Elsevier

Phytomedicine

Volume 63, October 2019, 153002
Phytomedicine

Boswellic extracts and 11-keto-ß-boswellic acids prevent type 1 and type 2 diabetes mellitus by suppressing the expression of proinflammatory cytokines

https://doi.org/10.1016/j.phymed.2019.153002Get rights and content
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Abstract

Background

Type 1 diabetes is an autoimmune disease directed to the pancreatic islets where inflammation leads to the death of insulin-producing ß cells and insulin deficiency. Type 2 diabetes, which is closely related to overweight, is characterized by insulin resistance. In both cases, proinflammatory cytokines play an important role by causing insulitis and insulin resistance.

The gum resin of Boswellia species and its pharmacologically active compounds, including 11-keto-ß-boswellic acids have been shown to suppress the expression of proinflammatory cytokines in various immune-competent cells.

Purpose

To review the present evidence of the therapeutic effects of boswellic extracts (BE) and/or 11-keto-ß-boswellic acids in the prevention/treatment of diabetes mellitus and to provide comprehensive insights into the underlying molecular mechanisms.

Methods

This review considers all available informations from preclinical and clinical studies concerning BEs, 11-keto-ß-boswellic acids, proinflammatory cytokines and diabetes mellitus collected via electronic search (PubMed) and related publications of the author.

Results

Type 1 diabetes: Studies in mice with autoimmune diabetes revealed that in the model of multiple injections of low doses of streptozotocin (MLD-STZ), an extract of the gum resin of Boswellia serrata and 11-keto-ß-boswellic acid (KBA) suppressed the increase in proinflammatory cytokines in the blood, infiltration of lymphocytes into pancreatic islets and increase in blood glucose. In a second model, i.e. the nonobese diabetic (NOD) mouse, KBA prevented the infiltration of lymphocytes into pancreatic islets. Regarding the clinical effects, a case report provided evidence that BE suppressed the blood levels of tyrosine phosphatase antibody (IA2-A), a marker for insulitis, in a patient with late-onset autoimmune diabetes of the adult (LADA).

Type 2 diabetes: In a preclinical study in rats where obesity was alimentary induced, the administration of BE significantly reduced food intake, overweight, proinflammatory cytokines such as interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) and ameliorated the parameters of glucose and lipid metabolism. Similar results were obtained in a second animal study, where type 2 diabetes was induced by a combination of a high-fat/high-fructose diet and a single dose of streptozotocin. Two clinical trials with patients with type 2 diabetes receiving the resin of Boswellia serrata demonstrated improvement in the blood glucose, HbA1c and lipid parameters.

Conclusion

Preclinical and clinical data suggest that BE and/or 11-keto-ß-boswellic acids by inhibiting the expression of proinflammatory cytokines from immune-competent cells, may prevent insulitis and insulin resistance in type 1 and type 2 diabetes, respectively, and therefore may be an option in the treatment/prevention of type 1 and type 2 diabetes. It is hypothesized that molecularly, BE and 11-keto-ß-boswellic acids act via interference with the IκB kinase/Nuclear Transcription Factor-κB (IKK/NF-κB) signaling pathway through inhibition of the phosphorylation activity of IKK. However, further investigations and well-designed clinical studies are required.

Keywords

Diabetes mellitus
Insulitis
Insulin resistance
Proinflammatory cytokines
Boswellic extracts
11-keto-ß-boswellic acids

Abbreviations

ABA
Acetyl-ß-boswellic acid
AKBA
Acetyl-11-keto-ß-boswellic acid
BA
ß-boswellic acid
BE
boswellic extract
CCL2
chemokine ligand 2
CEL
contrast enhancing lesions
COX
cyclooxygenase
GLP-1
glucagon like peptide 1
HBA1c
hemoglobin A1c
HDL
high density lipoprotein
IA2-A
tyrosine phosphatase IA2-antibody
IC50
inhibitory concentration 50 (half maximal)
IDDM
insulin dependent diabetes mellitus
IFN-γ
Interferon-γ
IKBα
NFĸB inhibitory protein
IKK
I kappa B alpha kinase (protein kinase B)
IL
interleukin
5-LO
5-lipoxygenase
KBA
11-keto-ß-boswellic acid
LADA
late onset autoimmune diabetes of the adult
LDL
low density lipoprotein
LPS
lipopolysaccharide
mets
metabolic syndrome
MLD-STZ
multiple low dose-streptozotocin
NFĸB
nuclear transcription factor ĸB
NOD
none obese diabetic
PAI-1
plasminogen-activator-inhibitor-1
PBMC
peripheral blood mononuclear cell
PGE2
prostaglandin E2
PL-A2
phospholipase-A2
PMNL
polymorph mononuclear neutrophil leucocytes
SGPT
serum glutamate pyruvate transaminase
SGOT
serum glutamate oxaloacetate transaminase
STZ
streptozotocin
TH1
TH1 lymphocyte
TH2
TH2 lymphocyte
TNF-α
tumor necrosis factor-α

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