Home | About PM | Editorial board | Search | Ahead of print | Current Issue | Archives | Instructions | Subscribe | Advertise | Contact us |  Login 
Pharmacognosy Magazine
Search Article 
  
Advanced search 
 

 
  Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 17  |  Issue : 73  |  Page : 140-145  

Protective effects of ginsenoside Rh1 on intervertebral disc degeneration through inhibition of nuclear factor kappa-B signaling pathway


1 Department of Clinical Laboratory, Yantai City Hospital for Infectious Diseases, Yantai, China
2 College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
3 Department of Rehabilitation Medicine, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
4 College of Rehabilitation Medicine, Binzhou Medical University, Yantai, China

Date of Submission06-Jan-2020
Date of Decision28-Mar-2020
Date of Acceptance22-Dec-2020
Date of Web Publication15-Apr-2021

Correspondence Address:
Faliang Lin
Department of Rehabilitation Medicine, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000
China
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/pm.pm_579_19

Rights and Permissions
   Abstract 


Background: In this study, we aim to explore the protective effect of ginsenoside Rh1 against intervertebral disc degeneration (IDD) and the related mechanism. Materials and Methods: IDD model in Sprague-Dawley rats was established and the animals were treated with different concentrations of ginsenoside Rh1 for 4 weeks, after this, the animals were sacrificed and the intervertebral disc of was collected for analysis using quantitative polymerase chain reaction. Western blot analysis was performed for quantifying the expression levels of glycosaminoglycans (GAGs) and Types I and Type II collagen. Moreover, serum samples were collected and the expression levels of some of the inflammatory cytokines such as interleukin (IL)-1 β and IL-6 were evaluated. Next, we collected the nucleus pulposus (NP) cells from the animals and were divided into five groups: control, IDD, treatment groups with different concentrations of ginsenoside Rh1 (10, 20, and 50 μg/mL). After treatment, the levels of IL-1 β and IL-6 in the cell culture supernatant were examined. Then, we performed western blot analysis to quantify the levels of B-cell lymphoma-2 (Bcl-2), B-cell lymphoma-extra-large (BCL-xL), and nuclear factor kappa-B (NF-κB) in different groups. Results: We observed that ginsenoside Rh1 significantly downregulated the expression of type I collagen and upregulated the expression of type II collagen and GAG under in vivo conditions. Moreover, the expression levels of IL-1 β and IL-6 in the serum samples of IDD rats and cell culture supernatant of NP cells isolated from the IDD rats were significantly increased. However, ginsenoside Rh1 significantly increased the levels of Bcl-2 and Bcl-xL and decreased the levels NF-κB both under in vitro and in vivo conditions. Conclusion: Ginsenoside Rh1 demonstrated protective effect against the IDD via regulation of IL-1 β/NF-κB signaling pathway.

Keywords: Ginsenoside Rh1, interleukin-1β, intervertebral disc degeneration, nuclear factor kappa-B, nucleus pulposus cells


How to cite this article:
Zhang S, Wang T, Wang X, Wang Y, Wang P, Li J, Wang Z, Lin F. Protective effects of ginsenoside Rh1 on intervertebral disc degeneration through inhibition of nuclear factor kappa-B signaling pathway. Phcog Mag 2021;17:140-5

How to cite this URL:
Zhang S, Wang T, Wang X, Wang Y, Wang P, Li J, Wang Z, Lin F. Protective effects of ginsenoside Rh1 on intervertebral disc degeneration through inhibition of nuclear factor kappa-B signaling pathway. Phcog Mag [serial online] 2021 [cited 2021 May 9];17:140-5. Available from: http://www.phcog.com/text.asp?2021/17/73/140/313545



SUMMARY

  • Ginsenoside Rh1 can play protective roles in the progress of intervertebral disc degeneration both under in vitro and in vivo conditions.
  • Ginsenoside Rh1 can inhibit the nuclear factor kappa-B signaling pathway in intervertebral disc degeneration rats and nucleus pulposus cells.




Abbreviations used: IDD: Intervertebral disc degeneration; NP: Nucleus pulposus; qPCR: Quantitative polymerase chain reaction; IL-1 β: Interleukin-1 β; IL-6: Interleukin-6; Bcl-2: B-cell lymphoma-2; BCL-xL: B-cell lymphoma-extra large; NF-κB: Nuclear factor kappa-B; LBP: Lower back pain; SD: Sprague-Dawley; FBS: Fetal-bovine serum; ELISA: Enzyme-linked immunosorbent assay; SDS-PAGE: Sodium dodecyl sulfate-polyacrylamide gel electrophoresis; PVDF: Polyvinylidene fluoride; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase; HRP: Horseradish peroxidase; ANOVA: Analysis of variance.


   Introduction Top


Nowadays, lower back pain has become a common muscular problem worldwide. Intervertebral disc degeneration (IDD) results in low back pain (LPB).[1] In some cases, patients with IDD cannot work resulting in a poor quality of life.[1],[2] With the increased life span of human beings and because of the high incidence rate, IDD has caused a huge burden to society, as well as to the healthcare system.[3] Unfortunately, the pathogenesis of IDD has not yet been fully elucidated and so far, there is no cure available to treat the disease. Therefore, it is important to search for new and effective medications for the treatment of IDD.

In recent years, great efforts have been made to explore the pathogenesis of IDD. Nucleus pulposus (NP), one of the three components of the intervertebral disc, has been shown to function as the primary component for maintaining the structure and the function of the intervertebral disc.[4],[5] NP cells are the major types of resident cells that exist in the NP.[6] Previous studies have suggested that the abnormal apoptosis and dysfunction of the NP cells may closely be correlated with the incidence and progress of IDD.[7],[8],[9],[10],[11] Therefore, increasing the number and restoring the function of NP cells may be an effective method to alleviate the problems associated with IDD.

Ginsenoside Rh1 is one of the primary active components of traditional Chinese medicine ginseng.[12] In the clinical field, ginsenoside Rh1 has been proven to play protective roles in against various disorders of the cardiovascular system, immune system, pulmonary system, the liver, bones and other tissues and organs. In China, products related to ginseng were widely used by physicians for the treatment of wounds and fractures.[13] Previous studies have indicated that ginsenoside Rh1 shows therapeutic effect in bone formation by stimulating the signal transduction pathway, which in turn, activates or inhibits the expression of the downstream genes.[14] However, the effects of ginsenoside Rh1 on IDD has never been discussed in previous studies.

In this study, we will investigate the effect of ginsenoside Rh1 on IDD and the related mechanism both under in vitro and in vivo conditions, our results may provide novel evidence for the application of ginsenoside Rh1 as a new medication for the treatment of IDD.


   Materials and Methods Top


Animals

A total of 50 Sprague-Dawley (SD) rats (male, about 200 g, 8–9 weeks old) were used in this study. To induce IDD, we performed surgery to remove the left facet joint of the SD rats and then used a 21-gauge needle to insert into the endplates. After surgery, the skin and muscle of the rats were closed by suture. Then, the rats were randomly divided into five groups: control group and Sham group and ginsenoside Rh1 low, medium, and high groups (10, 20, or 40 mg/[kg/day], respectively). The control group or Sham group was treated with phosphate buffer saline (PBS). The study protocol was approved by the Ethical Committee of Yantai Yuhuangding Hospital.

Culture of the nucleus pulposus cell and treatment

NP cells were isolated from the control or IDD rats according to the methods described previously.[15] NP cells were maintained in F12-Dulbecco's modified Eagle medium supplemented with 10% fetal bovine serum, 100 mg/mL streptomycin, and 100 U/mL penicillin. In addition, at the cells were incubated at 37°C with 5% CO2. NP cells were randomly divided into four groups: control group and treatment groups with different concentrations of ginsenoside Rh1 (0, 10, 20, and 50 μg/mL).

Enzyme-linked immunosorbent assay

The expression of interleukin-6 (IL-6) and interleukin-1 β (IL-1 β) in the serum of the rats and cell culture supernatants were evaluated using enzyme-linked immunosorbent assay (ELISA) kits (Beyotime, Haimen, China) based on the manufacturer's instructions.

Real-time quantitative reverse transcription-polymerase chain reaction

Total RNAs were isolated from the cells by the Trizol reagent based on the manufacturer's protocol. The expression of types I and II collagen, glycosaminoglycans (GAG), B-cell lymphoma-2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), and nuclear factor kappa-B (NF-κB) were evaluated by SYBR Premix Ex Taq II (Takara, Dalian, China) following the reverse transcription quantitative-polymerase chain reaction (PCR) analysis (PrimeScript™ RT reagent Kit, Takara, Dalian, China) on ABI 7500 Real-Time PCR System (Applied Bioscience, MA, USA). glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used for normalization.

Western blot

Protein samples from the different treatment groups was extracted from the cells, separated with 8% sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and then transferred to polyvinylidene fluoride membranes (purchased from Millipore, Billerica, MA, USA). The membranes were then washed and blocked by nonfat milk and then treated by the primary antibodies (Abcam, Cambridge, MA, USA) overnight at 4°C. On day 2, the membranes were treated with horseradish peroxidase-conjugated secondary antibodies (Beyotime). Next, the membranes were treated with the BeyoECL Plus (Beyotime, Shanghai, China) kit and were photographed by ChemiDoc™ XRS + imaging system (Bio-Rad, California, USA). GAPDH was applied as the internal control.

Statistical analysis

Statistical analysis was conducted with SPSS version 20.0 software (SPSS Inc., Chicago, IL, USA). The data were expressed as the mean ± standard deviation. Comparisons among the multiple groups were analyzed by analysis of variance. P < 0.05 was considered statistically significant.


   Results Top


Protective effects of ginsenoside Rh1 on intervertebral disc degeneration in vivo

First, we created a rat IDD model and examined the effects of ginsenoside Rh1 on the expression of IDD markers types I and II collagen and GAG in this model. As shown in [Figure 1], type I collagen was markedly increased, whereas type II collagen and GAG were dramatically decreased in lumbar NP tissue samples of the IDD rats. Moreover, the medium and high dose group showed an increase in both type II collagen and GAG, and showed a decrease in the level of type I collagen in NP tissues on both mRNA [Figure 1]a, [Figure 1]b, [Figure 1]c and protein [Figure 1]d levels. Furthermore, the expressions of IL-1 β and IL-6 in serum samples were examined by ELISA methods. As shown in [Figure 2], IL-1 β and IL-6 were markedly increased in the serum samples of IDD rats, and the medium and high dose ginsenoside Rh1 can decrease the expression of IL-1 β and IL-6 in IDD rats in a dose-dependent manner.
Figure 1: Effect of ginsenoside Rh1 on the mRNA (a-c) and protein (d) expressions of I collagen, type II collagen and glycosaminoglycans in vivo. **P < 0.01

Click here to view
Figure 2: Effect of ginsenoside Rh1 on the expressions of interleukin-1 β (a) and interleukin-6 (b) in vivo. *P < 0.05, **P < 0.01

Click here to view


Effect of ginsenoside Rh1 on nucleus pulposus cells in vitro

Next, NP cells were isolated from normal and IDD rats and the effects of ginsenoside Rh1 on these cells were examined. According to our results, compared with the normal NP cells, the secretion of IL-1 β and IL-6 was markedly increased in the cell culture supernatant of the NP cells isolated from the IDD rats. Moreover, 20 and 50 μg/mL ginsenoside Rh1 treatment significantly decreased the secretion of IL-1 β and IL-6 in the cell culture supernatant of NP cells isolated from the IDD rats [Figure 3], P < 0.05].
Figure 3: Effect of ginsenoside Rh1 on the expressions of interleukin-1 β (a) and interleukin-6 (b) in vitro. **P < 0.01

Click here to view


Effects of ginsenoside Rh1 on the levels of nuclear factor kappa-B-related signaling molecules in intervertebral disc degeneration rats in vivo and nucleus pulposus cells in vitro

To further explore the underlying mechanism of ginsenoside Rh1-induced therapeutic effects against IDD, we investigated whether NF-κB signaling pathway was affected by ginsenoside Rh1. According to our results, the expression of NF-κB was markedly increased and the expression of Bcl-2 and Bcl-xL was decreased in NP tissue [Figure 4] and NP cells [Figure 5] isolated from the IDD rats. However, treatment with medium-and high-dose ginsenoside Rh1 induced dramatic increase in the expression levels of Bcl-2 and Bcl-xL and decreased the expression levels of NF-κB in NP tissue samples of IDD rats in vivo and NP cells in vitro [Figure 4] and [Figure 5], P < 0.01].
Figure 4: Effect of ginsenoside Rh1 on the mRNA (a-c) and protein (d) expressions of nuclear factor kappa-B related signaling molecules in intervertebral disc degeneration rats in vivo. *P < 0.05, **P < 0.01

Click here to view
Figure 5: Effect of ginsenoside Rh1 on the mRNA (a-c) and protein (d) expressions of nuclear factor kappa-B related signaling molecules in nucleus pulposus cells in vitro. *P < 0.05, **P < 0.01

Click here to view



   Discussion Top


In this study, we aimed to determine the therapeutic effects of ginsenoside Rh1 in the treatment of IDD. According to our results, ginsenoside Rh1 can alter the expression of IDD markers both under in vitro and in vivo conditions, and we also proved that ginsenoside Rh1 can alleviate the inflammatory condition of IDD by regulating IL-1 β/NF-κB signaling. Our results suggest that ginsenoside Rh1 may serve as a potential alternative medication for the management of IDD.

In recent years, numerous reports on natural compounds in the treatment of bone diseases have been reported. Yuan et al. have reported that puerarin can prevent the bone loss of the ovariectomized mice models and also inhibit the formation of osteoclasts.[16] Caichompoo et al. have discussed the effect of extracts of Schisandra chinensis (Turcz.) on the proliferation of osteoblasts.[17] Hsieh et al. have discussed the roles of icariin in osteoblasts anabolism.[18] Tang et al. proved that Honokiol can alleviate IDD by suppressing TXNIP-NLRP3 inflammasome signal.[19] Zheng et al. have demonstrated that spermidine can lead to increased autophagy in NP and alleviate the symptoms of IDD.[20] Furthermore, the active components of ginsenoside (e.g., ginsenoside Rg1 and ginsenoside Rg3) have been shown to play protective effects in IDD.[21],[22] However, investigation on the roles of ginsenoside Rh1 in IDD was limited, and it remains unclear whether ginsenoside Rh1 can exert the same effect as Rg1 or Rg3 in the treatment of IDD.

NP cells are a group of cells located in the intervertebral disc, and the results of previous studies have suggested that abnormal degradation of extracellular matrix (ECM) in NP cells can ultimately lead to IDD.[23] The ECM of NP cells consists of different types of collagen and proteoglycan, and patients with IDD exhibit dramatic changes in the expression level of these proteins.[23],[24] In this study, we established rat IDD model and observed that the medium-and high-dose ginsenoside Rh1 significantly decreased the expression levels of type I collagen, and increased the expression levels of type II collagen and GAG in NP tissues of IDD rats, suggesting that ginsenoside Rh1 can alleviate IDD under in vivo conditions. Moreover, ginsenoside Rh1 can also change the expression levels of the above proteins in NP cells under in vitro conditions. In summary, these results suggest that ginsenoside Rh1 can alleviate IDD condition by suppressing the degradation of ECMs in NP cells.

The chronic inflammatory condition in the intervertebral disc is the other symptom of IDD, and in current clinical application, medications with anti-inflammatory functions have been applied for the treatment of IDD.[25] NF-κB has been known as an important regulator that exists in many types of cells and has been shown to be aberrantly activated in IDD, which may lead to chronic inflammatory condition and therefore contribute to the pathogenesis of the disease.[26],[27],[28] Previous studies have demonstrated the anti-inflammatory activity of ginsenoside Rh1;[13],[29] therefore, in this study, we hypothesized that ginsenoside Rh1 may exert its protective effect in IDD by inhibiting the activation of NF-κB. To further investigate the underlying mechanism of ginsenoside Rh1-induced therapeutic effects, we examined the expression levels of NF-κB and the downstream molecules, as well as the related cytokines IL-1 β and IL-6. We found that the medium and high doses of ginsenoside Rh1 significantly decreased the levels of NF-κB and increased the level of Bcl-2 and Bcl-xL. These results suggest that ginsenoside Rh1 shows its therapeutic effects by suppressing the NF-κB signaling pathway.

This study has some limitations. First, we only performed cell-based assay and animal studies, and clinical studies should be performed in the future to confirm the effects of ginsenoside Rh1.


   Conclusion Top


In conclusion, the results of this study demonstrate that ginsenoside Rh1 can alleviate IDD by regulating IL-1 β/NF-κB signaling pathway. Our results have provided novel evidence for the application of ginsenoside Rh1 as an effective medication for the treatment of IDD.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Li Y, Li K, Hu Y, Xu B, Zhao J. Piperine mediates LPS induced inflammatory and catabolic effects in rat intervertebral disc. Int J Clin Exp Pathol 2015;8:6203-13.  Back to cited text no. 1
    
2.
Yue B, Lin Y, Ma X, Zhang G, Chen B. Effect of survivin gene therapy via lentivirus vector on the course of intervertebral disc degeneration in an in vivo rabbit model. Mol Med Rep 2016;14:4593-8.  Back to cited text no. 2
    
3.
Zhao B, Yu Q, Li H, Guo X, He X. Characterization of microRNA expression profiles in patients with intervertebral disc degeneration. Int J Mol Med 2014;33:43-50.  Back to cited text no. 3
    
4.
Pattappa G, Li Z, Peroglio M, Wismer N, Alini M, Grad S. Diversity of intervertebral disc cells: Phenotype and function. J Anat 2012;221:480-96.  Back to cited text no. 4
    
5.
Yang H, Cao C, Wu C, Yuan C, Gu Q, Shi Q, et al. TGF-βl Suppresses Inflammation in Cell Therapy for Intervertebral Disc Degeneration. Sci Rep 2015;5:13254.  Back to cited text no. 5
    
6.
Yang H, Yuan C, Wu C, Qian J, Shi Q, Li X, et al. The role of TGF-β1/Smad2/3 pathway in platelet-rich plasma in retarding intervertebral disc degeneration. J Cell Mol Med 2016;20:1542-9.  Back to cited text no. 6
    
7.
Kang L, Hu J, Weng Y, Jia J, Zhang Y. Sirtuin 6 prevents matrix degradation through inhibition of the NF-κB pathway in intervertebral disc degeneration. Exp Cell Res 2017;352:322-32.  Back to cited text no. 7
    
8.
Cai P, Yang T, Jiang X, Zheng M, Xu G, Xia J. Role of miR-15a in intervertebral disc degeneration through targeting MAP3K9. Biomed Pharmacother 2017;87:568-74.  Back to cited text no. 8
    
9.
Lv F, Huang Y, Lv W, Yang L, Li F, Fan J, et al. MicroRNA-146a Ameliorates Inflammation via TRAF6/NF-κB Pathway in Intervertebral Disc Cells. Med Sci Monit 2017;23:659-64.  Back to cited text no. 9
    
10.
Li J, Guan H, Liu H, Zhao L, Li L, Zhang Y, et al. Epoxyeicosanoids prevent intervertebral disc degeneration in vitro and in vivo. Oncotarget 2017;8:3781-97.  Back to cited text no. 10
    
11.
Chen D, Xia D, Pan Z, Xu D, Zhou Y, Wu Y, et al. Metformin protects against apoptosis and senescence in nucleus pulposus cells and ameliorates disc degeneration in vivo. Cell Death Dis 2016;7:e2441.  Back to cited text no. 11
    
12.
Lyu X, Xu X, Song A, Guo J, Zhang Y, Zhang Y. Ginsenoside Rh1 inhibits colorectal cancer cell migration and invasion in vitro and tumor growth in vivo. Oncol Lett 2019;18:4160-6.  Back to cited text no. 12
    
13.
Lee W, Cho SH, Kim JE, Lee C, Lee JH, Baek MC, et al. Suppressive effects of ginsenoside Rh1 on HMGB1-mediated septic responses. Am J Chin Med 2019;47:119-33.  Back to cited text no. 13
    
14.
Tam DN, Truong DH, Nguyen TT, Quynh LN, Tran L, Nguyen HD, et al. Ginsenoside Rh1: A systematic review of its pharmacological properties. Planta Med 2018;84:139-52.  Back to cited text no. 14
    
15.
Liu P, Chang F, Zhang T, Gao G, Yu C, Ding SQ, et al. Downregulation of microRNA-125a is involved in intervertebral disc degeneration by targeting pro-apoptotic Bcl-2 antagonist killer 1. Iran J Basic Med Sci 2017;20:1260-7.  Back to cited text no. 15
    
16.
Yuan SY, Sheng T, Liu LQ, Zhang YL, Liu XM, Ma T, et al. Puerarin prevents bone loss in ovariectomized mice and inhibits osteoclast formation in vitro. Chin J Nat Med 2016;14:265-9.  Back to cited text no. 16
    
17.
Caichompoo W, Zhang QY, Hou TT, Gao HJ, Qin LP, Zhou XJ. Optimization of extraction and purification of active fractions from Schisandra chinensis (Turcz.) and its osteoblastic proliferation stimulating activity. Phytother Res 2009;23:289-92.  Back to cited text no. 17
    
18.
Hsieh TP, Sheu SY, Sun JS, Chen MH, Liu MH. Icariin isolated from Epimedium pubescens regulates osteoblasts anabolism through BMP-2, SMAD4, and Cbfa1 expression. Phytomedicine 2010;17:414-23.  Back to cited text no. 18
    
19.
Tang P, Gu JM, Xie ZA, Gu Y, Jie ZW, Huang KM, et al. Honokiol alleviates the degeneration of intervertebral disc via suppressing the activation of TXNIP-NLRP3 inflammasome signal pathway. Free Radic Biol Med 2018;120:368-79.  Back to cited text no. 19
    
20.
Zheng Z, Wang ZG, Chen Y, Chen J, Khor S, Li J, et al. Spermidine promotes nucleus pulposus autophagy as a protective mechanism against apoptosis and ameliorates disc degeneration. J Cell Mol Med 2018;22:3086-96.  Back to cited text no. 20
    
21.
Chen J, Liu GZ, Sun Q, Zhang F, Liu CY, Yuan L, et al. Protective effects of ginsenoside Rg3 on TNF-α-induced human nucleus pulposus cells through inhibiting NF-κB signaling pathway. Life Sci 2019;216:1-9.  Back to cited text no. 21
    
22.
Yu L, Hao Y, Peng C, Zhang P, Zhu J, Cai Y, et al. Effect of Ginsenoside Rg1 on the intervertebral disc degeneration rats and the degenerative pulposus cells and its mechanism. Biomed Pharmacother 2020;123:109738.  Back to cited text no. 22
    
23.
Zhan S, Wang K, Song Y, Li S, Yin H, Luo R, et al. Long non-coding RNA HOTAIR modulates intervertebral disc degenerative changes via Wnt/β-catenin pathway. Arthritis Res Ther 2019;21:201.  Back to cited text no. 23
    
24.
Li N, Gao Q, Zhou W, Lv X, Yang X, Liu X. MicroRNA-129-5p affects immune privilege and apoptosis of nucleus pulposus cells via regulating FADD in intervertebral disc degeneration. Cell Cycle 2020;19:933-48.  Back to cited text no. 24
    
25.
Deng X, Wu W, Liang H, Huang D, Jing D, Zheng D, et al. Icariin Prevents IL-1β-Induced Apoptosis in Human Nucleus Pulposus via the PI3K/AKT Pathway. Evid Based Complement Alternat Med 2017;2017:2198323.  Back to cited text no. 25
    
26.
Ge J, Chen L, Yang Y, Lu X, Xiang Z. Sparstolonin B prevents lumbar intervertebral disc degeneration through toll like receptor 4, NADPH oxidase activation and the protein kinase B signaling pathway. Mol Med Rep 2018;17:1347-53.  Back to cited text no. 26
    
27.
Zhang J, Li Z, Chen F, Liu H, Wang H, Li X, et al. TGF-β1 suppresses CCL3/4 expression through the ERK signaling pathway and inhibits intervertebral disc degeneration and inflammation-related pain in a rat model. Exp Mol Med 2017;49:e379.  Back to cited text no. 27
    
28.
Li X, Wang X, Hu Z, Chen Z, Li H, Liu X, et al. Possible involvement of the oxLDL/LOX-1 system in the pathogenesis and progression of human intervertebral disc degeneration or herniation. Sci Rep 2017;7:7403.  Back to cited text no. 28
    
29.
Lee SY, Jeong JJ, Eun SH, Kim DH. Anti-inflammatory effects of ginsenoside Rg1 and its metabolites ginsenoside Rh1 and 20(S)-protopanaxatriol in mice with TNBS-induced colitis. Eur J Pharmacol 2015;762:333-43.  Back to cited text no. 29
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]



 

Top
   
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
    Materials and Me...
   Results
   Discussion
   Conclusion
    References
    Article Figures

 Article Access Statistics
    Viewed86    
    Printed0    
    Emailed0    
    PDF Downloaded18    
    Comments [Add]    

Recommend this journal