Home | Register | Login | Inquiries | Alerts | Sitemap |  


Advanced Search
JKM > Volume 40(3); 2019 > Article
Kim: Effects of Curcuma longa Rhizoma on MIA-induced Osteoarthritis in Rat Model

Abstract

Objectives

The aim of this study was to investigate the anti-inflammatory effects of Curcuma longa rhizoma extract in an experimental rat model of osteoarthritis.

Methods

Osteoarthritis was induced in rats by injecting monosodium iodoacetate (MIA) into the knee joint cavity of rats. The rats were divided into 5 groups (Normal, Control, positive comparison, low (CL) and high (CH) concentration groups). Rats in the low concentration (CL) group had MIA-induced osteoarthritis; they were treated with Curcuma longa rhizoma extract at a dose of 50mg/kg body weight. Rats in the high concentration (CH) group had MIA-induced osteoarthritis; they were treated with Curcuma longa rhizoma extract at a dose of 100mg /kg body weight. Hind paw weight distribution and ROS levels were measured. At the end of all treatments, changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine levels were analyzed. In addition, inflammatory protein levels were evaluated by western blot analysis.

Results

In this study, hind paw weight distribution significantly improved in the CL and CH groups, while. Reactive oxygen species (ROS) production significantly decreased in both. The levels of ALT, AST, BUN, and creatinine did not significantly change in either group. The production of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), p47phox, and Ras-related C3 botulinum toxin substrate 1 (RAC1) decreased in both. Catalase, heme oxygenase-1 (HO-1) and superoxide dismutase (SOD) significantly increased in the CL and CH groups, respectively. Nuclear factor erythroid 2 (Nrf2) increased, but there were no significant differences between the experimental and control groups. Inflammatory cytokines, including nuclear factor-kappa Bp65 (NF-κBp65), interleukin-1beta (IL-1β), and tumor necrosis factor-alpha (TNF-α), decreased significantly in both the CL and CH groups.

Conclusions

Our results showed that Curcuma longa rhizoma extract has anti-inflammatory effects. Anti-inflammatory activity is regulated by the inhibition of inflammatory cytokines and mediators, such as NF-κB, therefore, it suppresses cartilage damage as well.

Fig. 1
HPLC profile of combined extract of Curcuma longa rhizoma 30% EtOH extract.
(a) Chemical structure of Curcumin (C21H20O6), (b) Linearity curve of curcumin, (c) HPLC profile of Curcumin and Curcuma longa rhizoma 30% EtOH extract.
jkm-40-3-35f1.gif
Fig. 2
Alanine transaminase (ALT) in serum.
Refer to Table 2 for groups. All data are expressed as the means ± SEM, n=6 rats per group. There is no significant difference in the experimental groups.
jkm-40-3-35f2.gif
Fig. 3
Aspartate transaminase (AST) in serum.
Refer to Table 2 for groups. All data are expressed as the means ± SEM, n=6 rats per group. #, Significantly different from the normal (##, p<0.01)
jkm-40-3-35f3.gif
Fig. 4
Blood urea nitrogen (BUN) in serum.
Refer to Table 2 for groups. All data are expressed as the means ± SEM, n=6 rats per group. There is no significant difference in the experimental groups.
jkm-40-3-35f4.gif
Fig. 5
Creatinine in serum.
Refer to Table 2 for groups. All data are expressed as the means ± SEM, n=6 rats per group.There is no significant difference in the experimental groups.
jkm-40-3-35f5.gif
Fig. 6
Scavenging activity of Curcuma longa rhizoma 30% EtOH extract on DPPH radical.
(A) Scavenging activity of L-ascorbic acid against DPPH radical, (B) Scavenging activity of Curcuma longa rhizoma 30% EtOH extract against DPPH radical.
jkm-40-3-35f6.gif
Fig. 7
Scavenging activity of Curcuma longa rhizoma 30% EtOH extract on ABTS radical.
(A) Scavenging activity of L-ascorbic acid against ABTS radical, (B) Scavenging activity of Curcuma longa rhizoma 30% EtOH extract against ABTS radical.
jkm-40-3-35f7.gif
Fig. 8
Oxidative stress biomarker (ROS) in serum.
Refer to Table 2 for groups. All data are expressed as the means ± SEM, n=6 rats per group. #, Significantly different from the normal (###, p<0.001). *, Significantly different from the control (***, p<0.001).
jkm-40-3-35f8.gif
Fig. 9
Western blot analysis of NADPH oxidase 4 (NOX4) expression.
Expression levels in the MIA-induced osteoarthritis rats. Refer to Table 2 for groups. All data are expressed as the means ± SEM, n=6 rats per group. #, Significantly different from the normal (##, p<0.01).
jkm-40-3-35f9.gif
Fig. 10
Western blot analysis of p47phox expression.
Expression levels in the MIA-induced osteoarthritis rats. Refer to Table 2 for groups. All data are expressed as the means ± SEM, n=6 rats per group. There is no significant difference in the experimental groups.
jkm-40-3-35f10.gif
Fig. 11
Western blot analysis of Ras-related C3 botulinum toxin substrate 1 (RAC1) expression.
Expression levels in the MIA-induced osteoarthritis rats. Refer to Table 2 for groups. All data are expressed as the means ± SEM, n=6 rats per group. #, Significantly different from the normal (##, p<0.01). *, Significantly different from the control (*, p<0.05).
jkm-40-3-35f11.gif
Fig. 12
Western blot analysis of nuclear factor erythroid 2 (Nrf2) expression.
Expression levels in the MIA-induced osteoarthritis rats. Refer to Table 2 for groups. All data are expressed as the means ± SEM, n=6 rats per group. There is no significant difference in the experimental groups.
jkm-40-3-35f12.gif
Fig. 13
Western blot analysis of glutathione heme oxygenase-1 (HO-1) expression.
Expression levels in the MIA-induced osteoarthritis rats. Refer to Table 2 for groups. All data are expressed as the means ± SEM, n=6 rats per group. *, Significantly different from the control (*, p<0.05).
jkm-40-3-35f13.gif
Fig. 14
Western blot analysis of superoxide dismutase (SOD) expression.
Expression levels in the MIA-induced osteoarthritis rats. Refer to Table 2 for groups. All data are expressed as the means ± SEM, n=6 rats per group. #, Significantly different from the normal (#, p<0.05). *, Significantly different from the control (*, p<0.05).
jkm-40-3-35f14.gif
Fig. 15
Western blot analysis of catalase expression.
Expression levels in the MIA-induced osteoarthritis rats. Refer to Table 2 for groups. All data are expressed as the means ± SEM, n=6 rats per group. *, Significantly different from the control (*, p<0.05 ; **, p<0.01).
jkm-40-3-35f15.gif
Fig. 16
Western blot analysis of glutathione peroxidase (GPx) expression.
Expression levels in the MIA-induced osteoarthritis rats. Refer to Table 2 for groups. All data are expressed as the means ± SEM, n=6 rats per group. *, Significantly different from the control (*, p<0.05).
jkm-40-3-35f16.gif
Fig. 17
Western blot analysis of nuclear factor-kappa B p65 (NF-κBp65) expression.
Expression levels in the MIA-induced osteoarthritis rats. Refer to Table 2 for groups. All data are expressed as the means ± SEM, n=6 rats per group. #, Significantly different from the normal (##, p<0.01). *, Significantly different from the control (**, p<0.01).
jkm-40-3-35f17.gif
Fig. 18
Western blot analysis of inducible nitric oxide synthase (iNOS) expression.
Expression levels in the MIA-induced osteoarthritis rats. Refer to Table 2 for groups. All data are expressed as the means ± SEM, n=6 rats per group. #, Significantly different from the normal (###, p<0.001).
jkm-40-3-35f18.gif
Fig. 19
Western blot analysis of tumor necrosis factor-alpha (TNF-α) expression.
Expression levels in the MIA-induced osteoarthritis rats. Refer to Table 2 for groups. All data are expressed as the means ± SEM, n=6 rats per group. #, Significantly different from the normal (##, p<0.01). *, Significantly different from the control (*, p<0.05).
jkm-40-3-35f19.gif
Fig. 20
Western blot analysis of interleukin-1beta (IL-1β) expression.
Expression levels in the MIA-induced osteoarthritis rats. Refer to Table 2 for groups. All data are expressed as the means ± SEM, n=6 rats per group. #, Significantly different from the normal (###, p<0.001). *, Significantly different from the control (*, p<0.05 ; **, p<0.01).
jkm-40-3-35f20.gif
Fig. 21
Western blot analysis of matrix metalloproteinase-2 (MMP-2) expression.
Expression levels in the MIA-induced osteoarthritis rats. Refer to Table 2 for groups. All data are expressed as the means ± SEM, n=6 rats per group. #, Significantly different from the normal (###, p<0.001).
jkm-40-3-35f21.gif
Fig. 22
Western blot analysis of matrix metalloproteinase-9 (MMP-9) expression.
Expression levels in the MIA-induced osteoarthritis rats. Refer to Table 2 for groups. All data are expressed as the means ± SEM, n=6 rats per group. #, Significantly different from the normal (#, p<0.05). *, Significantly different from the control (*, p<0.05).
jkm-40-3-35f22.gif
Fig. 23
Western blot analysis of tissue inhibitor of metalloproteinases 1 (TIMP1) expression.
Expression levels in the MIA-induced osteoarthritis rats. Refer to Table 2 for groups. All data are expressed as the means ± SEM, n=6 rats per group. *, Significantly different from the control (*, p<0.05).
jkm-40-3-35f23.gif
Fig. 24
Western blot analysis of tissue inhibitor of metalloproteinases 2 (TIMP2) expression.
Expression levels in the MIA-induced osteoarthritis rats. Refer to Table 2 for groups. All data are expressed as the means ± SEM, n=6 rats per group. There is no significant difference in the experimental groups.
jkm-40-3-35f24.gif
Fig. 25
The histological analysis of the knee joint tissues after treatment of CL and CH in MIA-induced osteoarthritis rats (H&E staining, ×200).
In the normal, synovial tissue and cartilage were well observed. In the control, most of aricular cartilage and synovial tissue were destructed. In the CL & CH, articular cartilage and synovial tissue were preserved, compared with the control. (A) Nor, (B) Con, (C) Indo, (D) CL, (E) CH. Refer to Table 2 for groups.
jkm-40-3-35f25.gif
Fig. 26
The histological analysis of the knee joint tissues after treatment of CL and CH in MIA-induced osteoarthritis rats (Safranin O staining, × 200).
In the normal, there are much of proteoglycan around the cartilage. In the control, most of proteoglycan was broken down. In the CL & CH, proteoglycan was well preserved compared with the control. Especially, CH group showed histologically similar to normal group. (A) Nor, (B) Con, (C) Indo, (D) CL, (E) CH. Refer to Table 2 for groups.
jkm-40-3-35f26.gif
Table 1
The Operating Condition of HPLC for Analysis of Curcumin
Instrument Agilent 1260 series
Column Zorbax Eclipse XDB-C18 4.6 mm× 150 mm
Mobile phase A (0.1% formic acid in water)
B (0.1% formic acid in acetonitrile)
Detector 420 nm
Flow rate 1.0ml/min
Temperature 40°C
Injection volume 10μl
Table 2
Body Weight and Food Intake
Group Body weight Food intake (g/day)

Initial (g) Final (g) Gain (g)
Nor 329.91 ± 6.53 373.82 ± 9.04 43.91 ± 5.63 22.76 ± 1.84
Con 310.73 ± 12.47### 355.64 ± 16.45# 44.91 ± 6.88 20.74 ± 3.03
Indo 312.00 ± 14.61 356.00 ± 27.56 44.00 ± 17.26 20.31 ± 1.00
CL 305.78 ± 8.54 339.56 ± 19.49 33.78 ± 20.33 21.85 ± 1.14
CH 315.33 ± 12.94 360.22 ± 15.87 44.89 ± 6.15 22.18 ± 0.97

All data are expressed as the means ± SEM, n=6 rats per group.

# Significantly different from the normal (#, p<0.05 ; ###, p<0.001).

Nor; normal rats not receiving MIA with normal diet, Con; MIA-induced osteoarthritis rats treated with water, Indo; MIA-induced osteoarthritis rats treated with indomethacin 5 mg/kg body weight, CL; MIA-induced osteoarthritis rats treated with Curcuma longa rhizoma extract at a dose of 50 mg/kg body weight, CH; MIA-induced osteoarthritis rats treated with Curcuma longa rhizoma extract at a dose of 100 mg/kg body weight.

Table 3
The Changes in Relative Hind Paw Weight Distribution in MIA-induced Osteoarthritis Rats
Group 0 weeks 1 weeks 2 weeks 3 weeks
Nor 100.18 ± 14.97 98.66 ± 12.03 97.45 ± 10.89 102.94 ± 21.87
Con 106.90 ± 15.84 180.14 ± 49.22## 279.32 ± 55.82### 644.25 ± 239.77###
Indo 103.25 ± 13.10 204.26 ± 36.02 191.39 ± 77.62* 127.89 ± 54.03***
CL 109.11 ± 14.74 194.94 ± 72.15 258.16 ± 103.42 257.79 ± 62.75***
CH 97.47 ± 13.11 193.96 ± 69.76 230.36 ± 108.48 160.98 ± 65.47***

All data are expressed as the means ± SEM, n=6 rats per group. Refer to Table 2 for groups.

# Significantly different from the normal (##, p<0.01 ; ###, p<0.001).

* Significantly different from the control (*, p<0.05 ; ***, p<0.001).

참고문헌

1 The Society of Korean Medicine Rehabilitation. Korean Rehabilitation Medicine. 4th ed. Seoul: Koonja publisher;2015. p. 102–51.


2 Korean Acupuncture & Moxibustion Medicine Society. Acupuncture Medicine. Seoul: Hanmibook;2016. p. 537–68.


3 Harrison’s Principles of Internal Medicine Edit committee of the Korean Association of Internal Medicine. Harrison’s Principles of Internal Medicine. 18th edition(2). Seoul: MIP;2013. p. 2782


4 Herbal medicine editorial committee of Korean medicine college. Herbal medicine. Seoul: Younglimsa;2011. p. 454–5.


5 Jung TS, Choi CW. The Effect of the Curcumae Longae Rhizoma (CLR) Extract on the Hepatocellular Carcinogenesis and Acute Liver Damage Induced by Diethylnitrosamine (DENA) and CCl4 in Rats. Herbal Formula Science. 2014; 22:1. 177–92.
crossref

6 Oh JS, Yang SY, Kim MH, Namgung O, Park YC. Effects of Root of Curcumin longa on LPS-induced Lung Injury. J Korean Oriental Med. 2013; 34:1. 89–102.


7 Kim SD. Effects of Curcuma longa Rhizoma (CLR) on chronic renal failure in rats. Dongshin University Graduate School. 2008.


8 Lee JH, Kim JH, Park SY, Choi JH. Effects of Curcuma longa Rhizoma on Asthma induced intra-nasal instillation of Ovalbumin in Mice. The Journal of Korean Oriental Medical Ophthalmology & Otolaryngology & Dermatology. 2008; 21:3. 20–35.


9 Seong KW. The Effect of Oral Curcuma longa ingestion on the gene expression in a Rat Model of Benign Prostatic Hyperplasia using microarray analysis. Kyunghee University Graduate School. 2012.


10 Lee JH. Effects of Curcumae Longae Rhizoma pharmacopuncture on MIA-induced Osteoarthritis Rats. Daegu Haany University Graduate School. 2018.


11 Lee OJ, Lee DG, Lee JH, Lee JH, Lee SH, Park GH, et al. Effects of Curcuma longa LINNE Pharmacopuncture at ST36 on Adjuvant Induced Arthritis in Rats. The Acupuncture. 2013; 30:4. 95–105.
crossref

12 Yang H, Huang S, Wei Y, Cao S, Pi C, Feng T, et al. Curcumin Enhances the Anticancer Effect Of 5-fluorouracil against Gastric Cancer through Down-Regulation of COX-2 and NF- κB Signaling Pathways. J Cancer. 2017; 8:18. 3697–706.
crossref

13 Haryuna TS, Munir D, Maria A, Bashiruddin J. The Antioxidant Effect of Curcumin on Cochlear Fibroblasts in Rat Models of Diabetes Mellitus. Iran J Otorhinolaryngol. 2017; 29:93. 197–202.
pmid pmc

14 Wang X, Hang Y, Liu J, Hou Y, Wang N, Wang M. Anticancer effect of curcumin inhibits cell growth through miR-21/PTEN/Akt pathway in breast cancer cell. Oncol Lett. 2017; 13:6. 4825–31.
crossref

15 Mohammadi S, Karimzadeh Bardei L, Hojati V, Ghorbani AG, Nabiuni M. Anti-Inflammatory Effects of Curcumin on Insulin Resistance Index, Levels of Interleukin-6, C-Reactive Protein, and Liver Histology in Polycystic Ovary Syndrome-Induced Rats. Cell J. 2017; 19:3. 425–33.


16 Guzman RE, Evans MG, Bove S, Morenko B, Kilgore K. Mono-iodoacetate-induced Histologic Changes in Subchondral Bone and Articular Cartilage of Rat Femorotibial Joints: an Animal Model of Osteoarthritis. Toxicol Pathol. 2003; 31:6. 619–24.
crossref pmid

17 Ratanavaraporn J, Soontornvipart K, Shuangshoti S, Shuangshoti S, Damrongsakkul S. Localized Delivery of Curcumin from Injectable Gelatin/Thai Silk Fibroin Microspheres for Anti-inflammatory Treatment of Osteoarthritis in a Rat Model. Inflammopharmacology. 2017; 25:2. 211–21.
crossref

18 Park S, Lee LR, Seo JH, Kang S. Curcumin and Tetrahydrocurcumin Both Prevent Osteoarthritis Symptoms and Decrease the Expressions of Pro-inflammatory Cytokines in Estrogen -deficient Rats. Genes Nutr. 2016; 11:2
crossref pmid pmc

19 Niazvand F, Khorsandi L, Abbaspour M, Orazizadeh M, Varaa N, Maghzi M, et al. Curcumin-loaded Poly Lactic-co-glycolic Acid Nanoparticles Effects on Mono-iodoacetate -induced Osteoarthritis in Rats. Vet Res Forum. 2017; 8:2. 155–61.


20 Li XS, Chen H, Zhen P, Li SS, Zhou SH, Tian Q, et al. JAK2/STAT3 Signal Pathway Mediating Curcumin in Cartilage Cell Metabolism of Osteoarthritis. Zhongguo Gu Shang. 2016; 29:12. 1104–9.


21 Wang J, Ma J, Gu JH, Wang FY, Shang XS, Tao HR, et al. Regulation of Type II Collagen, Matrix Metalloproteinase-13 and Cell Proliferation by Interleukin-1β Is Mediated by Curcumin via Inhibition of NF-κB Signaling in Rat Chondrocytes. Mol Med Rep. 2017; 16:2. 1837–45.
crossref

22 Li X, Feng K, Li J, Yu D, Fan Q, Tang T, et al. Curcumin Inhibits Apoptosis of Chondrocytes through Activation ERK1/2 Signaling Pathways Induced Autophagy. Nutrients. 2017; 9:4. 414
crossref

23 Henrotin Y, Gharbi M, Dierckxsens Y, Priem F, Marty M, Seidel L, et al. Decrease of a Specific Biomarker of Collagen Degradation in Osteoarthritis, Coll2-1, by Treatment with Highly Bioavailable Curcumin during an Exploratory Clinical Trial. BMC Complement Altern Med. 2014; 14:159
crossref pmid pmc

24 Nakagawa Y, Mukai S, Yamada S, Matsuoka M, Tarumi E, Hashimoto T, et al. Short-term Effects of Highly-bioavailable Curcumin for Treating Knee Osteoarthritis: a Randomized, Double-blind, Placebo-controlled Prospective study. J Orthop Sci. 2014; 19:6. 933–9.
crossref

25 Haroyan A, Mukuchyan V, Mkrtchyan N, Minasyan N, Gasparyan S, Sargsyan A, et al. Efficacy and Safety of Curcumin and Its Combination with Boswellic Acid in Osteoarthritis: a Comparative, Randomized, Double-blind, Placebo-controlled Study. BMC Complement Altern Med. 2018; 18:1. 7
crossref pmid pmc

26 Ramadan G, Al-Kahtani MA, El-Sayed WM. Anti-inflammatory and Anti-oxidant Properties of Curcuma longa (turmeric) versus Zingiber officinale (Ginger) Rhizomes in Rat Adjuvant -induced Arthritis. Inflammation. 2011; 34:4. 291–301.
crossref pmid

27 Funk JL, Oyarzo JN, Frye JB, Chen G, Lantz RC, Jolad SD, et al. Turmeric Extracts Containing Curcuminoids Prevent Experimental Rheumatoid Arthritis. J Nat Prod. 2006; 69:3. 351–5.
crossref pmid pmc

28 Blois MS. Antioxidant Determinations by the Use of a Stable Free Radical. Nature. 1958; 181:4617. 1199–200.
crossref

29 Seo CS, Kim JH, Shin HK, Kim BS. Quantitative Analysis of (+)-Catechin, Paeoniflorin, and Paeonol in Moutan Radicis Cortex and Its Processed Products. Kor J Pharmacogn. 2016; 47:3. 237–45.


30 Kooy NW, Royall JA, Ischiropoulos H, Beckman JS. Peroxynitrite-mediated oxidation of dihydrorhodamine 123. Free Radic Biol Med. 1994; 16:2. 149–56.
crossref pmid

31 Guccione AA, Felson DT, Anderson JJ, Anthony JM, Zhang Y, Wilson PW, et al. The Effects of Specific Medical Conditions on the Functional Limitations of Elders in the Framingham Study. Am J Public Health. 1994; 84:3. 351–8.
crossref pmid pmc

32 Felson DT, Zhang Y. An Update on the Epidemiology of Knee and Hip Osteoarthritis with a View to Prevention. Arthritis Rheum. 1998; 41:8. 1343–55.
crossref pmid

33 Ministry of the Interior and Safety. Population census. [cited 2018 Mar 05]. Available from: URL: http://www.mois.go.kr/frt/bbs/type010/commonSelectBoardArticle.do?bbsId=BBSMSTR_000000000008&nttId=59453


34 Jeon MH, Kim MH. Effect of Hijikia fusiforme Fractions on Proliferation and Differentiation in Osteoblastic MC3T3-E1 Cells. Journal of Life Science. 2011; 21:2. 300–8.
crossref

35 Kang YG, Nam JH, Lee KS. The Effect of Indomethacin on the Matrix Metalloproteinases in Canine Permanent Tooth Eruption. Korean J Orthod. 2006; 36:2. 91–102.


36 Kim HA. Pharmacological Treatment of Osteoarthritis. J of Korean Orthopaedic Research Society. 2010; 13:1. 16–22.
crossref

37 Korean Knee Society Subcommittee on Osteoarthritis Guidelines. Guidelines for the Treatment of Osteoarthritis of the Knee. J Korean Knee Soc. 2010; 22:1. 69–74.


38 Park SW, Kim YS, Lee DH, Kwon YB, Park JY, Lee SY, et al. Efficacy and Safety of HT008 and Glucosamine Sulfate in the Treatment of Knee Osteoarthritis : A Randomized Double-blind Trial. Kor J Herbology. 2014; 29:4. 45–52.
crossref

39 Ahn SI, Bok JH, Son JY. Antioxidative Activity and Nitrite-scavenging Abilities of Some Phenolic Compounds. Korean J Food Cookery Sci. 2007; 23:1. 19–24.


40 Lee JA, Jung DS. Screening of the Antioxidant and Anti-elastase Activities for the Extracts of Jeju Endemic Plants. Journal of Research in Education & Science. 2011; 13:2. 249–69.
crossref

41 Kim SJ, Kim HJ, Park JC. DPPH Radical Scavenging Effects of the Aerial Parts of Fagopyrum esculentum and Isolation of Bioactive Flavonoids. Herbal formula science. 2004; 12:1. 255–62.


42 Lee YM, Bae JH, Jung HY, Kim JH, Park DS. Antioxidant Activity in Water and Methanol Extracts from Korean Edible Wild Plants. J Korean Soc Food Sci Nutr. 2011; 40:1. 29–36.
crossref

43 Beckman KB, Ames BN. The free radical theory of aging matures. Physiol Rev. 1998; 78:2. 547–81.
crossref pmid

44 McCord JM. The Evolution of Free Radicals and Oxidative Stress. Am J Med. 2000; 108:8. 652–9.
crossref pmid

45 Bedard K, Krause KH. The NOX family of ROS-generating NADPH Oxidases: Physiology and Pathophysiology. Physiol Rev. 2007; 87:1. 245–313.
crossref pmid

46 Morel F, Doussiere J, Vignais PV. The Superoxide -generating Oxidase of Phagocytic Cells. Physiological, Molecular and Pathological Aspects. Eur J Biochem. 1991; 201:3. 523–46.
crossref pmid

47 Vignais PV. The Superoxide-generating NADPH Oxidase: Structural Aspects and Activation Mechanism. Cell Mol Life Sci. 2002; 59:9. 1428–59.
crossref pmid

48 Radermacher KA, Wingler K, Kleikers P, Altenhöfer S, Hermans JJR, Kleinschnitz C, et al. The 1027th Target Candidate in Stroke: Will NADPH Oxidase Hold Up? Exp Transl Stroke Med. 2012; 4:1–11.
crossref pmid pmc

49 Jin BM, Lee MK, Lee JS, Hyun KY. Anti-inflammatory Effects of Korean red ginseng Extract in formalin-induced Orofacial Pain in Rats. Journal of the Korea Academia -Industrial cooperation Society. 2014; 15:9. 5708–15.
crossref

50 Lim JS, Ahn KY. Potassium Depletion Upregulates Expression of Nrf2 Transcription Factor in Rat Kidney. Korean J Nephrol. 2011; 30:3. 239–45.


51 Lemos FB, Ijzermans JN, Zondervan PE, Peeters AM, Mol WM, Weimar W, et al. Differential Expression of Heme Oxygenase-1 and Vascular Endothelial Growth Factor in Cadaveric and Living Donor Kidneys after Ischemia-Reperfusion. J Am Soc Nephrol. 2003; 14:3278–87.
crossref pmid

52 Van Raamsdonk JM, Hekimi S. Superoxide Dismutase Is Dispensable for Normal Animal Lifespan. Proc Natl Acad Sci USA. 2012; 109:15. 5785–90.
crossref pmid pmc

53 Preiser JC. Oxidative Stress. JPEN J Parenter Enteral Nutr. 2012; 36:2. 147–54.
crossref pmid

54 Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: Biochemical Role as a Component of Glutathione Peroxidase. Science. 1973; 179:4073. 588–90.
crossref pmid

55 Park SH, Lee HJ, Ryu JH, Lee SY, Shin HD, Hong JH, et al. Effects of Silibinin and Resveratrol on Degradation of IκB and Translocation of NF-κB p65 Induced by Tumor Necrosis Factor-α in Cultured Airway Epithelial Cells. Yakhak Hoeji. 2014; 58:1. 1–6.


56 Asagiri M, Takayanagi H. The Molecular Understanding of Osteoclast Differentiation. Bone. 2007; 40:2. 251–64.
crossref pmid

57 Lee SM, Kim YK, Hwang YH, Lee CH, Lee HS, Lee CT, et al. Role of PI3K/Akt Pathway in the Activation of IκB/NF-κB Pathway in Lung Epithelial Cells. Tuberculosis and Respiratory Diseases. 2003; 54:5. 551–62.
crossref

58 Abramson SB. Osteoarthritis and Nitric Oxide. Osteoarthritis Cartilage. 2008; 16:15–20.
crossref pmid

59 Sakaguchi Y, Shirahase H, Ichikawa A, Kanda M, Nozaki Y, Uehara Y. Effects of Selective iNOS Inhibition on Type II Collagen-induced Arthritis in Mice. 2004; 75:19. 2257–67.
crossref pmid

60 Iwanami K, Matsumoto I, Tanaka-Watanabe Y, Inoue A, Mihara M, Ohsugi Y, et al. Crucial Role of the Interleukin-6/interleukin-17 Cytokine Axis in the Induction of Arthritis by Glucose -6-phosphate Isomerase. Arthritis Rheum. 2008; 58:3. 754–63.
crossref pmid

61 Hulejová H, Baresová V, Klézl Z, Polanská M, Adam M, Senolt L. Increased Level of Cytokines and Matrix Metalloproteinases in Osteoarthritic Subchondral Bone. Cytokine. 2007; 38:3. 151–6.
crossref pmid

62 Halliwell B. Oral inflammation and reactive species: a missed opportunity? Oral Dis. 2000; 6:3. 136–7.
crossref pmid

63 Zeng ZS, Cohen AM, Guillem JG. Loss of Basement Membrane Type IV Collagen Is Associated with Increased Expression of Metalloproteinases 2 and 9 (MMP-2 and MMP-9) during Human Colorectal Tumorigenesis. Carcinogenesis. 1999; 20:5. 749–55.
crossref pmid

64 Nagase H, Woessner JF. Matrix Metalloproteinases. J Biol Chem. 1999; 274:31. 21491–4.
crossref pmid

65 Hayakawa T. Tissue Inhibitors of Metalloproteinases and their Cell Growth-promoting Activity. Cell Struct Funct. 1994; 19:3. 109–14.
crossref pmid

66 Kwon OJ, Kim MY, Shin SH, Lee AR, Lee JY, Seo BI, et al. Antioxidant and Anti-Inflammatory Effects of Rhei Rhizoma and Coptidis Rhizoma Mixture on Reflux Esophagitis in Rats. Evid Based Complement Alternat Med. 2016; 1–13.
crossref

Editorial office contact information
3F, #26-27 Gayang-dong, Gangseo-gu Seoul, 157-200 Seoul, Korea
The Society of Korean Medicine
Tel : +82-2-2658-2658-3627   Fax : +82-2-2658-3631   E-mail : skom1953@daum.net
About |  Browse Articles |  Current Issue |  For Authors and Reviewers
powerd by m2community