ABSTRACT : Objectives: Boswellia serrata extract is a traditional remedy for joint health with an anti-inflammatory effect. The present trial investigated the effect of Boswellin® Super (BS), a standardized extract from the gum resin of B. serrata containing Boswellic acids, on reducing knee pain. Methods: This study was a randomized, double-blind, placebo-controlled trial. Patients reported with knee pain were assigned to receive either BS or placebo as one capsule daily for 8 weeks. The primary outcome measures, Visual Analog Scale (VAS), the Japanese Knee Osteoarthritis Measure (JKOM) and the Western Ontario & Mc Master Universities Osteoarthritis Index (WOMAC) were used to evaluate knee pain. In addition, serum hyaluronic acid and high sensitivity C-reactive protein were measured as secondary outcome measures. Results: Compared with baseline, the BS group patients showed significant improvements in the VAS, JKOM, and WOMAC scores after 8 weeks of intervention. Serum hyaluronic acid levels were lower in the BS group than those in the placebo group after 8 weeks of intervention. This may play a vital role in alleviating pain in rheumatoid arthritis. Conclusion: The results of this trial suggest that BS inhibits the secretion of hyaluronic acid into the blood. In addition, intervention with BS resulted in improvements in the VAS, JKOM and WOMAC scores. Therefore, BS could find potential use to relieve knee pain patients and manage related inflammatory conditions. Study for Boswellin SUPER
Effect of boswellin® super on knee pain in japanese adults: a randomized, double-blind, placebo-controlled trial - - Muhammed Majeed, Priti Vaidyanathan, Sankaran Natarajan, Shaheen Majeed, Kiran Kumar Vuppala - ejbps, 2016, Volume 3, Issue 10, 293-298.

A randomized, double- blind placebo-controlled study was conducted at Indira Gandhi Medical College, Nagpur, India, to assess the efficacy, safety and tolerability of Boswellia serrata extract from Geni Inc. in 30 patients with osteoarthritis (OA) of the knee. Two groups of 15 patients each were randomly allocated to receive either a 333 mg capsule of Boswellia serrata or a placebo three times a day, for eight weeks. After this intervention, a wash out period of 21 days was followed. Then the patients were crossed over to receive the opposite intervention.
Patients were asked to assess the severity of pain, loss of function and swelling at the start and completion of both the interventions--X- rays were also taken at the same time.
This review based on the biological role of Piper nigrum can provide that the peppercorn or other parts can be used as crude drug for various diseases while the secondary metabolites such as piperine can be used for specific diseases.
All the patients receiving Boswellia serrata extract treatment reported decrease in knee pain, increased knee flexion, and increased walking distance. The frequency of swelling in the knee joint was also decreased. When these findings were compared to the baseline data and effect obtained with placebo, the findings with Boswellia serrata extract were statistically significant (Wilcoxon signed rank test). Radiologically, there was no change in the findings.
Boswellia (Boswellin) : NSAID Alternative, by Vladimir Badmaev, MD, PhD, and Muhammed Majjed, PhD – Nutrition Industry Executive

Abstract : Boswellia serrata is a branching tree found abundantly in India, Boswellic acids extracted from resin of plant is used in inflammatory conditions, arthritis and hyperlipidaemia. However, any supplement used for long term use needs to be tested for potential mutagenicity and toxicity. Thus, we assessed the mutagenicity of Boswellia serrata extract by Mammalian Bone Marrow Chromosome Aberration Test and Mammalian Bone Marrow Micronucleus Test and in vitro Bacterial Reverse Mutation Test. Further we assessed in vivo toxicity by acute toxicity study and 90 days sub chronic toxicity study of Boswellia serrata extract. None of the mutagenic assays showed any increase in mutagenicity above background. Also, the acute oral toxicity and sub chronic toxicity study revealed that Boswellia serrata extract was not lethal to animals up to 2000mg/kg/day when observed for 14 days and 600mg/kg/day when observed for 90 days. Therefore, these data provide evidence that the Boswellia tested have no cytotoxic potency and are not mutagenic. Thus, our findings contribute to the risk assessment of preparations containing Boswellia serrata extract.
Conclusion : Our result shows that Boswellia serrata extract is non-mutagenic from Bacterial reverse phase mutation assay, bone marrow chromosomal aberration test and bone marrow micronucleus test. Single dose acute oral toxicity study up to 2000mg/kg body weight of Boswellia serrata extract didn’t show any mortality. 90 days sub-chronic study of Boswellia serrata extract up to the dose of 600mg/kg did not show any adverse effect and can be concluded that 600mg/kg repeated dose in the experimental animals is safe and can be considered as ―No Observed Adverse Effect Level‖ (NOAEL) under the experimental condition applied. Thus, Boswelliaserrata extract remains unclassified under the hazard category as per Globally Harmonized Classification System (GHS).CONCLUSION Our result shows that Boswellia serrata extract is non-mutagenic from Bacterial reverse phase mutation assay, bone marrow chromosomal aberration test and bone marrow micronucleus test. Single dose acute oral toxicity study up to 2000mg/kg body weight of Boswellia serrata extract didn’t show any mortality. 90 days sub-chronic study of Boswellia serrata extract up to the dose of 600mg/kg did not show any adverse effect and can be concluded that 600mg/kg repeated dose in the experimental animals is safe and can be considered as ―No Observed Adverse Effect Level‖ (NOAEL) under the experimental condition applied. Thus, Boswelliaserrata extract remains unclassified under the hazard category as per Globally Harmonized Classification System (GHS).
Keywords: Boswellia serrata extract, Mutagenicity, toxicity, Ames test, genotoxicity
Mutagenic, Genotoxic and Sub Chronic Oral Safety Analysis of Boswellia Serrata Extract (Boswellin® Super) (2020) - Muhammed Majeed, Sankaran Natarajan, Sarang Bani, Anjali Pandey, Prakriti Neupane - International Journal of Research Studies in Medical and Health Sciences - Volume 5, Issue 7, 2020

Abstract : 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.
Conclusion : The findings from the present study provide clinical evidence to support that biologically active components of BSE, specifically AKBBA and BBA, acted synergistically to exert anti‐inflammatory/antiarthritic activity efficaciously in reducing joint pain and improving the physical functional ability (Figure 4). No serious adverse events were observed, thus supporting the pharmacological safety of BSE (Boswellin®) to be considered as a viable candidate for the treatment of OA of the knee.
Keywords : anti-inflammatory, Boswellia serrata extract, cathepsin G, high-sensitive C-reactive protein, knee osteoarthritis, microsomal prostaglandin E synthase-1
A pilot, randomized, double-blind, placebo-controlled trial to assess the safety and efficacy of a novel Boswellia serrata extract in the management of osteoarthritis of the knee, Muhammed Majeed, Shaheen Majeed, Narayanan K. Narayanan, Kalyanam Nagabhushanam, Phytotherapy Research, 2019 Feb

Background: Boswellin® Super is a standardized extract of Boswellia serrata Roxb gum resin, standardized to contain 30% 3-acetyl-11-keto-β-boswellic acid along with other β-boswellic acids (BSE). A randomized, double-blind, placebocontrolled clinical trial was conducted at two doses of BSE to understand its safety and efficacy in supporting joint health and improving mobility and symptoms of osteoarthritis (OA) of the knee.
Methods: Based on the inclusion/exclusion criteria, 105 newly diagnosed participants with degenerative hypertrophy OA were recruited and randomized into Placebo, BSE-150 mg or BSE-300 mg (n = 35 in each group) to receive either 150 mg or 300 mg BSE or a placebo tablet twice a day for 90 days. All the participants were evaluated for pain and physical function using the standard tools including the Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lequesne Functional Index (LFI), EuroQol- 5 Dimension (EQ-5D) quality of life, 6-min walk test at day 0, days 5, 30, 60 and 90 of treatment. Additionally, the circulating levels of inflammatory biomarkers, tumor necrosis factor-α (TNFα), high-sensitive C-reactive protein (hs-CRP), and interleukin-6 (IL-6) were evaluated. Safety was evaluated by blood biochemical, hematological analysis, urinary analyses and by monitoring adverse events throughout the study.
Results: Ninety-eight subjects completed the study. Improvements in pain scores were observed as early as 5 days after the start of the supplement in the BSE-150 and BSE-300 groups. By 90 days, the VAS pain score reduced by 45.3% and 61.9%, WOMAC- total score improved by 68.5% and 73.6% in the BSE-150 and BSE-300 groups respectively. WOMAC pain (70.2%, 73.9%, WOMAC stiffness (65.6%,68.9%), WOMAC function (68.8%,74.2%), LFI severity (50%,53.3%), decreased and EQ5D (56.9%, 62.9%) and distance walked in 6 minutes (21.2%, 21.9%) improved in the BSE-150 and BSE-300 groups in 90 days. Further, the levels of TNFα, hs-CRP, and IL-6 were found to decrease in the serum in BSEsupplemented participants. No significant adverse events were recorded during the study.
Conclusion: The study confirms that Boswellin® Super can be used as a safe and effective supplement to support joint health and mobility in the management of osteoarthritis.
KEYWORDS Boswellia serrata extract, 3-acetyl-11-keto-β-boswellic acid, osteoarthritis, Boswellin Super, visual analog scale, WOMAC, lequesne functional index quality of life
A standardized Boswellia serrata extract shows improvements in knee osteoarthritis within five days-a double-blind, randomized, three-arm, parallel-group, multi-center, placebo-controlled trial - Anju Majeed, Shaheen Majeed, G. Satish, R. Manjunatha, Shaikh Nawazish Rabbani, Neelanagowda V. P. Patil and Lakshmi Mundkur - Frontiers in Pharmacology

Abstract :To assess the efficacy / safety of Nilin™ SR tablets in the management of osteoarthritis of knee. 32 subjects from the age group 40-65 years having osteoarthritis of the knee, with no other rheumatologic condition were enrolled. Subjects were judged to have osteoarthritis with clinical diagnostic features; Knee pain for most days of the month, Morning stiffness of less than 30 minute duration, stiffness while resting the affected joint and age over 40 years. The primary outcome was self-reported pain, stiffness and physical function scores as measured with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), 6-minute walk distance and VAS scale measured at 0hr and 1, 2 and 4hrs respectively. Secondary outcomes included laboratory investigations and serological biomarker, i.e. Hs-CRP. A significant improvement in the clinical and biochemical endpoints along with excellent tolerability indicates that NilinTM SR can be used for the long term management of Osteoarthritis. Of the 32 subjects 30 subjects completed the study. Wilcoxon paired sample test indicated WOMAC Score significantly reduced from baseline to final visit for all the three parameters; Pain (P max 0.0001) Stiffness (P max 0.0001) and Physical disability (P max 0.0001).A significant reduction was also noted in the visual analogue scale over the course of 4 hours after ingestion of medication. A significant improvement in the 6-minute walk distance (P max 0.05) and decrease in Hs-CRP levels was observed. No adverse events were reported in the trial.
Keywords : Nilin SR, Osteoarthritis, WOMAC, VAS scale
To assess the efficacy / safety of NILIN™ SR tablets in the management of osteoarthritis of knee Shankaran Natarajan and Muhammed Majeed, Int. J. of Pharm. / Life Sci. (IJPLS), Vol. 3, Issue 2: Feb.: 2012

Abstract: Objectives: The mitigation of knee pain leads to improved quality of life (QOL). NiLitis® SR is a dietary supplement containing Boswellin® Super (Boswellia serrata extract), Curcumin C3 Complex® (turmeric extract) and ginger extract, which is hypothesized to have an anti-inflammatory effect. This study examined the effect of NiLitis® SR on knee pain in healthy Japanese adults.
Methods: This was a double-blind, randomized placebo-controlled trial, comparing the ingestion of NiLitis® SR as against placebo over an 8-week period. In-hospital inspections were carried out three times, i.e., at 0 week, 4 weeks and 8 weeks. The primary outcome measure was the Japanese Knee Osteoarthritis Measure (JKOM). Secondary outcome measures were Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), serum hyaluronic acid (sero-HA), serum high sensitivity C-reactive protein (hs-CRP) and questionnaires (using Likert scale for Quality of Life).
Results: In the NiLitis® SR group, VAS, JKOM total score and WOMAC total score significantly decreased at the end of 8 weeks. Compared with the placebo group, subjects in the NiLitis® group showed significantly lower values in VAS and sero- hyaluronic acid. Conclusion: Intake of NiLitis® SR relieves knee pain and may control hyaluronic acid outflow into the bloodstream.
Keywords: QOL, JKOM, WOMAC, Boswellia serrata, turmeric, ginger.
Effect of Nilitis® SR on Knee Pain in Japanese Adults: A Double-Blind, Randomized, Placebo-Controlled Study Muhammed Majeed, Priti Vaidyanathan, Sankaran Natarajan, Shaheen Majeed, Kiran Kumar Vuppala, International Journal of Innovative Research in Medical Sciences (IJIRMS), Vol. 01, Issue 06, August 2016

Abstract : Frankincense extracts and boswellic acids, biologically active pentacyclic triterpenes of frankincense, block leukotriene biosynthesis and exert potent anti-inflammatory effects. Screening for additional effects of boswellic acids on further pro inflammatory pathways, we observed that acetyl-11- keto- beta- boswellic acid, an established direct, nonredox and noncompetitive 5-lipoxygenase inhibitor, decreased the activity of human leukocyte elastase (HLE) in vitro with an IC50 value of about 15 µM. Among the pentacyclic triterpenes tested in concentrations up to 20 µM, we also observed substantial inhibition by beta-boswellic acid, amyrin and ursolic acid, but not by 18 beta - glycyrrhetinic acid. The data show that the dual inhibition of 5-lipoxygenase and HLE is unique to boswellic acids: other pentacyclic triterpenes with HLE inhibitory activities (e.g., ursolic acid and amyrin) do not inhibit 5-lipoxygenase, and leukotriene biosynthesis inhibitors from different chemical classes (e.g., NDGA, MK-886 and ZM-230,487) do not impair HLE activity. Because leukotriene formation and HLE release are increased simultaneously by neutrophil stimulation in a variety of inflammation- and hypersensitivity-based human diseases, the reported blockade of two proinflammatory enzymes by boswellic acids might be the rationale for the putative antiphlogistic activity of acetyl- 11- keto- beta- boswellic acid and derivatives.
Inhibition by Boswellic Acids of Human Leukocyte Elastase / University of Tuebingen, Hasan Safayhi, Beatrice Rall, Eckart-Roderich Sailer And Hermann P T. Ammon, The Journal Of Pharmacology And Experimental Therapeutics Vol. 281, No. 1

BAs have been reported to have anti-inflammatory, anti­arthritic and anti-pyretic properties (Singh et al., 1993). In view of their potential as a new class of non-steroidal anti-­inflammatory agents and as required by the Drug Control­ler of India, toxicity and safety evaluation were carried out on laboratory rodents and primates The paper describes the work done in this respect
The acute, sub-acute and chronic toxicity studies on boswellic acids (BAs) were carried out on mice, rats and monkeys BAs did not cause any mortality in rats and mice when administered orally and intraperitoneally in doses up to 2 g/kg Daily oral administration of BAs in three dos­es (low and very high) to rats and monkeys revealed no significant changes in general behaviour or clinical, haematological, biochemical and pathological data BAs, therefore, can be regarded as safe for clinical studies.
Toxicity and safety evaluation of boswellic acids / Phytomedecine 3 / Phytomedecine vol3, (1), pp 87-90, 1996

Abstract : Isomers (alpha- and beta-) of boswellic acids (BAs), 11-keto-beta-BA and their acetyl derivatives were isolated from the gum resin of Boswellia serrata. BA and derivatives concentration dependently decreased the formation of leukotriene B4 from endogenous arachidonic acid in rat peritoneal neutrophils. Among the BAs, acetyl-11-keto-beta-BA induced the most pronounced inhibition of 5-lipoxygenase (5-LO) product formation with an IC50 of 1.5 microM. In contrast to the redox type 5-LO inhibitor nordihydroguaiaretic acid, BA in concentrations up to 400 microM did not impair the cyclooxygenase and 12-lipoxygenase in isolated human platelets and the peroxidation of arachidonic acid by Fe-ascorbate. The data strongly suggest that BAs are specific, nonreducing-type inhibitors of the 5-LO product formation either interacting directly with the 5-LO or blocking its translocation.
Boswellic acids : Novel, specific, nonredox inhibitors of 5-lipoxygenase / University of Tuebingen, the Journal of pharmacology and therapeutics, vol 261, n°3, H Safayhi, T Mack, J Sabieraj, M I Anazodo, L R Subramanian, H P Ammon

Mixed acetylboswellic acids, pentacyclic triterpenes extracted from the gum resin of Boswellia serrata Roxb., significantly inhibited the ionophore-stimulated release of the leukotrienes (LT) B4 and C4 from intact human polymorphonuclear neutrophil leukocytes (PMNLs), with IC50 values of 8.48 micrograms/ml and 8.43 micrograms/ml, respectively. Purified acetyl-11-keto-beta-boswellic acid was about three times more potent as inhibitor of the formation of both LTB4 (IC50 = 2.53 micrograms/ml) and LTC4 (IC50 = 2.26 micrograms/ml) from human PMNLs in the same assay. The comparative agent MK 886 (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]- 2,2-dimethylpropanoic acid, L-663,536, CAS 118, 414-82-7) was about 10 to 100-fold more active than the boswellic acids in inhibiting the formation of 5-lipoxygenase products in human PMNLs, with IC50 values of 0.0068 microgram/ml (LTB4) and 0.49 microgram/ml (LTC4). After daily intraperitoneal dosage the extract of mixed acetylboswellic acids (20 mg/kg) significantly reduced the clinical symptoms in guinea pigs with experimental autoimmune encephalomyelitis (EAE) between days 11 and 21. However, the inflammatory infiltrates in the brain and the spinal cord were not significantly less extensive in the treated animals than in the respective control group. The multiple intraperitoneal application of boswellic acids did not inhibit the ionophore-challenged ex vivo release of leukotrienes B4 and C4 from PMNLs separated from the blood of guinea pigs with EAE. The boswellic acids have thus been characterized as selective, non-redox and potent inhibitors of the biosynthesis of leukotrienes in vitro.
Effects of boswellic acids extracted from a herbal medicine on the biosynthesis of leukotrienes and the course of experimental autoimmune encephalomyelitis, - University of Tuebingen, Arzneim Forsch / drug - Res 48 (1) 668-674 (1998)

Abstract : Suspensions of rat peritoneal polymorphonuclear leukocytes (PMNL) elicited with glycogen were stimulated by calcium and ionophore to produce leukotrienes and 5-HETE from endogenous arachidonic acid (AA). We investigated the effect of ethanolic extracts of the gum resin exudate of Boswellia serrata. A concentration-dependent inhibition of LTB4 and 5-HETE production by different charges of exudate extracts were found. All products of the 5-lipoxygenase (5-LOx) from endogenous arachidonic acid (AA) in PMNL were reduced to the same extent by the extracts tested. The ethanolic extract of the gum resin also decreased 5-LOx mediated metabolisation of exogenously added AA to LTB4 and 5-HETE. Since steroidal-type anti-inflammatory drugs do not exert an immediate effect in the test system used, we conclude that the activity of the 5-LOx itself represents the side of inhibition by the gum resin extract. Therefore, an inhibition of 5-LOx catalysed mediator synthesis might be involved in the previously reported anti-inflammatory activity in vivo.
Keyword : 5-Lipoxygenase, leukotrienes, Boswellia serrata, Salai guggal.
Inhibition of Leukotriene B4 Formation in Rat Peritoneal Neutrophils by an Ethanolic Extract of the Gum Resin Exudate of Boswellia serrata / University of Tuebingen / Boswellin, Planta Med. 57(1991), H.P. T. Ammon, T. Mack, G. B. Singh, and H. Safayhi