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Randomized double blind trial of an Ayurvedic plant derived formulation for treatment of rheumatoid arthritis

Authors:
  • Centre for Rheumatic Diseases Pune
  • Bioved Pharmaceuticals, Inc., San Jose, California, USA

Abstract

To evaluate RA-1, a standardized plant extract formulation, traditionally considered a safe, effective antiarthritic in the Asian-Indian Ayurvedic medicinal system. One hundred eighty-two patients with active-on-chronic rheumatoid arthritis (RA) participated in a 16 week randomized, double blind, placebo controlled, parallel efficacy clinical drug trial in Pune, India. Tenderness, pain, swelling, and several other efficacy measures were assessed by (1) ACR core set 20% and 50% improvement; (2) ACR 20% improvement response. An intent-to-treat analysis was performed; p<0.05 considered significant. Seventeen patients withdrew (active = 9; placebo = 8); none withdrew due to drug toxicity. An unprecedented placebo response (often p<0.001 in within-group change) was observed. The active RA-1 group remained numerically superior at all evaluation timepoints. RA-1 demonstrated few significant differences: (1) increased proportion with 50% reduction in swollen joint count (95% CI approximately 1.52, 29.90) and swollen joint score (95% CI approximately 0.91, 28.73); (2) reduced rheumatoid factor (95% CI approximately -303.7, -2.72); 39% in the RA-1 group versus 30% placebo showed ACR 20% improvement (95% CI approximately -5.48, 24.59). Only minor side effects were seen, with no significant differences by treatment group. In a trial with sufficient power, RA-1 revealed efficacy that was not significantly superior to the strong placebo response, except for improvement in joint swelling. Further, the effect on RF and good safety profile led to an open label phase.
... Early use of H15 ® also appeared to be beneficial. (20). RA-1 is a traditional formulation consisted of B. serrata, Withania somnifera (ashwagandha), Zingiber officinale (ginger) and Curcuma longa (turmeric) purified extracts (extraction and formulation details were not given), which was administered to the participants in the dose of 444 mg/day (2 tablets 3 times a day), with discontinuation of other RA therapies. ...
... An intent-to-treat (ITT) analysis was performed (statistical tool that includes data collected from all subjects who underwent randomization, regardless of whether they completed the study or not); the number of participants required to assure at least 80% of the test power was calculated before the beginning of the experiment. Seventeen patients withdrew from the study, but none due to adverse drug reactions or toxicity (20). ...
... In this trial, significant improvements were achieved in both RA-active and placebo groups. The RA-1 results were superior to placebo in numerical sense, but the differences never reached statistical significance, except for a percentage of subjects with a 50% reduction in swollen joints count and swollen joint score, reduction in levels of rheumatoid factor (30% reduction vs. 0%, respectively) and relative improvement in the ACR 20% assessment score (39% vs. 30%, respectively) (20). ...
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Boswellia species (Burseraceae) are trees or shrubs whose area of distribution covers the wide geographic area between North Africa and India. After incision, their bark produces oleo-gum resin known as frankincense (Olibanum). In traditional medicine, frankincense is often used for medical treatment of arthritis, asthma, ulcerative colitis, coughs, sores, and wound healing. Various frankincense preparations are marketed almost exclusively as dietary supplements. Indian frankincense, or Olibanum indicum, is official in the European Pharmacopoeia. The major components of frankincense are boswellic acids, among which the most important and abundant is 3-O-acetyl-11-keto-β-boswellic acid (AKBA). AKBA is a 5-lipoxygenase inhibitor with anti-inflammatory and anti-arthritic effects. Besides, frankincense contains essential oil, whose composition greatly depends on the biological source, as well as arabinogalactans and glycoproteins. In small clinical trials, certain benefits of various frankincense preparations have been demonstrated in cases of ulcerative colitis, bronchial asthma, mild symptoms of irritable bowel syndrome, and various disorders of osteo-muscular system. However, for collagenous colitis and Crohn’s disease remission maintenance, the evidence is ambiguous or negative. AKBA-containing extract was found advantageous in patients with osteoarthritis, and to some extent with rheumatoid arthritis. Almost all the trials had serious flaws in experimental design, such as insufficient sample size and/or incomplete reporting of data. For any clinical recommendation of frankincense preparations, larger and better-designed studies are needed.
... Nearly 60% of people look for an alternative herbal remedy for the long term cure of RA (Rao et al., 1999) Chopra et al., 2000 demonstrated the antiarthritic potential of an ayurvedic tablet, RA-1 containing of Boswellia serrata, Withania somnifera, Z. officinale and Curcuma longa in 182 patients for 4 months. From the increase in the daily dose of 444 mg, almost 50% of arthritic patients showed significantly reduced the swelling of bones when compared with the placebo patients. ...
... From the increase in the daily dose of 444 mg, almost 50% of arthritic patients showed significantly reduced the swelling of bones when compared with the placebo patients. Studies using herbal medicines still need improvised and standardized trials considering the efficacy and safety for the global recognition of traditional herbal medicines (Chopra et al., 2000). Our investigation majorly focused on searching of nutraceutically valuable new molecules from herbal plant of Z. officinale with suitable biological efficacy and least toxicity for treatment of arthritis. ...
Article
Rheumatoid Arthritis (RA) is an autoimmune disorder that leads to joint and bone destruction. The available anti-inflammatory chemo drugs are associated with adverse side-effects providing only temporary relief. Herbal medicine can act as an alternative source for RA treatment with improved efficacy, lesser toxicity and side effects. An attempt was made to evaluate the antioxidant and anti-arthritic potential of ginger (Zingiber officinale Rosc.). Crude ginger extracts were prepared with different organic solvents using soxhlet approach. The extracts were assessed for their anti-oxidant activity using DPPH, ABTS and nitric oxide radical inhibition assays and anti-arthritic activity through membrane stabilization assay, anti-proteinase activity and protein denaturation inhibition assays. The highest scavenging potential was exhibited by Z. officinale methanolic extract (ZOME) as assessed by DPPH assay (86.26 § 0.97%), ABTS assay (91.04 § 0.96%) and nitric oxide assay (86.72 § 1.51%). Similarly, the ZOME showed 84.72 § 1.38% of inhibition in membrane stabilization assay, 82.72 § 1.48% in anti-proteinase activity and 81.68 § 1.66% in protein denaturation inhibition capacity. GCMS analysis of ZOME showed 30 different phytoconstituents. The major ginger bioactive compounds were virtually docked with novel RA targets using PyRx and the pharmacokinetic properties like ADMET properties were evaluated. Among all, 8-Gingerol showed the highest covalent interaction along with suitable binding affinity to the RA targets of COX-II (�7.2), TNF-a (�4.7), MCSF (�5.0), IL-1b (�5.7) and MMP9 (�6.7) kcal/ mol. 8-Gingerol can be a better drug candidate that must be further investigated for mechanistic studies to verify its therapeutic potential in treating RA.
... It has also been stated that mushrooms or mushroom-based dietary products mitigated autoimmune disorders and cancer . A standardized formulation made with purified extract of Withania somnifera, Boswellia serrata, and Curcuma longa has been found effective in improving joint-swelling condition and rheumatoid arthritis (Chopra et al. 2000). In addition, potent vaccine adjuvant properties of Withania somnifera and Asparagus racemosus have also been assessed and recommended for their importance in immunobiological preparations. ...
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Medicinally important plant-foods offer a balanced immune function, which is essential for protecting the body against antigenic invasion, mainly by microorganisms. immunomodulators play pivotal roles in supporting immune function either suppressing or stimulating the immune system's response to invading pathogens. Among different immunomodulators, plant-based secondary metabolites have emerged as high potential not only for immune defense but also for cellular immunoresponsiveness. These natural immunomodulators can be developed into safer alternatives to the clinically used immunosuppressants and immunostimulant cytotoxic drugs which possess serious side effects. Many plants of different species have been reported to possess strong immunomodulating properties. The immunomodulatory effects of plant extracts and their bioactive metabolites have been suggested due to their diverse mechanisms of modulation of the complex immune system and their multifarious molecular targets. Phytochemicals such as alkaloids, flavonoids, terpenoids, carbohydrates and polyphenols have been reported as responsible for the immunomodulatory effects of several medicinal plants. This review illustrates the potent immunomodulatory effects of 65 plant secondary metabolites, including dietary compounds and their underlying mechanisms of action on cellular and humoral immune functions in in vitro and in vivo studies. The clinical potential of some of the compounds to be used for various immune-related disorders is highlighted.
... The secondary outcome for the study consisted of a change in WOMAC subscales of pain (scale of 0-4; averaged response of 5 questions), stiffness (scale of 0-4; averaged response for 2 questions), and physical function (scale of 0-4; averaged response for 17 questions) [20]. Other measures performed included health-related quality of life as evaluated by a validated EQ-5D-5L ...
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Background Osteoarthritis (OA) of the knee is the most common type of arthritis, increasing with advancing age and external factors such as obesity. Joint health has historically relied on nutritional supplements derived from herbs and other natural products. Undenatured collagen type II demonstrated positive results with substantially lower therapeutic doses. Hence, the present study was designed to determine the efficacy and safety of Native CT-II®, an undenatured type II collagen, on the symptomatic effects in individuals having joint pain due to OA. Methods A randomized, double-blinded, placebo-controlled, parallel study was conducted on 101 slightly overweight volunteers, whose knee joint pain VAS score was ≥ 60 had been included in the study for at least three months. The participants were divided into three groups, with similar demographic and baseline characteristics. The test product containing Native CT-II®, positive control containing G+C, and the placebo were taken six tablets per day for 84 consecutive days (Three capsules to be taken post-breakfast and three capsules post-dinner). Improvement in overall joint health in each participant from baseline to end of the study was measured by WOMAC, self-administered questionnaire in Native CT-II® as compared to G+C and placebo group. Results This study demonstrated that Native CT-II® had an effective impact on the symptomatic effects of knee impairment associated with OA and in the quality of life of the participants. After 84 days, participants receiving Native CT-II® and G+C had significant improvement in overall joint health as compared to participants receiving placebo. Conclusion Native CT-II® was shown to be effective in relieving symptoms and improving quality of life for patients with knee joint pain associated with OA. Trial registration The trial was registered with the clinical trial registry of the U.S. National Library of Medicine under National Institutes of Health (NIH) (https://clinicaltrials.gov/) with the National Clinical Trial (NCT) No: NCT04470336, Date of first registration: 14/07/2020.
... The first RCT using polyherbal ayurvedic medicine was published in 2000 [21]. A standardized formulation was compared with a placebo group. ...
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