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AND PLANTS AS
A REVIEW OF NATURAL PRODUCTS POTENTIAL ANTIDIABETIC DRUGS
The present paper reviews the active, natural principles and crude extracts of plants which have been ~Kper~rneuta~~y studied for hypogly~om~~ activity in the last ten years. Phyto~o~stituents with known structures have been classified in appropriate chemical groups and the active crude extracts have been listed alphabetically according to genus. Data are reported on their pharmacological activity, mechanism of action, toxicity and other properties.
Diabetes mellitus is a metabolic disease as old as mankind and its incidence is considered to be high 44- St’loLTreatment of this disorder takes three main forms: i4 diet and exercise, 66;)insulin replacement therapy and G4 the use of oral hypoglycemic agents ~sulfonylureas and biguanidesl. However, since time immemorial, patients with non-insulin requiring diabetes have been treated orally in folk medicine with a variety of plant extracts. The evaluation of these plants and, especially, of their active natural principles is a logical way of searching for new drugs to treat this disease. We have reviewed the relevant literature on the plants which have been used in folk medicine and for which hypoglycemic activity has been scientifically documented in clinics or by the use of experimental methods.
0 1939 Elsevier ~~8~~~~~39~~1.~ Published and Printed in Ireland
TABLE 1 ISOLATED FROM PLANTS Part used Data on structure and action of principle :
These mice. duced action
Aconitans A, B, C and and D
glycans exhibited pronounced hypoglycemic effects in normal The main glycan, aconitan A, administered i.p. to aIloxan-prohyperglycemic mice, also exhibited a blood sugar lowering (Konno et al., 1985d).
Arborans A and B
Aloe arborescens Mill. var. natalensis Wood. et Ev.
These glycans elicited marked hypoglycemic effects in normal and alloxan-induced hyperglycemic mice (Hikino et al., 1986c).
Anemarans and D
A, B, C
These constituents displayed hypoglycemic effects in normal mice and the main glycan, anemaran C, administered i.p. to alloxaninduced hyperglycemic mice reduced plasma glucose level (Takahashi et al., 19851
A, B and C
Hypoglycemic effects were seen in normal mice and the main glycan, atractan A, also reduced blood glucose when injected i.p. to alloxaninduced hyperglycemic mice (Konno et al., 1985e). These components elicited hypoglycemic effects in normal mice and coixan A showed a hypoglycemic effect when administered to alloxan-induced hyperglycemic mice (Takahashi et al., 1986)
Coixans A, B and C L. var. maSeeds
yuen Stapf. (Gramineae) Tubers
Dioscorans A, B, C, D, E and F
All the dioscorans had a hypoglycemic effect when injected i.p. to normal mice and the main glycan, dioscoran C, also exhibited a hypoglycemic effect in alloxan-induced hyperglycemic mice (Hikino et al., 1986a).
Eleutherans A, B, C, D, E, F and G
When eleutherans A-G were injected i.p. to normal mice, hypoglycemic activity was observed with all the glycans except eleutheran E. 1.~. administration of eleutheran C to alloxan-treated mice also lowered blood glucose level (Hikino et al., 1986d3.
8 (Tomoda et al. I. branching positions and intermediate units is about 1: 1:1. J. C D. the ratio of terminals. 19871 with hypoglycemic effects were isolated from the roots of P. (Araliaceael Roots These glycans had a hypoglycemic action in normal mice and the i. Pterocarpus marsupium (Leguminosael Bark t .. 19841. 19851. M. The quinquefolans showed hypoglycemic effects in normal mice and of quinquefolan A to alloxan-induced hyper i. C. administration of panaxan A and B in alloxan-induced hyperglycemic mice also reduced the blood glucose levels (Konno et al.l-Epicatechin Roxb. respectively (Takagi.. 19851... (Gramineael Flavonoids and related products ( . officinarum (Hikino et al. 19861.. the ratio of terminals. N.l-Epicatechin was reported to protect rats from alloxaninduced diabetes when the compound was administered (30 mgikgl twice daily for 2 days prior to alloxan and 1 day after alloxan administration . E and F . S. B. 1985c1. 19871. Panaxan A has a molecular weight of 14. Aerial Saccharum officinarum L. G and H (Hikino et al.p. Roots Saccharans A.. B Panax quinquefolium (Araliaceael L. K and L (Oshima et al.800. ginseng. Other glycans. B. panaxans F. Quinquefolans and C A. Q. 1985c1. D and E Panax ginseng Mey. T and U (Konno et al.TABLE Part used Data on structure and action of principle 1 (continued) Active principle Plant species Panaxans A. Panaxan B was shown to be a peptidoglycan with molecular weight of about 1.p. R. branching positions and intermediate units is 1:1:2 (Tomoda et al.OOO and is composed mainly of a-l-% linked D-glUCOpyranOSe residues with branching at the C-3 position.. 19841. 1985dl. administration glycemic mice also produced a hypoglycemic effect (Oshima et al.000 and is composed mainly of a-1-6 linked D-g~UCOpyranOSC residues with branching at the C-3 position. parts These products had hypoglycemic and anti-atherosclerotic activity in mice and rats. 0 and P (Konno and Hikino. The accumulation of lipid peroxides induced by a high sugar diet was inhibited by combined feeding with a polysaccharide fraction of S..
l-Epicatechin had direct effects on islets of Langerbaus function.bl. streptozotoc~n-treated C57BL/65 mice Kolb et al. Iajeetion of epiestechin (30 m&kg twice daily for 4 days) into normal rats brought about an increase in insulin secretion from isolated islets when exposed to 20 mM glucose and in islet content in treated rats.. 1981c and 19821.. Bark These flavonoids are present in equal proportions in a fraction isolated from 2. This fraction produced hy~giyce~a in rabbits Khosa et al...05 m&I epi~techin &Iii and Wowell. 19831. Hii and Ifowell.. by changes in cyclic AMP metabolism (epicatechin at 1 mmol~ increased cyclic AMP concentrations in islets. 1983a.1 mmol/ll enhanced insulin release in isolated rat islets of Langerhans. rz~gosa.5 mhI giueose for 4 days showed a significant increase in DNA synthesis in the presence of 0. 1981b.~epicateehi~ in different experimenta diabetic models. Furthermore. in 2 rJ . However. other authors failed to confirm the antidiabetic effect of 4.OI--0.g. Ileguminosael Oral administration of this compound (100 mgkgl lowered the blood glucose level in normal rats 2 h after glucose injection (Abd-ElWahab et al. &R&iGo variegata L. Nii and Howe& 19851. 19821. (. 19851. 1981al. 1984al..01 mmol/lf also inhibited sea** efflux and increased the uptake of q5Caz+ isolated rat islets @Iii and Howell. this compound (0. Moreover. This compound (1 m&II increased insulin secretion from isolated rat islets in the presence of either 2 or 20 mlU glucose in static incubations or in perfosion. this compound could reverse ~lloxan-induced hyperglycemia when it was administered for 2-3 days (30 mg/kg twice daily) canning 24 h after alloxan adm~nistration ~~hakrsva~h~ et al. adult rat islets cultured with 5. The effect of epicatechin on insulin release coufd have been brought about. Kaempferol-~~rhamnoside Quercitin-3. Sheehan et al. quercetin fO.(Chakravarthy et al.. 1982. at least in part. vsr. candti Roxb.8 mmolll inhibited Y?az’ efflux and increased the uptake of 45Caz+ the presin ence of 20 m&I glucose. 19851. 1984b3 or by changes in Ca2+metabolism (epicatechin at 0. streptozotocin-diabetic or spontaneously diabetic BB/E rats (Bone et al. On the other hand. 19871. alloxan-treated Wistar rats (Kolb et al. e.~rhamnoside ~~i~tin~~rham~oside Leaves Quer~etjn ~uu~~n~ ~~reo L..
66 mM glucose but did not increase the insulinreleasing capacity of 16.. M. However. unpublished observations).5 mM1 stimulated insulin release from isolated rat islets of Langerhans in the presence of 1. 19791.1 .6 mM glucose. f3-sitosterol 36-u-glucoside did not change insulin and glucose levels in rats with streptozotocin-induced severe diabetes.p. The glyeoside (0. (Rubiaceael . 1988al. et al. their blood glucose fi-Sitosterol Coffeu arabica L.D. A high dose of those compound (600 mg/kg i. to mice) did not produce any symptoms of toxicity and none of the mice died during the ‘I-day observation period (Ivorra. These data suggest that 6sitosterol 3++glucoside exerts its action on intact pancreatic /3-cells by stimulating insulin secretion. (Compositae) levels at a dose of 20 mg/kg when given orally to glucose-induced hyperglycemic rats &War and Pay& 19851. It has been demonstrated that with an oral dose of 30 mg/kg this compound increased the fasting plasma insulin levels in normoglycemic rats and improved the oral glucose tolerance test with a corresponding increase in glueoseinduced insulin secretion (Ivorra et al...TABLE (continued) itima lge. Green beans This substance given orally ta mice decreased levels (Sampaio et al.0.
(IO mg/rat~day for 8 days) (Yvkvzawa et al. single i. successive i.p.G~nsenoside Rb.. The blood insulin levels remained unchanged throughout the Qday treatment. The ~~~noside~ Rb. in strepto~ta~ndiabetic rats iodu~ed a decrease in blood usea N level and an increase in total protein and several amino acids in serum. Roots txJ % .. 19841 or repeated administration (Yvkozawa et al. the hepatic g~ucv~nase was significantly increased and the liver glycvgen content tended to increase after 6 days of ginsenvside-Rb2 treatment fYokvsawa et al. remarkably improved diabetic symptoms such as overeating. 1985b). on the other hand. triglycerides non-shafted fatty acids and total chv~esterv~ forthermo~e.. polyuria and glyeosuria. Moreover. lowered the serum levels of ~~ydroxybuty~~te and ace~acetate in strep~~toci~induced diabetic rats. ~m~n~strat~on (Yv~osawa et al. 198%). 198%) of ginsenodde Rb. but no significant change in serum albumin was observed. 1985). treatment for 6 days (Yvkozawa et al.-treated group showed a decrease in the activity of he~atie glucose~-phosphate after 6 days of treatment.p. administration of gitwenosideRb. 1987aL ~nrthermore. 1981b). In contrast.. 1987aL The hypoglycemic action of ~~senoside-Rb* may be due to its effects on glucose meta~iism. administrat~vn (Yvkosawa et al. In addition to the hypoglycemic and hypvlipemic effect. which indica~s tbat the ~nse~osid~Rb~induced decrease in bfood sugar and the improvement in sugar and lipid metabolism in streptozotoc~~ diabetes are not associated with an increase in insulin (Kobayashi et al. administration of ~~senos~de Rb.p.. 198Sc. 1985ct to streptozot~in.diabetie rats decreased the elevated serum levels vf glucose. Roth single i... 19841 or repeated administration of gi~senvside Rb. This indicates au ~m~rvvement of diabetic ketoacidosis. The urea content of liver decreased with a concomitant increase in RNA content (Yokozawa et al. the IipoIyt~e activity of lipoprotein Iipase was stimulated with a co~co~~nt decrease in the levels of triglyceride and very low density lipoprotein in the serum after ginsenvside-Rb. G~nsenosid~Rb~ decreased ghxose in the hepatic tissue of diabetic rats while the g~ucose~~hos~~te level was unchanged and tke lactate fevel tended to decrease (Yokosawa et al. body weight increased in ginsenos~de-Rb~-trea~d diabetic rats Qokozawa et al.. 1985a...
Tormentic acid was not toxic in mice in that i. unpublished observations). et Zuec. Seeds (Cornaceael Isolated together with decreased the amount diabetic rats (Yamahara ursolic acid from C. 1981). 19811. with diabetes induced by Ursolic acid Cornus off%nalis Sieb. parts when et al. at least in part. tormentic acid (0. 19861..p. However. used Data on structure and action of principle 1 (continued) Active principle Plant species Saudin Cluytiu &hard&a (Euphorbiaceae) Tormentic acid Poterium ancistroides (Rosaceael Desf. a novel diterpene. Hypoglycemic streptozotocin activity was shown in rats (Yamahara et al. officinalis. 1988b). this compound of water consumption and urine volume in et al. et al. Leaves This principle. the compound (30 mglkg) did not change the glucose and insulin levels in streptozotocin-induced diabetic rats (Ivorra et al. 1989al..TABLE Part L.. These results suggest that tormentic acid rats.p. by increasing insulin secretion from intact pancreatic islets of Langerhans (Ivorra et al.D.05-0. The compound has no effect on the insulinreleasing capacity of 16.. Two glycosides were isolated. administration showed better activity than oral administation (Reza-Ul Jab1 et al.. Aerial This principle (10 mglkgl had a hypoglycemic effect in normal rats (Villar et al. one contained glucose and the other contained glucose and arabinose. et Zucc. Both glycosides contained oleanolic acid as aglycone and showed hypoglycemic action in streptozotocininduced diabetic rats at a dose of 25 mg/kg. On the other hand.p. administration of a high dose (600 mglkgl did not produce any symptoms of toxicity (Ivorra..5 mM) initiated insulin secretion by isolated rat islets of Langerhans in a dose-dependent fashion.6 mM glucose.1 (Mossa 19851. showed hypoglycemic activity it was administered to alloxanized mice (40 mglkg i.. It was been demonstrated that tormentic acid (30 mglkgl had a hypoglycemic effect in normoglycemic and glucoseinduced hyperglycemic rats with a corresponding increase in circulating insulin levels. Momordica cochinchinensis Sprengel Seeds (Cucurbitaceae) .. i. 19861. M. Seeds synonym: Macrocarpium officinale Nakai (Cornaceael Oleanolic acid Cornus officinalis Sieb.
122 g/kg ~Petrieic and Bever and Zahnd galegin 636 rn~~g~ The oral LD. It was a more potent antidiabetic agent than to~b~tamide 6% rng~g~ ~Karawya et al. afloxan diabetic and spontaneously dia~tic KK mice. Lathyrine and y-L-gIu~myl-L-lathyrine showed hypoglycemic activity in mice. Lathpus japmkus sic ~~~minosae) Seeds . 1962).. Latbyrine (66 m&g i. tecta Walt var. Hypog~yce~e activity seen at an oral dose of 10 mg&g. This effect may be due in part to a greater metabolic breakdown of glucose into lactic acid ~~onsereennnusorn. of Kalodera. Antagonized the hyperglycemic effect induced by i. galegin sulfate in mice was 0. Capsaicin (14 mg%t) inhibited the intestinal glucose transport in both rat and the hamster in vitro (~onseree~nsor~. 1979a). 19841. 1986).1 had a bypo~lyeemic effect on al~oxon-indn~ed diabetic mice t~itsubishi Ghem.v. 1979. ~admin~stration of glucose or adrenaline in normal mice and improved the glucose tolerance of KK mice after 15 days of ~eatment. Ind. synonym: C. 1979bj.p. in gb~coseinduced hyperglycemic rabbits. ~~psaicin Fruits Bulbs Thea sinends (~~ea~eae) L. 1978. (~nun~n~aEe~~ ~y~giycern~c effects in normal. cirinens& Fran&. 19791 or may be doe to a secondary inbibi~ry effect on the ATP~e-dependeat sodium pump (~onsereenusorn and G~insukon. More recently. furthermore. 1982).Berberine Aerial parts Co@ chinensis Fancb. the bypo~ly~emic effect of in al~oxan~a~ti~ rats has been remonstrated.. Leaves Seeds Galegin This principle is cited in the review of Gfiver (1979). be~~rine decreased serum ~hoIestero1 lev els of mice fed a high cholesterol diet and inhibited the platetet aggregation of rabbits in vitro Chen and Xie. ~onsereenusoro and G~insokoo.
TABLE Part Data on structure and action of principle used 1 (continued) Active principle Plant species Lepidine Lepidium ruderale L. Hypoglycemic and central nervous rabbits (Manhajan and Jolly. 1981) in alloxan-induced mild chronic diabetes (Boyadzhieva. Furthermore. 1982). However. 1982a). 1982a) and in adrenaline-induced hyperglycemic rats (Paskov and Boyadzhieva. this principle failed to affect carbohydrate metabolism in diabetic rats made absolutely insulininsufficient by surgical pancreatectomy (Boyadzhieva. 1985).2 Substituted dines pirroli- Tinospora cordifoliu Miers. 1982b3). polydipsia and increased glycogen in liver in alloxan-induced mild chronic diabetes (Boyadzhieva. this compound decreased glucosuria. (Menispermaceae) Whole plant . Aerial parts (Cruciferae) Hypoglycemic effects in mice and rabbits (Paskov and Boyadzhieva. 1981. system depressant activity in 1.
brega et al. Fruits (Tropical regions) (Solanaceael The aqueous extract caused a dose-dependent decrease in fasting blood glucose levels in rats either by p. The hypoglycemic effect of Copsicum may involve both the inhibition of intestinal glucose transport and its action upon the systemic glucose metabolism (Monsereenusorn.p.TABLE II (continoledl Data on action of extract Plant species (Family) Part used (country) Bride&u ferruginea Leaves (Africa) Benth. by the p. the daily administration of the ethanol extract (500 mg/kg per day p.1 for 12 days lowered the blood glucose levels from the 8th day of treatment. administration of extract reduced the intracardiac glucose tolerance curve.o. 19831. and the p. Besides hypoglycemic activity.o. Bryonia alba sic (Cucurbitaceael Methanol extracts (5 mglkg) and the fraction containing trihydroxyoctadecadienoic acids (0. 19801. An ethanol extract (250 and 500 mglkgl elicited a hypoglycemic effect in normal rats and rabbits. Bumelia sartorum (Sapotaceael Mart. or i.o. the ethanol extract also elicited antiinflammatory activity but did not show any significant effects on blood pressure and respiration. treatment (Panosyan et al.. LD. 19811.. the extract improved glucose tolerance in alloxan-induced diabetic rats. and by the i.m. glycosuria was eliminated after 2 weeks of therapy. was isolated from the ethanol extract but it was not established whether bassic acid is responsible for the observed hypoglycemic activity of the ethanol extract (Nobrega et al.5 mg/kgl decreased blood sugar in rats with alloxan diabetes after 20 days i.. the extract enhanced glucose uptake in skeletal muscle and inhibited glyeogenolysis in the liver. 1983). route in mice was 2580 mglkg and in rats 8670 mglkg.. In addition. Pretreatment with 500 mglkg of the extract p. 1985).o. route in mice was 127 mglkg and in rats 187 mglkg (No. Flavonoids quercetin and kaempferol and their glycosides were isolated from the methanol extract of this plant (Iwu. Root bark (Brazil) Capsicum annuum L. In alloxan-induced mild diabetic rats. . Moreover. route. improved the oral glucose curves.p.o. Bassic acid.p. or i. 1985). The aqueous and methanol extracts (200 mg/kgl lowered the fasting blood sugar in normal rats but not in alloxan-treated rats: however they lowered the hyperglycemia in alloxan-treated rats when they were administered 1 h prior to alloxan injection (Iwu. triterpenic acid. (~uphorbiaceae) The fasting blood sugar levels of maturity-onset diabetic patients were lowered to normal by daily doses of aqueous extracts.
cordifobia Cogn. Infusions (5 g/kg orally) decreased blood glucose levels in normoglycemic and glucose-induced hyperglycemic rats. synomym: C. a heavy release of insulin from isolated rat islets was induced by doses of 25.. 14. There was an increase in circulating insulin levels in normoglycemic rats. In intact normal animals there was no corresponding increase in insulin plasma levels.0. COTCUbionensis may be due to stimulation of insulin release by the pancreas (Chuela et al. 19861. In animals... ca~~trup~ 8. Moreover. .v..6 for C. routes (Perez et al. in&a with milk caused a reduction in blood glucose levels in alloxan diabetic dogs but did not induce hypoglycemia in a normal group of animals. An aqueous extract (15 mg/ml iv. 19801. s~~t~t~l~ and 4. 19851. C. 19881. aspera. the extract caused transitory bypotension in the anesthetized rat and cat and induced contractions in the iso lated guinea pig ileum.2 for C.p. Aqueous extracts (20 g/kg p. ~a~t~t~~~ L. Tbe aqueous extract of C. meliten&s L. the administration suspension of dried powdered leaves of C. the drug reduced blood glucose during glucose tolerance test conducted in both normal and diabetic dogs (Singb et al. (Cucurbi~~eae~ Leaves and roots (India1 A hypoglycemic effect and an improvement on oral glucose tolerance were observed in patients with maturity-onset diabetes mellitus treated with the leaves of this plant. asperu produced hypoglycemia in rats and mice while showing no central and autonomic nervous system or local anesthetic activity in rats. 50 and 160 mglml.1 exhibited hypoglycemic effects in normal and pancreatectomized dogs.6 for C. 19841. LD. in both groups of animals.pl to normal reduction in the blood glucose (Tilmisany and Ajabnoor. C. It showed no cholinergic OF fi-adrenergie activity &lasso. C..1 of these species were 4. 19861. Moreover. 19791.1 for C. values (g dried plant/kg) of aqueous extracts fi.1 of these species elicited hypoglycemic effects in normal mice.o. 19841. These results suggest that the effect of C. meliteneis (Mass0 et al. Administration of hexanie extract (106 mg/kg i. or i.. (Mora~eae~ Hypoglycemic effect of an aqueous extract in alloxan-diabetic mice was seen when administered by p. rabbits caused Leaves (Mexico1 Centaurea aspera L. These results suggest that the effect of the piant extract may not be related to stimuli of the p-pancreatic cells (Mellado and Loxoya. Aerial parts (Spain) Centaurea c~c~b~onens~e Lain2 (Compositael Leaves and flowers (Spain) Cluytiu richardha (~uphorb~ceae~ sic Whole plant (Saudi AraArabia1 Coccinia indica Wight et Am. The maximum effect was obtained after three weeks of of a treatment (Azad Khan et al. but had no effect on alloxan-diabetic animals.Cecropiu obtusifolia Bert. an increase in the concentration of triglycerides was observed. culcitrapa L.
nigrum seeds (l-4 g/kg) as well as the water and methanol extracts (4-8 g/kg) decreased blood glucose levels in normal and alloxan-diabetic rabbits. Total blood lipids were not influenced by this substance in either normal or diabetic rabbits..3% (w/w) glucose after 11 body weight gain reduced (Bailey et Coprinus comatus Fr. Acute toxicity studies carried out in rabbits revealed no adverse side effects of this folk medicine at the dosages used (2-8 g/kg p.p. (Nigeria) dumetorum Tubers (Dioscoreaceae) A hydroalcoholic extract administered to fasting normal rabbits induced a hypoglycemic effect accompanied by some serious toxic reactions (Akubue and Mittal. 1985). However.TABLE (country) Data on action of extract II (continued) Plant species (Family) Part used Cuminum nigrum L. 19841. (Leguminosae) gum) of seeds Fibre (guar (India) Urinary glucose excretion decreased in 9 diabetic patients when their diets were supplemented with the dietary fibre (guar gum. 25 g daily for 5 or 7 days) (Jenkins et al. Chronic treatment of normal mice dried C. 1985). Whereas the alkaloid-containing fraction was hyperglycemic in fasting normal mice. was interrupted although energy intake was not substantially al. administration of with 33. More recently it was demonstrated that the toxic reactions could be separated from hypoglycemic activity through fractionation of the extract by solvent partition.. 1986). (Coprinaceae) Fruits (Europe) Cyamopsis tetragonolobus L. Plasma glucose was somewhat lower 10 h after intragastric dried C. 1980). the decoction was effective at 40 gi kg (Pillai et al. coma&s (3.6 g/kg). . glucose tolerance.o. The whole fruit extract (20 g/kg) showed significant hypoglycemic activity in normal rabbits and the seeds (20 kg/kg) had a hypoglycemic effect in glucose-fed fasting rabbits. 1982). Fruits and seeds (India) Dioscorea Pax. In alloxan diabetic animals.. 1986). comatus in the diet resulted in a reduction in plasma days and an improvement in i. the whole extract and the fractions containing steroidal derivatives evidenced significant hypoglycemic activities in fasting normal mice or rabbits and in severely alloxan diabetic rabbits (Undie and Akubue. Treatment of 8 type 2 diabetic patients with guar gum improved plasma cholesterol and triglyceride values (Briani et al. Moreover... administration of 20 g of guar gum to 6 healthy volunteers improved tolerance to glucose by decreasing oral glucose absorption (Trinick et al.1 (Akthar and Ali. 1977). (Umbelliferae) Seeds (Asia) Oral administration of C.
The dose used did not produce acute toxicity (Noreen et al. 1981). The acute toxicity studies and behavioral pattern records indicate that the plant was quite safe at the dosages employed (3-6 g/kg1 since no visible signs of toxicity or adverse effects were observed 1Akhtar et al. 19881. the water extract 150 m&at) inbibited the elevation of blood glucose indueed by intravenous infusion of adrenaline without elevating the blood insulin level. Japan1 ..1 in nor. A hypoglycemic effect was seen for the powdered plant (l-3 g/kg. It was demonstrated that oral administration of the seeds to rats for 15 days caused a lowering of blood glucose accompanied by a significant increase in pancreatic cathepsin B activity. An aqueous extract (50 mgirat weighing 200-250 gl reduced blood glucose and insulin levels 10 min after oral glucose infusion and increased blood insulin without affecting blood glucose 30 and 60 min after oral giucose infusion. (Myrtaeeae~ Seeds (India1 Aerial parts (India) Oral administration of powdered plant (l-2 g/kg1 or the methanol extract (5 gl kg1 decreased the blood glucose level of normal rabbits but had no effect on alloxan. This extract inhibited adrenaline-induced lipolysis in rat adipoeytes while it failed to affect lipogenesis from glucose (Kimura et al.. (Rosae~ae~ Leaves &dial An alcoholic extract (100-200 mglkg. Syty g&m jambo~~um DC. p. These effects were comparable to those of chloropropamide (Bansal et al. (Fumariaceael Aerial parts (India) Ganoderma lddum &en (Polyporaceae) Kar- Fungus (China. Glucose absorption from the small intestine was not inhibited by the water extract (200 Kg/ml).Eriobotrya japonica Lind.o.. ma1 rabbits. In addition. Eugenda j~rnbo~~~ Lamk..treated rabbits. Acute toxicity studies and records of behavioral patterns carried out in rabbits and rats respectively showed no adverse effects at the dosages tested (3-6 g/kg1 (Akhtar et al.. cumini Skeels. 19841. Tbis suggests that the extract acts by initiating the release of insulin from pancreatic fi* cells of normal rabbits. the plant did not produce this effect. which suggests that it may act by stimulating pancreatic /l-cells in normal animals. 19841. This suggests that this plant acts probably by initiating the release of insulin from the pancreatic @ells of normal rabbits. Fumaria purvifolia Lamk. orally) exerted a significant hypoglycemic effect in normal rabbits but had no effect on alloxan-treated rabbits. synonym: E. In alloxan-diabetic rabbits. 19881..
When dried leaf powder of G. kidney and muscle of diabetic animals. 19861. Rathi et al. In this way.. but also corrected certain metabolic disorders in liver. gluconeogenic enzymes. sylwestre and pathological changes initiated in the liver during the hyperglycemic phase appeared to be reversed when G. sylvestre administration while there was a decrease in the elevated activities of enzymes catalysing insulin-independent pathways (glycogen phosphorylase. glyceraldehyde~3~phosphate dehydrogenase and glucose-g-phosphate dehydrogenasel that are lowered in the diabetic tissues. sylvestre was used to control hyperglycemia. The deposition and accumulation of these macromolecules in tissues is related to the vascular complications of diabetes mellitus. sylwestre treatment. however. hexosam~nes. Part used (country) Data on action of extract Gynmema sylvestre R.Plant species (Family) Oral administration of the powdered leaves decreased blood glucose and increased the circulating insulin levels in alloxan diabetic rabbits and in a single maturity-onset diabetic patient. This effect was associated with a reduction in the serum lipid levels (Shanmugasundaram et al. syluestre (200 mg/kg daily for a month) brought these elevated levels back to near normal values.. (Asclepiadaceael Leaves (India1 . it not only produced a decrease in blood glucose levels. kidney and muscle in diabetic animals given G. 1981). the glyeogen and protein depletion and lipid accumulation in the diabetic animal were reversed by G. glucose-@phosphatase.. in these groups the drug prolonged their survival time (Srivastava et al. hexoses. the levels of the 3ehondroitin sulfates and the sulfated to non-sulfated glycosaminoglycan ratio. which showed a decrease in diabetic animals. Br. These authors also showed that treatment of diabetic animals with a hydroalcoholic extra& of G. 19811.. sylvestre (250 mg/kg for 12 or 24 weeks) was administered to alloxan diabetic rabbits. Moreover. Moreover. The uptake and incorporation of f’%]glucose into glycogen and protein were increased in the liver. oral treatment of alloxan-diabetic rats for a period of two weeks with an aqueous extract corrected the hyperglycemia in moderately diabetic animals but did not reduce blood sugar levels in severe and toxic groups of diabetic rats. 1985. were increased by G. Moreover. the activities of the insulin-dependent enzymes (hexokinase. non~aminopolysaecharides and sialie acid) and some glyeosamino~lycans (hyaluronic acid and heparin sulfate) are increased in alloxan-induced diabetic rats. were restored to normal or near normal by Gymnema treatment (Rathi et al. fructose 1-6 diphosphatase and sorbitol dehydrogenase) during the administration of the herb (Shanmugasundaram et al. (19811 demonstrated that the levels of some protein-bound polysaeeharides (hexuronic acid. glycogen synthetase.
leaves and stems (Spain1 Several extracts of flowers. K’. Gymnemie acid was found to be a complex mixture of at least nine closely-related acidic glyeosides (Sinsheimer et al.1 exhibited a hypoglycemic effect on normal rabbits Kabo et al. eoumarins and saponins (Ajabnoor et al. On column chromatography. s~lve~tTe (0. 19801. In alloxan.o. 19821. sterols. tannins.. leaves and stem (10 g/kg p. Sinsheimer and Rao. An active fraction (4 mglkg p.or streptozotoein-hyperglycemic rats. Leucaena leucocephulu Seeds (India1 sic (Le~mino~e~ Lupine: albus L. a toxic amino acid (Singhal et al. which suggests that the presenee of @pancreatic cells is required for activity (Cab0 et al. The extract had no apparent adverse toxic effects. 1984al.and streptozotocin-diabetic rats..(Dechatiwongse et al. peptides or proteins. synonym: GIdenlandio Whole plant (India1 corgmbosa L. The ether extract was the most active extract and it caused a significant reductian in blood glucose in normal rats and a corresponding increase of circulating insulin. More recently. Hammado salicornica R. Powdered seeds have hypoglycemic and hypocholesterolemic effects in diabetic and hypercholesterolemie rats.1 also exhibited hypoglycemic activity in rats with glucose. The root was inactive (Cadavid and Calleja. Phytochemical analysis showed the presence of alkaloids. Khenopodiaceae) Whole plant (Saudi AraArabia) Hedyotk biflora Roth.1 possessed hypoglycemic activity in normal and in glucose-induced hyperglycemic rabbits. 19831.. moreover. (R~bia~eae~ A water extract showed a hypoglycemic effect in alloxan-dia~tic rabbits. 19831 and in glucose.. p. the daily administration of this extract (10 g/kg/day for 8 days) induced a partial reversal of the diabetic-like 8 . 19701. cardiac glycosides. there was an increase in circulating insulin in normoglycemic rabbits. volatile oil and bases. The seeds contain mimosine.1 inhibited the sucrose-induced etevation of the blood glucose level in rats (Yoshioka et al.o..2 g/kg p. this extract gave a hypoglycemic fraction composed of 13 free amino acids.o.o. (Leguminosael Seeds (India) Lythrum oa&ati L.and epinephrine-induced hyperglycemia and in alloxan-diabetic mice. the ether extract (50 mglmll increased insulin secretion in isolated rat isfets of Langerhans (Lamela et al. Br. An ethanol extract (ZOO-400 mg/kgl produced a decrease in blood sugar levels in alloxan-treated mice but had no effect on normal animals..19831. 19851. Na+ and Cl. isolated from the leaves of G. 19851. 19841. 1970.or diazoxide-induced hyperglycemic rabbits but had no effect in alloxan... flavonoids. it has been demonstrated that gymnemie acid. Ether extract (10 g/kg. (Lythraeeael Flowers.
19861. The flower extract clearly accentuated the elevated levels of aspartate aminotransferase induced by streptozotocin (Lamela et al.000 (Ng et al.Plant species (Family) state. polypeptide-p. oral administration of M. A peptide. These may include a principle called “charantin”. charant& fruit reduced blood glucose levels in normal rats and improved glucose tolerance in rats (Leatherdale et al. Central and South America1 Aqueous extracts of M. the extract lowered serum levels of triglycerides while increasing free fatty acids levels. charantia is not associated with an increase in circulating insulin (Leatherdale et al. Part used (country) Data on action of extract Momordica ~haran~~ L. Powdered fruit (0.5 g/kg) produced a hypoglycemic effect in normal and alloxan-induced diabetic rabbits (Akhtar et al.1 induced an enhancement of glycogen content in the liver but had no effect on muscular glycogen content and. 19811. Other polypeptides decreasing blood sugar levels in normal and diabetic mice were also isolated from the fruit of M... charuntia fruit contains more than one type of hypog lycemic component.. a homogeneous mixture of p-sitosterol fl+glueoside and 5. 1986bl and a galactose-binding lectin with a molecular weight of 124. in addition.. the ether extract (10 g/kg. 19663. 1981.. improved glucose tolerance in normal mice and reduced hyperglycemia in streptozotoein-diabetic mice. It was hypothesized that M. a wild variety of M. 19651 that can produce a hypoglycemic effect in normal rabbits (Lotlikar and Bajarama-Rao.. 19861. Bailey . has been isolated from fruit.o. This effect was not associated with increased circulating insulin. Welihinda et al.... charantiu juice improved glucose tolerance in noninsulin dependent diabetics (Leatherdale et al. 19851. Although some authors have indicated that the effect of M. churuntio (Lei et al. An aqueous extract of “cerasee”. p. There is evidence for the existence of insulin-like compounds..5-1. both stem and flower extracts reduced the elevated r-glutamyl transpeptidase activity induced by streptozotocin in rats while the stem extracts reduced the elevated lactic dehydrogenase activity.. Moreover.. ckaruntia and caused hypoglycemic effects when it was administered subcutaneously in patients with juvenile diabetes (Khanna et al. Moreover. 1981. seeds and tissue of M. 19811. No effect on serum cholesterol levels was observed (Lamela et al. 1981. 19851.. charuntia. different fractions (Ng et al. 1986al capable of antilipolytic and lipogenic aetivities in isolated rat adipocytes have been isolated from M.~-ol-glucoside (Suerow. Karunanayake et al. Moreover. 19851. charantiu seeds. (Cucurbitaeeael Fruits (Asia. which suggests that “cerasee” may exert an extrapancreatic effect (Bailey et al. 19841. On the other hand.25-stigmatadien-3.
. Moreover. 19841. in glucose-induced hyperglycemic rats and rabbits and in pan~eatec~mized rabbits (Ibaflez~~amacho and Oman-Ramos. (Composite) Leaves (Central America) Opuntia streptacantha Lemaire (~a~ceae~ Stems iMexico Oral administration of sap (5 ml/kg) obtained from Opuntia stems produced hypoglycemic effects in normal dogs. The hyperglycemic hormones. glucagon. M. c~uru~~~ was a potent stiiulator of insulin release from @-cellrich pancreatic islets isolated from obese-hyperglycemic mice.. This action may involve interaction with the membrane lipids in a way which differs from the physiological activation of secretion. The insulin-releasing effect of M. 19821. (Myrtaceael Leaves and branchlets (Libya1 N~u~~~ b&ata R. The extract had no effect on the blood glucose level of normal mice (Elfellah et al. free fatty acids and triglycerides. This effect was associated with an increase in liver gly cogen and a decrease in elevated levels of serum cholesterol. This indicates that in order to obtain the Opmtia hypoglycemic effect the presence of intact pancreatic tissue is required (IbanezCamacho et al. Br. Welihinda et al. nor did they decrease the elevated levels of urea and serum ereatinine (Kedar and ~bakrabarti. 19841. activity both in normal Myrtus commvnis L. it reduced the hyperglycemia and this effect could be maintained by repeated administration. 1979. (19821 demonstrated that an aqueous extract from the fruit of M. 19851. M. cortisol and growth hormone appeared not to be involved in the g . 19831... the seeds did not improve impaired renal function caused by streptozotocin.. 19861. chmantiu can not be attributed to “eharantin”. chaTant& seeds (l-3 glday per rabbit) induced a hypoglycemic effect and improved glucose tolerance in mildly streptozotocin-diabetic rabbits. 19861. Oral treatment with the juice prior to a glucose load was found to increase the glycogen content of liver and musde while it bad no effect on the triglyceride content of adipose tissue (Welihinda and ~runanayake. However. complementary daily administration of Opuntiu sap to diabetic volunteers under chlorpropamide treatment improved the general symptomatology of the patients as well as their insulin and glucose blood levels (Meckes-Lozoya and Roman-Ramos. When Myrtus extract was given 48 h after streptozotocin. Iba~ez-Camacho et al. but there was no effect in panereateetomized rabbits treated with alloxan. 19831. c~a~a~~~ juice (1 ml/l00 gf stimulated glucose uptake by diaphragm tissue in vitro.et al. A hydroalcobolic extract (2 g/kg) inhibited the acute phase of hyperglycemia induced by streptozotocin when a single dose was given intragastrically to mice 30 min before streptozot~in. An ethanolic extract (500 mg/kgl possessed hypoglycemic and alioxa~hy~ergly~emie mice (Gupta et al.
which suggests that the insulin release from the pancreas induced by DPG-3-2 was independent of insulin biosynthesis. Some ginseng fractions inhibited epinephrineinduced transient hyperglycemia in mice. decreased the blood levels of acetone bodies in alloxan diabetic mice and inhibited the release of free fatty acids from rat epididymal fat pads (Kimura et al. respectively.. (1981b) isolated two hypoglycemic fractions. (Araliaceael Roots (China. it has been suggested that Opuntia probably acts by interfering with intestinal dextrose absorption because Opuntia intake in healthy volunteers (100 gl diminished blood glucose in an oral glucose tolerance test but had no effect in an intravenous glucose tolerance test and no effect on basal glucose levels (Frati-Murani et al. This effect was also observed in the presence of cyclohexamide. the levels of these hormones were not modified by Opuntia administration (Fernandez et al. for which the chemical structures have yet to be determined but which possess hypoglycemic activity.. 19851. Some compounds are reported with antilipolytic activity: adenosine. 1981al. DPG-3-2 (0. On the other hand.. Finally. 19841. In an oral glucose tolerance test run on healthy volunteers. a carboxilic acid and a peptide with a molecular weight of 1400 that can inhibit catecholamine-induced lipolysis in rat epididymal fat pads (Ng and Yeung. This indicated a stimulatory action of the fraction on blood insulin levels. Moreover. Japan and on action of extract II (continued) Plant species (Family) Part used (country) Panax ginseng Mey. from P. (1982) demonstrated that DPG-3-2 . designated panaxans A to P and ginsenoside Rb. DPG-3-2 and EPG-3-2. More recently. 1987).v. Korea) Different hypoglycemic and insulin-like principles have been isolated from the roots and include various glycans.TABLE Data hypoglycemic effect of Opuntio. Waki et al.p. injection of antisera against bovine insulin. with glucose but had no effect in normal mice. increased glycogen content in rat liver.2 mglmll stimulated insulin release from perfused rat pancreas and enhanced glucose-stimulated insulin release from the pancreas of both normal and diabetic rats. (see Table 11. DPG-3-2 and EPG-3-2. the same dose of EPG-3-2 (lo-50 mglkgl increased blood insulin levels in alloxan diabetic mice and in normal mice loaded i. ginseng and demonstrated that the hypoglycemic effect of EPG-3-2 on alloxan diabetic mice was abolished by i. panax. Kimura et al. A hypoglycemic component was partially purified from ginseng roots by various methods of fractionation based on an assay system to evaluate hypoglycemic effects in alloxan diabetic mice. two fractions from water and methanolic extracts have been isolated from P.
The LD. Moreover. 19821. (50% inhibitory concentration) of 1. long-term treatment with RPG-3-2 10. and this did Poupartia birrea Aubr. xnk2a~ia Wall.. the aqueous extract was also effective in alloxan-diabetic rats but not in normoglycemie rats. The humping effect was enhanced by those hypogIycemics which promote insulin secretion from pancreatic islets (sulfonylureas~ and was decreased by those hypoglycemics which promote glucose utilization in peripheral tissues Cbiguanides).(0..5 mg/mll stimulated insulin biosynthesis in islets from KK-CAY mice (Waki et al.o. in mice1 (Laurens et al. Mucilage (Mexico) (~la~ta~na~eae~ Carranza et al. Frati-Munari et al. of aqueous extract was found to be 1. (19851 suggested interferred with intestinal glucose absorption since mucilage gl mixed with glueose in healthy volunteers lowered glucose not OCCUF when the mucilage was given prior to glucose. An aqueous extract lowered blood sugar leveis in normal and alloxan-diabetic rabbits (~amakrishnan et al. The curves were classified into several patterns by analysis of the humping effect (the transient rise in blood glucose level after a precipitous fall). However. 19881. It has been demonstrated that DPG3-2 inhibited the humping effect in a dose-dependent manner..p.81 pgiml.. Kimura and Suzuki 419811 analyzed the glucose tolerance curves of KK-CAY mice pharmacokinetically by the use of a mathematical model (Compartment-H model).35 rgiml and 0. both DPG-3-2 and tolbutamide have an insulin-releasing effect in pancreatic islets. for metabolic eonthat the mucilage administration (10 levels. These results indicate that .. 19841.2 mgimll increased incorporation of 14C-Ieucine into a protein fraction obtained by perfusing the pancreas of diabetic and normal rats. in vitro studies with purified aldose-reductase (enzyme that converts glucose into sorbitoll showed that the aqueous and ethyl acetate extract exhibited enzyme. two flavonoids isolated from the water-soluble fraction of the ethanol extract showed hypoglycemic activity in alloxan-treated albino rats when they were administered at a dose of 100 mg/ kg p. this effect was clearly distin~ishabIe from that of tolbutamide. Leaves (Africa1 synonym: Sc~Toear~o birrea Hoehst. but had no effect in normal rats (Hukeri et al. In addition.inhibiting activity with an IC. Phyllantus nkuri L. (Euphorbiaceae} Leaves (India) P~~tago ~syllium L. 19821... More reeently..9 g/kg (i. (19851 indicated that this plant can be useful trol of diabetic patients. synonym: P. (Ana~ardiaceae~ Oral administration of an aqueous or ethyl acetate extract ~250-1000 mg/kgl decreased the glucose levels in glucose-iudu~ed bypergly~emic rats. respectively.. Glucose increased incorporation of 13HJleueine into insulin in islets from normoglycemic mice fKK1 and hyperglycemic mice &K-CAY) whereas DPG-3-2 had this effect ony in KK-CAY mice.
19851.. An infusion and a suspension (0.. the daily administration of 5 g/kg of the infusion resulted in a decrease in the blood glucose levels. In alloxan-diabetic rabbits. In alloxan-diabetic rabbits. Absorption of glucose by the intestine may be a significant factor since there was an hypoglycemic effect in glucose-induced hyperglycemic rabbits when the plant infusion was administered simultaneously with glucose but this effect was not observed wken tke plant infusion was administered 60 min before glucose (Jimenez et al. 19361. 19801. the n-BuOHsoluble fraction and water-soluble fraction were found to suppress adrenalineinduced lipolysis in fat cells from rat epididymal adipose tissues (Maruyama et al.25 g/kg of infusion decreased blood glucose levels. 19831. for these diabetes complications (Laufens et al. p.25 g/kg p.. Aeute i.. 19851. (~yrta~eae~ Fruits (China1 Leaves (Japan1 Leaves (Spain1 Salvia lavandulifolia Vahl. since the accumulation of sorbitol is responsible. at least in part. The ethanbolic extract. E Plant species (Family1 Part used (country) Psidhn gaajava L.TABLE II (continued1 Data on action of extract this plant has a possible antidiabetic effect in respect to cataract and post-diabetic neuropathies. (Labiataef Aerial parts (Spain) . Oral administration of an infusion and an ethyl ether fraction (5 g/kg! exhibited kypogly~emic activity in n~~o~ly~ernie and in glucose-indu&ed kyper~ly~emic rabbits. daily administration of 0.1 showed hypoglycemic effects in nor moglycemic rabbits whereas no change was seen in insulin levels.o.1 and a n-BuOH soluble extract prepared from an ethanolic extract 125 or 100 mglkgl were found to inhibit the increase in plasma glucose level in alloxan-induced diabetic rats and also improve glucose tolerance in diabetic rats.p.o. treatment with I g/kg fruit juice produced a hypoglycemic effect in normal and alloxan-treated diabetic mice. An ethanolic extract from leaves (200 mglkg. Administration of the ethyl ether fraction produced an increase in circulating insulin in normoglycem~c animals. Oral administration in maturity-onset diabetic and healthy volunteers also lowered blood glucose (Cheng and Yang. This suggests that the hypoglycemic activity may be due to in part to stimulation of insulin secretion from islets of Langerhans (Alonso et al.
saponins. 19861. there was also a decrease in the hyperglycemic response to oral glucose tolerance. Valette et al. In contrast. in addition to insulin treatment for a period of 21 days) in alloxan-diabetic dogs resulted in a decrease of hyperglycemia and glyeosuria accompanied by a reduction of the high plasma glucagon and somatostatin levels in diabetic dogs. showed a general improvement in their clinical status in that hyperglycemia. displayed a more profound but shorter hypoglycemic activity in alloxan-diabetic rats. More recently it has been demonstrated that the antidiabetic action of Xrigonella can be associated with the defatted seed material which contains fibers.TABLE II (continued1 Data on action of extract Plant species (Family) Part used (country) Trigosellu foenum cum IA. which contains the cotyledons and axes and is rich in saponins and proteins. free fatty acids. 19841 and more specifically with subfraction a which contains the testa and endosperm and is rich in fibers (Ribes et al... had no effect on hyperglycemia or on the levels of pancreatic hormones in diabetic dogs (Ribes et al. Chronic administration of subfraction a (mixed with two daily meals. . other eomponents. Valette et al. Sham et al.. grae- Seeds (Israel) (Leguminosael Hypoglycemic activity has been reported in the review of Oliver Bever and Zahnd (19791.. chronic administration of subfraction b. Amin Riyad et al. and proteins (Ribes et al. (19881 demonstrated that treatment of streptozotocin diabetic rats with diets containing 20% fenugreek seeds for a period of 10 weeks did not improve the diabetic state: on the other hand. trigonelline. (19741 reported that ~~~go~e~~ seeds and the major alkaloid component. 1984). 1984.. cholesterol and triglyceride levels were reduced. exerted a mild hypoglycemic effect. diabetic animals pretreated for 5 weeks with fenugreek and followed by 6 weeks of feeding with the same diet. The defatted fraction caused a decrease in hyperglycemia and hypoeholesterolemia in alloxan-diabetic dogs while the lipid extract proved to be ineffective (Ribes et al. 19841.. nicotinie acid and eoumarin. 1986).
hepatotoxic agents can influence the activity of certain hepatie enzymes involved in gluconeogenesis. We have listed these different plants alphabetically according to their botanical genus (Table 21. 227 .A. F~to~era~~ 55. All are important since they potentially can be used to treat the different aspects of diabetes mellitus..M. careful collection of plant material and proper identification/verification is of primary importance. (1985) Study of hypo~l~caemic activity of ~~rn~~urn n~gr~rn seeds in normal and alloxan diabetic rabbits. 19791. A. plants have been used in the treatment of diabetes mellitus. Tariq. N..109. Planta Medica 51..S. and Hanna. we can say that there are a great many hypoglycemic plants and the chemical structure of their active principles varies widely. M. M. A. Discussion Since ancient times. Ajabnoor. Ajabnoor. and Ali.267 Our report covers the literature published during the last ten-year period (1979-19881 because there is an earlier review that Covers the literature up to 1978 (Oliver Bever and Zahnd. (1984a) Antidiabetic activity of Hammada salicomia Fitoterapda 55. For the study of antidiabetic plants. In the present work we describe the plants whose activities have been studied in the 1979-1988 decade. 27 . The second approach is devoted to those plants whose hypoglycemic action has been studied experimentally but whose active principles have not yet been isolated.A.M. The first classifies according to general chemical structure those hypoglycemic natural products which have been isolated from plants (Table 11. Other plant extracts or constituents act by modifying glucose metabolism and finally there are some that appear to correct the complications of diabetes. . M. This can lead to a reduction in the amount of glucose that reaches the blood resulting in false-positive results. The present information has been organized in two different ways. G. As is the case with any ethnopharma~ologi~ study. 107 . mechanisms of action. Herba Hungatica 26.A. Tariq. Al-Yahya.A. Wassel. Al-Yahaya. and Jayyab. and Jayyab. M..40. M. Ammar. Some act by in&easing the release of insulin and require a minimum of fi-cells to exert their action.A. there must also be considerable diversity in the mechanisms of action. It is important to do a toxicity study because. In general. 81-85. SM. M. Akhtar. (19871 Flavonoid constituents in the different organs of selected Bauhiniu species and their effect on blood glucose. toxicity and other properties. T. In both instances we give information about the pharmacological data.. M. as is known..R. M. we consider glucose-induced hyperglycemic rats and streptozotocin-induced diabetic rats as good preliminary models for hypoglycemic screening.230. They are a fertile source for new hypoglycemic agents. References Abd-EbWahab. Therefore. (1984b) Antidiabetic activity of Teuc~~rn ol~~e~~~rn.A.
Bilardo.. Akhtar. (1980) Treatment of diabetes mellitus with Coccidiu indict British Medical Journal 280. R.D. C. K. and Yaqub.J.. (1981al The prophylactic action of ( . (19861 Treatment of diabetes mellitus by Artemisia herba-ulba extract: Preliminary study. M.S. I. Tiengo. Marescotti. W.S. on the course of experimental sugar diabetes with absolute insulin insufficiency. Cabo. M. Chemical Abstracts 98.S. S. R.. 187. Plantes me’dicinales et phytothkrapie 23. Gupta.S.t-epicatechin. (1982) Clinical evaluation of a traditional herbal practice in Nigeria. Giornali della Arteriosclerosi 10.K.188. Boyadzhieva. (19811 Effect of ~orno~d~ca cha~unt~u on blood glucose levef of normal and alloxan~iabetic rabbits. M.. Crecca. and Zarzuelo. A...J.A.2047. 43-49. C. (1984) Effects of ~~~~orb~ ~0s~~~~~ and &mar&z mzruiforu in normogiycaemic and alloxan-treated hyperglycaemic rabbits. (19811 Study of the effect of lepidine on the course of a mild chronic form of alloxan-diabetes. Al-Awadi.A. regen- . Briani. Problemi na %Treshtnatu ~ed~ts~na 10.526. 5103. Bansal.K. Chemical Abstracts 98. 209841t (19831. 09851 Assessment of the antidiabetic activity of epicatechin in streptozotoein-diabetic and spontaneously diabetic BBiE rats. (198ib) Pancreatic beta-cell eration in rats by ( . J. Bailey. 102106.. Carranza. Cadavid. 1044. a traditional treatment for diabetes studies in normal and streptozotocin diabetic mice.290. Part II. A. N. Smith.M. 83431~ (19831. Pfanta Medica 42. C&&al and Experimental Pharmacology and Physiology 13.. 525. M.A. (1982bl Study on the influence of the plant Lepidium ruderale L. S. Brown. (19851 On the mechanism of the hypoglycaemie effect of a plant extract. Zolli. 237-242. Planta Medicu 50.559563. and Suleiman ~ohammad. M. Diobetologiu 28. (19831 Etudes sur I’action hypogly~~m. J..T.A. J. Khattar. Al-Waili N.. T. Chemical Abstracts 98. Compendium de Zn~est~g~iones Clinicas Latinoamerica~s 5.A. Jakeman. (1982al Study of the effect of lepidine on the chronic form of experimental alloxan diabetes in rats. Duner. G. Khan. Jimenez. 215-221. K. 2043 .. G. 182.286 . (19801 A preliminary study of hypoglycemic acivity of Lythrum salicaria Journal of Natural Products 43. J. 130-139. Journal of Ethnopharmacology 6. (19801 A preliminary study of hypoglycemic activity of Rubus fructicosus. Bruttomesso. and Leatherdale. Q. Chakravarthy. B. Boyadzhieva.142.I@ Sciences 29.A. A.M. M. Problemi na VTreshtnata Meditsina 9. Riseo. C. K. (19821. Ambike. Vitale.S. and Kidwai. J. Abdui-Salam. ELK. Cabo. Jimenez. Bioscience Reports 5.355-359. S. G. M. Valerio. and Crepaldi.M. Akubue. R.f-epicatechin against alloxan-induced diabetes in rats . 138.377. and Gode.R. and Rajarama-Rao. M.I.268 Akhtar.L. N.196. M. K. M. Zndmn Jownal of Biochemistry and Biophysics 18. S. Planta Medica 54.. Azad Khan.L. Plantes rn~d~~ina~s et phytoth~rupie 17.A. Planta Medica Suppl. and Gode.J. S.. Akhtar. S. Chakravarthy.. Boyadzhieva. E. D... and Zarzuelo. Day.. 191565~ (1983). (1984) Effect of Coprinus corn&us on plasma glucose concentrations in mice. S. and Gumaa. VIII: Stabilite de l’aetion hy~glyc~miante de la fraction active. I. Planta Medica 50. 759-760. S. and Howell. S... Turner.. The Lancet 2... Miro. Alonso. and Calleja. W.. and Rodriguez. Gambhir. J.91-94.. AbduI~Ghani. N. Biological Abstracts 74. A. and Mittal. (19811 Effects of oral administration of Eugenio jumbolana seeds and chlorpropamide on blood glucose level of pancreatic cathepsin B in rat. Gambhir. Athar. Diabetes Research 2.1.. (1985) Psyllium plantago in diabetic patient management. A. A. 432-434. 205-212. E. S.L.upinus albus L.. and Khaliq.. Fcwmatsiyu (Sofia) 32.J. Miro... Gupta. S. I). iante des graines du lupin ~~~~n~s albus L. Amin Riyad. J. Hii..D. Bone. Cadavid. G.1. B. Turner. (19831 Etudes sur l’action hypoglycemgraines du lupin cl.. Bailey. IX: Action hypoglyckmiante de la fraction active.H. Guillen. S. and Mahtab.. and Calleja.. Ahmad. (19851 Cerasee. N. C. J. C.20-32.81-84.569-5’73. S. M. H. and Hayes. Riseo. 125-130. (19851 Mediterranean diet and guar gum: Advantages for diabetic patients?.. 09671 Studies on a phytosterolin from the bark of Ficus religiosa The Indian Journal of Pharmacy 29.R.D. P.S.C. P. 11988) Effeet of fenugreek and Lupine seeds on the development of experimental diabetes in rats. M.
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