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TABLE 2.1 Therapeutic Applications of Bioactive in Arthritis
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Sl. Phytoconstituents Sources MOA and Significance Challenges References
No.
1. Thymoquinone (TQ) TQ is obtained from the It exerts antiarthritic action against It is safe and may cause Ahmed et
black Caraway seed (Nigella carrageenan-induced paw edema in allergic rashes al., 2013
sativa Ranunculaceae rats by inhibiting the inflammatory
family) mediators
2. Resveratrol It is obtained from grapes It mediated antiarthritic Poor oral bioavailability Baur and
and red wine action by targeting NF-Кb Sinclair,
and simultaneously decreases 2006
AGEs-stimulated expression
and prevented AGEs mediated
destruction of CIA
3. Hesperidin It is obtained from the fruit It suppresses the T lymphocyte Limited bioavailability Umar et al.,
of Citrus aurantium proliferation and IL-2 production in 2013
AA rats too.
4. Tumeric/Curcumin Curcumin It acts by inhibition of COX, Higher dose and long- Zheng et al.,
(Curcuma longa) 5-LOX, and glutathione S term administration cause 2015
Transferase nausea and diarrhea
5. Epigallocatechin-3- Camellia It acts by blocking the activity of – Ahmed,
gallate (EGCG) NF-ҡB. 2010; Datta
et al., 2012
6. Celastrol
And inhibits nitric oxide synthase
(iNOS)
Tripterygium wilfordii (lei Celastrol has beneficial antiarthritic Diarrhea, headache, Salminen
gong teng; Thunder of God effects by suppression of nausea, and infertility, et al., 2010;
Vine), which belongs to the proinflammatory cytokines such as especially at a high dose. Astry et al.,
Celastraceae family IL-17A, NF-jB mediated MMP-9 2015
expression and lipopolysaccharides
34
Biomarkers as Targeted Herbal Drug Discovery
Sl. Phytoconstituents Sources MOA and Significance Challenges References
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No.
7. Sinomenine
8. Lignans
9.
M. pentaphylla
10. Polysaccharide
11.
Boswellia Serrate The resin of Boswellia Acts via 5-LOX inhibition Stomach pain, nausea, Anthoni et
(Indian frankincense) species diarrhea, and allergic al., 2003
Salai/Salai guggul rashes reported
— Not founds.
Sinomenium acutum
Seeds of Vitex negundo
Dried whole plant used — Lee et al.,
suppressed the NO, PGE2,
MMP-2, MMP-9, and
COX-2
Anoectochilus roxburghii
Sinomenine suppressing MMP-2, Not founds Tong et al.,
MMP-9, and IL-6 2015
Reduction of the expression of — Rui et al.,
COX-2, iNOS, and p-IκB and the 2019
notable increase of IκB in synovial
tissues
2019
Antioxidant activity and inhibit NO — Guo et al.,
production significantly inhibited 2019
the activation of nuclear factor КB
35 Herbal Anti-Arthritic Drug Discovery Tool
36
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Biomarkers as Targeted Herbal Drug Discovery
In the experiments on animals, strongly suggest the anti-inammatory
role of an antioxidant such as superoxide dismutase (SOD) and vitamin E in
experimentally induced arthritis. Vitamin E seems to withdraw joint destruc-
tion and joint inammation in the transgenic KRN/NOD mouse model of
RA, on joint destruction. An antioxidant combination or dose of vitamin E
adding high therapeutic value to the treatment for the rheumatoid disease,
which can better control the symptoms of arthritis from the rst month, and
by the second month it controls the rheumatoid disease (Sukkar and Rossi,
2004). Cerhan et al. recommended that intake of certain antioxidants, micro-
nutrients, including of β-cryptoxanthin and supplement zinc and possibly
diet rich in fruits and cruciferous vegetables, which has dominant effect in
protective role against the development of RA (Cerhan et al., 2003).
Many herbs are still unknown to us and their potential for the treatment of
arthritis. But the scientific research has uncovered some of them which have
synergistically work to reduce chronic joint inflammation in osteoarthritis,
RA, and other types of arthritis (Patwardhan et al., 2010).
In animal studies, Ashwagandha was found more potent than the phenylbutazone in controlling inflammation. The studies show that animal groups treated
with Ashwagandha decrease inflammation proteins, whereas animals treated
with phenylbutazone, as well as the control group, had increased inflammatory
proteins (Begum et al., 1988). When Ashwagandha extract is compared with
hydrocortisone to decrease inflammation, Ashwagandha is far potent. One of
the studies shows Ashwagandha had a remarkable effect in decreasing swelling
of an arthritic paw, which may have due to COX-2 inhibition (Begum et al.,
1988). In another study, 46 patients with RA were given Ashwagandha root
powder, in a dose of 4, 6, or 9 grams for 3–4 weeks, which remarkably relieved
the pain and swelling in 14 patients, and showed considerable improvement in
10 patients and mild improvement in 11 patients. In one double-blind, placebocontrolled study, the combination of Ashwagandha with zinc and turmeric
showed positive effects in osteoarthritis patients with significant improvement
in pain severity and disability score (Sharma et al., 2001).
37 Herbal Anti-Arthritic Drug Discovery Tool
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Withania root extract in 1000 mg/kg given orally daily for 15 days to Freund’s
AIA in rats which shows a significant reduction in both paw swelling and
bony degenerative changes as observed by radiologic examination (Begum
et al., 1988).
The bark of Boswellia (family Burseraceae) having sweet, cooling, and tonic
effect and contain boswellic acid resin as the main chemical constituent and
it’s β-form has anti-inflammatory and anti-arthritic activities. Commonly
Boswellia is useful in fever, cough, asthma, urethrorrhea, diaphoresis,
convulsion, chronic laryngitis, and jaundice and is analgesic, antihyperlipidemic, and anti-atherosclerotic (James et al., 1991). In both adults and children with RA experienced effective relief from the symptoms when treated
with Boswellia, despite having responded poorly in the past to standard
therapies such as (NSAIDs) (Kimmatkar et al., 2003). In an animal study,
Boswellic acid show significantly reduced in the infiltration of leukocytes in
the knee joint and in turn, significantly reduced inflammation (Kimmatkar
et al., 2003). A clinical study was conducted to assess the efficacy, safety,
and tolerability of Boswellia serrata (BS). BS extract was given to the 30
patients of arthritis, 15 each receiving active drug or placebo for 8 weeks
founds decrease in knee pain, increase knee flexion, and a decrease in the
frequency of swelling in the knee joint (Anthoni et al., 2003).
Aujaie is one of the herbal products prepared by Hamdard Laboratories
(Waqf) Pakistan, is believed to have the potential for providing relief from
joint pain in (arthritis with or without swelling of joints), gout, lumbago,
sciatica, and stiffening of joints and it helps in the excretion of uric acid.
Aujaie is prepared from nine different plants; most of these plants have
been used in traditional medicines for treating rheumatism and gout-such
as Balsamodendron mukul, which is very potent in various type of joint
problems such as RA, osteoarthritis, gout, inammatory joints, swelling,
and tenderness in inammatory joints (Akhtar et al., 2003). In order to
understand the anti-inammatory mechanism and antinociceptive activity
of the Aujaie. The animal experimental studies in carrageenan induce
mice has been carried and founds signicant anti-inammatory results
with the dose-dependent manner via inhibition of kinins, cyclooxygenase,
38
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Biomarkers as Targeted Herbal Drug Discovery
histamine, and prostaglandins (Akhtar et al., 2003). Further, the antinociceptive activity of Aujaie was evaluated using of the writhing test in
mice. Algesia produces by the administration of acetic acid which liberates
endogenous substance leads to excite the pain nerve endings. Whereas the
Aujaie exerted a signicant inhibitory activity on the writhing response
with a dose range of 60–240 mg/kg of BW. Therefore, the studies reported
that Aujaie a signicant anti-inammatory action and up to the dose of 300
mg/kg/p.o. in mice and 6000 mg/kg/p.o. in rats, did not report any toxic
effects (Akhtar et al., 2003).
Treatments for RA have several demerits that hinder their efficacy. Based
on inflammatory biomarkers, herbal pharmacotherapy has wide structural
diversity and great potential against RA treatment, which is not commonly
seen with synthetic treatments. Administration of phyto molecules such as
polyphenols, thymoquinone, resveratrol, hesperidin, curcumin, celastrol,
and GA, in a dose-dependent manner, gives high efficacy against RA. The
benefits are attributed to their targeting action against cytokines, chemokines,
adhesion molecules, NF-kβ, NO, etc.
• adjuvant-induced arthritis
• arachidonic acid
• bone marrow-derived dendritic cells
• chemokine receptor 4
• collagen-induced arthritis
• disease-modifying anti-rheumatic drugs
Ahmed, A., Husain, A., Mujeeb, M., et al., (2013). A review on therapeutic potential of
Nigella sativa: A miracle herb. Asian Pac. J. Trop. Biomed., 3, 337–352.
Ahmed, S., (2010). Green tea polyphenol Epigallocatechin 3-gallate in arthritis: Progress and
promise. Arthritis Res. Ther., 12, 208.
39 Herbal Anti-Arthritic Drug Discovery Tool
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Akhtar, M. S., Malik, A., Saleem, M. S., & Murtaza, G., (2013). Comparative analgesic and
anti-inflammatory activities of two polyherbal tablet formulations (Aujaie and Surangeen)
in rats. Tropical Journal of Pharmaceutical Research, 12(4), 603–607.
Anderson, K. O., Bradley, L. A., Young, L. D., et al., (1985). Rheumatoid arthritis: Review
of psychological factors related to etiology, effects, and treatment. Psychol. Bull., 98,
358–387.
Anthoni, C., Laukoetter, M. G., & Rijcken, E., (2003). Mechanisms underlying the anti-
inflammatory actions of boswellic acid derivatives in experimental colitis. Indian J. Exp.
Biol., 41(12), 1460–1462.
Araki, Y., Tsuzuki, W. T., Aizaki, Y., et al., (2016). Histone methylation and STAT3
differentially regulate IL-6-induced MMP gene activation in rheumatoid arthritis synovial
fibroblasts. Arthritis Rheumatol., 68, 1111–1123.
Astry, B., Venkatesha, S. H., Laurence, A., et al., (2015). Celastrol, a Chinese herbal
compound, controls autoimmune inflammation by altering the balance of pathogenic and
regulatory T-cells in the target organ. Clin. Immunol., 157, 228–238.
Baur, J. A., & Sinclair, D. A., (2006). Therapeutic potential of resveratrol: The in vivo
evidence. Nat. Rev. Drug Discov., 5, 493–506.
Begum, V. H., & Sadique, J., (1988). Long term effect of herbal drug Withaniasomnifera on
adjuvant induced arthritis in rats. Indian J. Exp. Biol.,26(11), 877–882.
Cannon, G. W., Holden, W. L., Juhaeri, J., Dai, W., et al., (2004). Adverse events with disease
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Antioxidant micronutrients and risk of rheumatoid arthritis in a cohort of older women.
Am. J. Epidemiol., 157(4), 345–354.
Chang, X., He, H., Zhu, L., et al., (2015). Protective effect of apigenin on Freund’s complete
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Datta, P., Sarkar, A., Biswas, A. K., et al., (2012). Antiarthritic activity of aqueous extract
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Guo, Y., Ye, Q., Yang, S., et al., (2019). Therapeutic effects of polysaccharides from
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Ismail, H. M., Yamamoto, K., Vincent, T. L., Nagase, H., et al., (2015). Interleukin-1 acts
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CHAPTER 3
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Curcumin Nanomedicine and
Their Application in the
Management of Disease
SADAF JAMAL GILANI,1 SYED SARIM IMAM,2 MOHAMMED JAFAR,
2
SULTAN ALSHEHRI,
MOHAMMED ASADULLAH JAHANGIR
1
MOHAMAD TALEUZZAMAN,4 and
5
3
University, Riyadh 11671, Saudi Arabia
2
3
Dammam, Saudi Arabia
4
India
5
ABSTRACT
Curcumin is a naturally occurring bioactive compound obtained from the
rhizomes of Curcuma longa Linn. The therapeutic application of curcumin
has shown a wide range of biological actions in various diseases. It has shown
excellent therapeutic benefits in various diseases (cancer, inflammation,
cardiac disease, skin disease, Alzheimer’s disease (AD), etc.). Despite having
great therapeutic application their clinical use is limited due to low solubility,
physicochemical instability, poor bioavailability, rapid metabolism, and poor
pharmacokinetics (PKs). These problems can be overcome by delivering
an efficient nanodelivery system. The curcumin’s PKs, systemic bioavailability, and biological activity have been established by loading curcumin
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