. Participants in the wrinkled group were more likely to be post-menopausal, eat less fruit, take fewer vitamin supplements, exercise less, and be more tired after awakening in the morning than those in the less-wrinkled group. The PRS included EGFR_rs1861003, MMP16_rs6469206, and COL17A1_rs805698. Subjects with high PRS had a wrinkle risk 15.39-fold higher than those with low PRS after adjusting for covariates, and they had a 10.64-fold higher risk of a large skin pore size. Menopause, UV exposure, and water intake interacted with PRS for wrinkle risk: the participants with high PRS had a much higher incidence of wrinkle risk than those with low PRS, only among post-menopausal women and those with UV exposure. Only with low water intake did the participants with medium PRS have increased wrinkle risk. In conclusion, women aged >40 years with high PRS-related collagen metabolism may possibly avoid wrinkle risk by avoiding UV exposure by applying sunscreen, maintaining sufficient water intake, and managing estrogen deficiency.

Tetragonia tetragonioides Protected against Memory Dysfunction by Elevating Hippocampal Amyloid-ß Deposition through Potentiating Insulin Signaling and Altering Gut Microbiome Composition.

Alzheimer's disease (AD) is a progressive neurodegenerative disease. Herbal medicine may provide efficacious treatments for its prevention and/or cure. This study investigated whether a 70% ethanol extract of Tetragonia tetragonioides Kuntze (TTK; New Zealand spinach) improved the memory deficit by reducing hippocampal amyloid-ß deposition and modulating the gut microbiota in rats with amyloid-ß(25-35) infused into the hippocampus (AD rats) in an AD animal model. The AD rats had cellulose (AD-CON) or TTK (300 mg/kg bw; AD-TTK) in their high-fat diets for seven weeks. Rats with amyloid-ß(35-25) infused into the hippocampus fed an AD-Con diet did not have memory loss (Normal-Con). AD-TTK protected against amyloid-ß deposition compared to AD-Con, but it was higher than Normal-Con. AD-TTK protected against short-term and special memory loss measured by passive avoidance, Y maze, and water maze, compared to AD-Con. Compared to the Normal-Con, AD-Con attenuated hippocampal pCREB → pAkt → pGSK-3ß, which was prevented in the AD-TTK group. Brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) mRNA expression decreased in the AD-CON group, and their expression was prevented in the AD-TTK group. Hippocampal TNF-α and IL-1ß mRNA expressions were higher in the AD-Con group than in the Normal-Con, and AD-TTK groups protected against the increase in their expression. The AD-CON group showed an increase in insulin resistance compared to the Normal-Con group and the AD-TTK group showed improvement. AD-Con separated the gut microbiome community compared to the Normal-Con group and AD-TTK overlapped with the normal-Con. The AD-Con group had more Clostridiales, Erysipelotrichales, and Desulfovibrionales than the AD-TKK and Normal-Con group but fewer Lactobacilales and Bacteroidales. In conclusion, the 70% ethanol extract of TTK enhanced the memory function and potentiated hippocampal insulin signaling, reduced insulin resistance, and improved gut microbiota in amyloid-ß-infused rats.

The Combination of Mulberry Extracts and Silk Amino Acids Alleviated High Fat Diet-Induced Nonalcoholic Hepatic Steatosis by Improving Hepatic Insulin Signaling and Normalizing Gut Microbiome Dysbiosis in Rats.

Mulberry water extracts (MB) and silk amino acids (SA) are reported to improve oxidative stress and inflammation, respectively. We hypothesized whether the mixture of mulberry water extracts and silk amino acids can alleviate nonalcoholic fatty liver disease (NAFLD) induced by high fat diets. Male Sprague Dawley rats were orally provided with high fat diets containing different ratios of MB and SA (1:3, MS1:3, or 1:5, MS1:5) or cellulose (the disease-control) for 12 weeks. Rats had 200 or 600 mg/kg bw of MS1:3 and MS1:5 (MS1:3-L, MS1:3-H; MS1:5-L, and MS1:5-H). Rats in the normal-control group were fed the 20% fat diet with cellulose. Disease-control rats exhibited much greater triglyceride (TG) deposition in the liver than the normal-control rats along with increased body weight gain, visceral fat mass, serum concentrations of cholesterol, triglyceride and nonesterified fatty acid (NEFA), and insulin resistance. Disease-control rats also had liver damage with increased oxidative stress and inflammation compared to the normal-control rats. MS1:3-H and MS1:5-H were found to have greater hepatic glycogen accumulation and decreased hepatic TG, insulin resistance, and dyslipidemia, with MS1:5-H being similar to the normal-control. MS1:3-H alleviated oxidative stress with lower hepatic lipid peroxide compared to MS1:5-H whereas MS1:5-H ameliorated inflammation and hepatocyte damage better than MS1:3-H. Both MS1:3-H and MS1:5-H potentiated hepatic insulin signaling (pAkt⟶pACC) and reduced the mRNA expression of TG synthesis genes mRNA (FAS and SREBP-1c). In the gut microbiome MS1:3-H elevated the ratio of Bacteroidales to Clostridiales in the cecum better than MS1:5-H but MS1:5-H reduced the proinflammatory Turicibacterales. In conclusion, both MS1:3-H and MS1:5-H prevented liver damage induced by high fat diets, mainly by suppressing oxidative stress and inflammation, respectively. MS1:3 and MS1:5 might be used as therapeutic agent for NAFLD.

Rice Porridge Containing Welsh Onion Root Water Extract Alleviates Osteoarthritis-Related Pain Behaviors, Glucose Levels, and Bone Metabolism in Osteoarthritis-Induced Ovariectomized Rats.

Rice porridge containing Allium fistulosum (Welsh onion) root water extract (RAFR) has anti-inflammatory bioactive compounds. We examined whether the long-term administration of rice porridge with RAFR would prevent or delay the progression of osteoarthritis and menopausal symptoms in estrogen-deficient animals by ovariectomy. The rats consumed 40% fat energy diets containing 250 mg RAFR (rice: Allium fistulosum root = 13:1)/kg body weight (bw) (OVX-OA-RAFR-Low), 750 mg RAFR/kg bw (OVX-OA-RAFR-High) and 750 mg starch and protein/kg bw(OVX), respectively. After consuming the assigned diets for eight weeks, monoiodoacetate (OVX-OA) or saline (OVX) were injected into the knee joints of the rats for an additional three weeks. Sham rats were administered saline injections (normal-control). OVX-OA-RAFR improved oral glucose tolerance and also protected against decreases in bone mineral density and lean body mass in the legs and increases in fat mass in the abdomen, compared to the OVX and OVX-OA. OVX-OA-RAFR improved swelling and limping scores, normalized weight distribution between the osteoarthritic and normal limbs, and increased maximum running speeds compared to the OVX-OA. The OVX-OA deteriorated the articular cartilage by reducing the articular matrix and bone loss in the knee joint and it prevented knee joint deterioration when compared to the OVX. The improvement in osteoarthritis symptoms in OVX-OA-RAFR decreased the mRNA expression of matrix metallo-proteinase-1 and matrix metalloproteinase-13, tumor necrosis factor-α, and interleukin-1ß and interleukin-6 in the articular cartilage compared to OVX-OA rats. In conclusions, RAFR is effective in treating osteoarthritis symptoms and it may be used for a therapeutic agent in osteoarthritis-induced menopausal women.

Lactobacillus intestinalis efficiently produces equol from daidzein and chungkookjang, short-term fermented soybeans.

Equol improves menopausal symptoms and it is synthesized from daidzein, one of the isoflavonoids in soybeans, by the bacteria in the large intestines of some people. The purpose of this study was to isolate equol-producing bacteria using daidzein from the intestinal microflora and to produce equol-containing chungkookjang (short-term fermented soybean). Equol-producing bacteria from the feces of Sprague-Dawley female rats were isolated using media containing daidzein. The isolated bacteria were cultured in thioglycollate media and equol production was identified through thin-layer chromatography and ultraperformance liquid chromatography-mass spectrometry. The bacteria were identified by 16S rRNA sequencing. The rate of equol production in different concentrations of daidzein was assessed. The expression of genes that code for enzymes associated with the production of equol from daidzein was detected through reverse transcription quantitative PCR. The bacterium we isolated was Lactobacillus intestinalis (LC096206.1, 99%). L. intestinalis was found to express daidzein reductase, dihydrodaidzein reductase, and tetrahydrodaidzein reductase, the enzymes involved in producing equol from daidzein. The conversion rate of equol from daidzein was highest (29.5%) using 200 µM daidzein for 48 h of incubation. When chungkookjang fermented with Bacillus amyloquencies SRCM100001 was incubated with L. intestinalis, 0.32 ± 0.04 mg equol/g chungkookjang was produced. In conclusion, L. intestinalis efficiently produces equol from not only daidzein but also in chungkookjang.

Ojayeonjonghwan, an oriental medicine composed of five seeds, protects against vasomotor and neurological disorders in estrogen-deficient rats.

IMPACT STATEMENT: Menopausal symptoms impair the quality of life of many women, and although conventional treatments are often effective, their use is limited by adverse effects. Ojayeonjonghwan, OJa, is a traditional Oriental medicine that is used for both male and female reproductive health and has a long history of safe use. We evaluated the effectiveness of two variations of OJa (OJa1 and OJa2) for treating menopausal symptoms in ovariectomized (OVX) rats. Both OJa preparations were effective for relieving indicators of hot flashes and depression, and for preventing loss of bone mineral density and lean body mass. Only OJa 2 prevented memory dysfunction. These results show that the traditional Oriental medicine, Ojayeonjonghwan, has the potential to relieve menopausal symptoms in women and should be further evaluated in human clinical trials as an alternative to convention therapies in women for whom conventional therapies are not indicated or found to be ineffective.

Equol Decreases Hot Flashes in Postmenopausal Women: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Soy isoflavones may benefit some, but not all, menopausal women, and the ability of the women to produce equol may be the major determinant of effectiveness. We assessed the efficacy of soy isoflavones and equol for alleviating menopausal symptoms, especially vasomotor symptoms, in postmenopausal women who were equol producers and nonproducers by using systematic review and meta-analysis of randomized clinical trials (RCTs). We searched 12 English, Korean, and Chinese language scientific and medical databases. We selected all available RCTs that assessed the effect of equol, either equol itself or soy isoflavone in equol producers, on menopausal symptoms in peri- or postmenopausal women. The primary outcome was the effect on hot flashes. The severity of hot flashes was determined by the scores, and sensitivity and risk of bias analyses were conducted. Other outcomes of the review, but not meta-analysis, included depression and adverse events. Six studies (779 total subjects) met all criteria for the systematic review, 5 of those could be included in the meta-analysis (728 total subjects). Two studies included in the meta-analysis reported no statistically significant benefits of equol; the other three did report significant benefits of equol. Meta-analysis revealed a significant benefit of equol for lowering hot flash scores and revealed a generally low risk of bias. In conclusion, this study found that supplementing equol to equol nonproducers significantly lowered the incidence and/or severity of hot flashes in menopausal women.

Aloe vera Is Effective and Safe in Short-term Treatment of Irritable Bowel Syndrome: A Systematic Review and Meta-analysis.

BACKGROUND/AIMS: To evaluate the efficacy and safety of Aloe vera (AV) in patients with irritable bowel syndrome (IBS). METHODS: We searched the MEDLINE, EMBASE, and Cochrane databases for studies dated between 1st January 1960 and 30th December 2017. Eligible randomized controlled trials (RCTs) compared AV to placebo in patients with IBS. The primary outcome was standardized mean difference of the change in severity of IBS symptoms as measured by patient-rated scales. Secondary outcomes included response rate of IBS symptoms and adverse events. Heterogeneity among studies was assessed using Cochrane's Q and I2 statistics. RESULTS: Three RCTs with a total of 151 patients with IBS were included. The meta-analysis showed a significant difference for patients with AV compared to those with placebo regarding improvement in IBS symptom score (standardized mean difference, 0.41; 95% CI, 0.07-0.75; P = 0.020). Using intention-to-treat analysis, the AV patients showed significantly better response rates of IBS symptoms compared to placebo (pooled risk ratio, 1.69; 95% CI, 1.05-2.73; P = 0.030). No adverse events related with AV were found in included studies. There was no significant heterogeneity of effects across studies (P = 0.900; I2 = 0%). CONCLUSION: AV is effective and safe for the treatment of patients with IBS compared to placebo.