Effects of black raspberry extract on gut microbiota, microbial metabolites, and expressions of the genes involved in cholesterol and bile acid metabolisms in rats fed excessive choline with a high-fat diet.

In our previous study, black raspberry (BR) reduced the serum levels of trimethylamine-N-oxide and cholesterol in rats fed excessive choline with a high-fat diet (HFC). We hypothesized that gut microbiota could play a crucial role in the production of trimethylamine and microbial metabolites, and BR could influence gut microbial composition. This study aimed to elucidate the role of BR on changes in gut microbiota and microbial metabolites in the rats. The phylogenetic diversity of gut microbiota was reduced in the rats fed HFC, while that in the BR-fed group was restored. The BR supplementation enriched Bifidobacterium and reduced Clostridium cluster XIVa. In the BR-fed group, most cecal bile acids and hippuric acid increased, while serum lithocholic acid was reduced. The BR supplementation upregulated Cyp7a1 and downregulated Srebf2. These results suggest that BR extract may change gut bacterial community, modulate bile acids, and regulate gene expression toward reducing cholesterol. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01267-4.

Lactobacillus acidophilus KBL409 Reduces Kidney Fibrosis via Immune Modulatory Effects in Mice with Chronic Kidney Disease.

SCOPE: Intestinal dysbiosis has been reported to play an important role in the pathogenesis of various diseases, including chronic kidney disease (CKD). Here, to evaluate whether probiotic supplements can have protective effects against kidney injury in an animal model of CKD is aimed. METHODS AND RESULTS: An animal model of CKD is established by feeding C57BL/6 mice a diet containing 0.2% adenine. These model mice are administered Lactobacillus acidophilus KBL409 daily for 4 weeks. Features of adenine-induce CKD (Ade-CKD) mice, such as prominent kidney fibrosis and higher levels of serum creatinine and albuminuria are improved by administration of KBL409. Ade-CKD mice also exhibit a disrupted intestinal barrier and elevate levels of TNF-α, IL-6, and 8-hydroxy-2'-deoxyguanosine. These changes are attenuated by KBL409. Administration of KBL409 significantly reduces macrophage infiltration and promotes a switch to the M2 macrophage phenotype and increasing regulatory T cells. Notably, the NLRP3 inflammasome pathway is activated in the kidneys of Ade-CKD and decreases by KBL409. In primary kidney tubular epithelial cells treated with p-cresyl sulfate, short-chain fatty acids significantly increase M2 macrophage polarization factors and decrease profibrotic markers. CONCLUSIONS: These results demonstrate that supplementation with the probiotic KBL409 has beneficial immunomodulating effects and protects against kidney injury.

Antibacterial Photodynamic Inactivation of Fagopyrin F from Tartary Buckwheat (Fagopyrum tataricum) Flower against Streptococcus mutans and Its Biofilm.

The objective of this study was to determine reactive oxygen species (ROS) produced by fagopyrin F-rich fraction (FFF) separated from Tartary buckwheat flower extract exposed to lights and to investigate its antibacterial photodynamic inactivation (PDI) against Streptococcus mutans and its biofilm. ROS producing mechanisms involving FFF with light exposure were determined using a spectrophotometer and a fluorometer. S. mutans and its biofilm inactivation after PDI treatment of FFF using blue light (BL; 450 nm) were determined by plate count method and crystal violet assay, respectively. The biofilm destruction by ROS produced from FFF after exposure to BL was visualized using confocal laser scanning microscopy (CLSM) and field emission scanning electron microscope (FE-SEM). BL among 3 light sources produced type 1 ROS the most when applying FFF as a photosensitizer. FFF exposed to BL (5 and 10 J/cm2) significantly more inhibited S. mutans viability and biofilm formation than FFF without the light exposure (p < 0.05). In the PDI of FFF exposed to BL (10 J/cm2), an apparent destruction of S. mutans and its biofilm were observed by the CLSM and FE-SEM. Antibacterial PDI effect of FFF was determined for the first time in this study.

Protective Effects of Black Raspberry (Rubus occidentalis) Extract against Hypercholesterolemia and Hepatic Inflammation in Rats Fed High-Fat and High-Choline Diets.

Choline is converted to trimethylamine by gut microbiota and further oxidized to trimethylamine-N-oxide (TMAO) by hepatic flavin monooxygenases. Positive correlation between TMAO and chronic diseases has been reported. Polyphenols in black raspberry (BR), especially anthocyanins, possess various biological activities. The objective of this study was to determine the effects of BR extract on the level of choline-derived metabolites, serum lipid profile, and inflammation markers in rats fed high-fat and high-choline diets. Forty female Sprague-Dawley (SD) rats were randomly divided into four groups and fed for 8 weeks as follows: CON (AIN-93G diet), HF (high-fat diet), HFC (HF + 1.5% choline water), and HFCB (HFC + 0.6% BR extract). Serum levels of TMAO, total cholesterol, and low-density lipoprotein (LDL)-cholesterol and cecal trimethylamine (TMA) level were significantly higher in the HFC than in the HFCB. BR extract decreased mRNA expression of pro-inflammatory genes including nuclear factor-κB (NF-κB), interleukin (IL)-1ß, IL-6, and cyclooxygenase-2 (COX-2), and protein expression of NF-κB and COX-2 in liver tissue. These results suggest that consistent intake of BR extract might alleviate hypercholesterolemia and hepatic inflammation induced by excessive choline with a high-fat diet via lowering elevated levels of cecal TMA and serum TMAO in rats.

Black Raspberry Seed Oil Improves Lipid Metabolism by Inhibiting Lipogenesis and Promoting Fatty-Acid Oxidation in High-Fat Diet-Induced Obese Mice and db/db Mice.

The objective of this study was to evaluate the beneficial effect of α-linolenic acid-rich black raspberry seed (BRS) oil on lipid metabolism in high-fat diet (HFD)-induced obese and db/db mice. Five-week-old C57BL/6 mice were fed diets consisting of 50% calories from lard, 5% from soybean, and 5% from corn oil (HFD), or 50% calories from lard and 10% from BRS oil (HFD + BRS oil diet) for 12 weeks. Six-week-old C57BL/KsJ-db/db mice were fed diets consisting of 16% calories from soybean oil (standard diet), 8% from soybean, and 8% from BRS oil, or 16% from BRS oil for 10 weeks. The BRS oil diets lowered the levels of triacylglycerol, nonesterified fatty acids, and total cholesterol in serum and liver of both of the obese and db/db mice as compared with the HFD and standard diet, respectively. mRNA levels of lipogenesis markers including cluster of differentiation 36, fatty-acid-binding protein 1, sterol regulatory element binding protein 1c, fatty-acid synthase, and solute carrier family 25 member 1 in the liver of the BRS oil groups were lower than those in the liver of the HFD and standard groups in the obese and db/db mice, respectively. On the other hand, fatty-acid oxidation markers including carnitine palmitoyltransferase 1A, acyl-CoA dehydrogenase, hydroxylacyl-CoA dehydrogenase α, and acyl-CoA oxidase in the liver of the BRS oil groups were higher than those in the liver of the HFD and standard groups in the obese and db/db mice, respectively. Peroxisome proliferator-activated receptor α mRNA and protein levels increased in the liver and epididymal adipose tissue of the obese and db/db mice fed BRS oil compared with HFD and standard diet, respectively. BRS oil might improve lipid metabolism by inhibiting lipogenesis and promoting fatty-acid oxidation in HFD-induced obese and db/db mice.

Dietary Black Raspberry Seed Oil Ameliorates Inflammatory Activities in db/db Mice.

The objective of this study was to evaluate the status of the markers related to inflammation in db/db mice fed black raspberry seed (BRS) oil, which is rich in α-linolenic acid. Mice were divided into four groups: (1) C57BL/6 mice fed 16 % calories from soybean oil (normal CON); (2) C57BL/KsJ-db/db mice fed 16 % calories from soybean oil (CON); (3) C57BL/KsJ-db/db mice fed 8 % calories from soybean and 8 % calories from BRS oil (BRS 50 %); and (4) C57BL/KsJ-db/db mice fed 16 % calories from BRS oil (BRS 100 %). After 10 weeks, n-6/n-3 fatty acid ratios were significantly (P < 0.05) lower in the livers and epididymal adipose tissues of the BRS 50 % and BRS 100 % mice than in the CON. Serum TNFα and IL-6 were significantly (P < 0.05) lower in the BRS 50 % and BRS 100 % than in the CON. Serum IL-10 was significantly (P < 0.05) higher in the BRS 100 % than the CON. In the liver and epididymal adipose tissue, mRNA levels of pro-inflammatory markers in the BRS 50 % and BRS 100 % were lower than in the CON. Anti-inflammatory markers were higher in the epididymal adipose tissues of the BRS 50 % and BRS 100 % than in the CON. In the epididymal adipose tissue, macrophage infiltration markers (F4/80 and CD68) and leptin mRNA were significantly (P < 0.05) lower in the BRS 50 % and BRS 100 % than in the CON. Results of this study suggest that BRS oil may have anti-inflammatory effects in obese diabetic mice by ameliorating inflammatory responses.