Re: Boswellia Resin Activity Involves More than just Boswellic Acids
Moussaieff A, Mechoulam R. Boswellia resin: from religious ceremonies to medical uses; a review of in-vitro, in-vivo and clinical trials. J Pharm Pharmacol. Oct. 2009;61(10):1281-1293.
Frankincense
(Boswellia spp.) resin has been used
as incense in religious ceremonies for thousands of years. The medicinal uses
of frankincense resin include the treatment of inflammatory conditions,1
wounds, and skin conditions. Over 200 compounds have been isolated from frankincense
resin.
The
anti-inflammatory effects of frankincense resin have been attributed to the
boswellic acids and their derivatives: acetyl-β-boswellic acid (ABA), 11-keto-β-boswellic
acid, and acetyl-11-keto-β-boswellic acid (AKBA). Some studies have found the
anti-inflammatory effects of whole frankincense resin are greater than those of
purified boswellic acids. After bioassay-guided fractionation of Boswellia carteri resin, the authors of
this review discovered that the fraction containing boswellic acids did not
affect inhibitory κBα (IκBα) protein degradation, which is involved in the
activation of nuclear factor κβ (NF-κβ). NF-κβ is an inducible transcription
factor involved in immune response, carcinogenesis, and inflammation. They
found that the frankincense compounds incensole acetate and incensole
indirectly inhibit IκBα degradation and cytokine- and lipopolysaccharides (LPS)-mediated NF-κβ activation. One
study has found that frankincense extract affects 113 of 522 genes known to be induced
by tumor necrosis factor-α (TNF-α), an inflammatory cytokine. The study also
showed that frankincense extract blocked the expression of matrix
metalloproteinases and mediators of apoptosis induced by TNF-α.
The authors
write that the anti-inflammatory effect of frankincense resin "probably
involves boswellic acids to some extent," but incensole acetate and its
derivatives may be "the major anti-inflammatory constituents of Boswellia carterii [sic] resin."
Incensole acetate has also been shown in vitro to inhibit cytokines downstream
of NF-κβ activation, including interleukin-1β (IL-1β), IL-6, TNF-α, and
prostaglandin E2. An ethanolic extract of B.
serrata and one of its constituents, AKBA, inhibits the activity of
5-lipoxygenase, an enzyme which oxidizes arachidonic acid (AA), and β-boswellic
acid antagonizes this effect. Studies have suggested "that the
immunomodulatory effects of boswellic acids are not all inhibitory." Boswellic
acids, notably AKBA, have been shown to inhibit cyclooxygenase-1 (COX-1) and
less efficiently COX-2 activity, and incensole acetate has been shown to
inhibit COX-2 activity in pre-clinical studies. Boswellic acids, including AKBA,
also activate p42 and p38 mitogen activated protein kinases (MAPKs). Calcium
ions are involved in the MAPK activation and in the inhibition of
5-lipoxygenase by AKBA.
Extracts of
Boswellia spp. and boswellic acids
have been shown in vitro to potently and non-selectively inhibit cytochrome P450
(CYP) metabolic enzymes 2C8/2C9 and 3A4 and inhibit P-glycoprotein (Pgp) efflux
transporter protein, which could cause interactions with their drug substrates.
Boswellic acid derivatives have been shown to induce apoptosis (programmed cell
death) in multiple cancer cell lines. AKBA has a selective pro-apoptotic effect
on cancer cells, and does not induce apoptosis in normal human lung
fibroblasts. The mechanism of action for the pro-apoptotic effects of boswellic
acids may involve the inhibition of topoisomerase or inhibition of NF-κβ. AKBA
inhibits angiogenesis in vivo. Incensole acetate has been shown to potently
activate the transient receptor potential cation channel, subfamily V, member 3
(TRPV3).
In vivo
studies have confirmed the acute and chronic anti-inflammatory effects of
frankincense resin extract. In vivo studies have also demonstrated
anti-arthritic effects, including reduction of arthritis in rabbits and a
reduction in the degradation of glycosaminoglycans by boswellic acids. A
commercial Boswellia serrata extract
(H15) and AKBA have been shown to reduce indomethacin-induced ileitis in rats,
and AKBA has been shown to improve colitis effects in mice. AKBA has also been
shown to prevent experimental diarrhea and normalize intestinal motility in
mice. AKBA has been shown to reduce the size of atherosclerotic lesions in
mice, possibly through NF-κβ inhibition. In vivo studies have also demonstrated
prolonged survival times and reduced tumor volumes in rats inoculated with C6
glioma cells and treated with boswellic acids.
Topical
application of AKBA-γ-cyclodextrin has shown anticancer effects, including the
concentration-dependent inhibition of proliferation and tumor growth and the
induction of apoptosis. Studies have indicated that frankincense resin also possesses
antimicrobial effects on biofilms in vitro. B.
carteri resin possesses neuroprotective effects shown by the authors in
mice that "can be attributed, at least partially, to incensole acetate and
its derivatives." Animal studies indicate that an extract of B. serrata has sedative and analgesic
effects. The authors of this review have demonstrated that incensole acetate
possesses anxiolytic, anti-depressive, and sedative effects in vivo. The
compound does not bind to any of the known pharmacological targets, but it
activates the TRPV3 channel in vitro. The sedative effect, but not the
anti-depressive and anxiolytic effects, was observed in TRPV3-null mice.
"Although
Boswellia resin seems to exert
anti-inflammatory and anti-cancer effects in several clinical trials, these
remain to be further corroborated and underlying mechanisms are to be
characterized." Small clinical trials demonstrate that B. serrata resin may be beneficial in
the treatment of inflammatory conditions such as bronchial asthma and chronic colitis.2
The 5-Loxin® B. serrata extract with
30% AKBA (distributed by PL Thomas & Co. Inc.;Morristown, New Jersey;
manufactured by Laila Nutra; Vijayawada,
India) has been
shown to reduce pain and improve physical functioning in patients with
osteoarthritis. A small study has found that the H15 B. serrata extract reduces edema, but not tumor size, in 2 of 7
patients with glioblastoma brain tumors and progressive edemas; this resulted
in clinical improvement and was well-tolerated. There has been a single case
report of contact dermatitis associated with topical B. serrata resin. Other studies have found that B. serrata resin is well-tolerated in
human subjects with the exception of mild adverse gastrointestinal effects. They
note that boswellic acids are not well absorbed, but failed to mention that
absorption is much greater when taken with a high-fat meal as compared to
fasting.3
Research
indicates that frankincense gum resin possesses immunomodulatory and
anti-inflammatory effects. Additional clinical trials are needed to confirm the
biological effects of frankincense gum resin. Research on the wound-healing
properties of frankincense gum resin is also warranted.
—Marissa
Oppel-Sutter, MS
Reference
1. Oliff
HS. Indian frankincense gum resin and extracts as anti-inflammatories in
clinical studies.HerbClip.
December 15, 2008 (No. 080564-366). Austin,
TX: American Botanical Council.
Review of Monograph. Boswellia serrata. Altern Med Rev. 2008;13(2):165-167.