8.2.7 Metabolism / Diabetes
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Auszug aus Phytomedicine 18 (2011) 1037-1044
mit Erlaubnis: Elsevier GmbH, Urban & Fischer Verlag München

Prevention of Multiple Low-Dose Streptozotocin (MLD-STZ) diabetes
in mice by an extract from gum resin of Boswellia serrata (BE)

Ahmed M. Shehata (a, c), L. Quintanilla-Fend (b) , Sabrina Bettio (b), H.P.T. Ammon (a)
(a) Department of Pharmacology, Institute of Pharmaceutical Sciences, University of Tuebingen, Germany
(b) Institute of Pathology, University of Tuebingen, Germany
(c) Department of Pharmacology, Faculty of Pharmacy, Beni-Sueif University, Egypt

Abstract
Type 1-diabetes is an autoimmune disease, where a chronic inflammatory process
finally causes β-cell death and insulin deficiency. Extracts from gum resin of Boswellia
serrata (BE) have been shown to posses anti-inflammatory properties especially by
targeting factors/mediators related to autoimmune diseases. Multiple Low Dose-
Streptozotocin (MLD-STZ) treatment is a method to induce diabetes in animals similar
to Type 1 diabetes in humans.
It was aimed to study whether or not a BE could prevent hyperglycemia, inflammation of
pancreatic islets and increase of proinflammatory cytokines in the blood in MLD-STZ
treated mice.
In BK+/+ wild type mice, 5 days of daily treatment with 40 mg/kg STZ i.p. produced
permanent increase of blood glucose, infiltration of lymphocytes into pancreatic islets
(CD3-stain), apoptosis of periinsular cells (staining for activated caspase 3) after 10
days as well as shrinking of islet tissue after 35 days (H&E staining). This was
associated with an increase of granulocyte colony stimulating factor (G-CSF),
granulocyte/macrophage colony stimulating factor (GM-CSF) and proinflammatory
cytokines (IL-1A, IL-1B, IL-2, IL-6, IFN-γ, TNF-α) in the blood. Whereas BE alone did
not affect blood glucose in non diabetic mice, in STZ treated mice simultaneous i.p.
injection of 150 mg/kg of BE over 10 days prevented animals from increase of blood
glucose levels. Histochemical studies showed, that i.p. injection of 150 mg/kg BE for 10
days starting with STZ treatment, avoided lymphocyte infiltration into islets, apoptosis of
periinsular cells and shrinking of islet size 35 days after STZ. As far as the cytokines
tested are concerned, there was a significant inhibition of the increase of G-CSF and
GM-CSF. BE also significantly prevented the increase of IL-1A, IL-1B, IL-2, IL-6, IFN-γ
and TNF-α. It is concluded that extracts from the gum resin of Boswellia serrata prevent
islet destruction and consequent hyperglycemia in an animal model of type 1 diabetes
probably by inhibition of the production/action of cytokines related to induction of islet
inflammation in an autoimmune process.

Publications

1.

Polyphenol-rich Boswellia serrata gum prevents cognitive impairment and insulin resistance of diabetic rats through inhibition of GSK3β activity, oxidative stress and pro-inflammatory cytokines.
Gomaa AA, Makboul RM, Al-Mokhtar MA, Nicola MA

Biomed Pharmacother. 2019 Jan;109():281-292.
PMID: 30396086 [PubMed - as supplied by publisher]

2.

Inhibition of adiposity and related metabolic disturbances by polyphenol-rich extract of Boswellia serrata gum through alteration of adipo/cytokine profiles.
Gomaa AA, Farghaly HSM, El-Sers DA, Farrag MM, Al-Zokeim NI

Inflammopharmacology. 2018 Aug;():.
PMID: 30069718 [PubMed - as supplied by publisher]

3.

New α-Glucosidase inhibitors from the resins of Boswellia species with structure-glucosidase activity and molecular docking studies.
Ur Rehman N, Khan A, Al-Harrasi A, Hussain H, Wadood A, Riaz M, Al-Abri Z

Bioorg Chem. 2018 09;79():27-33.
PMID: 29715636 [PubMed - indexed for MEDLINE]

4.

11-Keto-β-Boswellic Acid Inhibits Lymphocyte (CD3) Infiltration Into Pancreatic Islets of Young None Obese Diabetic (NOD) Mice.
Shehata AM, Quintanilla-Fend L, Bettio S, Kamyabi-Moghaddam Z, Kohlhofer UA, Scherbaum WA, Ammon HPT

Horm Metab Res. 2017 Sep;49(9):693-700.
PMID: 28759942 [PubMed - indexed for MEDLINE]

5.

The effect of Boswellia serrata resin diet supplementation on production, hematological, biochemical and immunological parameters in broiler chickens.
Al-Yasiry ARM, Kiczorowska B, Samolińska W, Kowalczuk-Vasilev E, Kowalczyk-Pecka D

Animal. 2017 Nov;11(11):1890-1898.
PMID: 28436338 [PubMed - indexed for MEDLINE]

6.

Enzyme inhibitory metabolites from endophytic Penicillium citrinum isolated from Boswellia sacra.
Ali S, Khan AL, Ali L, Rizvi TS, Khan SA, Hussain J, Hamayun M, Al-Harrasi A

Arch Microbiol. 2017 Jul;199(5):691-700.
PMID: 28220202 [PubMed - indexed for MEDLINE]

7.

Anti-aggregatory effect of boswellic acid in high-fat fed rats: involvement of redox and inflammatory cascades.
Tawfik MK

Arch Med Sci. 2016 Dec;12(6):1354-1361.
PMID: 27904529 [PubMed - as supplied by publisher]

8.

β-Boswellic acid, a bioactive substance used in food supplements, inhibits protein synthesis by targeting the ribosomal machinery.
Casapullo A, Cassiano C, Capolupo A, Del Gaudio F, Esposito R, Tosco A, Riccio R, Monti MC

J Mass Spectrom. 2016 Sep;51(9):821-7.
PMID: 27460774 [PubMed - indexed for MEDLINE]

9.

11-Keto-β-Boswellic Acids Prevent Development of Autoimmune Reactions, Insulitis and Reduce Hyperglycemia During Induction of Multiple Low-Dose Streptozotocin (MLD-STZ) Diabetes in Mice.
Shehata AM, Quintanilla-Fend L, Bettio S, Jauch J, Scior T, Scherbaum WA, Ammon HP

Horm Metab Res. 2015 Jun;47(6):463-9.
PMID: 25951322 [PubMed - indexed for MEDLINE]

10.

Protective effect of boswellic acids versus pioglitazone in a rat model of diet-induced non-alcoholic fatty liver disease: influence on insulin resistance and energy expenditure.
Zaitone SA, Barakat BM, Bilasy SE, Fawzy MS, Abdelaziz EZ, Farag NE

Naunyn Schmiedebergs Arch Pharmacol. 2015 Jun;388(6):587-600.
PMID: 25708949 [PubMed - indexed for MEDLINE]

11.

Acetyl-keto-β-boswellic acid induces lipolysis in mature adipocytes.
Liu JJ, Toy WC, Liu S, Cheng A, Lim BK, Subramaniam T, Sum CF, Lim SC

Biochem Biophys Res Commun. 2013 Feb;431(2):192-6.
PMID: 23313487 [PubMed - indexed for MEDLINE]

12.

The Antioxidant Capacity and Anti-diabetic Effect of Boswellia serrata Triana and Planch Aqueous Extract in Fertile Female Diabetic Rats and the Possible Effects on Reproduction and Histological Changes in the Liver and Kidneys.
Azemi ME, Namjoyan F, Khodayar MJ, Ahmadpour F, Darvish Padok A, Panahi M

Jundishapur J Nat Pharm Prod. 2012;7(4):168-75.
PMID: 24624177 [PubMed - as supplied by publisher]

13.

In vitro and in vivo inhibitory activities of four Indian medicinal plant extracts and their major components on rat aldose reductase and generation of advanced glycation endproducts.
Rao AR, Veeresham C, Asres K

Phytother Res. 2013 May;27(5):753-60.
PMID: 22826152 [PubMed - indexed for MEDLINE]

14.

A novel synergistic galactomannan-based unit dosage form for sustained release of acarbose.
Kumar RV, Sinha VR

AAPS PharmSciTech. 2012 Mar;13(1):262-75.
PMID: 22234597 [PubMed - indexed for MEDLINE]

15.

Prevention of multiple low-dose streptozotocin (MLD-STZ) diabetes in mice by an extract from gum resin of Boswellia serrata (BE).
Shehata AM, Quintanilla-Fend L, Bettio S, Singh CB, Ammon HP

Phytomedicine. 2011 Sep;18(12):1037-44.
PMID: 21831620 [PubMed - indexed for MEDLINE]

16.

BHUx: a patented polyherbal formulation to prevent hyperlipidemia and atherosclerosis.
Tripathi YB

Recent Pat Inflamm Allergy Drug Discov. 2009 Jan;3(1):49-57.
PMID: 19149746 [PubMed - indexed for MEDLINE]

17.

A norsesquiterpene lactone and a benzoic acid derivative from the leaves of Cyclocarya paliurus and their glucosidase and glycogen phosphorylase inhibiting activities.
Li J, Lu Y, Su X, Li F, She Z, He X, Lin Y

Planta Med. 2008 Feb;74(3):287-9.
PMID: 18300194 [PubMed - indexed for MEDLINE]

18.

Hypoglycemic and other related effects of Boswellia glabra in alloxan-induced diabetic rats.
Kavitha JV, Rosario JF, Chandran J, Anbu P, Bakkiyanathan

Indian J Physiol Pharmacol. 2007 Jan-Mar;51(1):29-39.
PMID: 17877290 [PubMed - indexed for MEDLINE]

19.

Extract of gum resins of Boswellia serrata L. inhibits lipopolysaccharide induced nitric oxide production in rat macrophages along with hypolipidemic property.
Pandey RS, Singh BK, Tripathi YB

Indian J Exp Biol. 2005 Jun;43(6):509-16.
PMID: 15991575 [PubMed - indexed for MEDLINE]

20.

Coupling of boswellic acid-induced Ca2+ mobilisation and MAPK activation to lipid metabolism and peroxide formation in human leucocytes.
Altmann A, Poeckel D, Fischer L, Schubert-Zsilavecz M, Steinhilber D, Werz O

Br J Pharmacol. 2004 Jan;141(2):223-32.
PMID: 14691050 [PubMed - indexed for MEDLINE]