PLANT WITH ANTI-DIABETIC PROPERTIES

PROFILE OF SELECTED PLANT WITH ANTIDIABETIC PROPERTIES

DIOSCOREA DUMETORUM – PLANT WITH ANTIDIABETIC PROPERTIES

TAXONOMY (verdcourt et al., 1969)

                   Kingdom: Plantae

                   Phylum: Angiospermae

                   Subphylum: Dicotyledonea (kernick 1970)

                   Order: Dioscoreales

                   Family: Dioscoreaceae

                   Genus: Dioscorea

PLANT WITH ANTI-DIABETIC PROPERTIES

Dioscorea dumetorum (Ji Ona)

PLANT WITH ANTI-DIABETIC PROPERTIES

Leave of Dioscorea dumetorum

MORPHOLOGY:

         Dioscorea dumetorum is a member of the yam family found widespread in tropical Africa and growing annually in secondary bushlands, savanna, thickest forest edges, and plantations. It was under subphylum monocotyledons. But recent observations by kernick, 1970 suggested that yam has two cotyledons. Hence subphylum Dicotyledonae.

         The aerial part is thorny, hairy climbing stem bearing compound leaves divided into three ovate leaflets. Each leaflet taper to an excellent point, and the whole leaf may attain 18cm or more in length and 12cm or more in a breath. The male flowers are small and are borne on condensed spikes, which are themselves elongated in the branched inflorescence.

The fruits are capsules, and each is elongated oblong, glabrescent with slightly pressed hairs. The underground tubers portion consists mainly of fleshy tubers, some of which may weigh up to 100kg. A cross-section of the tuber reveals that the tuber has a yellowish color, and has a bitter taste (Verdcourt et al., 1969; Raymong, 1939).

CHEMISTRY OF DIOSCOREA DUMETORUM

         Members of the family screened contain alkaloids, anthocyanins, glycosides, carbohydrates, saponins, steroids, tannins, proteins, and phenolic compounds such as cyanidin, caffeic acid; kaemferol, p-coumaric acid, sinapic acid, ferulic acid and quercetin (Kernick, 1970).

        Dioscorea dumetorum tuber has been reported to contain sitosterol, and alkaloids Dioscorides, dihydrodioscorine, Dioscorea base, and dioscoretine, which is the hypoglycemic chemical compound present (Correia et al. 1964) and more recently (Iwu et al. 2004) confirmed the above constituents of the plant called dumetorine. Dioscorea is the primary alkaloid, and it is a beta tropane derivative containing an unsaturated 6-membered lactone ring (Sharaf et al. 1963). The structures of those constituents that have been confirmed characterized are shown below:-

PHARMACOLOGY OF DIOSCOREA DUMETORUM

The hypoglycemic agent or constituent dioscoretine is a hydrolysis product of dihydro-dioscorine. The tube of Dioscorea dumetorum contains hyperglycemic and hypoglycemic principles. The chloroform fraction of the plant affected a hyperglycemic when a dose of 125mg/kg was given to rabbit and was confirmed to contain the tertiary alkaloids, which have been identified earlier to be dihydrodioscorine, dioscorine and dumetorium. (Iwu, 1985 and Ohiaeri, 1988).

          While the aqueous fraction elicited a hypoglycemic effect and was confirmed to contain an alkaloid, which probably is a quarternary alkaloid (dioscoretine), saponins, or glycosides. (Undie, 1983) did establish that sitosterol may be responsible for the hypoglycemic action. But Iwu et al. in 1985 confirmed it to be dioscoretine.

GARCINIA KOLA HECKEL – IS A PLANT WITH ANTIDIABETIC PROPERTIES

PLANT WITH ANTI-DIABETIC PROPERTIES

GARCINIA KOLA HECKEL

TAXONOMY:

                                        Phylum:       Angiospermae

                                        Subphylum: Dicotyledons

                                        Grade:          Archichlamydae

                                        Order:           Guttiferae

                                        Genus:          Garcinia

                                        Family:          Guttiferae

                                        Species:        Kola
                                     

Common name: bitter cola

Local names:   Aki-ilu            (Igbo)

                       Cida-gworo    (Hausa)

                       Edun               (Benin)

                       Effiat               (Ibibio)

                       Efiari                (Efik)

                       Oju                  (Boki)

                       Okan               (Ijaro)

                       Orogbo           (Yoruba)

MORPHOLOGY:

             Garcinia kola Heckel, family Guttiferae is a small tropical tree, it is cultivated in southern Nigeria and some other parts of Africa, for its edible fruit and seed. This is a plant with antidiabetic properties.

             The bark is brown, smooth, and thick, yielding sap when incised. The leaves are about 5-6cm long and 2-3cm broad. They are elongated elliptic with short acute or short acuminate apex, leathery in texture. The fruits are round, about 8-10cm in diameter, with a depressed point of attachment. They ripen from green to an orange color pulp. Both pulp and seeds are edible. The seeds are obtained from the decayed fruits. They are covered with a light brown testa, which may be peeled off to reveal the white grain, which is elliptically shaped, about 4-5cm long and bitter when chewed. (Hussain et al. 1982, Iwu and Igboko, 1982).

CHEMISTRY OF GARCINIA KOLA

Phytochemical studies on Garcinia kola have established that the plant contains a complex mixture of phenolic compounds, triterpenes, and benzophenones. Kalanone (1), a poly-isoprenylated benzophenone with antimicrobial properties, has been isolated from the light petroleum extract (Hussain et al., 1982).

From the petroleum spirit extract of the seeds, Cycloartenol (ii) and its 24-methylene derivatives (iii) have been isolated.

(Aplin et al., 1967) sterols, as well as c-3/8 linked biflavanones, GB1, GB2, GB1a, and kolaflavanones (IV) has been with the ethylacetate soluble fraction of the acetone extract (Cottelril et al. 1978).

Simple flavonoids apigenin-5, 7, 4’ –trimethylether, (v), apigenin-4-methylether (vi) and flestin (3’, 4’, 7-trihydroxylflavol) (vii) were isolated together with the biflavonoids, amentoflavone, (5’, 8’’-biapigenin} (viiii), kolaflavnoids (i-3’-ii3-i-4’-i-5-ii-5-i-7-ii-7-octahydroxy-ii-3-methoxy-3/8”biflavonone {iv) and GB1 (ii-3-i-4’-ii-4’-i-5-ii-5-i-7-ii-7-heptahydroxy-3/8” biflavone) (ix), (Iwu and Igboko, 1982). The acetone extract has been reported to contain 8-c-hexosy1-5, 7, 4-trihydroxy flavone, and o-c-hexosy1-3-5-7-4’-tetrahydroxy-flavone (Olaniyi et al; 1979)

PHARMACOLOGY OF GARCINIA KOLA

The aqueous portion of the acetone extract of Garcinia kola was found to lower the blood sugar level in both normal (hypoglycaemic activity) and diabetic rabbits. A dose of 195mg/kg was found to be effective. The extract was found also to have a slow onset of action and long duration than tolbutamide which seems to have a quicker onset and shorter duration of action. The extract also maintains an effect in alloxan-induced diabetic rabbits until the drug is stopped being administered. It is not possible to predict the mechanism of action of this drug but it could be suggested that its hypoglycemic effect is exerted by a mechanism similar to that of sulphonylureas, that is in the presence of residual B-cell function (pancreatic reserve) (Iwu, 1982 and Ndife, 1988).

            Kolaviron is the confirmed hypoglycemic active constituent in Garcinia kola. It is made of GB-1, GB-2, and kolaflavanone, (Iwu, 1982 and igboko, 1983).

BRIDELIA FERRUGINEA – IS A PLANT WITH ANTIDIABETIC PROPERTIES

BRIDELIA FERRUGINEA

BRIDELIA FERRUGINEA

            Bridelia ferruginea, family Euphorbiaceae is used extensively in African ethnomedicine for the treatment of various diseases, including diabetes mellitus and management of hypertension (Ampform 1977 and iwu, 1980). On the west coast of Africa, aqueous infusion of the leaves is used for the treatment of chronic diabetes, particularly in a case where ketosis has set in. The antidiabetic properties of B. ferruginea were evaluated by monitoring the blood sugar of patients receiving treatment from a native healer.

 CHEMIISTRY OF BRIDELIA FERRUGINEA

            The premonitory and confirmatory chemical tests with the dried powdered leaves and extracts indicated the presence of coumestans (Isoflavonoids), carbohydrates, tannins, flavonoids, anthracene derivatives, sterols and terpenoids, alkaloids were not detected in any of the extracts or the crude using standard techniques. (Harbone, J.B. 1973). The plant extract was also found to contain apigenin, C-glycoside, and vitexin after analysis of its spectra with (U.V., I.R., MS, NMR) and co-TLC with an authentic sample of kaempferol. It contains tetrahydroxy coumestan and its 7-glucoside (Iwu, 1980).

After the GTT (glucose tolerance test), bridelia was found not to possess a hypoglycin type activity in healthy animals. The antidiabetic activity of Bridelia ferruginea could be attributed to a possible role in the release or activation of endogenous insulin since the drug is more active in rats with intact B-cells then in rats with B-cells damage caused by alloxan. The extracts completely checked the degranulation of B-cells (as evidenced histochemically) and the elevated blood glucose that are characteristics of alloxan diabetes.

This effect did not appear to be secondary to the direct inactivation of alloxan by the Bridelia extracts, as an injection of a mixture of the two agents did not approve protection, and the drug does not seem capable of reversing the B-cell damage caused by alloxan (Heikkila R.R. 1977). It is, however, clear that the coumestans, which are isoflavonoids, create the hypoglycemic effect in Bridelia ferruginea (Iwu, 1980).

BASIC STRUCTURE OF COUMESTANS

The fast blood sugar levels of maturity-onset diabetic patients were lowered to normal by a daily dose of aqueous extracts of Bridelia ferruginea leaves.

Glycosuria was eliminated after two weeks of therapy, even in cases where ketosis had already been established. In experimental animals, alcoholic and aqueous extracts of this plant significantly lowered the fasting blood sugar but failed to protect the animals adequately against alloxan-induced diabetes. They, however, significantly decreased the expected hyperglycaemic in alloxan rats when administered one hour before alloxan injection (Iwu, 1980).

ALLIUM CEPA (ONION)

ALLIUM CEPA (ONION)

ALLIUM CEPA (ONION)

The name of the plant is onion bulb, and the botanical name is Allium Cepa L. family Liliaceae, is a plant with antidiabetic properties.

            It was noticed that a totally depancreatized dog could be kept alive for 66 days on 3 injections of crude onion extract. Later a number of research workers confirmed that that onion and its extracts have a distinct, slowly developing hypoglycaemic action and that the effect is shown after peroral administration. (Jain R.C. 1974). Purification was carried out by extraction with light petroleum ether of the well dried sliced onions, producing a fraction with an oral hypoglycemic action equivalent to 62% of that of a standard dose (0.5g) 
of tolbutamide. An ethyl-ether extract of the evaporation residue of the petroleum extract had an action equivalent to 76.6% of that of the tolbutamide standard (Brahmachari H.D. et al. 1962).

            From the fresh onion using steam-distillation and solvent extraction, two active disulfides were isolated, 0.01% of allyl propyl disulfide (APDS) and ‘allicin’ (diallyl disulfide oxide). (Augusti et al., 1976).

HYPOGLYCAEMIC EFFECT OF ALLYL PROPYL DISULPHIDE

            Blood sugar rise and glycosuria were significantly less in alloxan diabetic rabbits receiving 100mg/kg APDS than in those of a control group, and glucose tolerance were also improved. In a 15-day test, the control animals suffered an average loss of weight of 50-100g. The treated rabbits appeared more healthy and gained 200-300g in weight.

            In a four hour test in six fastings, healthy subjects, APDS (capsule of 125mg/kg) caused a marked fall of blood sugar (hourly controls) and an increase of serum insulin levels, while the free fatty acid level remained the same. In contrast, in a controlled trial (one week earlier), the same subjects had shown no fall of the blood glucose, but the serum insulin level had decreased, and the free fatty acid has increased considerably.  Insulin is a disulfide protein, and its inactivation by compounds and albumins rich SH-group has been established. APDS probably removes insulin-inactivating compounds by competing with insulin for the SH-group these compounds, thus producing an insulin-sparing effect preventing the increase of free fatty acids on fasting (Augusti et al. 1976).

HYPOGLYCAEMIC EFFECT OF DIALLYL DISULPHIDE OXIDE (ALLICIN)

            The hypoglycaemic effect was reported in alloxan diabetic rabbits using 0.2g/kg of allicin, which produced a lowering of the blood sugar equivalent to 80% of that produced by the same dose of tolbutamide. The action is not noticeable in totally depancreatized rabbits (which also applies to tolbutamide).

            Thus the effect of both drugs depends on an endogenous or exogenous source of insulin, and the control of hyperglycemia by these drugs is only possible in mild cases of combination with a small dose of insulin. The glucose/nitrogen ratio (a measure of the capacity of the diabetic animal to utilize the glucose derived from protein) was only half as much reduced by allicin compared to tolbutamide in short treatment. Long term feeding of standard both 100mg/kg of allicin produced an important. Reduction in lipids constituents of the blood and liver and this respect allicin might have an advantage over tolbutamide, which under specific conditions can produce hyperlipaemia.

            In clinical trials, 100mg/kg allicin produced a significant drop in fasting blood glucose levels with a concomitant rise in serum insulin levels. Synthetic di-N-propyl disulfide oxide produced a reduction in blood sugar of 12.8% compared to 20% with onion oil and 25% with 0.25g/kg tolbutamide. The more significant effect of the oil may be due to the presence of much unsaturated sulphur compound. The glucose tolerance in a maturity-onset diabetic patient was also considerably improved by 12mg of onion oil administered 1hour before the glucose load (Augusti et al. 1976).

CHEMISTRY OF ALLIUM CEPA

            The tear-producing essential oil in onions contains allyl-propyl disulfide, diallyl disulphide oxide, and thiol propionic aldehyde. In fresh onions, which have bacteriostatic action, a glucoside of oleanolic acid is found. Cyanidin and peonidin-glucoside are also present in the bulbs, and in the outer scales of the bulb quercetin, spire side which is quercetin-4-mono-glucoside and other quercetin glucoside are present.

These flavonoids and anthocyanidins could well be partly responsible for crude oil (Vohora S.B. et al 1973).

CATHARANTHUS ROSEUS

CATHARANTHUS ROSEUS

Catharanthus roseus also known as Madagascar periwinkle is a plant with antidiabetic properties.

Synonym (vinca roser L) family Apocynaceae

The plant is perennial with wooden stems elliptic opposite leaves and axillary white or pink flowers; native of tropical America but naturalized all through the tropics.

In the folk medicine of several countries such as the Philippines, Jamaica, South Africa, Indian, and Australia, an infusion of the leaves is given to diabetics.

American research worker who wants to study the hypoglycaemic effect of the plant lost a great number of rats which had received an extract of the leaves through pseudomonas infection. Investigation revealed that the animals had lost their resistance through a substantial reduction of their lymphocytes. This stood at the beginning of the research undertaken on the treatment of leukaemia by Catharanthus alkaloids. (Noble R.L. et al. 1958).

Research on the hypoglycaemic effect was not abandoned. However, the different Catharanthus alkaloids were administered in doses of 100mg/kg to rats fasted previously for 18 hours. The blood sugar was determined by the Hoffman method after 1,2,3,5 and 7 hours, revealing that the hypoglycaemic action varied with the different significant alkaloids of the plants.

PHARMACOLOGY OF CATHARANTHUS ROSEUS

Cantharidine HCl, Leurosine Sulphate, Lochnerine, Tetrahydroalstonine, Vindoline Chloride, and Isovindolinine Chloride had a definite and relatively long-lasting hypoglycaemic effect characterized by a slow start (Svoboda et al., 1964).

At equivalent doses, Leurosine Sulphate, Vindoline Chloride, and Isovindolinine Chloride exerted a more potent action than that of tolbutamide, but inferior to that of acetohexamide-N (acetyl-phenylsulfonyl) N’cyclohexylurea. The above mentioned Catharanthus alkaloids had a less pronounced response. The hypoglycaemic alkaloid leurosine produces ball metaphase (with characteristically clumped chromosomes) but no classical c-metotic effect like Vinblastine and Vincaleurocristine (Svoboda et al., 1964).

TECOMA STANS

PLANT WITH ANTI-DIABETIC PROPERTIES

TECOMA STANS

Tecoma stans juss, (syn: Tecoma Molle) family Bignoniaceae, is a plant with antidiabetic properties.

                        It is an ornamental tree with opposite composite leaves and drooping clusters of yellow funnel-shaped flowers at the end of the branches. Found in many sub-tropical regions (Egypt, Central America, Mexico, and South America). Natives have long used the leaves of different species of Tecoma in Mexico as oral antidiabetic remedies. (Collin J. 1927).

HYPOGLYCAEMIC EFFECT OF TECOMINE AND TECOSTANINE

            In a test carried out on rabbits and patients, it was first claimed that extract of Tecoma leaves reduced glycosuria in people with diabetes when given orally and that hyperglycaemia is reduced 2 hours after subcutaneous injection. Then, in test on rats and mice with alloxan-induced hyperglycaemia, the hypoglycaemic effect of the leaf extracts of T. stans given by mouth, or in some cases by intramuscular route, could not be confirmed. (Garcia and Collin J. 1926).

            Later on, biological assays show that, when given intravenously, two alkaloids, namely tecomine and tecostanine which had been isolated from the leaves, had a strong hypoglycaemic action comparable to that of tolbutamide. The average lethal dose in mice was found to be 300mg/kg. Tests were then carried out to study the effect produced on fasting blood sugar in the glucose tolerance of the pancreatic rabbits with alloxan-induced diabetes in using tecomine citrates and tecostanine hydrochlorides orally. The results showed that the two alkaloids need a minimum of active B-cells for their action and are similar in these to certain other orally active hypoglycaemic substances as a sulphonylurea. At therapeutic doses of the alkaloids, no toxic effect was observed in rabbits. (Hammouda Y and Motawi, 1959).

CHEMISTRY OF TECOMA

Tecomanine, with a structure similar to Calpine, was isolated first in 1963, then the two further closely related alkaloids tecostanine and tecostidine were obtained, and their constituents elucidated. The leaves also contain a quinone similar to lapachol. Finally, the structure of the two hypoglycaemic alkaloids was established. (Hammouda Y. et al., 1964).

            It is noticed that the stability of tecomine is low, and the degradation appears to be dependent on the P.H. of its solution. Antioxidants are beneficial in delaying their deterioration (Khallafallah, N. 1971).

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