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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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CHAPTER 14
Garlic and Its Role in Arthritis
Management
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
1. INTRODUCTION
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.
1
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.
4
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.
511
Aged garlic is reported to have immunomodulatory func-
tions in mice bearing Sarcome-180.
12
The role of an important organosulfur compound
in garlic called allicin in treatments for cancer, microbial infections, arthritis, and
245
Bioactive Food as Dietary Interventions for Arthritis and Related Inflammatory Diseases ©2019 Elsevier Inc.
https://doi.org/10.1016/B978-0-12-813820-5.00014-3 All rights reserved.
cardiovascular diseases has been reviewed by Rahman.
13
The various methods of using
and extracting ajoene from garlic for different diseases were patented by Tatarintsev and
coworkers (US5856363A).
14
In further sections, we will discuss the role of garlic and its compounds as a miraculous
drug with special reference to arthritis.
2. GARLICA NATURAL REMEDY FOR 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.
15
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
acids
16
(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.
17
Garlic moxibustion was reported as an effective
treatment in curing patients of gonococcal arthritis.
18
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.
19
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.
20
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.
21
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.
22
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.
23
Similarly, garlic intake in the form of juice and salad
is suggested in the management of bone diseases and arthritis types.
24
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.
25
The overall
health benefits of garlic are also presented in recent reviews.
26, 27
3. ANTIINFLAMMATORY EFFECTS OF DIETARY GARLIC
The antiinflammatory and immunomodulatory effects of garlic were well reviewed by
Arreola et al.
28
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
2
, 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.
31
Still another
sulfur compound from garlic, alliin, was found to have antiinflammatory properties, evi-
dent by the suppression of activation of various inflammatory compounds.
32
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.
33
Diallylsul-
fide from garlic was also reported to inhibit the effect of matrix metalloproteinase and the
tissue inhibitor of metalloproteinase-1 responsible for causing inflammation.
34
The antiinflammatory effect of allicin from garlic was clearly demonstrated by Shin
et al.
35
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.
36
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
observed.
37
Different onion types and garlic were screened for their free radical scaveng-
ing activity.
38
The highest free radical reducing capacity was observed for garlic.
4. INHIBITORY ROLE OF GARLIC-DERIVED COMPOUNDS IN ARTHRITIS
SIGNALING PATHWAYS
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
(A)
(B)
(C)
(D)
(
E
)
34
2
5
OH
O
S
HO
Thiacremonone
Amyloidogenesis
NF-κB
S-Allylmercaptocysteine
Matrix metalloproteinase
Tissue inhibitor of metalloproteinase-1
NF-κBSS
O
NH
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.
4143
The sulfhydryl group of thiacremonone binds with the NF-κB molecule and
suppresses its activation, thereby inhibiting the NF-κB signaling pathway of arthritis.
42
Rheumatoid arthritis is characterized by the formation of amyloid bodies, resulting in
a person’s early death.
44
Thiacremonone from garlic has antiamyloidogenesis properties
via NF-κB inhibition.
45
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.
46
Similarly, allicin, another
compound from garlic, was found to significantly reduce the levels of IL-1β-induced
prostaglandins E
2
, 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.
48
Alli-
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.
37
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.
31
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.
41
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.
49
The inhibitory effect of various concentrations of diallyldisulfide was
observed on the IL-1β-induced stress and cell death in cultured chondrocytes.
50
The
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.
50
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.
51
The antiarthritic activity of garlic oil was enhanced by the
use of boron when administered to mice with formaldehyde-induced arthritis.
52
A significant reduction in the selenium concentration of plasma and the synovial fluid
of the arthritis patient has been observed.
53
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.
54
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
Article
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