Abstract
Infusions of Citrullus colocynthis Schrad. (Cucurbitaceae) fruits are traditionally used as antidiabetic medication
in Mediterranean countries, but to our knowledge no studies have been undertaken so
far to determine the possible mechanisms involved in the antidiabetic properties of
the fruit. The present study was designed to investigate whether these fruits possess
insulinotropic effects. For this purpose, different extracts of Citrullus colocynthis seed components were obtained: RN II (crude extract), RN VI (hydro-alcoholic extract),
RN X (purified extract) and RN XVII (β-pyrazol-1-ylalanine), the major free amino
acid present in the seeds. The insulin secretory effects of these different extracts
were evaluated in vitro in the isolated rat pancreas and isolated rat islets in the presence of 8.3 mM glucose.
All tested extracts, when perfused for 20 min at 0.1 mg/ml, immediately and significantly
stimulated insulin secretion. This effect was transient. In addition, the purified
extract (RN X) provoked a clear dose-dependent increase in insulin release from isolated
islets. Moreover, a significant and persistant increase in pancreatic flow rate appeared
during RN VI, RN X and RN XVII perfusions. In conclusion, our results show that different
Citrullus colocynthis seed extracts have an insulinotropic effect which could at least partially account
for the antidiabetic activities of these fruits.
Key words
Citrullus colocynthis
- Cucurbitaceae - seed fractionation - amino acids - HPLC - insulin secretion - antidiabetic
agent
References
- 1
Girard J..
Insulinorésistance: quel rôle dans le diabète de type 2. Role of insulin resistance
in Type 2 diabetes.
Diabète Métabol..
1994;;
20
330-6
- 2
Damsgaard E M,, Faber O K,, Froland A..
Prevalence of fasting hyperglycaemia and known non-insulin dependent diabetes mellitus
classified by plasma C-peptide: Fredericia survey of subjects 60 - 74 yr old.
Diabetes Care.
1987;;
10
26-32
- 3
Cerasi E,, Luft R,, Efendic S..
Decreased sensitivity of the pancreatic beta cells to glucose in prediabetic and diabetic
subjects.
Diabetes.
1972;;
21
224-34
- 4
De Fronzo R A,, Bonadonna R C,, Ferrannini E..
Pathogenesis of NIDDM.
Diabetes Care.
1992;;
12
318-68
- 5
Bailey C J,, Day C..
Traditional plant medicines as treatments for diabetes.
Diabetes Care.
1989;;
12
553-64
- 6
Ivorra M D,, Paya M,, Villar A..
Review of natural products and plants as potential antidiabetic drugs.
J. Ethnopharmacol..
1989;;
27
243-75
- 7
Shah A H,, Tariq M,, Ageel A M,, Qureshi S..
Cytological studies on some plants used in traditional Arab medicine.
Fitoterapia.
1989;;
60
171-2
- 8
Alkofahi A,, Batshoun R,, Owais W,, Najib N..
Biological activity of some Jordanian medicinal plant extracts.
Fitoterapia Vol. LXVII..
1996;;
5
435-42
- 9 Grifti D..
Etude de l'effet hypoglycémiant de la coloquinte. Thèse de Médecine,. Rabat (Maroc); 1989: 46
- 10 Chaabani N.. Etude expérimentale des propriétés hypoglycémiantes de Allium sativum L., Allium cepa L. et Citrullus colocynthis Schrad chez le rat Wistar. Thèse de 3ème cycle,. Université des sciences de Marrakech (Maroc) 1991: 140
- 11
Ziyyat A,, Legssyer A,, Mekhfi H,, Dassouli A,, Serhrouchni M,, Benjelloun W..
Phytotherapy of hypertension and diabetes in oriental Morocco.
J. Ethnopharmacol..
1997;;
58
45-54
- 12
Brunet Ph, , Sarrobert B,, Paris-Pireyre N..
Adaptation d'une méthode d'analyse des acides aminés par chromatographie liquide haute
performance dans les sèves xylémiques.
J. Chromatogr..
1988;;
455
173-82
- 13
Blanco Gomis D,, Picinelli Lobo A M,, Gutiérrez Alvarez M D,, Mangas Alonso J J..
Determination of amino acids in apple extracts by high performance liquid chromatography.
Chromatographia.
1990;;
29
155-60
- 14
Noe F F,, Fowden L..
β-Pyrazol-1-ylalanine, an amino acid from watermelon seeds (Citrullus vulgaris).
Biochem. J..
1960;;
77
543-6
- 15
Dunnill P M,, Fowden L..
The amino acids of seeds of the Cucurbitaceae.
Phytochem..
1965;;
4
933-44
- 16
Khanna P,, Jain S C..
Hypoglycemic activity of polypeptide-P from a plant source.
J. Nat. Prod..
1981;;
44
648-55
- 17
Dubey D K,, Biswas A R,, Bapna J S,, Pradhan S C..
Hypoglycaemic and antihyperglycaemic effects of Momordica charantia seed extracts in albinos rats.
Fitoterapia Vol, VIII..
1987;;
6
387-90
- 18
Loubatières A L,, Mariani M M,, De Malbosc H,, Ribes G,, Chapal J..
Etude expérimentale d'un nouveau sulfamide hypoglycémiant particulièrement actif le
HB419 ou glibenclamide. I. Action bêtacytotrope et insulinosécrétrice.
Diabetologia.
1969;;
5
1-10
- 19
Lacy P,, Kostianovsky M..
Method for the isolation of intact islets of Langerhans from the rat pancreas.
Diabetes.
1967;;
16
35-9
- 20
Herbert V,, Laws K S,, Gottlieb C W,, Bleicher S J..
Coated charcoal immunoassay of insulin.
J. Clin. Endocrinol..
1965;;
25
1375-84
- 21
Sauvaire Y,, Petit P,, Broca Ch,, Mananteghetti M,, Baissac Y,, Fernandez-Alvarez
J,, Gross R,, Leconte A,, Gomis R,, Ribes G,.
4-Hydroxyisoleucine, a novel amino acid potentiator of insulin secretion.
Diabetes.
1998;;
74
206-10
- 22
Cerasi E,, Luft R..
The plasma insulin response to glucose infusion in healthy subjects and in diabetes
mellitus.
Acta Endocrinol (Copenh).
1967;;
55
278-304
- 23
Kahn S E,, Porte D..
Islet dysfunction in non-insulin-dependent diabetes mellitus.
Am. J. Med..
1988;;
85
4-8
- 24
Kannel W B,, McGee D L..
Diabetes and cardiovascular risk factors. The Framingham Study.
Circulation.
1979;;
59
8-13
- 25
Day C,, Cartwright T,, Provost J,, Bailey C J..
Hypoglycaemic effect of Momordica charantia extracts.
Planta Med..
1990;;
56
426-9
- 26
Higashino H,, Suzuki A,, Tanaka Y,, Pootakham K..
Hypoglycemic effects of Siamese Momordica charantia and Phyllanthus urinaria extracts in streptozotocin-induced diabetic rats (the 1st report).
Nippon Yakurigaku Zasshi (5).
1992;;
100
415-21
- 27
Ali L,, Khan A K,, Mamun M I,, Mosihuzzaman M,, Nahar N,, Nur-e-Alam M,, Rokeya
B..
Studies on hypoglycemic effects of fruit pulp, seed, and whole plant of Momordica charantia on normal and diabetic model rats.
Planta Med..
1993;;
59
408-12
- 28
Sarkar S,, Pranava M,, Marita R..
Demonstration of the hypoglycemic action of Momordica charantia in a validated animal model of diabetes.
Pharmacol. Res..
1996;;
33
1-4
- 29
Rokeya B,, Ali L,, Azad Khan A K,, Mammun M R,, Mosihuzzaman M,, Nahar N,, Nur-e-Alam
M..
Insulin releasing effects of Momordica charantia fractions on isolated rat islets.
Diabetologia.
1995;;
38
suppl. 1-193
- 30
Sener A,, Somers G,, Devis G,, Malaisse W J..
The stimulus-secretion coupling of amino acid-induced insulin release: Biosynthetic
and secretory responses of rat pancreatic islet to L-leucine and L-glutamine.
Diabetologia.
1981;;
21
135-42
- 31
Sener A,, Owen A,, Malaisse-Lagae F,, Malaisse W J..
The stimulus-secretion coupling of amino acid-induced insulin release XI. Kinetics
of deamination and transmination reactions.
Horm. Metabol. Res..
1982;;
14
405-9
- 32
Fajans S S,, Floyd J C Jr,, Knopf R F,, Pek S,, Weissman P,, Conn J W..
Amino acids and insulin release in vivo.
Israel J. Med. Sci..
1972;;
8
233-43
Prof. Dr. Y. Sauvaire
Laboratoire de Recherche sur les Substances Naturelles Végétales Université Montpellier
II
UPRES EA 1677
Place E. Bataillon, Bât. 15, CC 024
34095 Montpellier Cedex 05
France
Email: sauvaire@arpb.univ-montp2.fr
Phone: +33 4 67 14 36 12