All extracts were lyophilized and subsequently used. In summary, 0. Then, the mixture was passed through a 0. The filtrate was analyzed with a column packed with a Hitachi custom ion exchange resin 4. The detection wavelength and flow rate of the buffer were nm and 0. Male Sprague-Dawley rats body weight [b. Rats were acclimatized to laboratory conditions for 7 days prior to the commencement of the experiment. Blood samples were collected at different time intervals 0, 1, 3, and 5 h , as shown in Figure 1 A [ 20 ].
Then, blood samples were collected at different time intervals 0, 1, 3, and 5 h , and alcohol metabolism-associated effects of FSC were studied. B The different groups of rats were fed Lieber-DeCarli ethanol 6. After sacrifice, the hepatoprotective effects of FSC were studied. HDE Hovenia dulcis was used as a positive hepatoprotective agent in alcohol-induced hepatotoxic rats. Blood samples were obtained from the tail vein and collected in microcentrifuge tubes.
Reaction mix without sample was used as a blank control. The protective effects of FSC from ethanol-induced liver damage were determined by measuring the activities of liver biomarkers in serum samples. Briefly, the blood samples were collected from the heart of rats in microcentrifuge tubes. Each sample was assayed thrice.
The histological scoring was based on the appearance of major pathologic changes such as degrees of hepatic necrosis, inflammation, balloon degeneration, and fatty degeneration, according to the report by Yang et al. The scores were 0, 1, 2, 3, or 4 with 0 being no lesion noted and 4 indicating the most severe lesions. According to the importance of pathological changes, scores were multiplied using weighting factors. KG, Germany on ice.
Finally, the specificity of each PCR product was analyzed from the melting peaks. Gyeonggi-do, Korea. The acute oral toxicity test was performed with slight modifications to a previously reported method. A standard pellet diet Hyochang Science, Daegu, Korea and distilled water were provided ad libitum.
The animals were under constant observation for abnormal signs and symptoms for the first 12 h after FSC administration. They were further observed once a day for 2 weeks. The body weight of each animal was recorded prior to FSC administration, and changes to body weight and feed consumption weight were measured twice per week for 14 days after treatment Figure 1 C. Animals were sacrificed after the experimental period, and major organs were collected and inspected for gross lesions.
For the acute oral toxicity study, a t -test was used. Statistical analysis was conducted using GraphPad Prism version 7. This finding indicated that fermentation with B.
Subsequent experiments in this study used the FSC after 7 d fermentation followed by lyophilization. Blood alcohol concentration BAC peaked 1 h after ethanol administration The final BACs 5 h after administration ranged from 1.
Furthermore, to measure the exposure that integrates concentration across time, the area under the concentration—time curve AUC was evaluated Figure 3 C. Blood was collected from the tail vein at 1, 3, and 5 h after ethanol administration. The blood acetaldehyde concentrations gradually increased after alcohol loading in rats. The blood acetaldehyde concentrations in groups pretreated with FSC 3.
To elucidate the mechanisms underlying the reduction in serum alcohol and acetaldehyde concentrations by FSC in the ethanol-loaded rats, livers were extracted 5 h after ethanol administration. There was a positive correlation between the reduction in serum alcohol and acetaldehyde concentrations. Livers were collected 5 h after ethanol administration. The gene expression of SOD, which is an antioxidant enzyme in the liver, was also evaluated. Serum ALP There was no difference in the level of ALB between groups.
The protective effect of FSC on chronic liver injury caused by alcohol consumption was determined based on the degree of pathological hepatic lesions scores 0—4 Figure 5 A. Liver histopathological scoring A , effects of FSC on the histopathological score B , and representative images of the liver histology C. The hepatocytes were analyzed to determine necrosis, fatty change, hepatocyte ballooning, and inflammatory cell infiltration.
The liver histopathological scores for the ethanol-treated group Group NC were 3. The scores for FSC-treated groups were 2. These findings indicated that FSC improved alcohol-induced liver injury.
These results indicate that FSC may inhibit lipid accumulation in the liver after alcohol consumption. IL-6 is a typical pro-inflammatory cytokine, and its gene expression was decreased in the ethanol-fed rats pretreated with FSC, with a These results were consistent with histopathological observations and indicated that FSC could potentially protect against chronic alcohol-induced liver injury.
The similarities in the number and type of detoxifying enzymes between rats and humans make rat models suitable for assessing the acute oral toxicity of FSC [ 24 ]. Conducting the same study in all FSC-treated animals, no clinical signs or deaths were observed.
Fermentation results in increased antioxidant activity of an extract due to the increased number of phenolic compounds and flavonoids as a direct result of microbial hydrolysis [ 27 ]. GABA is widely used as a food supplement [ 2 ]. BAC, which reflects the effects of alcohol on various tissues, depends on the absorption, distribution, metabolism, and excretion of alcohol from the body after ingestion [ 28 ]. Recent studies have reported various plant extracts that enhance alcohol metabolism in rats [ 17 , 21 ].
In the present study, we observed that FSC improved hangover by stimulating hepatic alcohol metabolism. Alcohol consumption reduces SOD activity in some of the major organs and in the serum of rats. CAT acts as an antioxidant enzyme and protects against the deleterious effects of free radicals, but alcohol abuse also significantly reduces its activity [ 29 ].
Chronic alcohol consumption and alcohol metabolism are strongly linked to several pathological consequences and tissue damage [ 6 , 30 ].
Therefore, in this study, the hepatoprotective effect of FSC was further evaluated in rats with chronic alcohol consumption. The accumulation of fat in the liver, which results in steatosis, occurs as a result of chronic alcohol consumption [ 32 ].
Alcohol ingestion induces fatty acid synthesis in the liver by increasing the expression of SREBP1c at both the gene and protein levels, which regulates the proteins involved in lipid synthesis by activating ATP citrate lyase and fatty acid synthase [ 33 ].
This agreed with our histopathological observations showing a slight fatty change in the group pretreated with FSC. IL-6 is a known important pro-inflammatory cytokine involved in hepatocyte injury due to chronic alcohol consumption [ 35 ]. FSC exhibits anti-inflammatory activity in chronic alcohol-induced liver damage by downregulating IL-6 gene expression. FSC administration did not markedly influence CAT oxidation, which is considered a minor pathway of alcohol oxidation [ 25 ], in rats administered a single alcohol load, whereas it increased CAT activity in chronic alcohol-treated rats.
This indicated that FSC pretreatment might improve alcohol metabolism, preventing liver damage. In addition, FSC exhibited a strong antioxidant activity through induction of hepatic SOD gene expression in rats with not only single ethanol consumption but also with chronic alcohol consumption. In addition, oxyresveratrol, resveratrol [ 38 ], and steroidal saponins [ 39 ] have anti-inflammatory and antioxidant properties. At present, it is not clear which single or multiple compounds present in FSC are responsible for its hepatoprotective activity.
The reported phenolic compounds in the extract of S. A study has also reported that GABA can protect against the cytotoxic effect of ethanol due to its ability to maintain the level of polyamines in the cell [ 40 ]. However, the specific physiological compounds for the hepatoprotective activity in FSC should be evaluated in future studies. Moreover, FSC significantly protected the liver cells and reduced the severity of liver lesions caused by alcohol intoxication. These results suggest that FSC could be used as a functional food ingredient for attenuating hangovers after excessive alcohol consumption, as well as for protecting against alcohol-induced hepatic damage.
Optimization of the fermentation process would greatly affect the duration and intensity of action of FSC. Therefore, the effect of physical parameters of the fermentation procedure temperature, duration, and number of cycles , the effect of various probiotics and their combinations on the polyphenolic content, and the effects of alcohol overdose, fatty liver, and cirrhotic liver in animal models are future directions of this study.
For this purpose, further detailed studies are required to develop FSC into a product with good clinical efficacy. Conceptualization, S. All authors have read and agreed to the published version of the manuscript. Data supporting the present study are available from the corresponding author upon request.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be considered a potential conflict of interest. Moreover, N. Therefore, there are no conflicts in the company. National Center for Biotechnology Information , U. Journal List Foods v. Published online Oct 8.
Find articles by Naila Boby. Find articles by Eon-Bee Lee. Find articles by Muhammad Aleem Abbas. Sekendar Ali. Find articles by Seung-Chun Park. Bohkyung Kim, Academic Editor. Author information Article notes Copyright and License information Disclaimer. Received Aug 20; Accepted Oct 3.
Associated Data Supplementary Materials foodss Abstract Chronic alcohol consumption can cause hepatic injury and alcohol-induced toxicities. Keywords: Smilax china , alcohol metabolism, superoxide dismutase, alcohol dehydrogenase, aldehyde dehydrogenase. Introduction The liver plays a pivotal role in regulating physiological processes and performs various vital activities such as metabolism, secretion, and storage. Materials and Methods 2.
Extract Preparation and Analysis 2. Animals and Experimental Design 2. Animals Male Sprague-Dawley rats body weight [b. Open in a separate window. Figure 1. Measurement of Liver Biomarkers in Serum The protective effects of FSC from ethanol-induced liver damage were determined by measuring the activities of liver biomarkers in serum samples.
Results 3. Figure 2. Figure 3. Effect of FSC on Alcohol-Metabolizing Enzymes of Liver To elucidate the mechanisms underlying the reduction in serum alcohol and acetaldehyde concentrations by FSC in the ethanol-loaded rats, livers were extracted 5 h after ethanol administration.
Figure 4. Table 1 Effects of FSC on liver biomarkers of alcohol-induced liver injury in rats. Treatment per kg b. Histopathology The protective effect of FSC on chronic liver injury caused by alcohol consumption was determined based on the degree of pathological hepatic lesions scores 0—4 Figure 5 A. Figure 5. Figure 6. In Vivo Acute Oral Toxicity The similarities in the number and type of detoxifying enzymes between rats and humans make rat models suitable for assessing the acute oral toxicity of FSC [ 24 ].
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