A double blind, randomized, placebo controlled study of the efficacy and safety of 5-Loxin® for treatment of osteoarthritis of the knee

Sengupta, Krishanu; Alluri, KrishnaRaju Venkata; Satish, Andey Rama; Mishra, Simanchala; Golakoti, Trimurtulu; Sarma, K.V.S.; Dey, Dipak K.; Raychaudhuri, S. P.

doi:10.1186/ar2461

Cited by 209 publications

(200 citation statements)

References 35 publications

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“…In fact, the mPGES1 inhibitor MF63 relieved pyresis and inflammatory pain in animal models, without NSAID-like gastric toxicity (Xu et al, 2008). BAs showed gastric ulcer protective effects in different experimental models (Singh et al, 2008), and a 90-day placebo-controlled study supports evidence for the safety of Boswellia serrata extracts in OA patients (Sengupta et al, 2008).…”

Section: Discussionmentioning

confidence: 80%

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Inhibition of microsomal prostaglandin E₂ synthase‐1 as a molecular basis for the anti‐inflammatory actions of boswellic acids from frankincense

Siemoneit

Koeberle

Rossi

et al. 2010

British J Pharmacology

109

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BACKGROUND AND PURPOSEFrankincense, the gum resin derived from Boswellia species, showed anti-inflammatory efficacy in animal models and in pilot clinical studies. Boswellic acids (BAs) are assumed to be responsible for these effects but their anti-inflammatory efficacy in vivo and their molecular modes of action are incompletely understood. EXPERIMENTAL APPROACHA protein fishing approach using immobilized BA and surface plasmon resonance (SPR) spectroscopy were used to reveal microsomal prostaglandin E2 synthase-1 (mPGES1) as a BA-interacting protein. Cell-free and cell-based assays were applied to confirm the functional interference of BAs with mPGES1. Carrageenan-induced mouse paw oedema and rat pleurisy models were utilized to demonstrate the efficacy of defined BAs in vivo. KEY RESULTSHuman mPGES1 from A549 cells or in vitro-translated human enzyme selectively bound to BA affinity matrices and SPR spectroscopy confirmed these interactions. BAs reversibly suppressed the transformation of prostaglandin (PG)H2 to PGE2 mediated by mPGES1 (IC50 = 3-10 mM). Also, in intact A549 cells, BAs selectively inhibited PGE2 generation and, in human whole blood, b-BA reduced lipopolysaccharide-induced PGE2 biosynthesis without affecting formation of the COX-derived metabolites 6-keto PGF1a and thromboxane B2. Intraperitoneal or oral administration of b-BA (1 mg·kg -1 ) suppressed rat pleurisy, accompanied by impaired levels of PGE2 and b-BA (1 mg·kg -1 , given i.p.) also reduced mouse paw oedema, both induced by carrageenan. CONCLUSIONS AND IMPLICATIONSSuppression of PGE2 formation by BAs via interference with mPGES1 contribute to the anti-inflammatory effectiveness of BAs and of frankincense, and may constitute a biochemical basis for their anti-inflammatory properties.

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Section: Discussionmentioning

confidence: 80%

“…Pilot clinical studies indicated some therapeutic efficacy of frankincense, mainly in OA and RA (Ammon, 2006;Sengupta et al, 2008). Clinical studies using 5-LOX inhibitors (i.e.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of microsomal prostaglandin E₂ synthase‐1 as a molecular basis for the anti‐inflammatory actions of boswellic acids from frankincense

Siemoneit

Koeberle

Rossi

et al. 2010

British J Pharmacology

109

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“…First, most of the patients had problems swallowing 12 large capsules a day; future trials should attempt to provide the boswellic acids in a more concentrated form. 22 Another possibility could be the development of a BS product with an isolated acting component and applicable intravenously. Second, considering the excellent toxicity profile of BS, a phase 3 study should use an even higher dose, particularly if the BS product can be more highly concentrated.…”

Section: Discussionmentioning

confidence: 99%

Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors

Kirste

Treier

Wehrle

et al. 2011

Cancer

114

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BACKGROUND:Patients irradiated for brain tumors often suffer from cerebral edema and are usually treated with dexamethasone, which has various side effects. To investigate the activity of Boswellia serrata (BS) in radiotherapyrelated edema, we conducted a prospective, randomized, placebo-controlled, double-blind, pilot trial. METHODS: Forty-four patients with primary or secondary malignant cerebral tumors were randomly assigned to radiotherapy plus either BS 4200 mg/day or placebo. The volume of cerebral edema in the T2-weighted magnetic resonance imaging (MRI) sequence was analyzed as a primary endpoint. Secondary endpoints were toxicity, cognitive function, quality of life, and the need for antiedematous (dexamethasone) medication. Blood samples were taken to analyze the serum concentration of boswellic acids (AKBA and KBA). RESULTS: Compared with baseline and if measured immediately after the end of radiotherapy and BS/placebo treatment, a reduction of cerebral edema of >75% was found in 60% of patients receiving BS and in 26% of patients receiving placebo (P ¼ .023). These findings may be based on an additional antitumor effect. There were no severe adverse events in either group. In the BS group, 6 patients reported minor gastrointestinal discomfort. BS did not have a significant impact on quality of life or cognitive function. The dexamethasone dose during radiotherapy in both groups was not statistically different. Boswellic acids could be detected in patients' serum. CONCLUSIONS: BS significantly reduced cerebral edema measured by MRI in the study population. BS could potentially be steroid-sparing for patients receiving brain irradiation. Our findings will need to be further validated in larger studies. Cancer 2011;117:3788-

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“…There has been some concern over the use of COX-2 inhibitors for therapeutic intervention, especially since some of the products based on COX-2 were either withdrawn or made to carry warning by the US FDA [8,9] . 5-Lipoxygenase (5-LOX) inhibitors of herbal origin on the other hand are reported to offer significant relief and devoid of adverse effects 5-LOX inhibitors are thus becoming first choice of treatment for chronic inflammatory disease such as arthritis [10,11] . Tumor necrosis factor α (TNF-α) is a pleotropic inflammatory cytokine produced by the immune system that suppresses tumor cell proliferation.…”

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory Activity of Vitex leucoxylon L. Bark Extracts Against Freund's Complete Adjuvant Induced Arthritis in Sprague Dawley Rat

Krishnaraju¹,

Rao²,

Dodda³

et al. 2009

American J. of Infectious Diseases

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Problem statement: Anti-inflammatory agents, particularly steroids and cyclooxygenase inhibitors are often associated with adverse side effects including, GI irritation, ulcers, hypertension and cardiac abnormalities. A safe and effective intervention is essential for the treatment of inflammatory disorders. Approach: Abstract Vitex leucoxylon L., a medicinal plant of the verbenaceae family, used in traditional medicine for relieving headache and catarrh. VL-89/185A, was obtained by bio activity-guided fractionation using 5-Lipoxygenase inhibitory activity. VL-89/185A was further tested against Freund's Complete Adjuvant (FCA) induced arthritis in Sprague Dawley (SD) rat. Results: Oral supplementation of VL-89/185A resulted in significant anti-inflammatory effects as indicated by reduction in paw edema both at 100 and 250 mg kg −1 doses when compared to untreated control rats. Furthermore, treatment with VL-89/185A significantly reduced circulating proinflammatory cytokines TNF-α and IL-1β. The safety of VL-89/185A was established (LD 50 >5000 mg kg −1 body) by acute oral toxicity limit test according to OECD guidelines 425. Conclusion:The safety and efficacy profiles indicated that VL-89/185A is a safe intervention for inflammatory disorders.

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A double blind, randomized, placebo controlled study of the efficacy and safety of 5-Loxin® for treatment of osteoarthritis of the knee

Cited by 209 publications

References 35 publications

Inhibition of microsomal prostaglandin E₂ synthase‐1 as a molecular basis for the anti‐inflammatory actions of boswellic acids from frankincense

Inhibition of microsomal prostaglandin E₂ synthase‐1 as a molecular basis for the anti‐inflammatory actions of boswellic acids from frankincense

Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors

Anti-Inflammatory Activity of Vitex leucoxylon L. Bark Extracts Against Freund's Complete Adjuvant Induced Arthritis in Sprague Dawley Rat

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A double blind, randomized, placebo controlled study of the efficacy and safety of 5-Loxin® for treatment of osteoarthritis of the knee

Cited by 209 publications

References 35 publications

Inhibition of microsomal prostaglandin E2 synthase‐1 as a molecular basis for the anti‐inflammatory actions of boswellic acids from frankincense

Inhibition of microsomal prostaglandin E2 synthase‐1 as a molecular basis for the anti‐inflammatory actions of boswellic acids from frankincense

Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors

Anti-Inflammatory Activity of Vitex leucoxylon L. Bark Extracts Against Freund's Complete Adjuvant Induced Arthritis in Sprague Dawley Rat

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Product

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Inhibition of microsomal prostaglandin E₂ synthase‐1 as a molecular basis for the anti‐inflammatory actions of boswellic acids from frankincense

Inhibition of microsomal prostaglandin E₂ synthase‐1 as a molecular basis for the anti‐inflammatory actions of boswellic acids from frankincense