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Boswellia (Boswellia serrata) and Arthritis / joint pain: evidence and sources
Osteoarthritis: reduces joint pain and stiffness and improves function (over at least 4 weeks); Supports inflammatory arthritis including rheumatoid arthritis
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Background Osteoarthritis (OA) is the commonest form of inflammatory joint disease. Unfortunately, to date, there is no appropriate treatment for OA. Boswellia serrata was considered as a potent anti-inflammatory, anti-arthritic and analgesic agent that may be a drug for OA. Methods In this meta-analysis, data from randomized controlled trials were obtained to assess the effects of Boswellia or its extract versus placebo or western medicine in patients with OA. The primary outcomes included visual analogue score (VAS), WOMAC pain, WOMAC stiffness, WOMAC function and lequesne index. Result Seven trials involving 545 patients were included. Compared with the control group, Boswellia and its extract may relieve the pain [VAS: (WMD -8.33; 95% CI -11.19, - 5.46; P Conclusion Based on current evidence, Boswellia and its extract may be an effective and safe treatment option for patient with OA, and the recommended duration of treatment with Boswellia and its extract is at least 4 weeks.
Objective To investigate the efficacy and safety of dietary supplements for patients with osteoarthritis. Design An intervention systematic review with random effects meta-analysis and meta-regression. Data sources MEDLINE, EMBASE, Cochrane Register of Controlled Trials, Allied and Complementary Medicine and Cumulative Index to Nursing and Allied Health Literature were searched from inception to April 2017. Study eligibility criteria Randomised controlled trials comparing oral supplements with placebo for hand, hip or knee osteoarthritis. Results Of 20 supplements investigated in 69 eligible studies, 7 (collagen hydrolysate, passion fruit peel extract, Curcuma longa extract, Boswellia serrata extract, curcumin, pycnogenol and L-carnitine) demonstrated large (effect size >0.80) and clinically important effects for pain reduction at short term. Another six (undenatured type II collagen, avocado soybean unsaponifiables, methylsulfonylmethane, diacerein, glucosamine and chondroitin) revealed statistically significant improvements on pain, but were of unclear clinical importance. Only green-lipped mussel extract and undenatured type II collagen had clinically important effects on pain at medium term. No supplements were identified with clinically important effects on pain reduction at long term. Similar results were found for physical function. Chondroitin demonstrated statistically significant, but not clinically important structural improvement (effect size -0.30, -0.42 to -0.17). There were no differences between supplements and placebo for safety outcomes, except for diacerein. The Grading of Recommendations Assessment, Development and Evaluation suggested a wide range of quality evidence from very low to high. Conclusions The overall analysis including all trials showed that supplements provided moderate and clinically meaningful treatment effects on pain and function in patients with hand, hip or knee osteoarthritis at short term, although the quality of evidence was very low. Some supplements with a limited number of studies and participants suggested large treatment effects, while widely used supplements such as glucosamine and chondroitin were either ineffective or showed small and arguably clinically unimportant treatment effects. Supplements had no clinically important effects on pain and function at medium-term and long-term follow-ups.
A double-blind, placebo-controlled human trial was conducted to evaluate the safety and efficacy of a standardized oral supplementation of Boswellin®, a novel extract of Boswellia serrata extract (BSE) containing 3-acetyl-11-keto-β-boswellic acid (AKBBA) with β-boswellic acid (BBA). A total of 48 patients with osteoarthritis (OA) of the knee were randomized and allocated to the BSE and placebo groups for intervention. Patients were administered BSE or placebo for a period of 120 days. The trial results revealed that BSE treatment significantly improved the physical function of the patients by reducing pain and stiffness compared with placebo. Radiographic assessments showed improved knee joint gap and reduced osteophytes (spur) confirming the efficacy of BSE treatment. BSE also significantly reduced the serum levels of high-sensitive C-reactive protein, a potential inflammatory marker associated with OA of the knee. No serious adverse events were reported. This is the first study with BSE conducted for a period of 120 days, longer than any other previous clinical trial on patients with OA of the knee. The findings provide evidence that biologically active constituents of BSE, namely, AKBBA and BBA, act synergistically to exert anti-inflammatory/anti-arthritic activity showing improvement in physical and functional ability and reducing the pain and stiffness.
Boswellic acids, which are pentacyclic triterpenes belong to the active pharmacological compounds of the oleogum resin of different Boswellia species. In the resin, more than 12 different boswellic acids have been identified but only KBA and AKBA received significant pharmacological interest. Biological Activity: In an extract of the resin of Boswellia species multiple factors are responsible for the final outcome of a therapeutic effect, be it synergistic or antagonistic. Moreover, the anti-inflammatory actions of BAs are caused by different mechanisms of action. They include inhibition of leukotriene synthesis and to a less extend prostaglandin synthesis. Furthermore inhibition of the complement system at the level of conversion of C3 into C3 a and C3 b . A major target of BAs is the immune system. Here, BEs as well as BAs including KBA and AKBA, have been shown to decrease production of proinflammatory cytokines including IL-1, IL-2, IL-6, IFN-γ and TNF-α which finally are directed to destroy tissues such as cartilage, insulin producing cells, bronchial, intestinal and other tissues. NFĸB is considered to be the target of AKBA. The complex actions of BEs and BAs in inflamed areas may be completed by some effects that are localized behind the inflammatory process as such tissue destruction. In this case, in vitro- and animal studies have shown that BAs and BEs suppress proteolytic activity of cathepsin G, human leucocyte elastase, formation of oxygen radicals and lysosomal enzymes. Pharmacokinetics Whereas KBA is absorbed reaching blood levels being close to in vitro IC 50, AKBA which is more active in in vitro studies than KBA, but undergoes much less absorption than KBA. However, absorption of both is increased more than twice when taken together with a high-fat meal.Clinical Studies There are a variety of chronic inflammatory diseases which respond to treatment with extracts from the resin of Boswellia species. Though, the number of cases is small in related clinical studies, their results are convincing and supported by the preclinical data. These studies include rheumatoid arthritis, osteoarthritis, chronic colitis, ulcerative colitis, collagenous colitis, Crohn's disease and bronchial asthma. It can not be expected that there is cure from these diseases but at least improvement of symptoms in about 60-70 % of the cases. Side Effects The number and severity of side effects is extremely low. The most reported complaints are gastrointestinal symptoms. Allergic reactions are rare. And most authors report, that treatment with BEs is well tolerated and the registered side effects in BE- and placebo groups are similar.
4 sources supporting Boswellia for Arthritis / joint pain. Includes scientific publications, books, monographs and traditional-use references.
Mechanistic basis
This use is associated with the plant's anti-inflammatory action. Further evidence for that pharmacology:
The resin of Boswellia species has been used as incense in religious and cultural ceremonies and in medicines since time immemorial. Boswellia serrata (Salai/Salai guggul), is a moderate to large sized branching tree of family Burseraceae (Genus Boswellia), grows in dry mountainous regions of India, Northern Africa and Middle East. Oleo gum-resin is tapped from the incision made on the trunk of the tree and is then stored in specially made bamboo basket for removal of oil content and getting the resin solidified. After processing, the gum-resin is then graded according to its flavour, colour, shape and size. In India, the States of Andhra Pradesh, Gujarat, Madhya Pradesh, Jharkhand and Chhattisgarh are the main source of Boswellia serrata. Regionally, it is also known by different names. The oleo gum-resins contain 30-60% resin, 5-10% essential oils, which are soluble in the organic solvents, and the rest is made up of polysaccharides. Gum-resin extracts of Boswellia serrata have been traditionally used in folk medicine for centuries to treat various chronic inflammatory diseases. 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 and acetyl-11-keto-β-boswellic acid, responsible for inhibition of pro-inflammatory enzymes. Out of these four boswellic acids, acetyl-11-keto-β-boswellic acid is the most potent inhibitor of 5-lipoxygenase, an enzyme responsible for inflammation.
Background and objective Aflapin ® , also known as AprèsFlex ® was developed as an enhanced bioavailable extract of Boswellia serrata gum resin, standardized to 20% 3-O-acetyl-11-keto-β-boswellic acid. This randomized, double-blind, placebo-controlled clinical trial confirms the efficacy of Aflapin in ameliorating the symptoms of osteoarthritis (OA) of the knee. Methods Based on the inclusion/exclusion criteria of the American College of Rheumatology, seventy subjects were recruited and randomized into Placebo (n = 35) and Aflapin (n = 35) groups. Subjects received either 100 mg Aflapin or a placebo for 30 days. All subjects were evaluated for pain and physical function using the standard tools i.e., Visual Analog Scale (VAS), Lequesne Functional Index (LFI), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at the baseline (Day 0), 5, and 30 days of treatment. Additionally, several inflammatory and cartilage biomarkers, including matrix metalloproteinase-3 (MMP-3), tumor necrosis factor-α (TNFα), high-sensitive C-reactive protein (hsCRP), Cartilage Oligomeric Matrix Protein (COMP), and collagen type II cleavage (C2C) were evaluated. Total blood chemistry analyses were conducted to affirm the safety of Aflapin. Results Sixty-seven subjects completed the study. Aflapin conferred significant improvements in pain scores as early as five days of treatment. Post-trial, VAS, LFI, WOMAC pain, WOMAC stiffness, WOMAC function, and total WOMAC scores decreased in the Aflapin group by 45%, 40.9%, 44.4%, 66.3%, 44.4%, and 48%, respectively. Aflapin supplementation also reduced circulating MMP-3, TNFα, hsCRP, and C2C. Conclusion This investigation affirms that Aflapin is clinically efficacious, fast-acting, and safe in the management of osteoarthritis. No significant adverse effects were observed.
Non-steroidal anti-inflammatory drug (NSAID) intake is associated with high prevalence of gastrointestinal or cardiovascular adverse effects. All efforts to develop NSAIDs that spare the gastrointestinal tract and the cardiovasculature are still far from achieving a breakthrough. In the last two decades, preparations of the gum resin of Boswellia serrata (a traditional ayurvedic medicine) and of other Boswellia species have experienced increasing popularity in Western countries. Animal studies and pilot clinical trials support the potential of B. serrata gum resin extract (BSE) for the treatment of a variety of inflammatory diseases like inflammatory bowel disease, rheumatoid arthritis, osteoarthritis and asthma. Moreover, in 2002 the European Medicines Agency classified BSE as an 'orphan drug' for the treatment of peritumoral brain oedema. Compared to NSAIDs, it is expected that the administration of BSE is associated with better tolerability, which needs to be confirmed in further clinical trials. Until recently, the pharmacological effects of BSE were mainly attributed to suppression of leukotriene formation via inhibition of 5-lipoxygenase (5-LO) by two boswellic acids, 11-keto-β-boswellic acid (KBA) and acetyl-11-keto-β-boswellic acid (AKBA). These two boswellic acids have also been chosen in the monograph of Indian frankincense in European Pharmacopoiea 6.0 as markers to ensure the quality of the air-dried gum resin exudate of B. serrata. Furthermore, several dietary supplements advertise the enriched content of KBA and AKBA. However, boswellic acids failed to inhibit leukotriene formation in human whole blood, and pharmacokinetic data revealed very low concentrations of AKBA and KBA in plasma, being far below the effective concentrations for bioactivity in vitro. Moreover, permeability studies suggest poor absorption of AKBA following oral administration. In view of these results, the previously assumed mode of action - that is, 5-LO inhibition - is questionable. On the other hand, 100-fold higher plasma concentrations have been determined for β-boswellic acid, which inhibits microsomal prostaglandin E synthase-1 and the serine protease cathepsin G. Thus, these two enzymes might be reasonable molecular targets related to the anti-inflammatory properties of BSE. In view of the results of clinical trials and the experimental data from in vitro studies of BSE, and the available pharmacokinetic and metabolic data on boswellic acids, this review presents different perspectives and gives a differentiated insight into the possible mechanisms of action of BSE in humans. It underlines BSE as a promising alternative to NSAIDs, which warrants investigation in further pharmacological studies and clinical trials.
Extracts from the gum resin of Boswellia serrata and some of is constituents including boswellic acids affect the immune system in different ways. Among the various boswellic acids 11-keto-beta-boswellic acid (KBA) and acetyl-11-keto-beta-boswellic acid have been observed to be active. However, also other boswellic acids may exhibit actions in the immune system. In the humoral defence system a mixture of boswellic acis at higher doses reduced primary antibody titres; on the other hand lower doses enhanced secondary antibody titres following treatment with sheep erythrocytes. In the cellular defence boswellic acides appear to increase lymphocyte proliferation whereas higher concentrations are even inhibitory. Moreover, BAs increase phagocytosis of macrophages. BAs affect the cellular defence system by interaction with production/release of cytokines. Thus, BAs inhibit activation of NFkappaB which is a product of neutrophile granulocytes. Consequently a down regulation of TNF-alpha and decrease of IL-1, IL-2, IL-4, IL-6 and IFN-gamma, which are proinflammatory cytokines by BEs and BAs has been reported. Suppressions of the classic way of the complement system was found to be due to inhibition of the conversion of C3 into C3a and C3b. However, which of these pharmacological actions contribute to the therapeutic effects and which is finally the best dosage of a standardized extract needs further examination. And it is also a question whether or not a single BA will have the same therapeutic effect as a standardized extract. Among the mediators of inflammatory reaction, mast cell stabilisation has been described by a BE. Inhibition of prostaglandin synthesis appears to play only a minor role as far as the anti-inflammatory effect is concerned. On the other hand the inhibitory action of BAs on 5-LO leading to a decreased production of leukotrienes has received high attention by the scientific community since a variety of chronic inflammatory diseases is associatied with increased leukotriene activity. At the end of the cascade of events in the cellular immune system as far as it directs to various tissues of the body - i.e. autoimmune diseases - formation of oxygen radicals and proteases (for example elastase) play an important destructive role. Here, BEs as well as BAs have been found to be inhibitory. From the pharmacological properties of BEs and BAs it is not surprising that positive effects of BEs in some chronic inflammatory diseases including rheumatoid arthritis, bronchial asthma, osteoarthritis, ulcerative colitis and Crohn's disease have been reported.
The boswellic acids, the active compounds in Boswellia serrata gum resin extract, are potent anti-inflammatory agents and are specific nonredox inhibitors of 5-Lipoxygenase (5-LOX). Here, we present the anti-osteoarthritis (OA) efficacy of LI13019F1 (also known as Serratrin®), a unique composition containing the acidic and nonacidic fractions of B. serrata gum resin. This composition strongly inhibited 5-LOX activity with the half-maximal inhibitory concentration (IC 50 ) of 43.35 ± 4.90 μ g/mL. Also, LI13019F1 strongly inhibited the leukotriene B 4 (IC 50 , 7.80 ± 2.40 μ g/mL) and prostaglandin E 2 (IC 50 , 6.19 ± 0.52 μ g/mL) productions in human blood-derived cells. Besides, LI13019F1 reduced TNF- α production with the IC 50 of 12.38 ± 0.423 μ g/mL. On average, 1, 2.5, and 5 μ g/mL doses of LI13019F1 protected 34.62, 47.66, and 62.29% SW1353 human chondrosarcoma cells from IL-1 β induced SOX-9 depletion, respectively. Further, a 28-day preclinical proof-of-concept study evaluated the pain relief efficacy of LI13019F1 in monoiodoacetate- (MIA-) induced Sprague-Dawley rats. At the end of the study, 150 and 300 mg/kg doses of LI13019F1 supplemented rats showed significant improvements (55.17 ± 5.81 g ( p p p p B. serrata gum resin extracts, reduces pain and protects articular cartilage from the damaging action of MIA in a rodent model.
Context Osteoarthritis (OA) of the hand is a common painful musculoskeletal disorder with no cure. There is a need for an efficient and safe treatment to relieve OA pain. Objective To investigate the effects of a Curcuma longa and Boswellia serrata food supplement in addition to standard care on hand pain. Materials and methods This open-label, non-controlled, post-observational study was based on 232 patients suffering from hand pain with or without joint deformity. Patients received a medical prescription for a three-month treatment with a food supplement containing 89 mg of C. longa dry extract, 120 mg of B. serrata resin, and 1.8 µg vitamin D. Pain was evaluated on a 10-point visual analog scale (VAS). The number of painful hand joints, patient satisfaction, nonsteroidal anti-inflammatory drugs intake, and side effects were also recorded. Results Baseline pain intensity (regression coefficient ± SE : -0.19 ± 0.01, p SE : -0.022 ± 0.0029, p p p Conclusion This is the first clinical trial showing that C. longa and B. serrata resin can relieve symptoms in patients with hand osteoarthritis. The study provides useful information for the design of a clinical trial including a broader population.
The review summarizes the published data on identification of biologically active compounds (BACs) and the pharmacological potential of various components of oleo-gum resin from the Indian frankincense Boswellia serrata Roxb. ex Colebr. Boswellia oleo-gum resin contains a wide range of BACs from the classes of mono-, sesqui-, di-, and triterpenes. Numerous in vivo and in vitro studies demonstrated their anti-inflammatory and antiproliferative effects. Boswellic acids (BAs), which belong to the tetra- and pentacyclic triterpenoid classes, showed the highest anti-inflammatory activity. The frankincense resin is traditionally used in Ayurvedic and Unani medicine and can provide a promising source to design drugs effective in treating musculoskeletal disorders.