Clinical Studies Used In The Research and Development of Heal-n-Soothe Arthritis®
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1) Taussig SJ, Batkin S. Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application. An update. J Ethnopharmacol. 1988 Feb-Mar;22(2):191-203.
Department of Food Science and Human Nutrition, School of Tropical Agriculture, University of Hawaii, Honolulu.
After a short description of the uses of pineapple as folk medicine by the natives of the tropics, the more important new pharmaceutical applications of bromelain, reported between 1975 and 1978, are presented. Although the exact chemical structure of all active components of bromelain is not fully determined, this substance has shown distinct pharmacological promise. Its properties include: (1) interference with growth of malignant cells; (2) inhibition of platelet aggregation; (3) fibrinolytic activity; (4) anti-inflammatory action; (5) skin debridement properties. These biological functions of bromelain, a non-toxic compound, have therapeutic values in modulating: (a) tumor growth; (b) blood coagulation; (c) inflammatory changes; (d) debridement of third degree burns; (e) enhancement of absorption of drugs. The mechanism of action of bromelain affecting these varied biological effects relates in part to its modulation of the arachidonate cascade.
4) Leonard BE. Inflammation, depression and dementia: are they connected? Neurochem Res. 2007 Oct;32(10):1749-56.
5) Barzilay JI, Abraham L, Heckbert SR, Cushman M, Kuller LH, Resnick HE, Tracy RP. The relation of markers of inflammation to the development of glucose disorders in the elderly: the Cardiovascular Health Study. Diabetes. 2001 Oct;50(10):2384-9.
6) Festa A, D'Agostino R Jr, Howard G, Mykk├Ąnen L, Tracy RP, Haffner SM. Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circulation. 2000 Jul 4;102(1):42-7.
7) Walker JA, Cerny FJ, Cotter JR, Burton HW. Attenuation of contraction-induced skeletal muscle injury by bromelain. Med Sci Sports Exerc. 1992 Jan;24(1):20-5.
8) Walker AF, Bundy R, Hicks SM, Middleton RW. Bromelain reduces mild acute knee pain and improves well-being in a dose-dependent fashion in an open study of otherwise healthy adults. Phytomedicine. 2002 Dec;9(8):681-6.
9) Ley CM, Tsiami A, Ni Q, Robinson N. A review of the use of bromelain in cardiovascular diseases. Zhong Xi Yi Jie He Xue Bao. 2011 Jul;9(7):702-10.
10) Loskutoff DJ, Quigley JP. PAI-1, fibrosis, and the elusive provisional fibrin matrix. J Clin Invest. 2000 Dec;106(12):1441-3.
11) Felton GE. Fibrinolytic and antithrombotic action of bromelain may eliminate thrombosis in heart patients. Med Hypotheses. 1980 Nov;6(11):1123-33.
12) Bracale G, Selvetella L. [Clinical study of the efficacy of and tolerance to seaprose S in inflammatory venous disease. Controlled study versus serratio-peptidase]. Minerva Cardioangiol. 1996 Oct;44(10):515-24.
13) Braga PC, Moretti M, Piacenza A, Montoli CC, Guffanti EE. Effects of seaprose on the rheology of bronchial mucus in patients with chronic bronchitis. A double-blind study vs placebo. Int J Clin Pharmacol Res. 1993;13(3):179-85.
14) Moretti M, Bertoli E, Bulgarelli S, Testoni C, Guffanti EE, Marchioni CF, Braga PC. Effects of seaprose on sputum biochemical components in chronic bronchitic patients: a double-blind study vs placebo. Int J Clin Pharmacol Res. 1993;13(5):275-80.
15) Fitzhugh DJ, Shan S, Dewhirst MW, Hale LP.Bromelain treatment decreases neutrophil migration to sites of inflammation. Clin Immunol. 2008 Jul;128(1):66-74.
16) Berg A, Peters M, Deibert P, K├Ânig D, Birnesser H. Bromelain - Overview and diskussion of therapeutic application and its importance in sports medicine and sports traumatology. Deutsche Zeitschrift F├╝r Sportmedizin. Jahrgang 56, Nr. 1 (2005) [German]
17) Hong J, Bose M, Ju J, Ryu JH, Chen X, Sang S, Lee MJ, Yang CS. Modulation of arachidonic acid metabolism by curcumin and related beta-diketone derivatives: effects on cytosolic phospholipase A(2), cyclooxygenases and 5-lipoxygenase. Carcinogenesis. 2004 Sep;25(9):1671-9
18) Sreejayan, Rao MN. Nitric oxide scavenging by curcuminoids. J Pharm Pharmacol. 1997 Jan;49(1):105-7.
19) Otsuki N, Dang NH, Kumagai E, Kondo A, Iwata S, Morimoto C. Aqueous extract of Carica papaya leaves exhibits anti-tumor activity and immunomodulatory effects. J Ethnopharmacol. 2010 Feb 17;127(3):760-7.
20) Gayathri B, Manjula N, Vinaykumar KS, Lakshmi BS, Balakrishnan A. Pure compound from Boswellia serrata extract exhibits anti-inflammatory property in human PBMCs and mouse macrophages through inhibition of TNFalpha, IL-1beta, NO and MAP kinases. Int Immunopharmacol. 2007 Apr;7(4):473-82. Source
21) Kokkiripati PK, Bhakshu LM, Marri S, Padmasree K, Row AT, Raghavendra AS, Tetali SD. Gum resin of Boswellia serrata inhibited human monocytic (THP-1) cell activation and platelet aggregation. J Ethnopharmacol. 2011 Sep 1;137(1):893-901.
22) Piacente S, Montoro P, Oleszek W, Pizza C. Yucca schidigera bark: phenolic constituents and antioxidant activity. J Nat Prod. 2004 May;67(5):882-5.
23) Cheeke PR, Piacente S, Oleszek W. Anti-inflammatory and anti-arthritic effects of Yucca schidigera: a review. J Inflamm (Lond). 2006 Mar 29;3:6.
24) Grzanna R, Lindmark L, Frondoza CG. Ginger--an herbal medicinal product with broad anti-inflammatory actions. J Med Food. 2005 Summer;8(2):125-32.
25) Ernst E, Pittler MH. Efficacy of ginger for nausea and vomiting: a systematic review of randomized clinical trials. Br J Anaesth. 2000 Mar;84(3):367-71.
26) Huang TH, Tran VH, Duke RK, Tan S, Chrubasik S, Roufogalis BD, Duke CC. Harpagoside suppresses lipopolysaccharide-induced iNOS and COX-2 expression through inhibition of NF-kappa B activation. J Ethnopharmacol. 2006 Mar 8;104(1-2):149-55.
27) Kidd P. Glutathione: Systemic Protectant Against Oxidative and Free Radical Damage. Alt Med Rev. 1997; Vol.2 (3):155-76.
28) Dieber-Rotheneder M, Puhl H, Waeg G, Striegl G, Esterbauer H. Effect of oral supplementation with D-alpha-tocopherol on the vitamin E content of human low density lipoproteins and resistance to oxidation. J Lipid Res. 1991 Aug;32(8):1325-32.
29) Reaven PD, Khouw A, Beltz WF, Parthasarathy S, Witztum JL. Effect of dietary antioxidant combinations in humans. Protection of LDL by vitamin E but not by beta-carotene. Arterioscler Thromb. 1993 Apr;13(4):590-600.
30) Boshtam M, Rafiei M, Sadeghi K, Sarraf-Zadegan N. Vitamin E can reduce blood pressure in mild hypertensives. Int J Vitam Nutr Res. 2002 Oct;72(5):309-14.
31) Office of Dietary Supplements - National Institutes of Health http://ods.od.nih.gov/factsheets/vitamine/#en6 last accessed 03/12/2012
32) Martha Clare Morris, ScD; Denis A. Evans, MD; Julia L. Bienias, ScD; Christine C. Tangney, PhD; Robert S. Wilson, PhD. Vitamin E and Cognitive Decline in Older Persons. Arch Neurol.┬ 2002;59:1125-1132.
33) Teixeira S. Bioflavonoids: proanthocyanidins and quercetin and their potential roles in treating musculoskeletal conditions. J Orthop Sports Phys Ther. 2002 Jul;32(7):357-63.
34) Ishita Chattopadhyay, Kaushik Biswas, Uday Bandyopadhyay and Ranajit K. Banerjee. Turmeric and curcumin: Biological actions and medicinal applications.
OTHER RELATED RESEARCH
Hale LP, Greer PK, Sempowski GD. Bromelain treatment alters leukocyte expression of cell surface molecules involved in cellular adhesion and activation. Clin Immunol. 2002 Aug;104(2):183-90.
Masson M. [Bromelain in blunt injuries of the locomotor system. A study of observed applications in general practice]. Fortschr Med. 1995 Jul 10;113(19):303-6.
Brien S, Lewith G, Walker A, Hicks SM, Middleton D. Bromelain as a Treatment for Osteoarthritis: a Review of Clinical Studies. Evid Based Complement Alternat Med. 2004 Dec;1(3):251-257.
Fossati A. Antiinflammatory effects of seaprose-S on various inflammation models. Drugs Exp Clin Res. 1999;25(6):263-70.
Esch PM, Gerngross H, Fabian A. [Reduction of postoperative swelling. Objective measurement of swelling of the upper ankle joint in treatment with serrapeptase-- a prospective study]. Fortschr Med. 1989 Feb 10;107(4):67-8, 71-2.
Selloum L, Bouriche H, Tigrine C, Boudoukha C. Anti-inflammatory effect of rutin on rat paw oedema, and on neutrophils chemotaxis and degranulation. Exp Toxicol Pathol. 2003 Mar;54(4):313-8.
Guardia T, Rotelli AE, Juarez AO, Pelzer LE. Anti-inflammatory properties of plant flavonoids. Effects of rutin, quercetin and hesperidin on adjuvant arthritis in rat. Farmaco. 2001 Sep;56(9):683-7.
Rotelli AE, Guardia T, Ju├írez AO, de la Rocha NE, Pelzer LE. Comparative study of flavonoids in experimental models of inflammation. Pharmacol Res. 2003 Dec;48(6):601-6.
S Sontakke, V Thawani, S Pimpalkhute, P Kabra, S Babhulkar, L Hingorani. Open, randomized, controlled clinical trial of Boswellia serrata extract as compared to valdecoxib in osteoarthritis of knee. Indian Journal of Pharmacology. 2007; 39(1) 27-29
Kimmatkar N, Thawani V, Hingorani L, Khiyani R. Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee--a randomized double blind placebo controlled trial. Phytomedicine. 2003 Jan;10(1):3-7.
Sengupta K, Alluri KV, Satish AR, Mishra S, Golakoti T, Sarma KV, Dey D, Raychaudhuri SP. A double blind, randomized, placebo controlled study of the efficacy and safety of 5-Loxin for treatment of osteoarthritis of the knee. Arthritis Res Ther. 2008;10(4):R85
A. Sharma, S. Bhatia, M. D. Kharya, V. Gajbhiye, N Ganesh, A. G. Namdeo, K. R. Mahadik. Anti-inflammatory and analgesic activity of different fractions of Boswellia serrata. Int Jnl of Phytomedicine. 2010 V 2 No 1
Kuptniratsaikul V, Thanakhumtorn S, Chinswangwatanakul P, Wattanamongkonsil L, Thamlikitkul V. Efficacy and safety of Curcuma domestica extracts in patients with knee osteoarthritis. J Altern Complement Med. 2009 Aug;15(8):891-7.
Olas B, Wachowicz B, Nowak P, Stochmal A, Oleszek W, Glowacki R, Bald E. Comparative studies of the antioxidant effects of a naturally occurring resveratrol analogue -- trans-3,3',5,5'-tetrahydroxy-4'-methoxystilbene and resveratrol -- against oxidation and nitration of biomolecules in blood platelets. Cell Biol Toxicol. 2008 Aug;24(4):331-40. Source
Piacente S, Montoro P, Oleszek W, Pizza C. Yucca schidigera bark: phenolic constituents and antioxidant activity. J Nat Prod. 2004 May;67(5):882-5.
Chantre P, Cappelaere A, Leblan D, Guedon D, Vandermander J, Fournie B. Efficacy and tolerance of Harpagophytum procumbens versus diacerhein in treatment of osteoarthritis. Phytomedicine. 2000 Jun;7(3):177-83.
Chrubasik S, Junck H, Breitschwerdt H, Conradt C, Zappe H. Effectiveness of Harpagophytum extract WS 1531 in the treatment of exacerbation of low back pain: a randomized, placebo-controlled, double-blind study. Eur J Anaesthesiol. 1999 Feb;16(2):118-29.
Gagnier JJ, van Tulder M, Berman B, Bombardier C. Herbal medicine for low back pain. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD004504.
REFERENCE NOTE ABOUT DEVIL'S CLAW: Devil's claw has been studied for low back pain, muscle pain, and osteoarthritis using daily doses of crude tuber up to 9 g daily, 1 to 3 g of extract, and 50 to 100 mg of harpagoside. Standardized preparations include LI 174 ( Rivoltan ), Doloteffin (more than 50 mg harpagoside), and WS 1531. A level of more than 1% harpagoside in root is considered acceptable. Commercial sources of devil's claw extract contain 1.4% to 2% harpagoside.
G├Âbel H, Heinze A, Ingwersen M, Niederberger U, Gerber D. [Effects of Harpagophytum procumbens LI 174 (devil's claw) on sensory, motor und vascular muscle reagibility in the treatment of unspecific back pain]. Schmerz. 2001 Feb;15(1):10-8.
Leblan D, Chantre P, Fourni├ę B. Harpagophytum procumbens in the treatment of knee and hip osteoarthritis. Four-month results of a prospective, multicenter, double-blind trial versus diacerhein. Joint Bone Spine. 2000;67(5):462-7.
Sasaki T, Kojima S. Ga uptake and heparan sulfate content of Ehrlich solid tumor in mice. Eur J Nucl Med. 1986;12(4):182-6.
Skyrme-Jones RA, O'Brien RC, Berry KL, Meredith IT. Vitamin E supplementation improves endothelial function in type I diabetes mellitus: a randomized, placebo-controlled study. J Am Coll Cardiol. 2000 Jul;36(1):94-102.
Li Y, Schellhorn HE. New developments and novel therapeutic perspectives for vitamin C. J Nutr. 2007 Oct;137(10):2171-84.
Singh RK, Rai D, Yadav D, Bhargava A, Balzarini J, De Clercq E. Synthesis, antibacterial and antiviral properties of curcumin bioconjugates bearing dipeptide, fatty acids and folic acid. Eur J Med Chem. 2010 Mar;45(3):1078-86. Epub 2010 Jan 19.
Maheshwari RK, Singh AK, Gaddipati J, Srimal RC. Multiple biological activities of curcumin: a short review. Life Sci. 2006 Mar 27;78(18):2081-7. Epub 2006 Jan 18.
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