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Garlic and Its Role in Arthritis Management


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Garlic is a proven potential natural remedy for arthritis. The advancement of medical science and research has made it possible to exploit its various components for the targeted administration of this wonder drug. Making nanoformulations of garlic compounds will help further the easy use and bioavailability for arthritis patients. Also, preclinical and clinical studies should be conducted to elucidate garlic’s beneficial and risk effects withrespect to arthritis.
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Garlic and Its Role in Arthritis
Shalini Pareek*, Meenal Dixit*, Sumit Govil*, Indrani Jadhav*, Divya
Shrivastava*, Maryam Vahedi
, Prakash S. Bisen*
School of Life Sciences, Jaipur National University, Jaipur, India
Department of Horticultural Science, Faculty of Agricultural Science and Engineering, University of Tehran, Tehran, Iran
Research and Development Division, Tropilite Foods Pvt Ltd, Gwalior, India
In the era of development and globalization, human beings are paying less attention to
their routine lifestyles, leading to various medical cases. The most prevalent and common
of all are the musculoskeletal diseases that lead to various forms of joint and bone diseases,
collectively termed arthritis. Arthritis is now not only prevalent in elderly people but also
in younger generations. Research is ongoing to detect the mechanism and cure for the
deadly and painful disease leading to joint destruction.
In rheumatoid arthritis, the lining layer becomes thick and the inflammatory cells
infilter into the sublining portion. Fibroblasts give the appearance of transformed cells
in this lining layer as a result of the influence of the proto-oncogenes of the cell cycle.
Cytokines such as IL-1, IL-10, IL-4, and TNF-αthat are present in the synovium pro-
duce inflammation and joint-destroying enzymes such as serine protease, matrix metal-
loproteinase, etc. Research has been done to target these enzymes and inflammatory
factors and suppress their activity as a cure for arthritis.
The role of transient receptor potential receptors—especially the transient receptor
potential vanilloid 1 and the transient receptor potential ankyrin 1 channels, commonly
known as TRPV1 and TRPA1—are reported to play an important role in inducing pain
and inflammation in arthritis.
2, 3
The functional dependence of TRPs on COX-2 path-
way sensitization in arthritis has been described.
Arthritis is reported to have a natural cure with the help of various natural herbs. One
of the best reported is garlic. Garlic is a pungent wonder drug in the treatment of various
major diseases such as cardiac diseases, cancer, high cholesterol, aging, arthritis, viral
fevers such as dengue, etc.
Aged garlic is reported to have immunomodulatory func-
tions in mice bearing Sarcome-180.
The role of an important organosulfur compound
in garlic called allicin in treatments for cancer, microbial infections, arthritis, and
Bioactive Food as Dietary Interventions for Arthritis and Related Inflammatory Diseases ©2019 Elsevier Inc. All rights reserved.
cardiovascular diseases has been reviewed by Rahman.
The various methods of using
and extracting ajoene from garlic for different diseases were patented by Tatarintsev and
coworkers (US5856363A).
In further sections, we will discuss the role of garlic and its compounds as a miraculous
drug with special reference to arthritis.
Garlic (Allium sativum) is one of the oldest cultivated herbal and spice plants. It was used in
World War II for the treatment of wounds.
The Dietary Supplement Health and Edu-
cation Act of 1994, passed by the US Congress, claimed that garlic possesses various
health supplements. This wonder spice contains various sulfur compounds, protein,
and inorganic elements such as selenium, copper, iron, polyphenols, and various amino
(Figure 14.1).
In Charaka Samhita, garlic is reported as a drug for the heart as well as arthritis. On the
other hand, in Historica Naturalis, garlic is reported to be a wonder drug for animal bites,
digestion-related problems, and arthritis.
Garlic moxibustion was reported as an effective
treatment in curing patients of gonococcal arthritis.
An 86.5% success rate was reported
for arthritis patients in Russia with the administration of alisate, which is a garlic prepara-
tion of a drug.
In a survey, garlic has been reported as a natural remedy used by local and
tribal people for the treatment of joints and related diseases.
Garlic grounding techniques
play an important role in the yield of chemically effective allicin from fresh garlic. Various
techniques, including bath sonication, probe sonication, microwave extraction and cold
maceration, were used.
Microwave radiation was found to be the most effective one.
Garlic soup alone or with the soup of some specific animals such as snakes, sharks, sea
Figure 14.1 Compounds from garlic having antiarthritic and antiinflammatory effects.
246 Bioactive Food as Dietary Interventions for Arthritis and Related Inflammatory Diseases
horses, goats, and chickens is recommended as a natural treatment of arthritis by the
Chinese community.
On the other hand, the administration of garlic along with exercise
and meditation has been recommended as a much better treatment than exercise and med-
itation alone for the arthritis patient.
Similarly, garlic intake in the form of juice and salad
is suggested in the management of bone diseases and arthritis types.
As far as the extraction
procedure is concerned, in comparison to aqueous extracts, methanolic extracts of garlic
were found to be more effective in antiarthritic and antihemolytic activity.
The overall
health benefits of garlic are also presented in recent reviews.
26, 27
The antiinflammatory and immunomodulatory effects of garlic were well reviewed by
Arreola et al.
Various sulfur compounds from garlic such as diallyl sulfide, S-allylmercap-
tocysteine, ajoene, etc., are involved in suppressing an important inflammatory factor
called NF-κB.
29, 30
The expression of various inflammatory factors, including nitric oxide,
prostaglandin E
, tumor necrosis factor-α, IL-6, and IL-1β, was found to be downregu-
lated as an effect of another sulfur compound Z- and E-ajoene from garlic.
Still another
sulfur compound from garlic, alliin, was found to have antiinflammatory properties, evi-
dent by the suppression of activation of various inflammatory compounds.
In chondrocyte-like cells, the activity of protease that degrades the matrix decreased as
a result of an organosulfur compound called diallyldisulfide, present in garlic.
fide from garlic was also reported to inhibit the effect of matrix metalloproteinase and the
tissue inhibitor of metalloproteinase-1 responsible for causing inflammation.
The antiinflammatory effect of allicin from garlic was clearly demonstrated by Shin
et al.
The fresh raw garlic extract was much more effective than heated raw garlic
extract in reducing the effect of inflammation-inducing cytokines and nitric oxide.
An increase in the activity of the antioxidant Heme oxygenase 1 enzyme was also
observed. The production of TNF-αand IL-6 decreased as an effect of garlic on placental
explants while at higher doses of garlic, a reduction in IL-10 was also observed.
The use
of allicin resulted in an enhancement of the expression of chondrocyte cell cycle proteins
D1, CDK4, and CDK 6. As a result, the cell cycle transition from G1 to S phase was
Different onion types and garlic were screened for their free radical scaveng-
ing activity.
The highest free radical reducing capacity was observed for garlic.
Compounds derived from garlic have been used to specifically target the inflammatory
factors involved in arthritis pathways (Figure 14.2). Thiacremonone (2,4-dihydroxy-2,5-
dimethyl-thiophene-3-one), earlier reported from fungal sps. Acremonium, was isolated
247Garlic and Its Role in Arthritis Management
Matrix metalloproteinase
Tissue inhibitor of metalloproteinase-1
Figure 14.2 (AE) Active compounds from garlic regulating the expression of gene coding for factors or
enzymes involved in arthritis and inflammatory pathways.
from garlic at high temperature (130°C) and pressure.
39, 40
Thiacremonone is known to
have various therapeutic effects such as being anticancerous, antiinflammatory, antiarthri-
tis, etc.
The sulfhydryl group of thiacremonone binds with the NF-κB molecule and
suppresses its activation, thereby inhibiting the NF-κB signaling pathway of arthritis.
Rheumatoid arthritis is characterized by the formation of amyloid bodies, resulting in
a person’s early death.
Thiacremonone from garlic has antiamyloidogenesis properties
via NF-κB inhibition.
Chondrocytes with IL-1βactivity that resemble osteoarthritis were treated with
S-allylmercaptocysteine, isolated from A. sativum. As a result, an increase in the viability
of chondrocytes and a reduction in type-II collagen degradation was observed due to
the inhibition of the NF-κB pathway. Also, a change in the ratio of matrix metallopro-
teinase and tissue inhibitors of metalloproteinase was induced.
Similarly, allicin, another
compound from garlic, was found to significantly reduce the levels of IL-1β-induced
prostaglandins E
, nitric oxide, collagenase-3 (MMP-13), NF-κB, and mitogen-activated
and protein-kinase production, thereby acting as a potential compound to alleviate the
effects of osteoarthritis.
18, 47
Ankylosing spondylitis, a type of arthritis, can be ameliorated by the use of allicin from
garlic by inhibiting the production of IL-6, IL-8, and TNF-αwhile downregulating the
expression of the HLA-B27 gene present in all patients suffering from the disease.
cin is also reported to enhance the transition of a cell cycle from one phase to another.
The enhancement in the expression of chondrocyte cell cycle proteins D1, CDK4, and
CDK 6 was reported by the use of allicin, as a result of which an early transition from G1
to S phase and a decrease in the G1/G0 phase of the cell cycle was observed.
Prostaglandins are the inflammatory compounds that occur during arthritis via the
cyclooxygenase pathway by expression of COX-1 and COX-2 genes. These COX genes
were found to be upregulated by monosodium urate crystals and IL-1β, involved in the
development of joint arthritis. On the other hand, they are downregulated by the admin-
istration of diallyl sulfide from garlic.
Compounds from garlic such as uracil, S-allyl cys-
teine, and caffeine were also reported to inhibit the activity of the NF-κB and COX-2
genes involved in arthritis signaling pathways.
The improvement in the degradation of
IL-1β-induced arthritis in cartilage and chondrocytes by downregulating the expression
of matrix metalloproteinase-1, -3, and -13 with the help of garlic-derived diallylsulfide has
been reported.
The inhibitory effect of various concentrations of diallyldisulfide was
observed on the IL-1β-induced stress and cell death in cultured chondrocytes.
application of diallyldisulfide increased the expression of various antioxidant enzymes
such as glutathione transferase, heme oxygenase, catalase, and peroxidase while reducing
the expression of various inflammation and cell death causing factors such as caspases 3,
IL-1β-induced reactive oxygen species, and the phosphorylation of c-Jun N-terminal
kinase and P58 protein.
249Garlic and Its Role in Arthritis Management
The use of selenium to reduce the effect of rheumatic diseases has been demonstrated
by Peretz and his colleagues.
The antiarthritic activity of garlic oil was enhanced by the
use of boron when administered to mice with formaldehyde-induced arthritis.
A significant reduction in the selenium concentration of plasma and the synovial fluid
of the arthritis patient has been observed.
The presence of selano compounds in garlic
and onion with the help of the EC/HPLC-APCI-MS-MS technique was reviewed by
Arnault and Auger.
Garlic is a proven potential natural remedy for arthritis. The advancement of medical
science and research has made it possible to exploit its various components for the tar-
geted administration of this wonder drug. Making nanoformulations of garlic compounds
will help further the easy use and bioavailability for arthritis patients. Also, preclinical and
clinical studies should be conducted to elucidate garlic’s beneficial and risk effects with
respect to arthritis.
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252 Bioactive Food as Dietary Interventions for Arthritis and Related Inflammatory Diseases
Objective Rheumatoid arthritis (RA) is a chronic disease associated and oxidative stress. The critical role of a dietary antioxidant in increasing the antioxidant defense system is undeniable and makes the assessment of the potential link between dietary antioxidants and diseases informative. Given the limited available data on dietary antioxidants, this study aimed to evaluate the association between DTAC and the risk of RA. Methods This case-control study was carried out on 100 patients with RA and 197 healthy individuals aged 19–69 years. Data on dietary intake were collected using a validated 168- items quantitative food frequency questionnaire. DTAC was calculated based on the ferric reducing ability of plasma (FRAP), the ability of dietary antioxidants to reduce ferric to ferrous ions, presented in mmol per 100 g of foods (mmol/100 g). To find the association between DTAC and risk of RA, binary logistic regression adjusted for potential confounders was used. Results The mean age of the study participants was 49.26 and 40.88 years in the case and control groups, respectively. Participants in the top tertile of DTAC were less likely to have RA in the crude model (OR, 0.34; 95% CI, 0.18 – 0.64; P-trend: 0.001). Such that, when multiple potential confounders were controlled, the association remained significant in the full adjustment model (OR, 0.28; 95% CI, 0.10 – 0.76; P-trend: 0.001). Conclusions The finding indicates a significant inverse association between DTAC and the risk of RA, suggesting that promoting a naturally elevated antioxidant capacity might help prevent the development of RA. Further prospective studies are required to confirm these findings.
Natural medicines have played an important role in Chinese and Ayurvedic medicine against various inflammatory diseases from time immemorial. Scientific research is also focusing on naturally occurring products because of the inefficiency of modern drugs that causes immense adverse effect and toxicity. Extensive studies on these medicinal plants are in need because of their therapeutic effects on inflammatory diseases along with natural abundance, no side effects, and low toxicity. This chapter is an attempt to understand the pharmacokinetic and pharmacodynamic parameters of different natural products that possess potential antiinflammatory activities that could trigger in promoting these products for further clinical studies.
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Background: Garlic-derived S-allylmercaptocysteine (SAMC) has widely been used in many disease therapies. However, the potential effects and mechanism of SAMC on IL-1β-stimulated chondrocytes are unclear. Methods: Chondrocytes were isolated, and 5 ng/mL of IL-1β was added to mimic the in vitro osteoarthritis (OA) model. SAMC (20 and 60 μM) was used for the treatment in OA model. Cell viability was assessed by MTT method. Western blotting, Quantitative RT-PCR, and ELISA were performed to evaluate the mechanisms in SAMC treated OA model. Results: Following 48 h of IL-1β exposure, SAMC exhibited protection effect on IL-1β-injured chondrocyte viability. Type II collagen was elevated with reduced degradation products, as a consequence of altered MMPs/TIMP-1 ratio after SAMC treatment in IL-1β-treated chondrocytes. The protein and mRNA level of TNF-α in cellular supernatant and cells were downregulated in a dose-dependent manner. Besides, IκBα in cytoplasmic fraction was increased, while p65 level in nuclear fraction was decreased after SAMC treatment in OA. Conclusions: This study showed that SAMC may play a protective role in IL-1β induced osteoarthritis (OA) model. This effect may be through inhibiting the NF-κB signaling pathway, therefore altering the MMPs/TIMP-1 ratio change which induced type II collagen destruction and decreasing inflammatory cytokine secretion such as TNF-α.
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Dengue virus (DENV) is a mosquito-borne flavivirus that causes significant global human disease and mortality. One approach to develop treatments for DENV infection and the prevention of severe disease is through investigation of natural medicines. Inflammation plays both beneficial and harmful roles during DENV infection. Studies have proposed that the oxidative stress response may be one mechanism responsible for triggering inflammation during DENV infection. Thus, blocking the oxidative stress response could reduce inflammation and the development of severe disease. Garlic has been shown to both reduce inflammation and affect the oxidative stress response. Here, we show that the garlic active compounds diallyl disulfide (DADS), diallyl sulfide (DAS) and alliin reduced inflammation during DENV infection and show that this reduction is due to the effects on the oxidative stress response. These results suggest that garlic could be used as an alternative treatment for DENV infection and for the prevention of severe disease development.
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Objective: In this study, the anti-inflammatory effects and the molecular mechanism of alliin were analyzed in dextran sulfate sodium (DSS)-induced colitis mice and lipopolysaccharide-stimulated RAW264.7 cell model. Methods: The phenotype of mice was recorded in the DSS-induced and/or alliin (500 mg/kg) groups. Histopathological alterations were analyzed by H&E staining. MPO and MDA of colon tissues were measured. The mRNA expression levels of inflammatory factors were determined by qRT-PCR, and protein expressions of inflammatory factors or activation of kinases were determined by Western blotting. Results: Oral administration of alliin significantly inhibited the decrease of body weight, improved the DAI and decreased the infiltration of inflammatory cells in colonic tissues. The content of NO, MDA and MPO, the expression of iNOS and inflammatory factors as well as MAPK and the phosphorylation of PPAR? were inhibited in alliin-treated group. Treatment with alliin significantly repressed the expression of inflammatory factors in LPS-stimulated RAW264.7 cells. Further research demonstrated that alliin repressed LPS-induced AP-1/NF-?B/STAT-1 activation by inhibiting the phosphorylations of p38, JNK and ERK1/2-regulated PPAR? activation. Conclusion: Our results show that alliin ameliorates DSS-induced ulcerative colitis and inhibits the inflammatory responses in LPS-stimulated RAW264.7 cells partly through inhibiting ERK1/2-, JNK-/PPAR?-stimulated NF-?B/AP-1/STAT-1 activations and p38-induced STAT-1 activation. This article is protected by copyright. All rights reserved.
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Rheumatoid Arthritis (RA) is a chronic auto-immune disease characterized by painful inflammation of the joints and surrounding tissues, leading to long term disability. Rheumatoid arthritis can begin at any age but has its peak between 35 to 55 years of age. RA shows hereditary linkage. Women and smokers are most often affected. The patient doesn’t feel any symptoms during inactive state of the disease. RA progresses in a symmetrical pattern involving both the sides of the body. Once rheumatoid arthritis is confirmed by diagnosis, treatment should start as early as possible. The treatment for rheumatoid arthritis focuses initially on reducing the joint inflammation and pain with the use of analgesics and anti-inflammatory agents. In the next stage, joint function is restored by administering Disease Modifying Anti-rheumatic Drugs (DMARDs) thus preventing joint deformity. Treatment is generally based on the degree of severity of RA. Patients with mild RA are advised to take rest and are prescribed analgesics and anti-inflammatory medicines, which include fast acting drugs like NSAIDs. Slow acting drugs like (DMARDs) such as methotrexate, sulfasalazine, lelflunomide etc., and Body’s reaction modifiers (BRMs) such as rituximab, anankinra, infliximab etc., are reserved for patients suffering from moderate to severe RA. The patient is advised to undertake regular exercises like walking, stretching, swimming or cycling, which are aimed at reducing body weight. The patient suffering from arthritis can carry out his normal day-to-day activities with the help of proper medication and regular exercise.
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Genus Allium belongs to the family Liliaceae, which contains more than 600 species. Garlic (Allium sativum) and onion (Allium cepa) are two the most popular food ingredients widely used all over the world. During the last few decades, garlic and onion have received tremendous attention for their wide range of therapeutic properties and great health benefits. The variety of garlic and onion species’ considerable differences in manufacturing process cause discrepancies in a spectrum of the ingredients derived. Current garlic preparations available on the market, including garlic powder, garlic oil, raw or cooked garlic and aged garlic extract. Garlic and onion extracts posses many therapeutic properties including antimicrobial, antiviral, antifungal, anti-protozoal, hepatoprotective, cardioprotective, anti-inflammatory, neuroprotective, anti-amnesic, anticarcinogenic, antimutagenic, antiasthmatic, immunomodulatory, hypolipidemic, anti-hypertensive, anti-diabetic and antioxidant. These therapeutic properties are caused by the combination and biological activity of organo-sulphur compounds such as S-allyl-l-cysteine, diallyl disulfide, diallyl trisulfide, ajoene, and allicin. Allicin, which is one of the most researched therapeutic compounds of garlic and onion, is extremely unstable and rapidly degrades with time, even at low temperatures, which causes its prompt degradation during contact with stomach acid during oral consumption. Present review discusses biochemical, pharmacological, therapeutic properties and nutritional value of garlic and onion, their use for prevention disease and maintenance of good health, as well as novel potential nanoparticles drug delivery systems for more effective oral and topical administration of natural organo-sulphur compounds.􀀁
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To examine the possibility of using thiacremonone isolated from high-temperature-high-pressure treated garlic, this study investigated the physiological activities properties. The IC50 values of hydroxyl, superoxide, hydrogen peroxide, and nitric oxide radical scavenging activities of thiacremonone were 92.50, 65.05, 12.60, and 81.53 μg/mL, respectively. On the other hand, the activities of vitamin C were 104.93, 99.43, 42.42, and 122.64 μg/mL, and the activities of butylated hydroxyanisole were 37.22, 68.45, 22.47, and 40.54 μg/mL, respectively. The IC50 value of ACE inhibition activities of thiacremonone and captoprill were 0.265 and 0.036 μg/mL, respectively. The IC50 value of xanthine oxidase inhibition activities of thiacremonone and allopurinol were 39.430 and 9.346 μg/mL, respectively. The IC50 value of tyrosinase inhibition activities of thiacremonone and kojic acid were 101.931 and 65.648 μg/mL, respectively.
The present study demonstrates the effect of allicin on the proliferation and the cell cycle distribution of the chondrocytes. MTT assay and flow cytometry were used for the evaluation of the effect of allicin on cell proliferative and the cell cycle distribution, respectively of the chondrocytes. The reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis were respectively used for the analysis of mRNA and protein expression levels of cyclin D1, CDK4 and CDK6. The results revealed that exposure of the chondrocytes to allicin at a concentration of 40 μM significantly promoted the cell viability. Treatment of the cells with 10, 20, 30, 40, and 50 μg/mL of allicin enhanced the cell viability by 2.5.47 ± 0.86, 5.43 ± 0.66, 10.74 ± 1.48, 35.89 ± 3.78, and 32.21 ± 2.92%, respectively after 36 h compared to control cells. Allicin exposure caused a marked decrease in the percentage of cells in G0/G1 phase with a subsequent increase in the S phase population. Furthermore, allicin treatment enhanced the expression of cyclin D1, CDK4 and CDK6. Therefore, allicin treatment enhances the proliferation of chondrocytes by promoting the transition from G1 to S phase of the cell cycle through increase in the expression of cyclin D1, CDK4 and CDK6 levels.
Objective: The protective effects and mechanisms of DADS on IL-1β-mediated oxidative stress and mitochondrial apoptosis were investigated in C28I2 human chondrocytes. Design: The effect of various concentrations of DADS (1, 5 10, 25, 50 and 100 µM) on C28I2 cell viability was evaluated in different times (2, 4, 8, 16 and 24 h) to obtain the non-cytotoxic concentrations of drug by MTT-assay. The protective effect of non-toxic concentrations of DADS on experimentally induced oxidative stress and apoptosis by IL-1β in C28I2 was evaluated. The effects of DADS on IL-1β-induced intracellular ROS production and lipid peroxidation were detected and the proteins expression of Nrf2, Bax, Bcl-2, caspase-3, total and phosphorylated JNK and P38 MAPKs were analyzed by Western blotting. The mRNA expression of detoxifying phase II and antioxidant enzymes including heme oxygenase-1, NAD(P)H quinine oxidoreductase, glutathione S-transferase-P1, catalase, superoxide dismutase-1 , glutathione peroxidase-1, -3, -4 were evaluated by reverse transcription-polymerase chain reaction. Results: DADS in 1, 5, 10 and 25 µM concentrations had no cytotoxic effect after 24 h. Pretreatment with DADS remarkably increased Nrf2 nuclear translocation as well as the genes expression of detoxifying phase II and antioxidant enzymes and reduced IL-1β-induced elevation of ROS, lipid peroxidation, Bax/Bcl-2 ratio, caspase-3 activation, and JNK and P38 phosphorylation. Conclusion: DADS could considerably reduce IL-1β-induced oxidative stress and consequent mitochondrial apoptosis, as the major mechanisms of chondrocyte cell death in an experimental model of osteoarthritis. It may be considered as natural product in protecting OA-induced cartilage damage in clinical setting. This article is protected by copyright. All rights reserved.
Allicin, a sulphur containing compound isolated from the bulb of Allium sativum, confirm the various pharmacological activity such as antioxidant and antiinflammatory effects. The current study was intended to evaluate the effect of allicin on the IL-1β-Induced inflammatory cytokines in Human Osteoarthritis Chondrocytes. The chondrocytes were stimulated with IL-1β in the presence or absence of allicin. Moreover, the western blot analyses was used for the estimation of the nuclear factor-κB (NF-κB), c-Jun N-terminal kinase (JNK), cyclooxygenase-2 (COX-2), inhibitory kappa B (IκBα), extracellular signal-regulated kinase (ERK), iNOS and p38 expression. The level of PGE2 and NO production in the IL-1β treatment were determined via using the ELISA and Griess reagent. In the current study, allicin was found to be significantly inhibited the IL-1β induced iNOS and COX-2 expression in dose dependent manner. On the other hand, allicin in dose-dependent manner causes significant (P < 0.01) reduction of the IL-1β-induced PGE2, NO and collagenase-3 (MMP-13) production. Allicin also showed significant reduction of the IL-1β-induced mitogen-activated protein kinase (MAPK) and NF-κB activation. In conclusion, allicin showed efficient attenuation of the osteoarthritis chondrocytes inflammatory response triggered by IL-1β. The result of the current study confirmed that allicin may be beneficial agent in the management or control of osteoarthritis.