CURRENT STRATEGIES IN HERBAL DRUG DELIVERY FOR ARTHRITIS: AN OVERVIEW
HTML Full TextCURRENT STRATEGIES IN HERBAL DRUG DELIVERY FOR ARTHRITIS: AN OVERVIEW
Sunita Y. Ranade* and Ram S. Gaud
Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM’s Narsee Monjee Institute of Management Studies, Vile Parle (West), Mumbai – 400 056, Maharashtra, India
ABSTRACT: Arthritis is still a challenge for medical research. Pharmaceutical research has resulted in several new approaches for treatment/management of arthritis including drugs like the biologic disease modifying anti-rheumatic drugs (DMARDs). Several disadvantages like serious side effects, high costs and requirement of parenteral administration still invite more research in this area to provide a convenient, affordable therapy with lesser or no side effects. Traditionally used herbal medicines, due to their anti-inflammatory and immunomodulatory properties, have potential to be a therapy of choice for arthritis patients and are now extensively being studied. Although a number of these medicines are being used traditionally for their therapeutic activity, development of their novel drug delivery systems was not attractive to the scientists due to insufficient knowledge about their exact mechanism of action and difficulties in processing, standardising, extracting and identification of active constituents. Current research demonstrates that the effectiveness and bioavailability of herbal actives can be improved by understanding of exact mechanism of action and by formulating them into novel technologies like liposomes, phytosomes and transdermal drug delivery. The present review focuses on herbal medicines for arthritis along with various strategies adopted by scientists so as to improve the bioavailability, stability and to reduce the side effects of these medicines so as to provide consistently effective alternative medication for arthritis. The strategies include understanding mechanisms of their action, enhancing solubilities of poorly soluble actives and developing novel drug delivery systems of these herbal medicines.
Keywords: |
Arthritis, Herbal, Therapy, Novel drug delivery
INTRODUCTION:Arthritis is the condition in which inflammation of a joint occurs, usually accompanied by pain, swelling, and stiffness. It may be caused by infection, trauma, degenerative changes, metabolic disturbances, or other causes.
Osteoarthritis (OA), rheumatoid arthritis (RA) or bacterial arthritis is usually the forms in which arthritis exists 1. Arthritis is a health problem prevailing throughout the globe and the rate at which the number of people suffering from this condition worldwide is alarming.
OA is reported to affect approximately 13.9% of adults who are ≥25 years of age in the USA. Frequency of OA is reported to be higher in women, particularly after reaching 50 years of age. Women are reported to have greater risk for developing OA in the knee or hip 2.
RA is estimated to affect 1.5 million adults in USA. RA sufferers are typically younger than those who develop OA, with the incidence at its peak at 35 to 50 years of age. Women are reported to have higher incidence of RA 3. It is estimated that the number of people with arthritis in the USA is expected to rise to 67 million by 2030 4, 5. In India, the prevalence of OA among elderly is nearly about 56.6% 6. Prevalence of OA was reported to be in the range of 17% to 60.6% in India as shown by community survey data in rural and urban areas. RA has a prevalence of 0.75%, this would give a total of about seven million patients in India if projected to the whole population.
The prevalence of RA in India is higher than that reported from China, Indonesia, and Philippines 6. Arthritis and related conditions have been found to be third largest contributors, behind cardiovascular disease and neurological disorders, to the direct expenditure on health in the western world and USA. 7.
The pathophysiology of OA and RA is distinct although the primary manifestations of both involve the joints. OA is characterized by progressive cartilage loss. Increased thickness of the subchondral plate, osteophytes and subchondral bone cysts are the characteristic features. Vascular invasion and further calcification of nearby articular cartilage may occur as the disease progresses, leading to decreased thickness of articular cartilage. Bone remodeling and enhanced cartilage deterioration takes place over time 8. The inflammation is generally milder in severity than that observed in rheumatoid arthritis and typically involves the periarticular tissues.
Rheumatoid arthritis is a chronic, autoimmune syndrome. Autoimmune inflammation is a result of a response to self-antigens. Thus, a dysregulated immune system results in autoimmune diseases 9. Synovial inflammation leading to cartilage and bone damage is characteristic of the disease. Persistent inflammation leads to progressive destruction of articular and periarticular structures which in turn, lead to deformity. Morning stiffness is a common problem for patients with rheumatoid arthritis 10, 11, 12. Characteristic features of RA pathophysiology are increased angiogenesis, cellular hyperplasia, influx of inflammatory cells, changes in the expression of cell surface adhesion molecules and presence of many cytokines. Tumour necrosis factor (TNF) and interleukin-1 are in abundance in the joints. They are the stimulators of proliferation, metalloproteinase expression, adhesion molecule expression, and further secretion of other cytokines 13. CD4 T cells, mononuclear phagocytes, fibroblasts, osteoclasts, and neutrophils play major role in pathophysiology of rheumatoid arthritis. Presence of anti-cyclic citrullinated protein antibody (ACPA) and rheumatoid factor (RF) is highly specific for RA.
Autoantibodies (i.e. RFs) are produced by B cells. Abnormal production of numerous cytokines, chemokines and other inflammatory mediators is involved 12. Formation of rheumatoid nodules is one of the most common extra-articular manifestations of RA. The outer zone of rheumatoid nodules is granulation tissue, palisading macrophages form the mid-zone, and a central zone is of necrotic material. Several pulmonary, ocular and neurologic manifestations are also observed 14.
Diverse options are available for treatment of arthritis in terms of their mechanisms of action and the mode of drug delivery; however, no single agent has been established to consistently offer a high level of tolerability and low incidence of adverse effects combined with a sustained level of efficacy in a broad patient population 15.
Management of osteoarthritis involves use of NSAIDS to control pain. Intra-articular corticosteroid injections, intra-articular injections of hyaluronic acid–like products, surgery for patients whose symptoms are not adequately controlled with medical therapy are other forms of therapy for osteoarthritis 16. Management of rheumatoid arthritis aims to control the pain and swelling, delay the progression of disease and improve the quality of life. The current therapies for rheumatoid arthritis are as follows 17, 18:
- Non-steroidal anti-inflammatory drugs (NSAIDs)
- Glucocorticoids
- Non-biologic disease-modifying anti-rheumatic drugs (DMARDs) and
- Biologic DMARDs
There is increasing evidence that many current drug therapies attempt to suppress symptoms than addressing the underlying disease processes 19.
Non-steroidal anti-inflammatory Drugs (NSAIDs), the drugs with analgesic, antipyretic and anti-inflammatory effects due to their inhibitory action on cyclooxygenase (COX), can very effectively relieve pain and stiffness at RA onset. They are usually employed as bridge therapy until the slow-acting DMARDs become effective. However, long-term administration of NSAIDs may result in persistent adverse events, gastrointestinal (GI) complications, such as gastric ulceration, bleeding, dyspepsia and nausea being most significant. They also have the potential to be nephrotoxic which may result in nephrotic syndrome and interstitial nephritis. Cardiovascular adverse events like myocardial infarction and cardiac arrest have been observed with NSAIDs which are selective COX-2 inhibitors 20, 21.
Glucocorticoids (GCs), belonging to class of steroid hormones, have potent anti-inflammatory and immunosuppressive properties. Recent studies have established potential of with low-dosage long-term treatment with glucocorticoids in reducing the rate of erosion progression in RA 22. Adverse effects of glucocorticoids occur in different organs and may be life threatening. The major complication of long-term GC therapy is gluococorticoid-induced osteoporosis. Side effects also include adrenal insufficiency, peptic ulcers, skin atrophy, infection and cataract 17.
Therapy with DMARDs is considered for all patients with rheumatoid arthritis. New, targeted biological therapies against proinflammatory cytokines have emerged as a result of increasing knowledge regarding the immunologic basis of RA and advances in biotechnology 23.
Newer drugs are designed with strict reference to pathophysiology of rheumatoid arthritis 24. Risks associated with methotrexate, most commonly prescribed DMARD, are hepatotoxicity and cytopenia, as well as pneumonitis, particularly during the first year of treatment. In case of TNF inhibitors, infection by bacterial pathogens, atypical fungi and opportunistic pathogens is a major risk.
Gastrointestinal perforation with tocilizumab, progressive multifocal leucoencephalopathy with rituximab and pulmonary infections with abatacept are some of the specific risks associated with biologic DMARDs 23, 25.
Appropriate management of arthritis can result in reduced pain and help to overcome functional limitations to a greater extent. Medication, physical or occupational therapy, patient education, weight loss, and surgery may be included in treatment and management of arthritis 26. Though conventional treatment of rheumatoid arthritis is improving, treatment still remains unsatisfactory as remission is rare. Therefore, search remains on going for effective alternative and additional therapies for this disease. Complementary and alternative medicine (CAM) therapies are now being increasingly used. These therapies are a group of practices or products that are not currently used in the practice of conventional medicine 27. Callahan LF, et al reported estimates of CAM use among adults with arthritis to be ranging from 59% to 90% 28.
The literature of Ayurveda describes various plants, to be used as whole, in part or as extracts for treating painful and inflammatory conditions like arthritis. Table 1 gives a list of some of the herbs reported for use in arthritis 29.
TABLE 1: SOME HERBS REPORTED FOR USE IN ARTHRITIS 29
Name of the herb | Family |
Alpinia galanga | Zingiberaceae |
Aquilaria agallocha | Thymeleaceae |
Argreiay nervosa | Convolvulaceae |
Boswellia serrata | Burseraceae |
Butea monosperma | Fabaceae |
Callicarpa macrophylla | Verbenaceae |
Capparis decidua | Capparaceae |
Capsicum annuum | Solanaceae |
Cardiospermum halicacabum | Sapindaceae |
Carthamus tinctorus | Asteraceae |
Ficus benghalensis | Moraceae |
Gossypium herbaceum | Malvaceae |
Hyocyamus niger | Solanaceae |
Illicium verum | Magnoliaceae |
Justicia gendarussa | Acanthaceae |
Ocimum basilicum | Lamiaceae |
Pandanus odoratissimus | Pandanaceae |
Piper nigrum | Piperaceae |
Ricinus communis | Euphoebiaceae |
Rubia cordifolia | Rubiaceae |
Sida Cordata | Malvaceae |
Sida rhombifolia | Malvaceae |
Tectona grandis | Verbenaceae |
Trachyspermum roxburghianum | Apiaceae |
Tribulus terrestris | Zygophyllaceae |
Vitex negundo | Verbenaceae |
A number of inexpensive herbal medicines have been reported in literature to be useful in rheumatoid arthritis due to their anti-inflammatory and immunosuppressive potential 30, 31. The World Health Organization (WHO) recognizes Ayurveda as a complete system of natural medicine. It sponsored the first-ever study of a traditional medical system of complete, classical Ayurvedic treatment for rheumatoid arthritis (RA). The study was conducted in collaboration with the Indian Council for Medical Research (ICMR) and the Ayurvedic Trust, Coimbatore, Tamil Nadu, India, from 1977 to 1984 32.
Herbal medicines have been recognized by physicians and patients for their lower incidences of side effects as compared to allopathic medicines. However, standardization and their quality assurance have been the major problem faced with herbal products. Herbal medicines were not considered for development of novel formulations for a long time as due to processing difficulties, such as standardization, extraction and identification of individual drug components in complex polyherbal systems and due to lack of scientific justification 33. Batch-to-batch variations in efficacies of the herbal formulations which may result from natural and genetic alterations, seasonal changes, differences in soil and climatic conditions, and nutritional status of the medicinal plant have also been cause of concern as this may lead to issues regarding quality and purity of these formulations 34.
Therefore, there is a need to identify the active principles of these medicines as potential chemotherapeutic agents and monitor the safety of these active constituents 35. There has been, thus, a need of scientific approach towards phytotherapeutics to deliver the components in a sustained manner so as to increase patient compliance and minimize the need for repeated administration.
A possible way to achieve this is designing novel drug delivery systems for herbal constituents. Novel drug delivery systems help to the reduce toxicity and increase the bioavailability thereby improving the therapeutic value of the active constituent.
Recently, pharmaceutical scientists have shifted their focus to designing a drug delivery system for herbal medicines using a scientific approach 36, 37.
Novel herbal formulations like polymeric nanoparticles, nanocapsules, liposomes, phyto-somes, nanoemulsions, microsphere, transfer-osomes, and ethosomes have been reported using plant extracts and active constituents. Enhancement of solubility, bioavailability, protection from toxicity, enhancement of pharmacological activity, enhancement of stability, improved tissue macrophages distribution, sustained delivery, and protection from physical and chemical degradation are among the remarkable advantages that these novel formulations are reported to have over conventional formulations of plant actives and extracts 38.
This review focuses on some of herbs used traditionally for arthritis along with some of the strategies adopted by researchers to improve the efficacy of these herbs.
Curcuma longa (Zingiberaceae): Curcuma longa(turmeric) has been used traditionally for its pain and wound-healing properties. Curcumin is a major curcuminoid found in turmeric to which the main biological effects of turmeric have been attributed to. Curcumin has been seen to have action on lymphocytes 39.
Curcumin is a polyphenolic phytochemical. It is a strong anti-inflammatory agent and an antioxidant 40. Curcumin is reported to change the expression of various transcription factors, cell cycle proteins, and signal transducing kinases 41. It is found to down regulate the secretion of a variety of proinflammatory cytokines and chemokines 42. Studies in human or animal models have shown that curcumin ameliorates multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease 43. The systemic bioavailability of orally administered curcumin is relatively low 44.
Various studies have been reported for solubility improvement of curcumin and hence its bioavailability 45. Several nanocarriers are now emerging as promising systems to overcome poor solubility and inconsistent bioavailability of curcumin 46. A highly bioavailable form of curcumin is reported to be more effective in alleviating rheumatoid arthritis (RA) symptoms than the NSAID drug Voltaren 47. A study by Kumar K et al reports floating microspheres of curcumin prepared with hydroxypropylmethyl cellulose, hydroxyethyl cellulose, polyvinyl pyrollidone (PVP K30) and Eudragit RS 100 in different ratios by emulsion solvent diffusion method. The study concluded that curcumin microspheres can be a promising drug delivery to obtain sustained release of curcumin 48. Microparticles containing Curcumin with Eudragit S 100 have been reported for colon targeting by Madhavi M et al 49.
In another study, curcumin biodegradable microspheres were shown to be promising as prolonged release drug delivery system as compared to oral or subcutaneous route for better therapeutic management of inflammation 50. The starch microspheres cross-linked by N, N’-methylene bisacrylamide were studied as carrier for curcumin by Zhu minpeng and Li suhong. According to the study, 80.53% of curcumin was released after 25 hours; sustained release of curcumin was observed 51.
Increased permeation through the skin was observed with transferosomes containing curcumin gel when compared with simple gel by Patel R. et al 52. Cui J et al formulated self microemulsifying drug delivery system of curcumin using surfactant, co surfactant and ethyl oleate. Increased oral absorption of curcumin has been reported with this drug delivery system as compared to simple emulsion 53.
Tripterygium wilfordii (Celastraceae): In Chinese medicine, extracts of Tripterygium wilfordii (Tw) are used to treat autoimmune and inflammatory conditions such as rheumatoid arthritis, systemic lupus erythmatosus, psoriatic arthritis and Behcet’s disease 54. Triptolide, a diterpenoid component isolated from Tw has been shown to have anti-inflammatory and immunosuppressive activities by its inhibitory effect on T-cells 55.
A trial compared Tw extract with sulfasalazine in 121 patients with active rheumatoid arthritis who continued oral prednisone and non-steroidal anti-inflammatory drugs but not disease modifying antirheumatic drugs. Among patients who continued treatment for 24 weeks, achievement of 20% improvement in American College of Rheumatology criteria was greater with TwHF than with sulfasalazine 56.
Immunosuppressive, cartilage protective and anti-inflammatory effects of Tripterygium wilfordii have been studied in literature. From these studies Tw has shown promise that it could serve as a source and template for novel antiarthritic and cartilage protective drugs. MMP inhibition may be an important mechanism for the observed beneficial effects of TWHF in patients with arthritis57.
Liposomes of extracts of Tripterygium wilfordii have been reported to increase its stability and reduce side effects58. Celastrol, also known as tripterine, is derived from Trypterygium wilfordii. Celastrol exhibits potent anti-angiogenic and anti-inflammatory activities. Celastrol, potentiates TNF-induced apoptosis and suppresses invasion of tumor cells by inhibiting NF-kappaB-regulated gene products and TAK1-mediated NF-kappaB activation 59.
Despite the powerful beneficial bioactivity of celastrol, its clinical use has been limited mainly due to its poor water solubility. Therefore, improvement in its water solubility is necessary while still retaining its activities in order to develop new celastrol-based formulations. Nanoformulated poly(ethylene glycol)-block-poly(ɛ-caprolactone) (PEG-b-PCL) micelles have been reported to improve the water solubility of celastrol 60.
Surface-charged tripterine-loaded nanostructured lipid carriers (NLCs) were evaluated by Yan Chen et al. for the influence of the surface charge of NLCs on in vitro skin permeation and in vivo pharmacodynamics of tripterine. In the study, NLCs exhibited first order release of tripterine. Cationic NLCs were observed to increase the tripterine permeability coefficient 1.15- and 1.38-fold compared to that of neutral and anionic NLCs, respectively 61.
Boswellia serrata (Burseraceae): The resin of Boswellia species (Salai guggul) has been used in medicines since ancient times. Gum-resin extracts of Boswellia serrata have been traditionally used in folk medicine for centuries to treat various inflammatory diseases like arthritis 62. The resinous part of Boswellia serrata possesses monoterpenes, diterpenes, triterpenes, tetracyclic triterpenic acids and four major pentacyclic triterpenic acids i.e. β-boswellic acid, acetyl-β-boswellic acid, 11-keto-β-boswellic acid(KBA) and acetyl-11-keto-β-boswellic acid, responsible for inhibition of pro-inflammatory enzymes 63.
Studies have found that 3-O-acetyl-11-keto-beta-boswellic acid (AKBA) is the most biologically active component in the herb. It inhibits the action of 5-lipoxygenase, an enzyme in the biochemical cascade leading to inflammation 64. Extracts from the gum resin of Boswellia serrata and some of its constituents including boswellic acids are also reported to affect the immune system in different ways. 11-keto-beta-boswellic acid and acetyl-11-keto-beta-boswellic acid have been observed to be active among the various boswellic acids (BA). However, other boswellic acids may also exhibit activity on the immune system 65.
Some of the branded formulations of Boswellia available for inflammatory and arthritic conditions are 66: Boswellin®, a registered trademark by Sabinsa Corporation, is in the form of capsules or tablets containing boswellic acids ranging from 150-250 mgs/capsules or tabletsto be taken orally two to three times a day. Shallaki® contains 125 mg Boswellia serrata in each capsule and is manufactured by Himalayan Drug Company, Makali, Bangalore, as Licensed User of the Trade Mark owned by MMI Corporation. Rheumatic-X®, contains 20 mg 'Shallaki' besides a number of ingredients, manufactured by Sunrise Herbals, Varanasi (U.P., India), meant for rheumatoid, gouty, osteoarthritis and sciatic pain 66.
Pharmacokinetic studies of boswellic acid reveal its poor absorption through the intestine. Various studies to improve bioavailability of boswellic acids have been reported in literature 67. Complexation of boswellic acid with phosphatidylcholine has been studied by Sharma et al. to enhance its bioavailability 68.
They prepared a complex of boswellic acid with phosphatidylcholine (PC). The complex was also converted into vesicles (phytosomes) and compared with other vesicular systems (liposomes and niosomes) by evaluating its anti-inflammatory effect. The complex showed better anti-inflammatory and hypolipidemic activity as compared to BA. Phytosomes, among all vesicular systems, were reported to show maximum anti-inflammatory activity. The study reports that enhanced bioavailability of the BA-PC complex may be due to the amphiphilic nature of the complex, which greatly enhanced the water and lipid solubility of the boswellic acid 68.
Husch J et al did a comparative murine of bioavailability study of Casperome™, a soy lecithin formulation of standardized B. serrata gum resin extract (BE), and its corresponding non-formulated extract. The study showed significantly higher plasma levels (up to 7-fold for KBA, and 3-fold for βBA quantified as area under the plasma concentration time curve, AUClast) for weight equivalent and equimolar oral administration of Casperome™ compared to the non-formulated extract 69.
3-Acetyl-11-keto-beta-boswellic acid loaded-polymeric nanomicelles were developed and studied for topical anti-inflammatory and anti-arthritic activity by Goel A et al 70.The study suggested that AKBA polymeric nanomicelle gel significantly enhanced skin permeability, and anti-inflammatory and anti-arthritic activity. In another study, transdermal films containing boswellic acid and curcumin were formulated for treatment of inflammation by Verma M et al. Combination of boswellic acid and curcumin was used to produce synergistic action. Transdermal films showed increased efficacy of the drugs 71.
Fartyal S et al studied of floating microspheres using boswellic (BA) as model drug for prolongation of the gastric retention time. Diffusion- controlled drug release from the microspheres was demonstrated in in vitro studies 72.
Zingiber officinale (Zingiberaceae): Zingiber officinale (Ginger) has been known for its anti-inflammatory properties for centuries.
Ginger suppresses prostaglandin synthesis through inhibition of cyclooxygenase-1 and cyclo-oxygenase-2. Ginger has also been reported to suppress leukotriene biosynthesis by inhibiting 5-lipoxygenase 73.
Major focus of research related to anti-inflammatory effects of ginger has been on phenolic gingerols and related compounds. However literature reports that nongingerol components are also bioactive and can enhance the antiarthritic effects of gingerols 74. Ginger oil has been demonstrated for its potent antiinflammatory and/or antirheumatic properties 75.
Baskar V et al demonstrated improved bio-availability ratio of anti-inflammatory compound from ginger from a nano transdermal delivery 76. The ultra-flexible or ultra-deformable vesicle system was observed to be much more efficient in delivering a low/high molecular weight, hydrophobic/hydrophilic drugs deep into to the skin. In this study, transdermal mode of delivery showed substantial increase in the ratio of bioavailability of the gingerol in comparison to the other delivery methods.
WIPO Patent Application WO/2012/026829 titled ‘Transdermal Patch’ describes a transdermal patch containing one active ingredient, namely Zingiber officinale rhizome (commonly known as 'ginger'), for the treatment of an inflammatory condition such as in an arthritic condition. The invention aims to provide non-invasive treatment of the inflammatory condition, in the form of transdermal patch 77.
Tanacetum parthenium (Asteraceae):Tanacetum parthenium (Feverfew), has been used as a folk remedy for rheumatoid arthritis and fever 78. Sesquiterpene lactones are the important biologically active principles, parthenolide being the principal one. Greater than 30 sesquiterpene lactones have been identified in feverfew. In general, there are 5 different types of sesquiterpene lactones. These may be classified based on chemical ring structures. The eudesmanolides, germacranolides, and guaianolides are present in feverfew 79. Parthenolide is a germacranolide. Parthenolide binds to and inhibits IκB kinase complex (IKK)β, it inhibits prostaglandin synthetase and reduces human neutrophil oxidative burst activity 80.
The crude feverfew extract and its purified parthenolide can modulate adhesion molecule expression in human synovial fibroblasts 81.
It is also reported that parthenolide depleted feverfew extract too has capacity to inhibit several pro-inflammatory enzymes including 5-lipoxygenase, phosphodiesterase-3 and phosphor-diesterase-4. It inhibits the release of proinflammatory mediators nitric oxide, prostaglandin (PG) E2 and TNF- from macrophages and IFN- and IL-4 from human peripheral blood mononuclear cells 82.
Standardized spray-dried extract of feverfew was developed by Chaves SJ et al and enteric coated tablets of this extract were further designed and standardized. They evaluated the spray-dried extract of feverfew for its parthenolide, santin and total flavonoid content, parthenolide solubility, particle size, tapped density, hygroscopicity, angle of repose and moisture content. Enteric coated tablets containing the spray-dried extract were tested for their average weight, friability, hardness, and disintegration time. They observed that spray-dried extract exhibited consistent pharmaco-technical properties and direct compression technique could be used to produce tablets with required specifications 83.
Camellia sinensis (Theaceae): The polyphenolic compounds from Camellia sinensis(green tea) are reported to possess anti-inflammatory properties 84. Immunosuppressive effect of green tea has been shown in various experiments using animal models. Green tea has been reported to reduce autoimmune symptoms in the rat adjuvant arthritis, a model of human rheumatoid arthritis 85. Epigallocatechin-3-gallate (EGCG), a component of green tea has been studied for its anti-inflammatory and immunomodulatory activities.
It has shown inhibitory effects on human monocyte-derived DCs (dendritic cells) and, consequently, on the T-cell-mediated immune responses 86. Cartilage-preserving and chondro-protective action of EGCGs, its mechanisms and beneficial effects in arthritis have been reported through various studies 87. Phytosomes of epigallocatechin 3-o-gallate from Camellia sinensis have been reported 88.
(−)-Epigallocatechin-3-gallate or (−)-EGCG loaded lipid nanocapsules (LNC) were prepared by Barras A. et al by applying the phase inversion process, and to enhance their apparent solubility and/or the stability. They observed that high encapsulation rates (95%) could be reached with simple chemical modification of (−)-EGCG. Thus, a stable colloidal suspensions of (−)-EGCG in water over 4 weeks was obtained. 100% degradation within 4 hours was observed with free (−)-EGCG solubilised in water. It was concluded that the drug-loaded LNC resolved initial problems of solubility and stability of (−)-EGCG 89.
Commiphora mukul (Burseraceae): Commiphora mukul (Guggulipid) has been used in history of Ayurveda since a long time. The Commiphora tree, from which guggulipid is obtained is use in the treatment of bone fractures, arthritis, obesity, inflammation as mentioned in the classic Ayurvedic literature 90. The beneficial effect of guggul in arthritis has been demonstrated in scientific studies 91.
Guggulsterone [4, 17(20)-pregnadiene-3, 16-dione] is the gum resin of the Commiphora tree. The sterol down regulates the expression of inflammatory gene products such as COX-2 and MMP-9 which are major players in the development of arthritis 92.
Patent EP 2088865 A2 (WO2008058156A2), ‘Guggulphospholipid methods and compositions’, describes methods for preparing synthetic Guggul-phospholipids, their fatty acid analogues and other bioactive molecules 93. The invention mentions E-guggulsterone and Z- guggulsterone or mixture of E- and Z-guggulsterones. The patent relates to complexes such as liposomes, complexes, emulsions, vesicles, micelles, and mixed micelles, into which guggulphospholipids and other bioactive molecules can be incorporated, which can also include other active agents, such as hydrophobic or hydrophilic drugs.
A study by Verma S. et al reports preparation of ‘guggulosomes’ using guggulipid as a lipid drug carrier 94. The guggulosomes were loaded with ibuprofen. Sustained release of the drug was observed. Also guggulusome prepared exhibited significant anti-inflammatory activity at 5 hours against carrageenan injection, suggesting that it may have a sustained and synergistic action 94.
Glycyrrhiza glabra (Fabaceae): Glycyrrhiza glabra (Liquorice) is used for its immuno-modulatory, laxative, emmenagogue, contraceptive, galactagogue, anti-asthmatic, anti-viral properties in folk medicine 95. Anti-microbial, anti-oxidant and anti-inflammatory properties are also demonstrated in literature 96. The major metabolite of glycyrrhizin, present in liquorice root is glycyhrritinic acid. Liquorice extracts as well as glycyhrritinic acid have shown anti-inflammatory effects in various studies and may prove beneficial in conditions like rheumatoid arthritis 97, 98.
Glycyrrhizin has shown to possess absorption enhancing (bioavailability enhancing) activity 99,100.
Ammonium glycyrrhizinate was reported by Paolino D. et al. to be incorporated into ethosomes for dermal administration and used for treatment of inflammatory diseases of the skin. The ethosomal preparation showed increased bioavailability as a result of increased permeability of the drug 101.
Wang W. et al. prepared glycyrrhizinic acid nanoparticles by supercritical antisolvent process and explored the anti-inflammatory activity and mechanisms of in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. They compared the activities of nanoparticles with those exhibited by unprocessed glycyhrrizinic acid particles. They found that glycyrrhizinic acid nanoparticle suspensions showed better anti-inflammatory activities than the unprocessed glycyrrhizinic acid 102.
Plumbago zeylanica (Plumbaginaceae): The crude extracts of P. zeylanica have been used in china and other Asian countries as folk medicine for the treatment of cancer, rheumatoid arthritis and dysmenorrhea. Immunosuppressive properties of aqueous extract of Plumbago zeylanica were demonstrated in Balb/c mice 103. Anti-arthritic potential has also been demonstrated 104.
Plumbagin is a natural bicyclic naphthoquinone derived from roots of P. zeylanica. The inhibitor has been known for its potent biological activities including anti-inflammatory, anti-tumor, and anti-bacterial activities 105. Plumbagin was recrystallized by cold crystallisation technique using a variety of polar and non-polar solvents by Bothiraja C and plumbagin so obtained was investigated for pharmaceutical properties. It was observed that size and shape of plumbagin varied with different solvents. Improvement in therapeutic efficacy of recrystallized plumbagin was demonstrated in in-vivo anti-inflammatory study in Wistar rats. The researchers concluded that surface modification led to enhanced efficacy of plumbagin. This approach is capable of improving the bioavailability and clinical efficacy of other poorly water soluble phytomedicines 106.
Vitis vinifera (Vitaceae): Vitis vinifera (Grape Seed) contains proanthocyanidins, resveratrol, with known antioxidant and anti-inflammatory properties, through the inhibitory effects of these on transcription factors like nuclear factor kappa B (NF-KB) or activator protein-1 (AP-1) 107. The effect of resveratrol on the proliferation and apoptosis of synoviocytes in patients with rheumatoid arthritis (RA) in vitro was investigated by Tang LL et al. They concluded that resveratrol inhibits the proliferation of synoviocytes and induces cell apoptosis in rheumatoid arthritis in vitro 108. Various studies have reported beneficial effects of reservatrol indicating its potential use as anti-arthritic 109, 110, 111.
Resveratrol has poor bioavailability, low water solubility, and is chemically unstable, has less favorable pharmacokinetic properties. To overcome these problems, Neves AR et al. developed solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) loaded with resveratrol by a modified hot homogenization technique and characterized them to evaluate the quality of the developed resveratrol-loaded nanoparticles 112.
Both SLNs and NLCs showed an average resveratrol entrapment efficiency of ~70%. Studies indicated good stability of these systems.
Also, resveratrol was found to mostly remain associated with the lipid nanoparticles after their incubation in digestive fluids in the in vitro simulation of gastrointestinal transit. The researchers concluded that SLNs and NLCs can be considered suitable carriers for oral administration of reservatrol, conferring protection to the incorporated resveratrol and allowing its controlled release after uptake 112.
Ansari KA et al studied complexation of reservatrol with cyclodextrin-based nanosponges (NS) to increase its solubility, stability and permeation. Ex vivo studies on these complexes indicated their potential to administer resveratrol NS complex as buccal delivery and topical application 113.
Withania somnifera (Solanaceae): Withania somnifera (Ashwagandha) is an herb widely used in the traditional medical system of India for a variety of musculoskeletal conditions like arthritis, rheumatism 114. The anti-inflammatory activity of the herb has been studied 115. The effect of a Withania somnifera (WS) crude ethanol extract was studied on peripheral blood mononuclear cells of normal individuals and rheumatoid arthritis (RA) patients and synovial fluid mononuclear cells of RA patients in vitro by Singh D et al 116.
They found that the WS extract significantly suppressed lipopolysaccharide (LPS) induced production of proinflammatory cytokines TNF-alpha, IL-1beta and IL-12p40 in normal individuals and patients and in patients with rheumatoid arthritis. Their study demonstrated that the production of proinflammatory molecules was suppressed in vitro by WS crude ethanol extract. This activity was attributed partly through the inhibition of transcription factors NF-kappaB and AP-1 by the constituent withanolide. Goyal S et al have reviewed this herb so as to prepare novel topical gels containing this herb 117.
CONCLUSION: Herbal medicines are a promising alternative to conventional therapy for arthritis due to their lesser side effects and low cost. Formulation into new drug delivery technologies would further enhance the effectiveness of plant actives/extracts as a result of increased bio-availability and/or drug targeting.
Thorough studies are required to gain knowledge about the exact mechanism of action of these actives in order to make correct choice of drug delivery system to achieve maximum efficacy. Herbal medicines formulated into a novel drug delivery system thus can prove to be a therapy of choice for arthritis patients due to its safety, efficacy and affordability.
REFERENCES:
- The free dictionary by Farlex. Available at http://www.thefreedictionary.com/arthritis. Last accessed on 25th may 2013.
- Centers for Disease Control and Prevention. Osteoarthritis, http://www.cdc.gov/arthritis/basics/osteoarthritis.htm, last accessed on 22nd May 2013.
- Centers for Disease Control and Prevention. Rheumatoid arthritis. http://www.cdc.gov/arthritis/basics/rheumatoid.htm, last accessed on 22nd May 2013
- Helmick CG, Felson DT, Lawrence RC, Gabriel S, Hirsch R, Kremers HM, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum 2008; 58:15–25.
- Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA. et al. Estimates of the Prevalence of Arthritis and Other Rheumatic Conditions in the United States.Part II. Arthritis & Rheumatism 2008; 58(1): 26–35.
- http://www.sanofi.in/l/in/en/layout.jsp?scat=F56FCF04-B400-4F35-A18C-82E58BE502FE#p3. Last accessed on 21st May 2013.
- AIHW 2009. Health expenditure for arthritis and musculoskeletal conditions, 2004-05. Arthritis series no. 10. Cat. no. PHE 115. Canberra: AIHW. Last accessed on 22 May 2013 <http://www.aihw.gov.au/publication-detail/?id=6442468282>.
- Osteoarthritis and Rheumatoid Arthritis 2012: Pathophysiology, Diagnosis, and Treatment. http://www.clinicaladvisor.com/osteoarthritis-and-rheumatoid-arthritis-2012-pathophysiology-diagnosis-and-treatment/article/265549/# . Last accessed on 17 May 2012.
- Vojdani A. Antibodies as predictors of complex autoimmune diseases. International Journal of Immunopathology and Pharmacology 2008; 21(2): 267–278.
- Shivaprasad H, Venkatesha, Rajaiah R, Berman BM, and Moudgil KD. Immunomodulation of Autoimmune Arthritis by Herbal CAM. Evidence-Based Complementary and Alternative Medicine. 2011 (2011), 13 pages. Available at http://www.hindawi. com/journals/ecam/2011/986797/, last accessed: 24th May 2013.
- Kaur A and Harikumar SL. Controlled Drug Delivery Approaches for Rheumatoid Arthritis. Journal of Applied Pharmaceutical Science 2012; 02 (08): 21-32.
- Temprano KK, Diamond HS. Rheumatoid Arthritis. Medscape reference. Updated Feb 20, 2013. Available from http://emedicine.medscape.com/article/331715-overview#a0101. Last accessed on 24th May 2013.
- BestPractice last updated, Jul 26, 2012. http://bestpractice.bmj.com/best-practice/monograph/105/basics/pathophysiology.html, accessed on 24th May 2013.
- Ruffing V, Bingham CO. Rheumatoid Arthritis Signs and Symptoms. The Johns Hopkins Arthritis Centre. Last updated Nov 28, 2012. Available at: http://www.hopkinsarthritis.org/arthritis-info/rheumatoid-arthritis/ra-symptom/. , last accessed on 24th May 2013.
- Singh R, Akhtar N and Haqqi TM. Green tea polyphenol epigallocatechin-3-gallate: inflammation and arthritis. Life Sci. 2010; 86(25-26): 907–918.
- Manek NJ, Lane NE. Osteoarthritis: Current Concepts in Diagnosis and Management. Am Fam Physician. 2000; 61(6):1795-1804.
- Quan L., Thiele GM, Tian J, and Wang D. The Development of Novel Therapies for Rheumatoid Arthritis Expert Opin Ther Pat. 2008; 18(7): 723–738.
- Gaffo A, Saag KG, Curtis JR. Treatment of rheumatoid arthritis. Am J Health Syst Pharm. 2006; 63(24):2451-65.
- Chopra A, Saluja M, and Tillu G. Ayurveda–modern medicine interface: A critical appraisal of studies of Ayurvedic medicines to treat osteoarthritis and rheumatoid arthritis. J Ayurveda Integr Med. 2010; 1(3): 190–198
- FitzGerald GA, Patrono C. The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med. 2001;345:433–42
- Solomon DH. Selective cyclooxygenase 2 inhibitors and cardiovascular events. Arthritis Rheum. 2005; 52(7):1968–78.
- Jacobs JW, van Everdingen AA, Verstappen SM, Bijlsma JW. Followup radiographic data on patients with rheumatoid arthritis who participated in a two-year trial of prednisone therapy or placebo. Arthritis Rheum. 2006; 54(5):1422–8.
- Doan T, Massarotti E. Rheumatoid arthritis: an overview of new and emerging therapies. J Clin Pharmacol. 2005; 45(7):751-62
- Fantini F. New drugs and treatment strategies for rheumatoid arthritis. Recenti Prog Med. 2003; 94(9):361-79.
- Ruderman EM. Overview of safety of non-biologic and biologic DMARDs Rheumatology (Oxford). . 2012; 51 Suppl 6:vi37-43.
- http://www.mayoclinic.com/health/osteoarthritis/DS00019/DSECTION=treatments-and-drugs. Last accessed on 18th May 2013.
- Subhadra E, Mona M , Kirsten L, Jennie T, Beth S, Mihaela T, Lonnie Z . Impact of Iyengar Yoga on Quality of Life in Young Women with Rheumatoid Arthritis, Clinical Journal of Pain: Published Ahead-of-Print. Last updated on May 17, 2013. Available at:http://journals.lww.com/clinicalpain/toc/publishahead. Last accessed on 24th May 2013.
- Callahan LF, Wiley-Exley EK, Mielenz TJ, Brady TJ, Xiao C, Currey SS, et al. Use of complementary and alternative medicine among patients with arthritis. Prev Chronic Dis. 2009; 6(2).
- Edited by: Warrier PK, Nambiar VPK, Ramankutty C. Indian Medicinal Plants a compendium of 500 species. Vol.1-5, Orient Longman, 2005.
- Patil KR, Patil CR, Jadhav RB, Mahajan VK, Patil PR, Gaikwad PS. Anti-Arthritic Activity of Bartogenic Acid Isolated from Fruits of Barringtonia racemosa Roxb. (Lecythidaceae). Evidence-Based Complementary and Alternative Medicine 2011, 1-7. Published online 2011 February 20.
- Baranwal VK, Irchhaiya R, Alok S. Antiarthritic activity of some indigenous plants: A Review. International Journal of Pharmaceutical Sciences and Research2012, 3, 981-986.
- Krishna KPR. The efficacy of Ayurvedic treatment for rheumatoid arthritis: Cross-sectional experiential profile of a longitudinal study. J Ayurveda Res. 2011; 2(1): 8–13.
- Musthaba SM, Baboota S, Ahmed S, Ahuja A and Ali J. Status of novel drug delivery technology for phytotherapeutics. Expert Opinion on Drug Delivery, 2009; 6(6): 625-637.
- Girish C, Pradhan SC. Indian herbal medicines in the treatment of liver diseases: problems and promises. Fundam Clin Pharmacol. 2012; 26(2):180-9.
- Gogtay NJ, Bhatt HA, Dalvi SS, Kshirsagar NA. The use and safety of non-allopathic Indian medicines. Drug Saf. 2002. 25(14):1005-19.
- Goyal A, Kumar S. , Nagpal M , Singh I and Arora S. Potential of Novel Drug Delivery Systems for Herbal Drugs, Ind J Pharm Edu Res, 2011, 45(3).
- Kusum Devi V, Jain N, and Valli KS Importance of novel drug delivery systems in herbal medicines. Pharmacogn Rev. 2010; 4(7): 27–31.
- Ajazuddin, Saraf S. Applications of novel drug delivery system for herbal formulations. Fitoterapia. 2010; 81(7):680-9.
- Gao X, Kuo J, Jiang H, Deeb D, Liu Y, Divine G, Chapman RA, Dulchavsky SA, Gautam SC. Immunomodulatory activity of curcumin: suppression of lymphocyte proliferation, development of cell-mediated cytotoxicity, and cytokine production in vitro. Biochem Pharmacol. 2004; 68(1):51-61.
- Menon VP, Sudheer AR. Antioxidant and anti-inflammatory properties of curcumin. Adv Exp Med Biol. 2007; 595:105-25.
- Duvoix A, Blasius R, Delhalle S, Schnekenburger M, Morceau F. et al. Chemopreventive and therapeutic effects of curcumin. Cancer Letters 223 (2005) 181–190.
- Jagetia GC and Aggarwal BB. “Spicing Up” of the Immune System by Curcumin. Journal of Clinical Immunology. 2007; 27(1).
- Bright JJ. Curcumin and autoimmune disease. Adv Exp Med Biol. 2007;595:425-51
- Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm. 2007; 4(6):807-818.
- Modasiya MK and Patel VM. Studies on solubility of curcumin. Int. J. of Pharm. & Life Sci. (IJPLS), 2012; 3(3): 1490-1497.
- Mohanty C, Das M, Sahoo SK. Emerging role of nanocarriers to increase the solubility and bioavailability of curcumin. Expert Opin Drug Deliv. 2012; 9(11):1347-64.
- The Spice that Is Better than Drugs for Rheumatoid Arthritis ,13 June, 2012 , Available from http://articles.mercola.com
- Kumar K, Rai AK Evaluation of anti-inflammatory and anti-arthritic activities of floating microspheres of herbal drug. Internal Research Journal of Pharmacy 2012; 3(1).
- Madhavi M, Madhavi K, Jithan A V. Preparation and in vitro/in vivo characterization of curcumin microspheres intended to treat colon cancer. J Pharm Bioall Sci 2012; 4:164-71.
- Kumar V, Lewis SA, Mutalik S, Shenoy DB, Venkatesh, Udupa N.. Biodegradable microspheres of curcumin for treatment of inflammation. Indian J Physiol Pharmacol. 2002; 46(2):209-17.
- Zhu minpeng, Li suhong. The Stability of Curcumin and Drug-Loading Property of Starch Microspheres for It. 2012 International Conference on Biological and Biomedical Sciences. Advances in Biomedical Engineering, Vol.9.
- Patel R, Singh SK, Singh S, Sheth NR, Gendle R. Development and Characterization of Curcumin Loaded Transfersome for Transdermal Delivery, Journal of Pharmaceutical Sciences and Research 01/2009.
- Cui J, Yu B, Zhao Y, Zhu W, Li H, Lou H, Zhai G. Enhancement of oral absorption of curcumin by self-microemulsifying drug delivery systems. Int J Pharm. 2009; 371(1-2):148-55.
- Ma J, Dey M, Yang H, Poulev A, Pouleva R., Dorn R. et.al. Anti-inflammatory and immunosuppressive compounds from Tripterygium wilfordii. Phytochemistry. 68(2007):1172-1178.
- Chen BJ. Triptolide, a novel immunosuppressive and anti-inflammatory agent purified from a Chinese herb Tripterygium wilfordii Hook F. Leuk Lymphoma. 2001;42(3):253-65.
- Bao J, Dai SM. A Chinese herb Tripterygium wilfordii Hook in the treatment of rheumatoid arthritis: mechanism, efficacy and safety. Rheumatol Int. 2011; 31:1123-1129.
- Sylvester J , Liacini A, Li WQ, Dehnade F and Zafarullah M. Tripterygium wilfordii Hook F Extract Suppresses Proinflammatory Cytokine-Induced Expression of Matrix Metalloproteinase Genes in Articular Chondrocytes by Inhibiting Activating Protein-1 and Nuclear Factor-kB Activities. Mol Pharmacol 59, No.5:1196–1205, 2001.
- Zhongguo Zhong Yao Za Zhi. Preparation of liposomes containing extracts of Tripterygium wilfordii and evaluation of its stability. 2007 Oct; 32(20):2128-31.
- Sethi G, Ahn KS, Pandey MK, Aggarwal BB. Celastrol, a novel triterpene, potentiates TNF-induced apoptosis and suppresses invasion of tumor cells by inhibiting NF-kappaB-regulated gene products and TAK1-mediated NF-kappaB activation. Blood. 2007; 109(7):2727-35.
- Li Z, Yao L, Li J, Zhang W, Wu X, Liu Y, et al. Celastrol nanoparticles inhibit corneal neovascularization induced by suturing in rats, Int J Nanomedicine. 2012; 7: 1163–1173.
- Chen Y, Zhou L, Yuan L, Zhang Z., Liu X, and Wu Q. Formulation, characterization, and evaluation of in vitro skin permeation and in vivo pharmacodynamics of surface-charged tripterine-loaded nanostructured lipid carriers. Int J Nanomedicine. 2012; 7: 3023–3033.
- Chatterjee GK, Pal SD. Antiinflammatory agents from Indian medicinal plants. Indian Drugs 1984; 21:431.
- Safayhi H, Mack T, Sabieraj J, Anazodo MI, Subramanian LR, Ammon HP. Boswellic acids: Novel, specific, non-redox inhibitors of 5-lipoxygenase. J Pharmacol Exp Ther 1992; 261:1143-6.
- Sengupta K, Alluri KV, Sathis AR, et al. A double blind, randomized, placebo controlled study of the efficacy and safety of 5-Loxin ® for treatment of osteoarthritis of the knee. Arthritis Research & Therapy 2008; July 30.Arthritis Foundation. Available at http://www.arthritis.org/research/funded-research/ research-update/ru-s-o-08/boswellia-oa/. Last viewed: 19th May 2013.
- Ammon HP. Modulation of the immune system by Boswellia serrata extracts and boswellic acids Phytomedicine. 2010; 17(11):862-7.
- Siddiqui MZ. Boswellia serrata, a potential antiinflammatory agent: An overview. Indian Journal of Pharmaceutical Sciences. 73 (3), 255-261.
- Krüger P, Daneshfar R, Eckert GP, Klein J, Volmer DA, Bahr U. et al. Metabolism of Boswellic Acids in Vitro and in vivo. Drug Metabolism and Disposition. DMD 2008; 36(6): 1135-1142.
- Sharma A, Gupta NK, Dixit VK. Complexation with phosphatidyl choline as a strategy for absorption enhancement of boswellic acid. Drug Delivery November 2010; 17(8): 587-595.
- Hüsch J, Bohnet J, Fricker G, Skarke C, Artaria C, Appendino G et al. Enhanced absorption of boswellic acids by a lecithin delivery form (Phytosome®) of Boswelliaextract. Fitoterapia. 2013; 84: 89–98.
- Goel A, Ahmad FJ, Singh RM, Singh GN. 3-Acetyl-11-keto-beta-boswellic acid loaded-polymeric nanomicelles for topical anti-inflammatory and anti-arthritic activity. J Pharm Pharmacol. 2010; 62(2):273-8.
- Verma M, Gupta PK, Pokharkar VB, Purohit AP. Development of transdermal drug dosage formulation for the anti-rheumatic ayurvedic medicinal plants. Available at http://www.ayurvedam.com/pdf/deverhematic.pdf, last accessed on 24th May 2013.
- Fartyal S, Jha SK, Karchuli MS, Gupta R, Vajpayee A. Formulation and Evaluation of Floating Microspheres of Boswellic acid. International Journal of PharmTech Research. 2011; 3(1): 76-81.
- Grzanna R, Lindmark L, Frondoza CG. Ginger--an herbal medicinal product with broad anti-inflammatory actions. J Med Food. 2005 Summer; 8(2):125-32.
- Funk JL, Frye JB, Oyarzo JN, Timmermann BN. Comparative effects of two gingerol-containing Zingiber officinale extracts on experimental rheumatoid arthritis. J Nat Prod. 2009; 72(3):403-7.
- Sharma JN, Srivastava KC, Gan EK. Suppressive effects of eugenol and ginger oil on arthritic rats. Pharmacology. 1994; 49(5):314-8.
- Baskar V, Selvakumar K., Madhan R, Srinivasan G, Muralidharan M. Study on improving bioavailability ratio of anti-inflammatory compound from ginger through nano transdermal delivery. Asian Journal of Pharmaceutical & Clinical Research. 2012; 5(3): 241.
- Therkleson, Tessa C, Transdermal Patch. Wipo Patent Application WO/2012/026829.
- Vanta B. Feverfew & Arthritis. Jan 30, 2011 |. Available at http://www.livestrong.com/article/369466-feverfew-arthritis/#ixzz2TnZxptwh, last accessed: 24th May 2013.
- Tanacetum Parthenium (Feverfew). http://flipper.diff.org/ app/items/4741. Last accessed: May 2013.
- Kwok BH, Koh B, Ndubuisi MI, Elofsson M, Crews CM. The anti-inflammatory natural product parthenolide from the medicinal herb Feverfew directly binds to and inhibits IkappaB kinase. Chem Biol.; 8(8):759-66
- Piela-Smith TH, Liu X. Feverfew extracts and the sesquiterpene lactone parthenolide inhibit intercellular adhesion molecule-1 expression in human synovial fibroblasts.Cell Immunol. 2001; 209(2):89-96
- Sur R, Martin K, Liebel F, Lyte P, Shapiro S, Southall M.. Anti-inflammatory activity of parthenolide-depleted Feverfew (Tanacetum parthenium) Inflammopharmacology. 2009; 17(1):42-9.
- Chaves JS; Da Costa FB; Luís Alexandre Pedro de Freitas. Development of enteric coated tablets from spray dried extract of feverfew (Tanacetum parthenium L.). Braz. J. Pharm. Sci. São Paulo. 2009; 45(3) .
- Haqqi TM., Anthony DD., Gupta S., Ahmad N., Lee MS, Kumar GK. et al. Prevention of collagen-induced arthritis in mice by a polyphenolic fraction from green tea. Proceedings of the National Academy of Sciences of the United States of America. 96(8): 4524–4529.
- Kawaguchi K, Matsumoto T, Kumazawa Y. Effects of Antioxidant Polyphenols on TNF-alpha-Related Diseases. Curr Top Med Chem 2011. 11(14):1767-79.
- Yoneyama S, Kawai K, Tsuno NH, Okaji Y, Asakage M, Tsuchiya T, et al. Epigallocatechin gallate affects human dendritic cell differentiation and maturation. J Allergy Clin Immunol 2008; 121(1):209-14.
- Ahmed S. Green tea polyphenol epigallocatechin 3-gallate in arthritis: progress and promise. Arthritis Research & Therapy 2010, 12:208.
- Saurabh KV, Kesari A. Herbosome – A Novel Carrier for Herbal Drug Delivery, Review article, International Journal of Current Pharmaceutical Research.2011; 3(3).
- Barras A, Mezzetti A, Richard A, Lazzaroni S, Roux S, Melnyk P. Pharmaceutical Nanotechnology.Formulation and characterization of polyphenol-loaded lipid nanocapsules. International Journal of Pharmaceutics. 2009; 379(2): 270–277.
- Natural Remedies Explorer. http://naturalremediesexplorer.com/remedy-ingredients/gugulipid/. Last accessed on 24th May 2013.
- Singh BB, Mishra LC, Vinjamury SP, Aquilina N, Singh VJ, Shepard N.. The effectiveness of Commiphora mukul for osteoarthritis of the knee: an outcomes study. Altern Ther Health Med. 2003; 9(3):74-9.
- Khanna D, Sethi G, Ahn SK., Pandey MK, Kunnumakkara AB, Sung B et al. Natural Products as a gold mine for arthritis treatment. Current Opinion in Pharmacology. 2007; 7(3): 344–351.
- Ahmad MU, Ali MS, Ahmad A, Sheikh S, Ahmad I. Guggulphospholipid methods and compositions EP 2088865 A2 (WO2008058156A2).
- Verma S, Jain A and Gupta VB. Synergistic and sustained anti-inflammatory activity of guguul with the ibuprofen: a preliminary study. International Journal of Pharma and Bio Sciences 2010.V1 (2).
- Saxena S. Glycyrrhiza glabra: Medicine over the millennium. Nat product red. 2005; 4:358-367.
- Harwansh RK, Patra KC, Pareta SK, Singh J, Biswas R. Pharmacological studies on Glycyrrhiza glabra: A review. Pharmacologyonline. 2011; 2: 1032-1038.
- Assessment report on Glycyrrhiza glabra L. and/or Glycyrrhiza inflata Bat. and/or Glycyrrhiza uralensis Fisch., radix EMA/HMPC/571122/2010.
- Gumpricht E, Dahl R, Devereaux MW, Sokol RJ. Licorice compounds glycyrrhizin and 18beta-glycyrrhetinic acid are potent modulators of bile acid-induced cytotoxicity in rat hepatocytes. J. Biol Chem. Mar 18; 280(11):10556-63.
- Imai T, Sakai M, Ohtake H, Azuma H, Otagiri M. Absorption enhancing effect of glycyrrhizin induced in the presence of capric acid. Int J Pharm. 2005; 27: 11-21.
- Sakai M, Imai T, Ohtake H, Azuma H, Otagiri M. Simultaneous use of sodium deoxycholate and dipotassium glycyrrhizinate enhances the cellular transport of poorly absorbed compounds across Caco-2 cell monolayers. J Pharm Pharmacol. 1999; 51: 27-33.
- Paolino D, Lucania G, Mardente D, Alhaique F, Fresta M. Ethosomes for skin delivery of ammonium glycyrrhizinate: in vitro percutaneous permeation through human skin and in vivo anti-inflammatory activity on human volunteers. J Control Release. 2005; 106(1-2):99-110.
- Wang W, Luo M, Fu Y, Wang S, Efferth T, and Zu Y. Glycyrrhizic acid nanoparticles inhibit LPS-induced inflammatory mediators in 264.7 mouse macrophages compared with unprocessed glycyrrhizic acid. Int J Nanomedicine. 2013; 8: 1377–1383.
- Poosarla A and Athota RR. Immunosuppressive properties of aqueous extract of Plumbago zeylanica in Balb/c mice. Journal of Medicinal Plants Research. 18 October 2010. 4(20): 3041-3046. Available online at http://www.academicjournals.org/JMPR.
- Poosarla A, Veerendra Kumar B., Raghava Rao T., Rao DN and Athota RR. Alleviation of Collagen-induced Arthritis by Plumbago zeylanica. In Mice. Pharmaceutical Biology 2007; 45(1): 54-59.
- Imgenex - Pathway Profiling Antibodies & Reagents. Available at http://www.imgenex.com/tds-inhibitor /Plumbagin-IL-17A-Inhibitor-IMG-2016-10MG. Last accessed on: 24th May 2013.
- Bothiraja C, Pawar AP, Mali AJ, K.S. Shaikh KS. Improved pharmaceutical properties of surface modified bioactive plumbagin crystals. International Journal of Surface Science and Engineering 01/2013.
- Sonlimar M, Sarmalina S. Effect of Grape (Vitis vinifera L.) Seed on Reducing Serum Uric Acid Level in Gout-Animals Model. Artikel Penelitian Majalah Kesehatan PharmaMedika, 2010; 2(1): 106.
- Tang LL, Gao JS, Chen XR, Xie X. Inhibitory effect of resveratrol on the proliferation of synoviocytes in rheumatoid arthritis and its mechanism in vitro Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2006; 31(4):528-33.
- Liu FC, Hung LF, Wu WL, ChangDM, Huang CY, Lai JH et al. Chondroprotective effects and mechanisms of resveratrol in advanced glycation end products-stimulated chondrocytes. Arthritis Research & Therapy2010; 12:R167.
- Elmali N, Esenkaya I, Harma A, Ertem K, Turkoz Y, Mizrak B: Effect of resveratrol in experimental osteoarthritis in rabbits. Inflamm Res 2005; 54:158-162.
- Shakibaei M, Csaki C, Nebrich S, Mobasheri A: Resveratrol suppresses interleukin-1beta-induced inflammatory signaling and apoptosis in human articular chondrocytes: potential for use as a novel nutraceutical for the treatment of osteoarthritis. Biochem Pharmacol 2008; 76:1426-1439.
- Neves AR, Lúcio M, Martins S, Lima JL, Reis S. Novel resveratrol nanodelivery systems based on lipid nanoparticles to enhance its oral bioavailability. International Journal of Nanomedicine. 2013; 2013(8):177 – 187.
- Ansari KA, Vavia PR, Trotta F, and Cavalli R. Cyclodextrin-Based Nanosponges for Delivery of Resveratrol: In Vitro Characterization, Stability, Cytotoxicity and Permeation Study. AAPS PharmSciTech. 2011; 12(1): 279–286.
- Chatterjee A, Pakrashi SC. The Treatise on Indian Medicinal Plants 1995; 4:208-212.
- Anbalagan K, Sadique J. Influence of an Indian medicine (Ashwagandha) on acutephase reactants in inflammation. Indian J Exp Biol 1981; 19:245-249.
- Singh D, Aggarwal A, Maurya R, Naik S. Withania somnifera inhibits NF-kappaB and AP-1 transcription factors in human peripheral blood and synovial fluid mononuclear cells. Phytother Res. 2007; 21(10):905-13.
- Goyal S, Sharma P, Ramchandani U, Shrivastava SK, Dubey PK. Novel Anti-Inflammatory Topical Herbal Gels Containing Withania somnifera and Boswellia serrata. International Journal of Pharmaceutical & Biological Archives 2011; 2(4):1087-1094.
How to cite this article:
Ranade SY and Gaud RS: Current strategies in Herbal Drug Delivery for Arthritis: An Overview. Int J Pharm Sci Res 2013: 4(10); 3782-3794. doi: 10.13040/IJPSR. 0975-8232.4(10).3782-94
All © 2013 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
Article Information
10
3782-3794
504KB
4424
English
IJPSR
Sunita Y. Ranade* and Ram S. Gaud
Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM’s Narsee Monjee Institute of Management Studies, Vile Parle (West), Mumbai – 400 056, Maharashtra, India
sunitaranade12@gmail.com
26 May, 2013
17 July, 2013
13 September, 2013
http://dx.doi.org/10.13040/IJPSR.0975-8232.4(10).3782-94
01 October, 2013