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Research Article
Open Access Peer-reviewed

Preventive Effects of Ophiocordyceps sinensis Mycelium on High-Fat Diet Induced Lipid Dysregulation and Hepatic Inflammation of Mice

Chung-Hsi Chou, Hui-Wen Lin, Yi-Hsieng Samuel Wu, Yi-Ling Lin, Chia-Chun Chiang, Shih-Guei Fu , Yi-Chen Chen

Chung-Hsi Chou, Hui-Wen Lin, and Yi-Hsieng Samuel Wu contributed equally as co-first authors

Journal of Food and Nutrition Research. 2017, 5(11), 859-866. DOI: 10.12691/jfnr-5-11-10
Published online: November 18, 2017

Abstract

Dyslipidemia is regarded as one of risk factors related to cardiovascular disease and hepatosteatosis widely. Due to westernized diet habits and lifestyle changes, there is a high prevalence of those lipid-dysregulated diseases, i.e. fatty liver, hyperlipidemia, diabetes etc. However, the liver holds the lipid homeostasis so hepatoprotective nutraceuticals against high-fat diet (HFD) induced dyslipidemia may be potential for a public demand. This study demonstrated that OSM containing 10% polysaccharides and 0.25% adenosine can decrease (p<0.05) serum and liver triglyceride (TG) contents, and meanwhile, increased (p<0.05) fecal cholesterol (TC) levels in HFD fed mice. Moreover, Ophiocordyceps sinensis mycelium (OSM) also decreased (p<0.05) serum low-density lipoprotein cholesterol (LDLC) levels and the atherosclerosis index (LDLC/high-density lipoprotein cholesterol (HDLC)) in HFD fed mice. Regarding the liver damage, OSM supplementation attenuated serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values, and liver tumor necrosis factor-α (TNF-α) levels in HFD fed mice. Taken together, OSM showed an ameliorative effect of the hepatosteatosis development and lipid-dysregulated-related diseases in a HFD habit.

1. Introduction

Recently, pathological changes that threat the public wellness in the modern society may relate to the westernized lifestyle, nutritional imbalance and so on. Consequently, a high prevalence of metabolic syndromes, i.e. hyperlipidemia, fatty liver, diabetes, cardiovascular diseases, results in a major problem globally. According to a statistical data from World Health Organization 1, more than 10% of the adults are obese in the world. Meanwhile, lipid dysregulation and obesity has been regarded as major factors enhancing the mortality on the human clinical research. It also occurs in Taiwan, where there are more than 51.5% male and 32.6% female obese or overweight, respectively 2.

Ophiocordyceps sinensis (OS, renamed from Cordyceps sinensis in 2007), regarded as a traditional tonic food supplementation, is usually found in elevation of 3000 to 5000 meters of mountains in southwest of China. It is rare and precious due to its slow generation time and its bioacive benefits in the oriental society. An ancient Chinese medical book, Compendium of Materia and Medic, revealed its therapeutic functions, which inspire scientists’ studies. Due to the rareness of OS, Ophiocordyceps sinensis mycelium (OSM) has become another major subject in following investigations. Based on previous studies, the bioactivities of OS and OSM were found as immunomodulation 3, anti-inflammation 4, anti-tumor 5, antioxidation 6, cardiovascular-protection 6, anti-fibrosis 7, and regulating male reproductive function 8. Besides, the evidences for exercise-endurance promotion and anti-fatigue activities of OS were demonstrated, and it meditated upregulation of some metabolic regulators, such as AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1), and peroxisome proliferator activated receptor (PPAR), in the skeletal muscle 9. Recently, it was reported that cordycepin, one nucleotide derivatives in OS, could activate AMPK in HepG2 cells and then decrease intracellular lipid accumulation 10. These evidences showed that OS or OSM would affect lipid metabolism in vitro. Briefly, OS-origin materials have shown its potential of medical and nutraceutical candidates; hence, the aim of the present study was to investigate the alleviative effects of OSM on the development of dyslipidemic diseases by a high-fat diet (HFD) induced mouse model.

2. Materials and Methods

2.1. Ophiocordyceps sinensis Mycelium

OSM powder (TCM-606F®) which contains 10% polysaccharides and 0.25% adenosine was obtained from the TCM Biotech International Corp. (Taipei, Taiwan). According to the composition analysis, the dry matter mass of OSM powder is 72.82%.

2.2. Animal, Treatment, and Diet

C57BL/6 mouse is the most widely used strain in HFD inducing fatty liver model, and it was proven to highly similarity with clinical symptoms 11. Totally 60 male C57BL/6 mice (4 weeks old) were used in this study and obtained from Laboratory Animal Center, College of Medicine, National Taiwan University (Taipei, Taiwan). The animal use and protocol was reviewed and approved by the National Taiwan University Animal Care Committee (IACUC No.: 101-032). Two animals with an ear tag (No. 1 or 2) were housed in one cage in an animal room at 22±2°C and approximately 60 to 80% relative humidity with a 12 h light/dark cycle. A chow diet (Laboratory Rodent Diet 5001, PMI® Nutrition International/Purina Mills LLC, USA) and water were freely accessible for mice. After an acclimatization for 4 weeks, mice were randomly divided into 5 groups as followings: 1) Control: control diet with 0.2 mL ddH2O; 2) HFD: HFD with 0.2 mL ddH2O; 3) OSML (low dosage of OSM supplemented group): HFD with 405.6 mg TCM-606F®/Kg BW/day in 0.2 mL ddH2O; 4) OSMM (medium dosage of OSM supplemented group): HFD with 1216.8 mg TCM-606F®/Kg BW/day in 0.2 mL ddH2O; 5) OSMH (high dosage of OSM supplemented group): HFD with 2433.6 mg TCM-606F®/Kg BW/day in 0.2 mL ddH2O. Control diet and HFD were manufactured according to the AIN-93G formulation where control diet and HFD contain 7.0 and 25.8% fat, respectively, and their energy contents are 4.00 and 4.88 Kcal/g, respectively (Table 1). The OSM powder was re-dissolved in sterile saline without heat, and given to animal via an oral administration.

2.3. Sample Collection and Preparation of Liver Homogenate

During the experimental period, food and water intakes, and body weights were recorded weekly. At the end of the experimental period, all mice fasted overnight before sacrificed, and blood and tissue samples were harvested for further analyses. The heart, liver, and kidney from each mouse were removed and weighted individually. Livers were cut into one cubic millimeter for histopathology section, and others were placed into liquid N2. A 0.5 g of liver was homogenized on ice in 4.5 mL of phosphate-buffered saline (PBS, pH 7.0, containing 0.25 M sucrose) and centrifuged at 10,000 x g for 15 min at 4°C (Model 3740; KUBOTA, Tokyo, Japan) to obtain clear supernatant for further analyses. The protein content in the supernatant was measured based on the procedures of a Bio-Rad protein assay kit (catalog #500-0006; Bio-Rad Laboratories, Inc., Hercules, CA, USA) using bovine serine albumin (Sigma-Aldrich Co., Ltd.) as a standard.

2.4. Analyses of Serum Biochemical Values, as well as Liver and Fecal Lipids

Blood samples were collected and placed for one h at room temperature for clotting. Then, the sera were collected by a centrifugation at 3,000 × g for 10 min (Model 3740; KUBOTA, Tokyo, Japan) and then stored at -80°C for subsequent analyses. Serum ALT, AST, ALP, TG, TC, HDLC, and LDLC levels were assayed using commercial enzymatic kits with the SPOTCHEMTM EZ SP-4430 automated analyzer (ARKRAY, Inc., Kyoto, Japan). An atherosclerosis index was calculated by a formulation of LDLC level/HDLC level. Liver and fecal lipid concentrations were measured based on the methods of a previous report 12. Briefly, liver and fecal lipids were extracted by a chloroform/methanol solution (2:1, v/v). For an efficient dissolution, the extracts were dried under N2 and resuspended in isopropanol via an ultrasonic cleaner (model: DC150H, Taiwan Delta New Instrument Co. Ltd., Taiwan). Liver and fecal cholesterol and triglyceride concentrations were measured using commercial kits (Randox Laboratories Ltd., Antrim, U.K.).

2.5. Antioxidative Capabilities and Cytokine Analyses

The liver TBARS was used to represent the level of liver lipid peroxidation while reduced glutathione (reduced GSH), trolox equivalent antioxidant capacity (TEAC), and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were assayed as indices for liver antioxidant capacities. They all were performed according to procedures described by Lin et al. (2017) 12. Hepatic TNF-α (R&D System DuoSet® ELISA mouse TNFα, Cat.: DY410) and IL-1β (R&D System DuoSet® ELISA mouse IL-1β/ IL-1F2, Cat.: DY401) levels were measured by using ELISA kits and then performed in an ELISA reader (Bio Tek Inc. Synergy H1 Hybrid Multi-Mode Microplate Reader, Winooski, Vermont, USA) according to the commercial manufacturer’s instructions (R&D system Inc., Minneapolis, Minnesota, USA). Hepatic TNF-α and interleukin-1β (IL-1β) levels were both expressed by pg/mg protein.

2.6. Histological Sections and Stainings

For a histopathological study, liver tissues from No. 1 mouse of each cage were placed in formalin for more than 24 h and were fixed in new neutral-buffered formalin solution, dehydrated in graded alcohol, cleared in xylene, and embedded in paraffin. These blockers were later sectioned using a microtome, dehydrated in graded alcohol, embedded in paraffin section, and stained with hematoxylin and eosin (H&E). For Oil-red staining, the liver tissues from No. 2 mouse of each cage were immersed in graded sucrose buffers directly and embedded in optimal cutting temperature (OCT) compound (Sakura Finetek Inc., Torrance, CA, USA) and then frozen under -80°C. The frozen block was removed from the -80°C freezer and allowed to equilibrate in the cryostat chamber. The molten tissue-freezing medium was added to the block in order to fix it onto the cryostat holder. The block on the holder was then trimmed by a razor blade. Then the trimmed tissue was carefully transferred from the cryostat blade onto a slide. The slides were then treated as the same protocol as H&E staining and then stained with Sudan red and haematoxylin or Sudan red only. Finally, the results of microscopic examination were demonstrated as a prevalence table. Photomicrographs under H&E and Oil red staining were taken under a Zeiss Axioskop microscope AxioCam ERc 5s camera system with AxioVision Release 4.8.2 (06-2010) software (Carl Zeiss Microscopy, LLC, Thornwood, NY, USA). The quantitative results of Oil red stain were based on former studies 13, 14. All photos for H&E and Oil red stainings, respectively, were taken under the same multiple factor, and the area calculation was conducted according to the scale bar on ImageJ. The total area indicated the total stained area in red color.

2.7. Statistical Analysis

The experiment was conducted using a completely random design. Data were analyzed using analysis of variance. When a significant difference was determined at 0.05 probability level, the differences among treatments were distinguished byusing the Duncan's multiple range test. All statistical analyses of data were performed using SAS 9.0 (SAS Institute, Inc., NC, USA, 2002).

3. Results

3.1. Effects of OSM on Growth Performance, Organ Sizes, and Liver Injury Indices

Prospective greater increases in final body weight of HFD-fed mice (HFD, OSML, OSMM, and OSMH groups) were showed after 20 weeks of feeding while significantly increased (p<0.05) body weight gain in HFD fed mice compared to Control mice were observed (Table 2). There were no (p>0.05) differences in average daily water and energy intakes among all experimental groups (Table 2) although the average daily food intake in HFD group was lower (p<0.05) than that of Control group. Regarding organ (heart, liver, and kidney) weights, although there was a higher tendency of liver weights toward HFD feedings, no (p>0.05) differences among groups were observed (Table 2). Regarding serum liver damage indices (AST, ALT, and ALP values) and hepatic cytokines (TNFα and IL-1β), serum ALP values and hepatic IL-1β levels (except OSMM group) were not (p>0.05) altered among groups, but higher (p<0.05) ALT, AST values, and hepatic TNFα levels in HFD group than those in Control group were detected, but those increases were decreased (p<0.05) by OSM supplementation (Table 2). According to the H&E stainings, the liver tissue morphology among all HFD fed groups were determined as hepatic hypertrophy without severe monocyte infiltration (Figure 1).

3.2. Effects of OSM on Serum, Liver, and Fecal Lipids

According to serum lipid profile (Table 3), higher (p<0.05) both serum TG and TC levels of HFD group were assayed compared to those of Control group. Meanwhile, only serum TG levels were normalized (p<0.05) by OSM supplementation. Regarding the serum cholesterol profile, although HFD fed groups (HFD, OSML, OSMM, and OSMH) had higher (p<0.05) HDLC levels than Control group, OSM supplementation alleviated (p<0.05) the increased LDLC levels in HFD fed mice. Hence, OSML, OSMM, and OSMH groups had lower (p<0.05) atherosclerosis indices (LDLC/HDLC) compared to that of HFD group while those calculated values were even similar (p>0.05) to that of Control group (Table 3). Similarly, the higher (p<0.05) liver TG level in HFD group was assayed compared to that of Control group, and also was alleviated (p<0.05) by OSM supplementation. Liver TC levels were not (p>0.05) different among groups. Although fecal TG levels were not (p>0.05) different among all groups, the significantly increased (p<0.05) fecal TC levels in HFD fed mice was observed in medium dosage of OSM supplemented group. Meanwhile, there was a higher tendency in those of OSML and OSMH. Based on results of H&E staining, the OSM supplementation attenuated the lipid accumulation (lipid vacuoles) form medium to light (Figure 1B). Similarly, the more red-color spots which are Oil-red-stained lipid droplets were illustrated in livers of HFD fed mice compared to Control mice, but OSM supplementation decreased (p<0.05) the spot aggregation under microscope observation in an amplification factor of 400X (Figure 2A & Figure 2B). Figure 2C also showed that OSMsupplementation ameliorates the status of lipid accumulation from severe to medium in prevalence table.

  • Figure 1. Pathohistological analysis and morphology of hepatocytes on H&E stained liver sections of experimental mice. (A) The central of hepatic classic lobules in different amplification factors were showed from left (100X, the scale is 100 μm) to right (200X, the scale bar is 50 μm), back-side appearances of livers were shown in right-upper part of first column with the scale. Each cavity that locates in central of the view was hepatic central vein that as abbreviated as CV. The nuclei were stained by hematoxylin, whereas the cytoplasms were stained by Eosin. (B) The prevalence table indicated the quantitative results of microscopic examination, the scores were given according to the density of micro- (as where red triangle indicates) or macro-steatosis (as where red arrow indicates)
  • Figure 2. Pathohistological analysis and morphology of hepatocytes based on Oil red stained liver sections of experimental mice. (A) The results of Oil red O staining were showed. The lipid droplets were shown as light red in Oil red stainings (green triangle), and all tissues were also stained by hematoxylin in order to remark the cell nucleus. All the pictures of Oil red stainings were shown in an amplification factor of 400X (the scale is 20 μm). (B) The quantitative results of lipid-droplet densities via ImageJ. The means of total area and SEM were showed below the bar chart. The bars are given as means±SEM (n=6). Data points without the common letter (a-c) indicate significant differences (p<0.05). (C) The prevalence table indicated the quantitative results of microscopic examination, the scores were given according to the density of lipid droplets
3.3. Effects of OSM on Anti-oxidative Capacities

Under HFD feedings, only a higher tendency toward liver TBARS values were assayed in HFD group compared to Control group, but OSM supplementation indeed reduced TBARS values (OSML and OSMM groups vs. vs. HFD group, p<0.05) (Table 2). OSMsupplementation also increased (p<0.05) liver reduced GSH levels (OSML group vs. HFD group, p<0.05), but in comparison with HFD group, OSM supplementation only performed a higher tendency of TEAC levels. Regarding antioxidative enzymatic activities, liver SOD and CAT activities were not (p<0.05) influenced among groups, except the lower (p<0.05) SOD activity in OSMH group, while the lower (p<0.05) liver GPx activity in HFD fed mice compared to Control mice was amended in OSML group where the GPx activity of OSML group was similar as that of Control group (Table 2).

4. Discussion

In our results, the major pathological outcomes were consistent to what mentioned by Hebbard and George (2011) 15. They proclaimed that remarkable pathological outcomes of high fat diet induced mouse model are obesity and increased level of visceral fat, but the degree of liver injury is not as severe as other non-alcoholic fatty liver disease (NAFLD) models. It showed increased weight gains (Table 2) in this study, and the inflammatory levels in livers was not severe according to H&E stainings (Figure 1) although AST, ALT, and hepatic TNF-α levels showed statistical differences (Table 2). The liver weight showed no significant differences (p>0.05) but a heavy tendency in HFD fed mice (Table 2) while the lipid accumulation was obvious according to liver TG contents by HFD feedings (Table 3). Moreover, the lipid droplets were observed in results of H&E (Figure 1) and Oil red stainings (Figure 2A) as well, while the quantification of stained areas showed the significant increase (p<0.05) between Control and HFD groups (Figure 2B). Several previous studies also indicated the similar phenotypes under a HFD induced mouse model 16, 17. In addition, it was proclaimed that chronic inflammatory responses in livers or adipose tissues might be the driving force for NAFLD pathological progressing 15. It may involve intrinsic and extrinsic factors at the same time where lipotoxicity 18, 19, hepatocytes necrosis/apoptosis 20, 21, oxidative stress 22, 23 etc. are possible intrinsic factors, and a constant exposure to microbiota from gut may also trigger innate immune reaction 24, 25. As matters stand, our results demonstrated that the HFD enhances the secretion (p>0.05) of pro-inflammatory cytokine, TNF-α, in liver tissues (Table 2), but monocyte infiltration and necrotic cells were not clearly observed under a microscopic examination in the H&E stainings. According to histological activity index (HAI) score analysis which followed by Brunt’s method 26, liver tissues of HFD fed mice were considered as slight inflammation in portal, intra-lobular, and periportal area (data not shown). Hence, it can be demonstrated that the HFD induction manner performed the diagnostic NAFLD phenotype of hepatosteatosis.

As we know, a high-fat dietary habit always results in an increased serum or liver lipids that stimulates an oxidative stress and further leads to liver damage. Higher serum AST, ALT, and free fatty acids, as well as liver TC, TG, TBARS, and cytokine levels were easily observed in a HFD fed rodent models 22, 27, 28. It has been reported that the hepatoprotection of OSM against CCl4 resulted in decreased serum AST and ALT values. Concurrently, increased antioxidative capabilities by OSM supplementation were also observed 29. Based on our results, there are not (p>0.05) differences on antioxidant enzymatic activities in livers among groups, except GPx activity; and meanwhile, OSM supplementation did not powerfully enhance those enzymatic activities in our study. That phenomenon may be explained that the experimental period in this study is quite longer (20 weeks), and meanwhile, the neutralization ability of OSM on reactive oxygen species (ROS) has reached the maximum effect in this study. Apparently, it demonstrated a tendency of higher CAT, GPx activities, and TEAC values in OSML group compared with those of HFD group because the severity of hepatic lipid accumulation was the least among other groups (Figure 1 & Figure 2 and Table 3). However, the overall antioxidant levels (reduced GSH and TEAC levels) and lipid peroxidation status (TBARS values) in livers of HFD fed mice were still improved by OSM supplementation which could highly result from the lower serum and liver TG levels (Table 3 and Figure 2). Besides, the lower liver TBARS in HFD fed mice supplemented with OSM were also corresponding the lower liver damages (Table 2). Many phytochemicals, i.e. polysaccharide, glycopeptide, showed powerful immunomodulatory, anti-inflammatory, and antioxidative activities 30, 31, 32, 33. Furthermore, Ophiocordyceps sinensis revealed the improvement of an exercise endurance capacity of rats by activating not only the skeletal muscle metabolic regulators but also a coordinated antioxidative response 9.

Obesity, accompanying with hypertriglyceridemia and hepatic lipid accumulation, is the outcome of abnormal lipid homeostasis. Previous studies showed that fatty-liver development is associated with the metabolic syndrome 34. In this investigation, the fat in the HFD offers a majority of caloric intake (47.7%) which is from lard (high proportion of saturated fatty acids and oleic acids) which shown to be a strong stimulator of triglyceride synthesis and secretion by hepatocytes 35. Some previous reports indicated that polysaccharides can prevent obesity and liver lipid accumulation via decreasing food consumption 36, 37, but our results are not the same as theirs (Table 1). It is reasonable to infer that the increasing tendency of hepatic lipid accumulation among OSM supplemented groups (Figure 1 & Figure 2 and Table 3) was resulted from consumption manner (food and energy intakes) (Table 2) while antioxidative capacities and enzymatic activities of OSMH were also influenced (Table 2). Based on our data, OSM regulated the lipid homeostasis via advancing excretion of cholesterol into feces, thus decreasing the serum LDLC levels and atherosclerosis index (Table 3). A previous investigation of red algae which contains 45.9 and 15.4% water soluble dietary fiber and insoluble dietary fiber, respectively, showed similar results of serum and fecal lipid profile as ours 38. In addition, Kim et al. found two new anti-obesity compounds from Cordyceps, cordyrroles A and B, which are effectively inhibited pancreatic lipase activity 39. Surprisingly, the OSM use in this study also decreased the liver TG levels, but it did not enhance (p>0.05) the TG output in feces, so it may not be related to lipase activities. Probably, the decreased liver TG levels by OSM treatment may be related to the energy expenditure in hepatic or other tissues like skeletal muscle 9. It has been proclaimed the Cordymin, a compound in OS, could enhance the mitochondria biogenesis in livers 40, 41. On the other hand, OS supplementation on HFD-fed rats can enhance the protein expression of uncoupling protein 2 (UCP-2), further increasing energy expenditure in electronic transport chain, and then attenuate the steatosis 42. The UCP-2 was considered as an important therapeutic target in NAFLD 43, and many pharmacological researches had focused on related mechanisms to restore the lipid homeostasis 27, 42, 43, 44. Overall, the OSM or its metabolites may modulate the whole body lipid regulation.

5. Conclusion

Based on the results of this investigation (Figure 3), the HFD clearly induced features of steatosis in livers of mice. This OSM supplementation could modulate the lipid contents in sera and livers of HFD fed mice where decreased serum TG and LDLC levels, and atherosclerosis indices, as well as the liver TG accumulation were assayed. Besides, increased serum AST and ALT, and liver TNF-α levels by HFD feedings were also ameliorated by supplementing our food-grade OSM. Hence, the ameliorative effects of OSM on the NAFLD development induced by HFD were expounded in this study.

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[27]  Su, C. H., Chang, C. S., Chou, C. H., Wu, E. H. S., Yang, K. T., Tseng, J. K., Chang, Y. Y. and Chen, Y.C., “L-carnitine ameliorates dyslipidemic and hepatic disorders induced by a high-fat diet via regulating lipid metabolism, self-antioxidant capacity, and inflammatory response,” Journal of Functional Foods 15. 497-508. May 2015.
In article      View Article
 
[28]  Chien, M. Y., Ku, Y. H., Chang, J. M., Yang, C. M. and Chen, C. H., “Effects of herbal mixture extracts on obesity in rats fed a high-fat diet,” Journal of Food and Drug Analysis 24(3). 594-601. Jul. 2016.
In article      View Article  PubMed
 
[29]  Ko, W. S., Hsu, S. L, Chyau, C. C., Chen, K. C. and Peng, R. Y., “Compound Cordyceps TCM-700C exhibits potent hepatoprotective capability in animal model,” Fitoterapia 81(1), 1-7. Jan. 2010.
In article      View Article  PubMed
 
[30]  Huang, F., Zhang, R., Dong, L., Guo, J., Deng, Y., Yi, Y. and Zhang, M., “Antioxidant and antiproliferative activities of polysaccharide fractions from litchi pulp,” Food & Function 6(8). 2598-2606. Aug. 2015.
In article      View Article  PubMed
 
[31]  Zhu, Z. Y., Meng, M., Sun, H., Li, Y., Yu, N. and Zhang, Y. M., “Structural analysis and immunostimulatory activity of glycopeptides from Paecilomyces sinensis,” Food & Function 7(3), 1593-1600. Mar. 2016.
In article      View Article  PubMed
 
[32]  Yan, W.., Li, T. and Zhong, Z., “Anti-inflammatory effect of a novel food Cordyceps guangdongensis on experimental rats with chronic bronchitis induced by tobacco smoking,” Food & Function 5(10). 2552-2557. Oct. 2014.
In article      View Article  PubMed
 
[33]  Zhu, Z. Y., Meng, M., Sun, H., Li, Y., Ren, Y. Y. and Zhang, Y., “Immunostimulatory activity of glycopeptides from Paecilomyces sinensis under normal and cyclophosphamide induced immunosuppressive conditions in mice models,” Food & Function 7(8). 3566-3576. Aug. 2016.
In article      View Article  PubMed
 
[34]  Kulkarni, N. M., Jaji, M. S., Shetty, P., Kurhe, Y. V., Chaudhary, S., Vijaykant, G., Raghul, J., Vishwakarma, S. L., Rajesh, B. N., Mookkan, J., Krishnan, U. M. and Narayanan, S. “ A novel animal model of metabolic syndrome with non-alcoholic fatty liver disease and skin inflammation,” Pharmaceutical Biology 53(8). 1110-1117. Aug. 2015.
In article      View Article  PubMed
 
[35]  Lottenberg, A. M., Afonso Mda, S., Lavrador, M. S. F., Machado, R. M. and Nakandakare, E. R., “The role of dietary fatty acids in the pathology of metabolic syndrome,” Journal of Nutritional Biochemistry 23(9). 1027-1040. Sep. 2012.
In article      View Article  PubMed
 
[36]  Wang, H., Tang, X., Cheserek, M. J., Shi, Y. and Le, G., “Obesity prevention of synthetic polysaccharides in high-fat diet fed C57BL/6 mice” Journal of Functioanl Foods 17. 563-574. Aug. 2015.
In article      View Article
 
[37]  Wu, Y. H. S., Chiu, C. H., Yang, D. J., Lin, Y. L., Tseng, J. K. and Chen, Y. C., “Inhibitory effects of litchi (Litchi chinensis Sonn.) flower-water extracts on lipase activity and diet-induced obesity,” Journal of Functional Foods 5(2). 923-929. Apr. 2013.
In article      View Article
 
[38]  Liu, H. C., Chang, C. J., Yang, T. H. and Chiang, M. T., “Long-term feeding of red algae (Gelidium amansii) ameliorates glucose and lipid metabolism in a high fructose diet-impaired glucose tolerance rat model,” Journal of Food and Drug Analysis 25(3). 543-549. Jul. 2017.
In article      View Article  PubMed
 
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In article      View Article
 
[43]  Jin, X., Xiang, Z., Chen, Y. P., Ma, K. F., Ye, Y. F. and Li, Y. M., “Uncoupling protein and nonalcoholic fatty liver disease,” Chinese Medical Journal 126(16). 3151-3155. Aug. 2013.
In article      View Article
 
[44]  Yang, K. T., Lin, C., Liu, C. W. and Chen, Y. C., “Effects of chicken-liver hydrolysates on lipid metabolism in a high-fat dietary habit,” Food Chemistry 160. 148-156. Oct. 2016.
In article      View Article  PubMed
 

Published with license by Science and Education Publishing, Copyright © 2017 Chung-Hsi Chou, Hui-Wen Lin, Yi-Hsieng Samuel Wu, Yi-Ling Lin, Chia-Chun Chiang, Shih-Guei Fu and Yi-Chen Chen

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Cite this article:

Normal Style
Chung-Hsi Chou, Hui-Wen Lin, Yi-Hsieng Samuel Wu, Yi-Ling Lin, Chia-Chun Chiang, Shih-Guei Fu, Yi-Chen Chen. Preventive Effects of Ophiocordyceps sinensis Mycelium on High-Fat Diet Induced Lipid Dysregulation and Hepatic Inflammation of Mice. Journal of Food and Nutrition Research. Vol. 5, No. 11, 2017, pp 859-866. http://pubs.sciepub.com/jfnr/5/11/10
MLA Style
Chou, Chung-Hsi, et al. "Preventive Effects of Ophiocordyceps sinensis Mycelium on High-Fat Diet Induced Lipid Dysregulation and Hepatic Inflammation of Mice." Journal of Food and Nutrition Research 5.11 (2017): 859-866.
APA Style
Chou, C. , Lin, H. , Wu, Y. S. , Lin, Y. , Chiang, C. , Fu, S. , & Chen, Y. (2017). Preventive Effects of Ophiocordyceps sinensis Mycelium on High-Fat Diet Induced Lipid Dysregulation and Hepatic Inflammation of Mice. Journal of Food and Nutrition Research, 5(11), 859-866.
Chicago Style
Chou, Chung-Hsi, Hui-Wen Lin, Yi-Hsieng Samuel Wu, Yi-Ling Lin, Chia-Chun Chiang, Shih-Guei Fu, and Yi-Chen Chen. "Preventive Effects of Ophiocordyceps sinensis Mycelium on High-Fat Diet Induced Lipid Dysregulation and Hepatic Inflammation of Mice." Journal of Food and Nutrition Research 5, no. 11 (2017): 859-866.
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  • Figure 1. Pathohistological analysis and morphology of hepatocytes on H&E stained liver sections of experimental mice. (A) The central of hepatic classic lobules in different amplification factors were showed from left (100X, the scale is 100 μm) to right (200X, the scale bar is 50 μm), back-side appearances of livers were shown in right-upper part of first column with the scale. Each cavity that locates in central of the view was hepatic central vein that as abbreviated as CV. The nuclei were stained by hematoxylin, whereas the cytoplasms were stained by Eosin. (B) The prevalence table indicated the quantitative results of microscopic examination, the scores were given according to the density of micro- (as where red triangle indicates) or macro-steatosis (as where red arrow indicates)
  • Figure 2. Pathohistological analysis and morphology of hepatocytes based on Oil red stained liver sections of experimental mice. (A) The results of Oil red O staining were showed. The lipid droplets were shown as light red in Oil red stainings (green triangle), and all tissues were also stained by hematoxylin in order to remark the cell nucleus. All the pictures of Oil red stainings were shown in an amplification factor of 400X (the scale is 20 μm). (B) The quantitative results of lipid-droplet densities via ImageJ. The means of total area and SEM were showed below the bar chart. The bars are given as means±SEM (n=6). Data points without the common letter (a-c) indicate significant differences (p<0.05). (C) The prevalence table indicated the quantitative results of microscopic examination, the scores were given according to the density of lipid droplets
  • Figure 3. The graphic illustration of this study. The red arrow shows effects of high-fat diet, and the protective effects of OSM were indicated with the blue arrow
  • Table 2. Growth parameters, organ sizes, hepatic injured indices, lipid peroxidation value, and antioxidant capacities in experimental mice
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In article      View Article
 
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In article      View Article  PubMed
 
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In article      View Article  PubMed
 
[30]  Huang, F., Zhang, R., Dong, L., Guo, J., Deng, Y., Yi, Y. and Zhang, M., “Antioxidant and antiproliferative activities of polysaccharide fractions from litchi pulp,” Food & Function 6(8). 2598-2606. Aug. 2015.
In article      View Article  PubMed
 
[31]  Zhu, Z. Y., Meng, M., Sun, H., Li, Y., Yu, N. and Zhang, Y. M., “Structural analysis and immunostimulatory activity of glycopeptides from Paecilomyces sinensis,” Food & Function 7(3), 1593-1600. Mar. 2016.
In article      View Article  PubMed
 
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In article      View Article  PubMed
 
[33]  Zhu, Z. Y., Meng, M., Sun, H., Li, Y., Ren, Y. Y. and Zhang, Y., “Immunostimulatory activity of glycopeptides from Paecilomyces sinensis under normal and cyclophosphamide induced immunosuppressive conditions in mice models,” Food & Function 7(8). 3566-3576. Aug. 2016.
In article      View Article  PubMed
 
[34]  Kulkarni, N. M., Jaji, M. S., Shetty, P., Kurhe, Y. V., Chaudhary, S., Vijaykant, G., Raghul, J., Vishwakarma, S. L., Rajesh, B. N., Mookkan, J., Krishnan, U. M. and Narayanan, S. “ A novel animal model of metabolic syndrome with non-alcoholic fatty liver disease and skin inflammation,” Pharmaceutical Biology 53(8). 1110-1117. Aug. 2015.
In article      View Article  PubMed
 
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In article      View Article  PubMed
 
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In article      View Article
 
[37]  Wu, Y. H. S., Chiu, C. H., Yang, D. J., Lin, Y. L., Tseng, J. K. and Chen, Y. C., “Inhibitory effects of litchi (Litchi chinensis Sonn.) flower-water extracts on lipase activity and diet-induced obesity,” Journal of Functional Foods 5(2). 923-929. Apr. 2013.
In article      View Article
 
[38]  Liu, H. C., Chang, C. J., Yang, T. H. and Chiang, M. T., “Long-term feeding of red algae (Gelidium amansii) ameliorates glucose and lipid metabolism in a high fructose diet-impaired glucose tolerance rat model,” Journal of Food and Drug Analysis 25(3). 543-549. Jul. 2017.
In article      View Article  PubMed
 
[39]  Kim, S. B., Ahn, B., Kim, M., Ji, H. J., Shin, S. K., Hong, I. P., Kim, C. Y., Hwang, B. Y. and Lee, M. K. Effect of Cordyceps militaris extract and active constituents on metabolic parameters of obesity induced by high-fat diet in C58BL/6J mice. Journal of Ethnopharmacology 151(1). 478-484. Nov. 2014.
In article      View Article  PubMed
 
[40]  Manabe, N., Ahn, B., Kim, M., Ji, H. J., Shin, S. K., Hong, I. P., Kim, C. Y., Hwang, B. Y. and Lee, M. K., “ Effects of the mycelial extract of cultured Cordyceps sinensis on in vivo hepatic energy metabolism in the mouse,” Japanes Journal of Pharmacology 70(1). 85-88. Jan. 1999.
In article      View Article
 
[41]  Manabe, N., Azuma, Y., Sugimoto, M., Uchio, K., Miyamoto, M., Taketomo, N., Tsuchita, H. and Miyamoto, H., “Effects of the mycelial extract of cultured Cordyceps sinensis on in vivo hepatic energy metabolism and blood flow in dietary hypoferric anaemic mice,” British Journal of Nutrition 83(2). 197-204. Feb. 2000.
In article      View Article  PubMed
 
[42]  Dai, D. L., Shen, W., Yu, H. F., Guan, X. Q. and Yi, Y. F., “Effect of Cordyceps sinensis on uncoupling protein 2 in experimental rats with nonalcoholic fatty liver,” Journal of Health Science 52. 390-396. Aug. 2006.
In article      View Article
 
[43]  Jin, X., Xiang, Z., Chen, Y. P., Ma, K. F., Ye, Y. F. and Li, Y. M., “Uncoupling protein and nonalcoholic fatty liver disease,” Chinese Medical Journal 126(16). 3151-3155. Aug. 2013.
In article      View Article
 
[44]  Yang, K. T., Lin, C., Liu, C. W. and Chen, Y. C., “Effects of chicken-liver hydrolysates on lipid metabolism in a high-fat dietary habit,” Food Chemistry 160. 148-156. Oct. 2016.
In article      View Article  PubMed