Organic vegetable juice supplement alleviates hyperlipidemia in diet-induced obese mice and modulates microbial community in continuous colon simulation system.

In this study, we investigated the effects of organic vegetable juice (OVJ) supplementation on modulating the microbial community, and how its consumption ameliorated blood-lipid profiles in diet-induced obese mice. Here, we studied the alleviating effect of hyperlipidemia via animal experiments using diet-induced obese mice and analyzed the effect of OVJ on the microbial community in continuous colon simulation system. OVJ consumption did not have a significant effect on weight loss but helped reduce the weight of the epididymis fat tissue and adipocytes. Additionally, blood-lipid profiles, such as triglyceride, high-density lipoprotein, and glucose, were improved in the OVJ-fed group. Expression levels of genes related to lipid synthesis, including SREBP-1, PPARγ, C/EBPα, and FAS, were significantly decreased. In addition, OVJ treatment significantly reduced inflammatory cytokines and oxidative stress. OVJ supplement influenced intestinal bacterial composition from phylum to genus level, including decreased Proteobacteria in the ascending colon in the phylum. At the family level, Akkermansia, which are associated with obesity, were significantly augmented in the transverse colon and descending colon compared to the control juice group. In addition, treatment with OVJ affected predicted lipid-metabolism-function genes related to lipid synthesis. These results suggest that OVJ supplementation may modulate gut microbial community and reduce the potential symptom of hyperlipidemia in diet-obese mice.

Did air pollution continue to affect bike share usage in Seoul during the COVID-19 pandemic?

INTRODUCTION: The role of cycling has become more important in the urban transport system during the Covid-19 pandemic. As public transport passengers have tried to avoid crowded vehicles due to safety concerns, a rapid surge of cycling activities has been noted in many countries. This implies that more cyclists might be exposed to air pollution, potentially leading to health problems in cities like Seoul where the level of air pollution is high. METHODS: We utilised three years of bike sharing programme (Ddareungi) data in Seoul and time series models to examine the changes in the relationship between particulate concentration (PM2.5) and total daily cycling duration before and during the pandemic. RESULTS: We find that cyclists reacted less to the PM2.5 level during the pandemic, potentially due to the lack of covid-secure travel modes. Specifically, our results show significant negative associations between concentrations of PM2.5 and total daily cycling duration before the pandemic (year 2018 and 2019). However, this association became insignificant in 2020. CONCLUSIONS: Building comprehensive cycling infrastructure that can reduce air pollution exposure of cyclists and improving air quality alert systems could help build a more resilient city for the future.

Lactobacillus paracasei HY7015 Promotes Hair Growth in a Telogenic Mouse Model.

In this study, we describe the effects of Lactobacillus paracasei HY7015 (HY7015) on promoting mouse hair growth. Since our purpose was to increase hair growth through oral administration, medicinal yeast, at a suitable concentration for application in mice, was used as a positive control. First, experiments were conducted to determine the effect of HY7015 on proliferation of hair follicle dermal papilla cells (HFDPC), which are important contributors to hair growth. HY7015 stimulated HFDPC proliferation in vitro and increased their secretion of vascular endothelial growth factor and insulin-like growth factor-1. In mouse experiments, oral administration of HY7015 promoted hair growth and hair follicle maturation in the dorsal skin, as well as increasing growth factor levels in mouse serum. In summary, we demonstrate that L. paracasei HY7015 consumption can promote hair growth by stimulating HFDPC proliferation and growth factor secretion. Follow-up studies are warranted to determine the underlying mechanism, using various approaches, including investigation of changes in intestinal microbiota and alteration of gene and protein expression.

Fermented Red Ginseng Alleviates Ovalbumin-Induced Inflammation in Mice by Suppressing Interleukin-4 and Immunoglobulin E Expression.

Ginseng (the root of Panax ginseng Meyer) has been reported to have many biologic therapeutic effects, including anti-inflammatory properties, and ginsenosides are considered as one of the factors responsible for these therapeutic effects. To improve their therapeutic action, probiotic bacteria are used to ferment and chemically transform ginsenosides in red ginseng (RG). In this study, we aimed to investigate the beneficial effects of RG fermented by probiotic bacteria (FRG) against ovalbumin (OVA)-induced allergic rhinitis in a mouse model. We induced the mouse model via OVA inhalation; experimental results revealed increased immunoglobulin E (IgE) and interleukin (IL)-4 levels, leading to Th2-type cytokine response. The mice with induced allergy were then orally administered RG and FRG over 2 weeks, as a result of which, IL-4 and IgE levels in bronchoalveolar lavage fluid, nasal fluid, and serum were found to be ameliorated more effectively by FRG than by RG, suggesting that FRG has better immune regulatory effects than RG. FRG also downregulated immune cell levels, such as those of eosinophils and basophils, and significantly decreased the thickness of OVA-induced respiratory epithelium compared to RG. Collectively, the results showed that FRG treatment alleviates inflammation, thereby extending a protective effect to mice with OVA-induced inflammatory allergic rhinitis.

Lactic Acid Bacteria and Natural Product Complex Ameliorates Ovalbumin-Induced Airway Hyperresponsiveness in Mice.

The incidence of respiratory diseases, such as asthma, has substantially increased in recent times owing to environmental changes, such as air pollution. Induction of a chronic inflammatory response begins with production of biologically active mediators from the airway epithelium, which attracts and recruits inflammatory cells into the lung airway. In our previous study, we confirmed that Lactobacillus casei HY2782 and Bifidobacterium animalis spp. lactis HY8002 could improve lung inflammation in the COPD animal model. In this study, we investigated the effect of the HY2782 complex against airway hyperresponsiveness by using an ovalbumin (OVA)-induced animal model. An orally administered HY2782 complex on OVA-induced allergic asthma in a BALB/c mouse model was used. The present results showed that the HY2782 complex suppressed total immunoglobulin E in serum and bronchoalveolar lavage fluid (BALF). The cytokine production profile in BALF and serum revealed that the HY2782 complex showed reduced levels of Th2 cytokines among immune factors released due to the elevated allergic response. Levels of inflammatory mediators in BALF, MCP-1, MIP-2, and CXCL-9 were decreased by oral administration of the HY2782 complex. Lower numbers of eosinophils and neutrophils in BALF suggested that inflammation was ameliorated by the HY2782 complex. Histological observation of lung sections also showed infiltration of fewer cells. From results, we suggested that the HY2782 complex effectively responds to improvement of the immune response and airway hypersensitivity reaction because of the anti-inflammatory effect of the Pueraria lobata root extract and antioxidant effect of HY2782.

Selection of Lactococcus lactis HY7803 for Glutamic Acid Production Based on Comparative Genomic Analysis.

Comparative genomic analysis was performed on eight species of lactic acid bacteria (LAB)-Lactococcus (L.) lactis, Lactobacillus (Lb.) plantarum, Lb. casei, Lb. brevis, Leuconostoc (Leu.) mesenteroides, Lb. fermentum, Lb. buchneri, and Lb. curvatus-to assess their glutamic acid production pathways. Glutamic acid is important for umami taste in foods. The only genes for glutamic acid production identified in the eight LAB were for conversion from glutamine in L. lactis and Leu. mesenteroides, and from glucose via citrate in L. lactis. Thus, L. lactis was considered to be potentially the best of the species for glutamic acid production. By biochemical analyses, L. lactis HY7803 was selected for glutamic acid production from among 17 L. lactis strains. Strain HY7803 produced 83.16 pmol/µl glutamic acid from glucose, and exogenous supplementation of citrate increased this to 108.42 pmol/µl. Including glutamic acid, strain HY7803 produced more of 10 free amino acids than L. lactis reference strains IL1403 and ATCC 7962 in the presence of exogenous citrate. The differences in the amino acid profiles of the strains were illuminated by principal component analysis. Our results indicate that L. lactis HY7803 may be a good starter strain for glutamic acid production.

Effects of PrObiotics on the Symptoms and Surgical ouTComes after Anterior REsection of Colon Cancer (POSTCARE): A Randomized, Double-Blind, Placebo-Controlled Trial.

We investigated microbiota changes following surgical colon cancer resection and evaluate effects of probiotics on microbiota and surgical recovery. This randomized double-blind trial was performed at four medical centers in South Korea. Of 68 patients expected to undergo anterior sigmoid colon cancer resection, 60 were eligible, of whom 29 and 31 received probiotics and placebo, respectively, for four weeks, starting at one week preoperatively. Third- and/or fourth-week information on anterior resection syndrome (ARS), inflammatory markers, and quality of life was obtained. Stool sample analysis was conducted after randomization and bowel preparation and at three and four postoperative weeks. Bacteria were categorized into Set I (with probiotic effects) and II (colon cancer-associated). The probiotic group's ARS score showed an improving trend (p = 0.063), particularly for flatus control (p = 0.030). Serum zonulin levels significantly decreased with probiotics. Probiotic ingestion resulted in compositional changes in gut microbiota; greater increases and decreases in Set I and II bacteria, respectively, occurred with probiotics. Compositional increase in Set I bacteria was associated with reduced white blood cells, neutrophils, neutrophil-lymphocyte ratio, and zonulin. Bifidobacterium composition was negatively correlated with zonulin levels in the probiotic group. Probiotics improved postoperative flatus control and modified postoperative changes in microbiota and inflammatory markers.

Gastroprotective Effects of Cudrania tricuspidata Leaf Extracts by Suppressing Gastric cAMP and Increasing Gastric Mucins.

Cudrania tricuspidata has been used as an East Asian folk remedy to treat various symptoms. Recently, scientific evidence of the efficacy of C. tricuspidata has emerged. The objective of this study was to elucidate protective role of C. tricuspidata in the gastric mucosa using pylorus-ligated Sprague-Dawley rats and primary parietal cells. C. tricuspidata ethanol extracts attenuated gastric mucosal damage, secretion, and juice acidity in pylorus-ligated rats; however, it did not affect expression of gastric acid-related genes [muscarinic acetylcholine receptor M3 receptor (M3R), histamine H2-receptors (H2R), and cholecystokinin-2/gastrin receptors (CCK2R)] or serum gastrin concentrations. Furthermore, extracts greatly reduced levels of gastric cyclic adenosine monophosphate (cAMP) and significantly increased mRNA levels of gastric-type mucins (MUC5AC and MUC6). To identify the mode of action of C. tricuspidata extract in regulating gastric acid secretion, intracellular cAMP and mRNA for H2R, M3R, and CCK2R were measured in primary parietal cells. mRNA levels of H2R, M3R, and CCK2R did not significantly differ following treatment with C. tricuspidata extract, whereas cAMP induced by the H2R-specific agonist was significantly decreased. C. tricuspidata may therefore reduce gastric acid secretion by inhibiting H2R activity rather than regulating mRNA expression. These finding suggest that ethanol extracts of C. tricuspidata inhibit H2R-related gastric acid secretion and increase gastric mucus to help prevent gastric mucosal damage. Therefore, C. tricuspidata extract has potential to be used in foods and medicines to prevent diseases related to gastric mucosal damage, such as gastritis and functional dyspepsia.

Metabolic and Lipidomic Profiling of Vegetable Juices Fermented with Various Probiotics.

Fermented vegetable juices have gained attention due to their various beneficial effects on human health. In this study, we employed gas chromatography-mass spectrometry, direct infusion-mass spectrometry, and liquid chromatography-mass spectrometry to identify useful metabolites, lipids, and carotenoids in vegetable juice (VJ) fermented with Lactobacillus plantarum HY7712, Lactobacillus plantarum HY7715, Lactobacillus helveticus HY7801, and Bifidobacterium animalis ssp. lactis HY8002. A total of 41 metabolites, 24 lipids, and 4 carotenoids were detected in the fermented and non-fermented VJ (control). The lycopene, α-carotene, and ß-carotene levels were higher in VJ fermented with L. plantarum strains (HY7712 and HY7715) than in the control. Proline content was also elevated in VJ fermented with HY7715. Uracil, succinic acid, and α-carotene concentration was increased in VJ fermented with HY7801, while glycine and lycopene levels were raised in VJ fermented with HY8002. This study confirmed that each probiotic strain has distinctive characteristics and produces unique changes to metabolic profiles of VJ during fermentation. Our results suggest that probiotic-fermented VJ is a promising functional beverage that contains more beneficial metabolites and carotenoids than commercial non-fermented VJ.

Lactobacillus HY2782 and Bifidobacterium HY8002 Decrease Airway Hyperresponsiveness Induced by Chronic PM2.5 Inhalation in Mice.

Epidemiological studies have shown that exposure to particulate matter (PM) is associated with adverse health effects. Inhalation of fine particulate matter (PM2.5) is associated with elevated pulmonary diseases. However, the molecular mechanism underlying the initiation of lung inflammation following inhalation is unclear. In this study, we investigated the beneficial effects of two probiotics, Lactobacillus casei HY2782 and Bifidobacterium lactis HY8002, against PM-induced pulmonary inflammation. Model mice were subjected to chronic exposure of PM2.5. The results showed that PM2.5 enhanced oxidative stress and led to Th2 cytokine responses in the mice. PM2.5-exposed mice were orally administered with HY2782 and HY8002 from the day of first exposure to the end point of the study. The results showed that HY2782 ameliorated PM 2.5 exposure-enhanced leukocyte migration and activation of proinflammatory cytokines. HY2782 and HY8002 also prevented exacerbation of eosinophil and neutrophil infiltration in the bronchoalveolar lavage fluid. HY2782 and HY8002 significantly increased scavenging of PM2.5-induced reactive oxygen species and activated superoxide dismutase and catalase activity in the blood. These results indicate that the probiotics HY2782 and HY8002 protect against PM-induced pulmonary inflammation.

Protective effect of Lactobacillus casei HY2782 against particulate matter toxicity in human intestinal CCD-18Co cells and Caenorhabditis elegans.

OBJECTIVES: To investigate the preventive effect of Lactobacillus casei HY2782 on toxicity induced by particulate matter (PM, inhalable particles less than 10 µm in diameter) in human intestinal CCD-18Co cells and a model animal Caenorhabditis elegans. RESULTS: L. casei HY2782 treatment prevented PM-induced intestinal cell death via cellular reactive oxygen species production and membrane disruption attenuation. PM significantly decreased the total number of eggs laid and the body bending activity of C. elegans, demonstrating PM toxicity. L. casei HY2782 treatment restored the reproductive toxicity and decline in locomotion activity induced by PM in C. elegans. Overall, L. casei HY2782 attenuated PM toxicity in vitro in cultured intestinal cells and in vivo in the model nematode. CONCLUSION: Our study provides a potential clue for developing L. casei HY2782 probiotics that attenuate PM-induced cellular and physiological toxicity; however, further in-depth preclinical trials using mammalian animal models and clinical trials are required.

Oral Administration of Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 with Cinnamomi Ramulus Extract Reduces Diet-Induced Obesity and Modulates Gut Microbiota.

Obesity is a major health issue worldwide, and is associated with many diseases including type 2 diabetes. In this study, we evaluated the anti-obesity effects of combinations of two lactic acid bacteria (LAB), Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032, and Cinnamomi Ramulus (CR) extract, and explored the mechanism through which they modulate gut microbiota using diet-induced obese mice. Male C57BL/6J mice were randomly divided into five groups that received a high-fat diet (HFD), HFD and LAB (HFD+LAB), HFD and CR extract (HFD+CR), HFD with LAB and CR extract (HFD+LAB+CR), or normal diet for 10 weeks. The mice in the HFD+LAB+CR group showed significant reductions in body weight gain, in particular epididymal fat and liver, blood leptin levels, and an increase in the levels of blood adiponectin. In addition, the LAB and CR extract altered the gut microbiota, mainly increasing the alpha diversity. These results demonstrate that a mixture of two LAB (Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032) and CR extracts alleviate HFD-induced obesity, and has potential of being used as a strategy for the treatment of obesity.

Cudrania tricuspidata Extract Protects against Reflux Esophagitis by Blocking H2 Histamine Receptors.

Cudrania tricuspidata has been used in East Asia as a folk medicine for symptoms such as inflammation, allergy, and gastritis. Administration of C. tricuspidata extract to pylori-ligated rat stomachs reduces gastric acid secretion and alleviates esophagus damage caused by gastric reflux. Therefore, in this study we aimed to investigate whether C. tricuspidata extracts inhibit reflux esophagitis by blocking H2 histamine receptor (H2R). Dimaprit, a H2R specific agonist, induced intracellular cyclic adenosine monophosphate (cAMP) production in U937 cells. Pretreatment with C. tricuspidata extracts significantly blocked dimaprit-induced cAMP production in a concentration-dependent manner. To extracted C. tricuspidata with different ethanol concentrations to determine the optimum method. We found that the 70% ethanol extract showed the most potent H2R antagonistic effect against dimaprit-induced cAMP production. However, water extract did not show any H2R blocking effect. These findings suggest that C. tricuspidata extracted using ethanol specifically inhibits gastric acid secretion and reduces esophageal injury by blocking H2R in a competitive manner. Therefore, C. tricuspidata extracts may be used in food or medicine to prevent H2R-related diseases, such as gastric hyperacidity and reflux esophagitis.

Lactobacillus plantarum HY7714 Restores TNF-α Induced Defects on Tight Junctions.

In addition to intestinal balance, probiotics are known to have beneficial effects on skin inflammation, metabolic diseases, and emotions. Previously, we have reported the skin anti-aging effects of Lactobacillus plantarum HY7714 (HY7714) in a clinical trial. To prove the protective skin effects of HY7714 through the intestinal tight junction (TJ), we investigated the effects of HY7714 on the intestines through tumor necrosis factor (TNF)-α induced TJ defects in Caco-2 cells. Specifically, 24 h treatment with HY7714 restored the decreased expression of zonula occludens-1, occludin, and claudin-1 compared to the TNF-α-treated groups (P<0.05). It also attenuated the level of pro-inflammatory cytokines interleukin-6, 8, and 1ß. Further, increases in the mRNA levels of Elk-1, nuclear factor-κB, and myosin light chain kinase expression induced by TNF-α were recovered by HY7714. These findings imply that HY7714 improves intestinal barrier integrity and is a potential therapeutic agent for dysfunctions derived from TJ defects.

Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 Cell Extracts Inhibit Adipogenesis in 3T3-L1 and HepG2 Cells.

Some lactic acid bacteria (LAB) and their cellular components have antiobesity effects. In this study, we evaluated the antiadipogenic effects of a mixture of two LAB-Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032-using 3T3-L1 preadipocytes and HepG2 hepatocarcinoma cells. 3T3-L1 cells treated with a 1:1 ratio of HY7601 and KY1032 during differentiation showed reduced lipid accumulation by Oil Red O staining, as well as decreased leptin secretion and mRNA expression of peroxisome proliferator-activated receptor-γ and CCAAT/enhancer binding protein-α. HY7601 and KY1032 treatment also suppressed mitochondrial biogenesis and inhibited the expression of genes encoding mitochondrial transcription factors, as well as those related to fatty acid synthesis in HepG2 cells. The antiadipogenic effects of LAB were associated with the cell membrane fraction. These results demonstrate that a mixture of two LAB (HY7601 and KY1032) inhibits adipogenesis in preadipocytes and liver cells and is a potential therapeutic strategy for the treatment of obesity.

Metabolomics and Lipidomics Approaches in the Science of Probiotics: A Review.

The intestinal microflora plays important roles in the health of the host, such as nutrient processing and the modulation of intestinal immune responses. The constituents of the diet greatly affect the composition of the microbiota and its metabolites. The human intestinal microbiota is made up of around 100 trillion microbial cells encompassing at least 300 species. Consuming probiotics may lead to changes in the intestinal microflora that influence host health. Metabolomics is a powerful tool for revealing metabolic changes in biofluids, tissues, and organs of hosts induced by the consumption of probiotics, and lipidomics in particular is a technical approach that focuses on the analysis of lipids in various cells and biofluids. Metabolomics and lipidomics have been used to investigate intracellular and extracellular metabolites as well as for the nontargeted profiling and fingerprinting of metabolites. Based on metabolomics and lipidomics investigations, we reviewed the effects of consuming probiotics on metabolic profiles in controlled intestinal environments. We also discuss the associations between metabolic changes and human diseases after consuming probiotics in uncontrolled intestinal environments. In addition, we review the metabolic changes that take place within the food matrix during probiotic fermentation.

In vitro and in vivo inhibition of Helicobacter pylori by Lactobacilllus paracasei HP7.

The efficacy of standard therapeutic strategies for Helicobacter pylori (H. pylori) infection is decreasing over time due to the emergence of drug-resistant strains. As an alternative, the present study investigated the capacity of Lactobacilllus paracasei (L. paracasei) HP7, isolated from kimchi, to inhibit H. pylori growth. The effects of L. paracasei HP7 on H. pylori adhesion and H. pylori-induced inflammation were examined in AGS human gastric adenocarcinoma epithelial cells and a mouse model of H. pylori SS1 infection. L. paracasei HP7 reduced H. pylori adhesion to AGS cells and suppressed the inflammatory response in infected cells by downregulating interleukin-8. H. pylori colonization in the stomach of C57BL/6 mice was demonstrated by rapid urease test, and results showed significant decrease in mice post-treated with L. paracasei HP7. Additionally, L. paracasei HP7 decreased gastric inflammation and epithelial lesions in the stomach of H. pylori-infected mice. These results demonstrate that L. paracasei HP7 treatment can inhibit H. pylori growth and is thus a promising treatment for patients with gastric symptoms such as gastritis that are caused by H. pylori infection.

Tyndallized Lactobacillus plantarum HY7712 Restores Whole-Body γ-Irradiation-Impaired Th Cell Differentiation in Mice.

In the present study, we investigated the effect of tyndallized HY7712 (tHY7712) on the expression of Th cell specific transcription factors and cytokines in whole-body γ-irradiated mice. Oral administration of tHY7712 strongly recovered the γ-irradiation-suppressed expression of helper T (Th) cell- and regulatory T cell-related transcription factors and cytokines, such as T-bet, Foxp3, IFN-γ, TNF-α, and IL-10, and suppressed Th2 cell-associated transcription factor and cytokine GATA3 and IL-5, respectively. Furthermore, compared with the control, tHY7712 treatment also restored γ-irradiation-impaired natural killer and cytotoxic T cell activities against YAC-1 tumor cells to 97.8% and 98.6%, respectively.

Effects of weight loss using supplementation with Lactobacillus strains on body fat and medium-chain acylcarnitines in overweight individuals.

Our previous study showed that supplementation with a combination of Lactobacillus curvatus (L. curvatus) HY7601 and Lactobacillus plantarum (L. plantarum) KY1032 reduced the body weight, body fat percentage, body fat mass and L1 subcutaneous fat area in overweight subjects. We aimed to evaluate whether the changes in adiposity after supplementation with Lactobacillus strains were associated with metabolic intermediates. A randomized, double-blind, placebo-controlled study was conducted on 66 non-diabetic and overweight individuals. Over a 12-week period, the probiotic group consumed 2 g of probiotic powder, whereas the placebo group consumed the same product without the probiotics. To investigate metabolic alterations, we performed plasma metabolomics using ultra-performance liquid chromatography and mass spectrometry (UPLC-LTQ/Orbitrap MS). Probiotic supplementation significantly increased the levels of octenoylcarnitine (C8:1), tetradecenoylcarnitine (C14:1), decanoylcarnitine (C10) and dodecenoylcarnitine (C12:1) compared with the levels from placebo supplementation. In the probiotic group, the changes in the body weight, body fat percentage, body fat mass and L1 subcutaneous fat area were negatively associated with changes in the levels of C8:1, C14:1, C10 and C12:1 acylcarnitines. In overweight individuals, probiotic-induced weight loss and adiposity reduction from the probiotic supplementation were associated with an increase in medium-chain acylcarnitines.

Enhanced Absorption Study of Ginsenoside Compound K (20-O-ß-(D-Glucopyranosyl)-20(S)-protopanaxadiol) after Oral Administration of Fermented Red Ginseng Extract (HYFRG™) in Healthy Korean Volunteers and Rats.

To evaluate the pharmacokinetics of compound K after oral administration of HYFRG and RG in humans, an open-label, randomized, single-dose, fasting, and one-period pharmacokinetic study was conducted. After oral administration of a single 3 g dose of HYFRG and RG to 24 healthy Korean males, the mean (±SD) of AUC0-t and C max of compound K from HYFRG were 1466.83 ± 295.89 ng·h/mL and 254.45 ± 51.20 ng/mL, being 115.2- and 80-fold higher than those for RG (12.73 ± 7.83 ng·h/mL and 3.18 ± 1.70 ng/mL), respectively; in case of Sprague Dawley rats the mean (±SD) of AUC0-t and C max of compound K from HYFRG was 58.03 ± 32.53 ng·h/mL and 15.19 ± 10.69 ng/mL, being 6.3- and 6.0-fold higher than those from RG (9.21 ± 7.52 ng·h/mL and 2.55 ± 0.99 ng/mL), respectively. T max of compound K in humans and rats was 2.54 ± 0.92 and 3.33 ± 0.50 h for HYFRG and 9.11 ± 1.45 and 6.75 ± 3.97 hours for RG, respectively. In conclusion, the administration of HYFRG resulted in a higher and faster absorption of compound K in both humans and rats compared to RG.