Research - Boswellia serrata
A randomized, double blind, placebo controlled, cross over study to evaluate the analgesic activity of Boswellia serrata in healthy volunteers using mechanical pain model.
Prabhavathi K1, Chandra US1, Soanker R1, Rani PU1.
Abstract
OBJECTIVE:Experimental pain models in human healthy volunteers are advantageous for early evaluation of analgesics. All efforts to develop nonsteroidal anti-inflammatory drugs (NSAIDs) which are devoid of gastrointestinal and cardiovascular system effects are still far from achieving a breakthrough. Hence we evaluated the analgesic activity of an ayurvedic drug, Boswellia serrata by using validated human pain models which has shown its analgesic activity both in-vitro and preclinical studies to evaluate the analgesic activity of single oral dose (125 mg, 2 capsules) of Boswellia serrata compared to placebo using mechanical pain model in healthy human subjects.
MATERIALS AND METHODS:After taking written informed consent, twelve healthy subjects were randomized (1:1) to receive single oral dose of Boswellia serrata (Shallaki (®)) 125 mg, 2 capsules or identical placebo in a crossover design. Mechanical pain was assessed using Ugo basile analgesymeter (by Randall Selitto test) at baseline and at 1 hr, 2 hrs and 3 hrs after test drug administration. Pain Threshold force and time and Pain Tolerance force and time were evaluated. Statistical analysis was done by paired t-test.
RESULTS:Twelve healthy volunteers have completed the study. Mean percentage change from baseline in Pain Threshold force and time with Boswellia serrata when compared to placebo had significantly increased [Force: 9.7 ± 11.0 vs 2.9 ± 3.4 (P = 0.05) and time: 9.7 ± 10.7 vs 2.8 ± 3.4 (P = 0.04)] at third hr. Mean Percentage change from baseline in Pain Tolerance force and time with Boswellia serrata when compared to placebo had significantly (P ≤ 0.01) increased at 1 hr, 2 hrs and 3 hrs.
CONCLUSION:In the present study, Boswellia serrata significantly increased the Pain Threshold and Pain Tolerance force and time compared to placebo. Both study medications were well tolerated. Further multiple dose studies may be needed to establish the analgesic efficacy of the drug.
Source : Indian Journal of Pharmacology
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Curcumin downregulates expression of opioid-related nociceptin receptor gene (OPRL1) in isolated neuroglia cells
Ean-JeongSeoaThomasEfferthaAlexanderPanossianb
Abstract
Background
Curcumin (CC) exerts polyvalent pharmacological actions and multi-target effects, including pain relief and anti-nociceptive activity. In combination with Boswellia serrata extract (BS), curcumin shows greater efficacy in knee osteoarthritis management, presumably due to synergistic interaction of the ingredients.
Aim
To elucidate the molecular mechanisms underlying the analgesic activity of curcumin and its synergistic interaction with BS.
MethodsWe performed gene expression profiling by transcriptome-wide mRNA sequencing in human T98G neuroglia cells treated with CC (Curamed®), BS, and the combination of CC and BS (CC-BS; Curamin®), followed by interactive pathways analysis of the regulated genes.
Results
Treatment with CC and with CC-BS selectively downregulated opioid-related nociceptin receptor 1 gene (OPRL1) expression by 5.9-fold and 7.2-fold, respectively. No changes were detected in the other canonical opioid receptor genes: OPRK1, OPRD1, and OPRM1. Nociceptin reportedly increases the sensation of pain in supra-spinal pain transduction pathways. Thus, CC and CC-BS may downregulate OPRL1, consequently inhibiting production of the nociception receptor NOP, leading to pain relief. In neuroglia cells, CC and CC-BS inhibited signaling pathways related to opioids, neuropathic pain, neuroinflammation, osteoarthritis, and rheumatoid diseases. CC and CC-BS also downregulated ADAM metallopeptidase gene ADAMTS5 expression by 11.2-fold and 13.5-fold, respectively. ADAMTS5encodes a peptidase that plays a crucial role in osteoarthritis development via inhibition of a corresponding signaling pathway.
Conclusion
Here, we report for the first time that CC and CC-BS act as nociceptin receptor antagonists, selectively downregulating opioid-related nociceptin receptor 1 gene (OPRL1) expression, which is associated with pain relief. BS alone did not affect OPRL1 expression, but rather appears to potentiate the effects of CC via multiple mechanisms, including synergistic interactions of molecular networks.
Source : Journal Phytomedicine
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Combination of Boswellia and Curcumin in Chronic Kidney Disease
Moreillon JJ, Bowden RG, Deike E, et al. The use of an anti-inflammatory supplement in patients with chronic kidney disease. J Complement Integr Med. 2013;10(1):1-10. doi: 10.1515/jcim-2012-0011.
Chronic kidney disease (CKD), which affects about 20 million Americans, is expected to rise in incidence because of the increase in diabetes, hypertension, and obesity. CKD is characterized by a chronic inflammatory state, with elevated levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in all stages of the disease. Patients with CKD also exhibit lower levels of plasma glutathione peroxidase (GPx) and other antioxidant enzymes. In most patients, CKD is not diagnosed early when the disease is asymptomatic, which is of concern because of the relationship between the systemic inflammation of the disease and the risk for cardiovascular disease (CVD). In addition to pharmaceuticals such as statins and angiotensin-converting enzyme inhibitors, complementary and alternative medicine therapies used to treat CKD are gaining interest in the scientific community. The authors conducted a study to evaluate the inflammatory and antioxidant responses of 8 weeks of curcumin (from turmeric; Curcuma longa) and boswellia (Indian frankincense; Boswellia serrata) supplementation in patients with mild-to-moderate CKD.
Patients at a community health center in Central Texas who were older than 18 years of age and had CKD in stages 1 through 5 were recruited for the study. Patients completed a medical history questionnaire and underwent a general physical examination by their physician to determine eligibility. The patients were randomly chosen to receive an herbal supplement of curcumin and boswellia (824 mg purified turmeric extract, 95% curcuminoids, and 516 mg boswellia extract, 10% 3-acetyl-11-keto-β-boswellic acid) or placebo (roasted rice [Oryza sativa] powder). The study supplement was added to the patients' existing treatment protocols. The study outcome variables were plasma IL-6, TNF-α, GPx, and serum C-reactive protein (CRP).
The patients participated in 2 testing sessions 8 weeks apart. During session 1, they donated blood after a 12-hour fast and underwent measurements for height, weight, heart rate, blood pressure, and waist and hip circumferences. They were then given an 8-week supply of the supplement or placebo and instructed to ingest 2 capsules daily (1 in the morning with breakfast and 1 in the evening with dinner) and to continue their usual medications. After 8 weeks, the patients returned to the clinic for another blood draw and a pill count to determine compliance. The patients' diets were not standardized; they maintained their normal dietary habits during the study.
Sixteen patients (out of an original 23) completed the study. At baseline, the placebo group (n=7) had significantly higher values for height (P=0.05), body mass index (BMI) (P=0.01), waist circumference (P=0.03), and hip circumference (P=0.02). Glomerular filtration rate (GFR), used to determine kidney function, was not significantly different between the groups. The authors report that baseline data demonstrated elevated inflammation and low antioxidant levels.
A significant time effect (P=0.03; effect size [ES]=0.32) and time × compliance interaction effect (P=0.05; ES=0.30) were observed for IL-6, with a decrease in the treatment group and an increase in the placebo group. No significant group, time, or interaction effects were seen for any of the other outcome variables. Noting that these findings partially support earlier research on the anti-inflammatory effects of curcumin and boswellia, the authors write: "Reasons for [only] partial support of previous literature could be due to a dose-response relationship, short study duration, influence of anti-inflammatory medications, small sample size, or lack of interaction between curcumin, Boswellia serrata, and some markers of inflammation." CRP and IL-6 have been shown to be significantly correlated.1 The authors explain that the lack of change in CRP in this study may be due to the high prevalence of nonsteroidal anti-inflammatory drug use by the study subjects, as most patients were taking aspirin to reduce the risk for myocardial infarction, which may have inhibited curcumin's effectiveness against CRP.
According to the authors, the lack of a statistical change in GPx levels may be due to the study duration and sample size: "A supplementation period of 8 weeks may have been of insufficient magnitude to observe changes in GPx, and the sample size used in the present study was small, with larger studies needed to determine if curcumin's antioxidant benefits observed in animal studies carry over to humans."
Only minor adverse side effects were reported during the study.
These results support those of previous studies suggesting that CKD is associated with an ongoing inflammatory state and impaired antioxidant activity. The study treatment was well tolerated and resulted in decreased inflammation as measured by IL-6; however, no changes were observed in any other inflammatory or antioxidant markers.
―Shari Henson
Reference
1Heinrich PC, Castell JV, Andus T. Interleukin-6 and the acute phase response. Biochem J. 1990;265(3):621-636.
Source : American Botanical Council
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Turmeric and Boswellia Combination Reduces Knee Osteoarthritis Symptoms More Effectively than Celecoxib
Kizhakkedath R. Clinical evaluation of a formulation containing Curcuma longa and Boswellia serrata extracts in the management of knee osteoarthritis. Mol Med Rep. November 2013;8(5):1542-1548.
The degenerative joint disease osteoarthritis (OA) is physically debilitating and significantly impairs quality of life. As the cause of OA remains unknown, current medical treatment is directed towards alleviating pain and restoring movement using nonsteroidal anti-inflammatory drugs (NSAIDs). However, long term use of NSAIDs is associated with significantly increased risk of gastrointestinal, renal, and cardiovascular adverse effects. Turmeric (Curcuma longa) rhizome has been shown to have both anti-inflammatory and antioxidant activity. In clinical trials, boswellia (Indian frankincense; Boswellia serrata) gum resin has shown positive effects in treating both rheumatoid arthritis and OA. This randomized, observational trial tested the efficacy of a turmeric and boswellia (CB) combination in comparison to celecoxib (a standard NSAID) in alleviating the symptoms of knee OA.
The CB combination consisted of 350 mg of turmeric extract standardized to contain 70% curcumin, 17% demethoxycurcumin, 3.5% bisdemethoxycurcumin, and 7.5% turmeric essential oils, and 150 mg boswellia extract consisting of 75% boswellic acids and 10% 3-O-acetyl-11-keto-boswellic acid (AKBA). Although the turmeric constituent curcumin has been shown to have significant anti-inflammatory activity, oral bioavailability is very poor. A formulation providing improved curcumin bioavailability was used in this study. And while the boswellia constituent AKBA also has significant anti-inflammatory activity, the authors point out that most commercial boswellia extracts contain a relatively low concentration of AKBA (~2%). The boswellia extract used in this study was "enhanced" to contain 10% AKBA. The CB combination was provided in 500 mg capsules produced by Arjuna Natural Extracts Ltd.; Aluva, Kerala, India. No other information on the proprietary formula was provided.
In this 12-week study, conducted at Anugraha Medical Centre in Kochi, Kerala, India, 30 patients with OA were randomly assigned to receive either 500 mg of CB twice daily or 100 mg of celecoxib 2 times per day. The study included 8 clinic visits where vital signs, OA symptom scores, and physical exam results were recorded. Included patients were men and women between 18-65 years old diagnosed with moderate OA based upon radiographic evidence. Those with gross OA deformity, severe OA, severe swelling and restricted mobility, rheumatoid or reactive arthritis, other systemic diseases, malnutrition, history of alcohol or drug abuse, and breastfeeding women were excluded.
The OA symptoms scored were joint pain (no pain, mild, moderate, or severe), walking distance (greater than 1,000 m, 500-1,000 m, 100-500 m, or less than 100 m), joint tenderness (no tenderness, improved, same, or worsened), and crepitus or crackling sounds (no crepitus, mild, moderate, or severe). Knee swelling and thigh circumference were quantified using a measuring tape and range of movement was assessed in degrees using a goniometer. Joint warmth (yes, no) and gait (normal or abnormal) were also assessed. To evaluate safety, vital signs, hemogram (laboratory blood parameters), and liver and kidney function were measured at baseline, 6 weeks, and 12 weeks. The authors did not indicate whether they queried patients about possible adverse effects.
In total, 28 patients finished the study, with 1 patient from each group dropping out due to personal reasons or uncontrolled symptoms. At baseline, no significant differences were observed in age, height, weight, body mass index (BMI), temperature, blood pressure, pulse rate, or respiration between the groups. Although pain severity significantly improved from baseline to endpoint (P<0.05) in both groups, no significant differences between groups were observed. However, the number of patients improved was markedly higher in the treatment group; 85.71% of patients were classified in the moderate/severe range at baseline, and at endpoint, only 21.43% of patients were in this category. In the control group, 78.57% of the patients had moderate/severe pain at baseline and 50% still had moderate/severe pain at the endpoint.
Improvement in walking distance was seen in both groups (P<0.05), with 92.86% of those in the treatment group and 85.71% of those in the control group able to walk more than 1000 m at endpoint; however, there were no significant differences between groups. Also, both groups had significantly less joint tenderness at the end of the study (P<0.05). In the treatment group, 85.71% had moderate/severe joint tenderness at baseline, and this decreased to 7.14% of patients at the end of the study. Patients in the control group showed a smaller improvement in joint tenderness, declining from 78.57% at baseline to 21.43% of patients after 12 weeks of treatment. Crepitus improved in both groups from baseline to endpoint (P<0.05); there was also a significant beneficial effect seen in range of movement (P<0.05) in both groups. Swelling, joint warmth, gait, and thigh measurements were not changed in either group. Vital signs, blood parameters, and liver and kidney function remained unchanged. No adverse effects were reported in either group.
The authors conclude that improvements in pain severity, walking distance, and joint tenderness were superior in those taking the CB supplement compared to the NSAID control medication and that CB was comparable to celecoxib in increasing range of movement and decreasing crepitus. They state, "The efficacy and tolerability of [the] CB formulation used in the current study was shown to be superior to those of celecoxib (NSAID) for treating active OA."
The authors hypothesized that the CB formulation would be as effective as celecoxib in reducing OA symptoms, and cause fewer adverse effects. While the effectiveness of the 2 treatments appeared to be comparable, no adverse effects were reported in either group. Studies with a larger sample size are needed to confirm the efficacy of CB and to detect differences in the occurrence rate of adverse effects.
--Amy C. Keller, PhD
Source : American Botanical Council
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