Review Article

Review of Ameliorative Potentials of Plant-Derived Phytochemicals against Arthritics

Manoj GS¹, Bosco Lawarence² Sreelekshmi SG³ and Murugan K³*

¹Department of Botany, NSS College, India

²Department of Botany, Govt. Arts College, India

¹Department of Botany, University College, India

Submission: May 05, 2017; Published: June 02, 2017

*Corresponding author: Murugan K, Plant Biochemistry and Molecular Biology Laboratory, Department of Botany, University College, Thiruvananthapuram, Kerala, 695 034, India, Email:harimurukan2gmail.com; 1000229@uba.cat

How to cite this article:Kazuo Y, Noritaka K, Naoko Y, Rie K. Cartilage Tissue Engineering-A Novel Biomaterial for Cartilage Repair Generated by Self-Assembly: Creation of a Self-Organized Articular Cartilage-like Tissue. Nov Tech Arthritis Bone Res. 2017; 1(2) : 555557.

Abstract

Traditional herbals are practiced from time immemorial for the treatment of arthritis especially in developing countries. Plants inhabiting across the countries especially India, China, Korea and Nigeria were traditionally used by different tribes/ethnic groups for ameliorating arthritis. Herbals/their parts/crude extracts/polyherbal combinations against arthritis have been accounted reviewed in the study. Plants such as Matricaria chamomilla , Cichorium intybus , Rhododendron campanulatum, Plumbago rosea, Salvadora oleoides, Acacia polyanthawere being used traditionally to ameliorate painful inflammatory conditions but not fully explored experimentally in the treatment of arthritis. 124 plant species are documented in the present study as tribal knowledge against arthritis. Similarly, polyphenols are the major phytochemical reported in most of the species. Even though, plant extracts or individual phytochemicals derived from herbals exhibit remarkable potential but the underlying biochemical or molecular mechanism has not been properly elucidated. There is an urgent need to screen the active molecule of these herbals as potential agents and monitor the biosafety of these novel constituents.

Keywords:Herbals; Phytochemicals; Arthritis; Tribal knowledge; Polyphenols

Introduction

Arthritis is the inflammation in the joints which leads problem in moving around. It can lead to stiffness, pain, swelling and redness in the joints. There are diverse types of arthritis such as osteoarthritis, rheumatoid arthritis, infectious arthritis, gout and psoriatic arthritis. Generally, it is considered as a part of aging posed disease however it occur to others also. The major reasons for the incidence of this disease were injury, autoimmune i.e., immune system starts attacking its own cells and tissues, external infection and excess uric acid accumulation.

Herbals are employed for the treatment of many ailments from historical periods and herbal drugs use is as old as mankind. Herbal drugs are synthesized from ancient system of medicine by the traditional practitioners. Nowadays, pharmacologists show much interest in those novel drugs derived from herbals because of their safety and less expensive. Nature has empowered with wealth of herbals and is widely distributed all over the world as source of therapeutic drugs for the prevention and cure of many diseases. According to WHO, world’s 80% population use plant based drugs for their primary health needs. The medicinally important parts of these herbals are phytochemical constituents that produce a desired physiological reaction on the body and there by curative action.

Results and Discussion

141 plant species are identified by local interview and questionnaire analysis used by the Kani tribals from Kerala used for curing arthritis. They are listed in the Table 1 in terms of binomial, family and parts used.

Major Phytochemicals

Flavonoids

The mode of action of the flavonoids with antiarthritic activity is narrated below:

1. 6-shogaol is identified from the ginger rhizome.
2. 6-Shogaol treatment reduced the concentration of soluble vascular cell adhesion molecule-1 (VCAM-1) in the blood, as well as the infiltration of leukocytes, lymphocytes, and monocytes/macrophages into the synovial cavity of the knee joint [1].
3. 6-Shogaol also protected morphological integrity of the cartilage lining the femur in CFA-induced monoarthritis of the knee joint of rats.
4. Naringin, a citrus flavanone, reduced arthritis as assessed clinically and histologically and afforded protection against interchondral joints damage in rats with CIA [2].
5. A similar effect was observed with another citrus flavonoid, hesperidin, against CIA [3].
6. Total flavonoid of orange (TFO) decreased paw thickness and improved pathological condition of ankle joint in rats with AA. TFO also suppressed elevated TNF-, IL-1, and PGE2 levels in serum and COX-2 expression in the synovial tissue [4].
7. Genistein is an isoflavone, which suppressed the levels of IFN-, increased the production of IL-4, and normalized the Th1/Th2 balance in CIA. Genistein also inhibited the proliferation of FLS in rats with CIA by inhibiting phosphorylation of ERK and down regulating tyrosine kinase of MAPK signal transduction pathway [5,6].

Triterpenes

Triterpenes possessing antiarthritic properties were Lupeol, a pentacyclic triterpene isolated from the latex of Calotropis gigantea, showed potent antiarthritic activity as evaluated in the rat AA model. Lupeol ameliorated the paw swelling and reduced the levels of proinflammatory cytokines such as TNF-, IL-1, and IL-6 [7]. Celastrol, a triterpene extracted from Celastrus, is a potent antiarthritic biomolecule. Both Celastrus extract and its bioactive component Celastrol suppressed the expression of proinflammatory cytokines (IL-17, IL-6, and IFN-), the transcription factor STAT3 for IL-6/IL-17, and the activity of matrix-degrading enzyme MMP-9. In addition, it inhibited the phosphorylation of ERK. Celastrol also has a bone damage-protective effect. Celastrol inhibits osteoclastic activity via reducing RANKL production and suppressing the elevated RANKL/OPG ratio in rats with AA [8]. Tripterygium wilfordii Hoog-derived trypterine reduced the paw swelling and bone destruction in AA. It also suppressed the expression of IL-1 and TNF- in arthritic rats. Boswellic acid is a pentacyclic triterpene isolated from boswellia plants. It reduced leukocyte infiltration into the knee joint and the pleural cavity as observed in bovineserum- albumin- (BSA-) induced arthritis in rabbits. 3-Acetyl- 11-keto-beta-boswellic acid (AKBA), which is well known for anti-inflammatory activity, also has antiarthritic activity. Topical application of the polymeric nanomicelles of AKBA showed potent anti-inflammatory and antiarthritic activities [9].

Phenols

Several polyphenols have been studied extensively for their beneficial effect against arthritis and the mechanisms involved in that process; for example, green tea prepared from the dried leaves of Camellia sinensis is a commonly consumed beverage in many parts of the world. The polyphenolic compounds from green tea (PGT) possess anti-inflammatory and antiarthritic properties. PGT-induced reduction in clinical and histological features of arthritis was associated with a decrease in proinflammatory cytokine IL-17 and increase in anti-inflammatory cytokine IL-10. In another study using the CIA model of arthritis, PGT treatment reduced the expression of COX-2, IFN-, and TNF-. Epigallocatechin-3-gallate (EGCG) is one of the most well-studied purified plant components against different diseases. EGCG inhibits IL-1-induced inducible nitric oxide synthase (iNOS), nitric oxide (NO), and JNK activity, all of which mediate cartilage degradation. It also suppresses IL-1-induced glycosaminoglycan release from cartilage via inhibiting ADAMTS (A disintegrin and metalloproteinase with thrombospondin motifs), MMP-1, and MMP-13 in chondrocytes. EGCG reduces osteoclast formation by inhibiting osteoblast differentiation without affecting their viability and proliferation. Osteoclast-specific NFATc1 and bone resorption associated with RA are also suppressed. EGCG also inhibits RANKL-induced activation of JNK and NFB pathways, thereby suppressing the expression of c-Fos and NFATc1 in osteoclast precursors. In another study, combination therapy of methotrexate and EGCG inhibited arthritis progression as evidenced by histopathology and radiographical examination. Furthermore, this combination suppressed the expression of TNF- and IL-6 in the joints of rats with AA. Grape seed proanthocyanidin extract (GSPE), an antioxidant derived from grape seeds, showed antiarthritic effect as evident from suppression of clinical signs of arthritis and IL-17 response along with increased Foxp3-expressing CD4+ regulatory T cells. Oligomeric procyanidins (HOPC) isolated from Jatoba, a South American herb, ameliorated arthritic inflammation and joint pathology in mice with CIA.

Resveratrol, a polyphenolic compound derived from grapes, suppressed swelling and bone erosion in the paws of mice with CIA. This effect was associated with reduced serum levels of proinflammatory cytokines including IL-17 and reduced numbers of Th17 cells. The antiarthritic effect of resveratrol also involves suppression of IL-1, ROS, PGE2, and MMPs, and enhancement of proteoglycan synthesis and chondrocyte proliferation in vitro. Curcumin, a principle component of turmeric, possesses antiinflammatory and antiarthritic activity. Curcumin treatment down regulated clinical arthritis score, proliferation of splenic T cells, expression of TNF- and IL-1 in the ankle joint, and serum IgG2a levels. In addition, curcumin ameliorated the NF-B transcriptional activity in FLS and inhibited the production of PGE, COX-2 and MMP. A randomized, pilot study conducted to assess the efficacy and safety of curcumin in RA patients revealed an improvement in overall disease activity score (DAS) and American College of Rheumatology (ACR) scores, and the treatment was safe without any significant adverse events. Capsaicin treatment suppressed bone erosion and trabecular damage in osteoarthritis in rats. Ferulic acid isolated from corn germ promotes bone remodeling and prevents bone loss in ovariectomized rats. Oleuropein aglycone, an olive oil-derived compound, improved clinical and histological features of arthritis in the joints of mice with CIA. Quercetin isolated from onion has a bone damage-protective attribute. It inhibited RANKLinduced osteoclast differentiation and RANKL-stimulated osteoclast-related genes in rats with ovariectomy-induced bone loss Silibinin, a major active constituent of silymarin, inhibits osteoclast formation by attenuating the downstream signaling cascades associated with RANKL and TNF-, such as osteoclast-associated receptor (OSCAR), NFATc1, Cat K, and MMP-9. Rosmarinic acid is an active component of Plectranthus amboinicus. It inhibited RANKL-induced formation of TRAPpositive multinucleated cells and suppressed NF-B activation and NFATc1 nuclear translocation in the CIA model [10-13]. Aleomannan and acemannan found in the species of Aloevera showed anti-tumor, immune-suppressive and anti-inflammatory properties. The anti-inflammatory property enabled it to inhibit the activity of COX-2 (cyclooxygenase) enzyme which is involved in the inflammatory pathways. Similarly, Tag et al. [14], analyzed potential anti-inflammatory effect of lemon and hot pepper extracts on adjuvant-induced arthritis in mice. Shivaprasad et al. [15] reported about control of autoimmune arthritis by herbal extracts and their bioactive components. Choudhary et al. [16], reviewed medicinal plants with potential anti-arthritic activity.

Conclusion

It is increasingly been realized that inflammation and bone damage are generally linked in arthritis and various other disorders. A better understanding of the shared processes would help define the molecules and pathways that can serve as targets for effective antiarthritic therapy. In parallel, it is essential to search for newer therapeutic agents that are both effective but safe. In this regard, herbal products may offer promising alternatives or adjuncts to conventional antiarthritic agents. In this paper, we have elaborated upon both these important aspects of immune pathology and herbal therapy of arthritis.

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