Evidence for Efficacy -Human data on Boswellia Serrata in Arthritics

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Evidence for Efficacy -Human data on Boswellia Serrata in

Arthritics

JoAnn Guest

Sep 02, 2006 14:30 PDT

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Clinical Trials

http://www.herbmed.org/Herbs/Herb94.htm

 

30 patients with osteoarthritis of knee, 15 each receiving active

Boswellia serrata extract or placebo for eight weeks were assessed.

Patients receiving drug treatment reported decrease in knee pain,

increased knee flexion and increased walking distance. Kimmatkar

2003

 

Out of 83 patients with Crohn's disease 44 treated with H15 and 39

treated with mesalazine. Crohn Disease Activity Index between the

status

of enrolment and end of therapy after treatment with H15 was reduced

by

90 and after therapy with mesalazine by 53 scores in the mean.

[Article

in German]. Gerhardt 2001

 

Twenty patients with chronic colitis were given a preparation of the

gum resin of Boswellia serrata (900 mg daily divided in three doses

for

6 weeks). 18 patients showed an improvement in more than one of the

parameters, including stool properties and histopathology. Gupta

2001

 

Bronchial asthma was reduced in 70% of 40 patients treated with gum

resin at 300 mg thrice daily for 6 weeks in a double-blind trial

Gupta

1998

 

Usage of NSAIDs declined 5.8% in the Boswellia group vs. 3.1% in the

placebo group but no other benefit was noted in a study with 78

rheumatoid arthritis out-patients taking 9 tablets (3600 mg)

Boswellia

or placebo daily Sander 1998

 

Ulcerative colitis (where leukotrienes have been implicated) was put

into remission for 82% of the Boswellia gum resin (350 mg thrice

daily)

group vs. 75% of the sulfasalazine (1 g thrice daily) group after 6

weeks Gupta 1997

 

Osteoarthritic pain and disability were reduced by a mixture of

Withania somnifera roots, Boswellia serrata stem, Curcuma longa

rhizomes

and a zinc complex in a double-blind trial with 42 patients Kulkarni

1991

 

Observational Studies/Case Reports

Two cases of therapy with frankincense and myrrh in children Michie

1991

 

Traditional and Folk Use

Evidance from different excavations revealed that record of

frankincense use is 300 years ahead of the existing record

shown.[Article in Chinese]. Zhang 2001

 

Bark resin contains up to 16% oil (esp thujene and p-cymene).

Pentacyclic triterpenes inhibit 5-lipoxygenase products (5-HETE and

leukotriene B4) which cause bronchoconstriction, chemotaxis, and

vascular permeability. Traditionally used for arthritis

Monograph:Boswellia serrata 1998

 

Salai Guggal - Boswellia serrata: from a herbal medicine to a

non-redox inhibitor of leukotriene biosynthesis. Ammon 1996

 

Gold, frankincense, myrrh, and medicine. Greene 1993

 

Gold, frankincense and myrrh. Cameron 1989

 

Gold, frankincense and myrrh Hillson 1988

 

Of five plants in use by Kuwaiti diabetics only myrrh and aloe gums

increased glucose tolerance in both normal and diabetic rats while

gum

Olibanum, Nigella sativa seeds and gum Assafoetida were without

effect

Al-Awadi 1987

 

Frankincense and myrrh. Miller 1968

 

Frankincense in Mrs. M. Grieve's A Modern Herbal

 

Description of frankincense at King's American Dispensatory

 

Boswellia species at Liber Herbarum II

 

 

 

SAFETY DATA

 

 

Adverse Effects & Toxicity

No Records

 

Interactions

No Records

 

Contraindications

No Records

 

 

 

EVIDENCE OF ACTIVITY

 

 

Animal Studies

Reduction of severity and resolution of typical clinical signs, such

as intermittent lameness, local pain and stiff gait, were reported

after

6 weeks in 29 dogs administered resin extract of Boswellia serrata

(BSB108, product of Bogar AG) at a dose of 400 mg/10 kg body weight.

Reichling 2004

 

Pretreatment of aqueous extracts of Zyrulina (Spirulina), Aswagandha

(Withania) and Nopane (Boswellia) on colchicine induced chromosome

damage showed weakness of clastogenic activity in Swiss albino mice.

Ghoshal 2001

 

Boswellia extract or AKBA significantly reduces macroscopic and

microcirculatory inflammatory features normally associated with

indomethacin administration, in Sprague-Dawley rats. Krieglstein

2001

 

Paw inflammation induced by papaya latex is alleviated by boswellic

acids whereas no benefit was seen in the carrageenan model Gupta

1994

 

Carrageenan-induced rat paw edema was reduced by four species of the

plant family Burseraceae, Boswellia dalzielli, Boswellia carteri

(gum

olibanum), Commiphora mukul and Commiphora incisa Duwiejua 1993

 

Proliferation of HL-60 cells was inhibited by Bc-4 from Boswellia

carterii at 5-10 micrograms/ml. Growth of HL-60 cells in mice was

inhibited by Bc-4 at 50 mg/kg Jing 1992

 

Hepatic gluconeogenesis decrease appears to be the mechanism of

blood

glucose lowering by Nigella sativa, Myrrh, Gum Olibanum, Gum

Asafoetida

and Aloe in streptozotocin diabetic rats al-Awadi 1991

 

Protection by boswellic acids against galactosamine/endotoxin-

induced

hepatitis in mice Safayhi 1991

 

Glycosaminoglycan content in rats was decreased in the

ketoprofen-treated group but unaltered in the boswellic acids or

salai

guggal treated groups Reddy 1989

 

Leucocytes of BSA-induced arthritis in rabbits decreased by

boswellic

acids (25, 50 and 100 mg/kg/day) Sharma 1989

 

Antibody production and cellular responses to sheep red blood cells

in

mice was inhibited by Boswellia ethanolic extract Sharma 1988

 

Arthritis associated elevation of urinary hydroxyproline (free,

total,

nondialysable and dialysable), hexosamine and uronic acid was

slightly

decreased in the acute phase and significantly decreased in the

chronic

phase by boswellic acids in rats Kesava 1987

 

Arthritis associated elevation of beta-glucuronidase is reduced by

boswellic acids or salai-guggal Kesava 1987

 

Carrageenan or dextran induced edema and formaldehayde induced

arthritis were reduced by Boswellia extract. It lacked any analgesic

or

anti-pyretic effects and no significant effect was seen on

cardiovascular, respiratory and central nervous systems Singh 1986

 

Pharmacodynamics

11-keto-BAs might function as potent activators of PMNL by

stimulation

of MAPK and mobilization of intracellular Ca(2+). Altmann 2002

 

Boswellic acids inhibit the leukotriene biosynthesis in neutrophilic

granulocytes by inhibition of 5-lipoxygenase & elastase in

leukocytes,

to inhibit proliferation,induce apoptosis & to inhibit

topoisomerases of

leukoma- & glioma cell lines.[Article in German]. Ammon 2002

 

Effect of Boswellia serrata gum resin containing boswellic acids, in

terms of cytotoxic, cytostatic & apoptotic activity on five leukemia

(HL-60, K 562, U937, MOLT-4, THP-1) & 2 brain tumor(LN-18, LN-229)

cell

lines expressed in GI50 was more potent than pure

3-O-acetyl-11-keto-beta-boswellic acid. Hostanska 2002

 

Beta-boswellic acid and keto-beta-boswellic acid have

antiproliferative and apoptotic effects mediated via a pathway

dependent

on caspase-8 activation but independent of Fas/FasL interaction in

human

HT-29 cells. Liu 2002a

 

Boswellic acids have anti-proliferation and anti-cancer effects on

Hep

G2 cells and the apoptotic effect is mediated by a pathway dependent

on

caspase-8 activation. Liu 2002b

 

Acetyl-11-keto-beta-boswellic acid inhibits the phosphorylation of

extracellular signal-regulated kinase 1 and 2 in meningioma cells

stimulated with platelet-derived growth factor BB by interrupting

signaling of pathway. Park 2002a

 

Treatment of meningioma AKBA revealed potent cytotoxic activity with

half-maximal inhibitory concentrations in range of 2 - 8 microM by

inhibiting phosphorylation of Erk-1/2 and impairing the motility of

meningioma cells stimulated with platelet-derived growth factor BB.

Park

2002b

 

Tetracyclic triterpene 3-oxo-tirucallic acid contributes

significantly

to the overall biological effects of B. serrata resin. Boden 2001

 

Boswellia serrata affects the interleukin-4 (IL-4), IL-5, IL-6, IL-

9,

IL-10, and IL-13, which stimulate the growth, differentiation, and

recruitment of mast cells, basophils, eosinophils, and B-cells, all

of

which are involved in humoral immunity, inflammation, and the

allergic

response. Miller 2001

 

Apoptosis of leukemia cells is increased by

acetyl-11-keto-beta-boswellic acid (AKBA) but not by amyrin, a

structural analog without effect on 5-lipoxygenase (EC 1.13.11.34).

DNA

laddering and PCR indicates inhibition of topoisomerase I Hoernlein

1999

 

 

Boswellic acid acetate at 12.5 microg/ml (24.2 microM) from

Boswellia

carterii Birdw induces differentiation of myeloid leukemia HL-60,

U937

and ML-1 cells but not erythroid leukemia DS-19 and K562 cells. 20

microg/ml killed 60% of all cells at 24 h Jing 1999

 

Apoptosis observed in leukemia cell line HL60 and bone marrow

leukemic

cells from 30 acute non-lymphocytic leukemic (ANLL) patients on

treatment with Boswellia Carterii Birdw. [Article in Chinese]. Qi

1999

 

Acetyl-11-keto-beta-boswellic acid (AKBA) inhibition of 5-

lipoxygenase

(EC 1.13.11.34) is allosteric (non competitive) and calcium

dependent

Sailer 1998

 

3-O-acetyl-11-keto-beta-boswellic acid inhibited DNA, RNA and

protein

synthesis in HL-60 cells with IC50 = 0.6, 0.5, and 4.1 microM,

respectively, and inhibited cell growth but not viability Shao 1998

 

Nonredox type 5-lipoxygenase inhibitors generally are activated by

glutathione or dithiothreitol. However, no such redox-dependent

effects

were observed with acetyl-11-keto-beta-boswellic acid Werz 1998

 

Leukotrienes B4 and C4 from ionophore stimulated PMNLs wre inhibited

by (IC50 in microgm/ml) acetylboswellic acids (IC50=8.5),

11-keto-beta-boswellic acid (IC50=3), or MK 886 (IC50=0.0068)

Wildfeuer

1998

 

Contracture of sketal muscle and inhibition of the twitch response

to

nerve stimulation was seen with essential oils of clary sage, dill,

fennel, frankincense and nutmeg Lis-Balchin 1997

 

Human leukocyte elastase is inhibited by acetyl-11-keto-beta-

boswellic

acid (IC50 = 15 microM), beta-boswellic acid, amyrin and ursolic

acid,

but not by 18beta-glycyrrhetinic acid. Ursolic acid and amyrin do

not

inhibit 5-lipoxygenase Safayhi 1997

 

5-Lipoxygenase inhibition requires the 11-keto and a hydrophilic

group

on C4 of ring A of boswellic analogs. Potency of AKBA was only

slightly

diminished by deacetylation or by reduction of the carboxyl to

alcohol.

It is inhibited by amyrin Sailer 1996

 

5-lipoxygenase (EC 1.13.11.34) inhibition by AKBA is reduced by

noninhibitory pentacyclic triterpenes, concentration-dependently.

This

isn't due to nonspecific lipophilic interactions, because

cholesterol,

cortisone, testosterone (4 rings) lack effect Safayhi 1995

 

Review of anticancer plants with emphasis on Boswellia, Indigofera,

Camptotheca, Curcuma, Iris, Ginseng, Cephalotaxus and Taxus Han 1994

 

Curcumine inhibits 5-lipoxygenase in rat peritoneal neutrophils and

12-lipoxygenase and cyclooxygenase in human platelets while

boswellic

acid only inhibits 5-lipoxygenase and did not impair the

peroxidation of

arachidonic acid by iron and ascorbate Ammon 1993

 

HL-60 differentiation induced by low concentrations of daidzein,

Boswellia carterii and Ara-C was not impressive but in combination

80%

of HL-60 cells exhibited NBT reduction and 82% of the cells showed

phagocytosis after 4 days of daidzein with Boswellia Jing 1993

 

Papaya latex induced inflammation was reduced by prednisolone,

aspirin, indomethacin, phenylbutazone, ibuprofen, piroxicam,

chloroquine, levamisole or a mixture of boswellic acids Gupta 1992

 

Among boswellic acid isomers, acetyl-11-keto-beta-BA (AKBA) induced

the most pronounced inhibition of 5-lipoxygenase with IC50 of 1.5

microM. Unlike NDGA (Larrea) it did not impair cyclooxygenase and

12-lipoxygenase Safayhi 1992

 

Inhibition of 5-lipoxygenase and its products (LTB4 and 5-HETE) are

inhibited by ethanolic extracts of the gum resin exudate of

Boswellia

serrata Ammon 1991

 

Molluscicidal activity was found with Boswellia dalzielii and other

Nigerian plants Kela 1989

 

Analgesic and psychopharmacological effects of the gum resin of

Boswellia serrata. Menon 1971

 

Analgesic effect of the gum resin of Boswellia serata Roxb. Kar 1969

 

Analytical Chemistry

Palmitic acid and eight triterpenoids belonging to lupane, ursane,

oleanane, and tirucallane skeleta were isolated form the oleogum

resin

of frankincense (Boswellia carterii Birdwood) and structures deduced

based on spectroscopic evidences. Badria 2003

 

Analysis of 12 different pentacyclic triterpenic acids in Indian and

African frankincense gum resins (Boswellia carterii Birdwood) as

well as

in related phytopharmaceuticals by HPLC gradient method was

developed.

Buchele 2003

 

Lupane-type triterpene, 3alpha-hydroxy-lup-20(29)-en-24-oic acid

were

isolated from methanolic extract of " Erytrean-type " resin of

commercial

frankincense (Boswellia carterii Birdwood) and structures

characterized

by two dimensional NMR and and mass spectrometric techniques.

Culioli

2003

 

Frankincense essential oil (Boswellia carterii Birdwood) exhibited a

strong immunostimulant activity when assessed by a lymphocyte

proliferation assay & when analysed by Capillary GC/MS its contents

were

found be monoterpenes (13.1%), sesquiterpenes(1%),and diterpenes

(42.5%). Mikhaeil 2003

 

A reversed phase HPLC method for the separation of boswellic acids,

the active constituents in Boswellia serrata resin was developed.

Ganzera 2001

 

HPTLC method was developed for simultaneous quantitative estimation

of

biologically active anti-inflammatory triterpenoids 3-O

acetyl-beta-boswellic acid, 11-keto-beta-boswellic acid and

3-O-acetyl-11-keto-beta-boswellic acid from gum resin of Boswellia

serrata. Krohn 2001

 

Isolation and structure of a 4-O-methyl-glucuronoarabinogalactan

from

Boswellia serrata. Sen 1992

 

Derivatives of boswellic acids. el-Khadem 1972

 

Pharmacokinetics (ADME)

No Records

 

Genetics & Molecular Biology

Boswellic acids act via G(i/0) protein(s) stimulating signalling

pathways that control functional leucocyte responses as

chemoattractants, that is, N-formyl-methionyl-leucyl-phenylalanine

or

platelet-activating factor. Altmann 2004

 

Bursera genus is more closely related to Commiphora than to

Boswellia

based on genetic phylogeny of 57 species using internal transcribed

spacer regions of 18S-26S and the 5.8S coding region of nuclear

ribosomal DNA Becerra 1999

 

C3-convertase of the classical complement pathway is inhibited by

boswellic acid at 100 micrograms Kapil 1992

 

Topoisomerase II unwinding of pBR 322 DNA is inhibited by

frankincense

extracts Wang 1991

 

 

 

FORMULAS/BLENDS

 

 

Contemporary Formulas

Current research on the processing of olibanum [Article in Chinese]

Lu

1996

 

Processing of frankincense [Article in Chinese] Yin 1986

 

Folk Blends

No Records

 

Patents

Bone/joint inflammation treatment with a mixture including

470

mg Boswellia extract; US Patent 5,888,514

 

Boswellic acid may be added to a chromium picolinate

composition; US Patent 5,948,772

 

Anti-inflammatory, antiathritic and antiulcerogenic use of

Boswellic acid compositions; US Patent 5,629,351

 

Arthritis treatment with Boswellia, Withania, Curcuma and

Zingiber; US Patent 5,494,668

 

 

 

OTHER INFORMATION

 

 

Pictures & Distribution Maps

Drawing of Boswellia carteri at Missouri Botanical Garden

 

Cultivation, Conservation & Ecology

Boswellia serrata in the PLANTS National Database