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Effect of Momordica charantia on the glucose tolerance in maturity onset diabetes
Journal of Ethnopharmacology, 17 (1986) Elsevier Scientific Publishers Ireland Ltd.
277
277-282
EFFECT OF MOMORDZCA CHARANTZA ON-THE TOLERANCE IN MATURITY ONSET DIABETES
J. WELIHINDAa, E.H. KARUNANAYAKEa, JAYASINGHEb
M.H.R. SHERIFFb and K.S.A.
Departments of “Biochemistry and bMedicine, Colombo, Kynsey Road, Colombo 8 (Sri Lanka) (Accepted
GLUCOSE
Faculty
of Medicine,
University
of
July 1, 1986)
Summary Investigations were carried out to evaluate the effect of Momordica charantia on the glucose tolerance of maturity onset diabetic patients. The fruit juice of M. charantia was found to significantly improve the glucose tolerance of 73% of the patients investigated while the other 27% failed to respond.
Introduction Although substantial work has been done on the hypoglycaemic activity of M. charantia on normal and diabetic laboratory animals (Rivera, 1942; Sharma et al., 1960; Akhtar et al., 1981) relatively few reports are available on its activity in humans. A possible synergestic interaction in a patient between chlorpropamide and a curry made from M. charantia and garlic has been previously reported (Aslam and Stockley, 1979). An improvement in the tolerance of an external load of glucose by non-insulin dependent diabetics has been observed by Leatherdale et al. (1981) after an oral administration of 50 ml of M. charuntiu fruit juice. The same authors observed a similar improvement after a daily intake of 0.23 kg of fried M. charantiu for 8-11 weeks. A similar observation has been made by Akhtar (1982) in patients 7 days after oral ingestion (50 mg/kg body wt) of dried M. charantiu powder. Furthermore, an insulin like protein called “plant insulin” (Khanna et al., 1981) isolated from M. charantia has been shown to possess hypoglycaemic properties when injected subcutaneously (Baldwa et al., 1977). We have previously reported (Karunanayake et al., 1984) significant oral hypoglycaemic activity of M. charactiu (that is locally cultivated and used in 0378~8741/86/$02.45 0 1986 Elsevier Scientific Publishers Ireland Ltd. Published and Printed in Ireland
218
the treatment of diabetes) available in Sri Lanka in laboratory animals. The present studies were undertaken to further evaluate the oral hypoglycaemic activity of Sri Lankan variety of ikf. charantia in non-insulin dependent maturity onset diabetics.
Materials and methods Diabetic patients
Eighteen newly diagnosed maturity onset diabetic patients (average age 38.2 years) free from ketoacidosis, cerebrovascular disease, acute myocardial infarction and renal complications were selected. These patients were not on any anti-diabetic drugs. Preparation
of juice
Fresh unripe fruits of M. charantia were obtained from the market, washed well and the seeds removed. The fleshy part was then cut into thin slices and macerated in a mechanical grinder. The pulp was then squeezed in a thick cloth and the juice obtained immediately frozen. Before using, the frozen juice was thawed and centrifuged at 10,000 rev./mm in a Damon I.E.C. B-20A centrifuge at 4°C for 10 min. The supematant was decanted and lOO-ml aliquots of the clear juice was given orally to patients. Oral glucose
tolerance
test
Following an overnight fast, standard glucose tolerance test (50 g glucose) was performed with all patients receiving 100 ml distilled water instead of M. charuntia 30 min before the glucose load. The oral glucose tolerance test was repeated on a subsequent day with all patients receiving 100 ml M. charantia juice 30 min before the oral glucose load. Blood sugar estimation
Blood samples (0.05 ml) were obtained by finger tip puncture using microcaps (Drummond Scientific Company, U.S.A.) and the blood glucose levels were estimated by the glucose-oxidase method of Hugget and Nixon (1957). Results and discussion
The glucose tolerance curves of all 18 patients are illustrated in Fig. 1 with a normal glucose tolerance curve of a healthy adult for comparison. It is apparent that all 18 patients were clearly diabetic. Comparative analysis of the percentage increase of blood sugar of each of these curves with the corresponding ones obtained with the administration of M. charantiu juice 30 min prior to glucose loading revealed that the patients could be divided into two groups. The first group, consisting of 13 patients, showed a significant improvement in glucose tolerance following
279
*
i
I
1
I
t
,
1;
2
2;
TIME
J
(h)
Fig. 1. Glucose tolerance curves of the diabetic patients and that of a normal healthy adult. All individuals were given 100 ml distilled water 30 min before the glucose load. s--.---* glucose tolerance curves of diabetics; *-, glucose tolerance of noTa human. ’
the prior administration of M. charantia juice. The second group, consisting of 5 patients, showed no significant improvement in their glucose tolerance. In Fig. 2, the mean (mean of the percentage increase of blood glucose + S.E.M.) glucose tolerance curve of the responding group is compared with that obtained with prior administration of M. c~u~u~~~ujuice. Statistical analysis by Student t-test revealed a si~ific~t difference between the two
Fig. 2. The pooled glucose tolerance curves of diabetic patients responding to M. charantia. During test all patients received 100 ml M. charantia 30 min before the glucose load and in the control all patients received 100 ml distilled water instead of M. charantio. The results are given as percentage increase of blood glucose. The S.E.M. values are given controls; Aby bars. l-, A, tests.
curves from the 1.5 h time point (0.5 > P > 0.1, 0.5 > P > 0.1, 0.02 > P > 0.01, P < 0.001, P < 0.001 at 0.5,1,1.5, 2 and 2.5 h, respectively). Similar curves for the group showing no improvement in the glucose tolerance are given in Fig. 3. There was no statistical difference between the two curves. However, the analysis of the total data, irrespective of the apparent difference in response to treatment, still confirmed the oral hypoglycaemic activity of M. charuntia. The mean total area under the test (AI. churuntiu treated) glucose tolerance curves (187.0 cm2) was significantly lower (0.01 > P > 0.001)than the area (243.6 cm2) under the control glucose tolerance curves (Table 1). The difference in response observed with the five patients in this study could also have been due to intra-individual variation usually seen in biological systems. The present study while confirming the oral hypoglycaemic activity of M. churuntia grown in Sri Lanka, gives scientific validity for the use of M. churuntiu as an oral hypoglycaemic agent by the traditional medical practitioners of Sri Lanka.
281
1
:
TIME
1’
2
2'
b
(h)
Fig. 3. The pooled glucose tolerance curves of diabetic patients not responding to M. charantia. The test received 100 ml of M. charantia juice 30 min before the glucose load while the control received 100 ml distilled water instead. The results are given as percentage increase of blood glucose. S.E.M. values are given as bars. l -0, controls; A----A , tests .
Acknowledgements This work was supported by grant No. 531 from the International Foundation for Science, Sweden, and by the grant No. RG 83/29 from the Natural Resources, Science and Energy Authority of Sri Lanka. TABLE 1 COMPARISON OF MEAN TOTAL AREAS OF GLUCOSE TOLERANCE UNDER DIFFERENT TREATMENTS The results are given as mean + S.E.M. Total area k S.E.M. (cm2 ) (n = 18) Control
Test
243.6 k 14.5
187.0 + 13.82 0.01 > P > 0.001
CURVES
282
References Akhtar, M.S., Athar, M.A. and Yaqub, M. (1981) Effect of Momordica charuntia on blood glucose levels of normal and Alloxan diabetic rabbits. Planta Medicu 42, (3), 205-212. Akhtar, M.S. (1982) Trial of Momordicu churuntiu Linn. (karela) powder in patients with maturity onset diabetes. Journal of the Pakistan Medical Association 32, 106-107. Aslam, M. and Stockley, J.H. (1979) Interaction between curry ingredients and drug (Chlorpropamide). Lancet i, 607. Baldwa, VS., Bhandari, CM., Pangaria, A. and Goyal, R.K. (1977) Clinical trial with patients with Diabetes mellitus of an insulin like compound obtained from a plant source. Uppsulu Journal of Medical Science 82, 39-41. Hugget, A. St. G. and Nixon, D.A. (1957) Use of glucose oxidase, peroxidase and dianisidine in the determination of blood and urinary glucose. Luncet ii, 368-370. Karunanayake, E.H., Welihinda, J., Sirimanne, S.R. and Sinnadorai, G. (1984) Oral hypoglycaemic activity of some medicinal plants of Sri Lanka. Journal of Ethnopharmacology 11, 223-231. Khanna, P., Jain, S.C., Pangaria, A. and Dixit, V.P. (1981) Hypoglycaemic activity of polypeptide p from plant source. Journal of Natural Products 44, 648-655. Leatherdale, B.A., Panesar, R.K., Singh, G., Atkins, T.W., Bailey, C.J. and Bignell, A.H.C. (1981) Improvement in glucose tolerance due to Momordica churantiu (Karela). British Medical Journal 282, 1823-1824. Rivera, G. (1942) Preliminary chemical and pharmacological studies on “Cundeamor” Momordicu charuntia L. Part 2. American Journal of Phurmucology 1114, 72-87. Sharma, V.N., Sogani, R.K. and Arora, R.B. (1960) Some observations on the hypoglycaemic activity of Momordicu churuntiu. Indian Journal of Medical Research 48, (4), 471-477.
277
277-282
EFFECT OF MOMORDZCA CHARANTZA ON-THE TOLERANCE IN MATURITY ONSET DIABETES
J. WELIHINDAa, E.H. KARUNANAYAKEa, JAYASINGHEb
M.H.R. SHERIFFb and K.S.A.
Departments of “Biochemistry and bMedicine, Colombo, Kynsey Road, Colombo 8 (Sri Lanka) (Accepted
GLUCOSE
Faculty
of Medicine,
University
of
July 1, 1986)
Summary Investigations were carried out to evaluate the effect of Momordica charantia on the glucose tolerance of maturity onset diabetic patients. The fruit juice of M. charantia was found to significantly improve the glucose tolerance of 73% of the patients investigated while the other 27% failed to respond.
Introduction Although substantial work has been done on the hypoglycaemic activity of M. charantia on normal and diabetic laboratory animals (Rivera, 1942; Sharma et al., 1960; Akhtar et al., 1981) relatively few reports are available on its activity in humans. A possible synergestic interaction in a patient between chlorpropamide and a curry made from M. charantia and garlic has been previously reported (Aslam and Stockley, 1979). An improvement in the tolerance of an external load of glucose by non-insulin dependent diabetics has been observed by Leatherdale et al. (1981) after an oral administration of 50 ml of M. charuntiu fruit juice. The same authors observed a similar improvement after a daily intake of 0.23 kg of fried M. charantiu for 8-11 weeks. A similar observation has been made by Akhtar (1982) in patients 7 days after oral ingestion (50 mg/kg body wt) of dried M. charantiu powder. Furthermore, an insulin like protein called “plant insulin” (Khanna et al., 1981) isolated from M. charantia has been shown to possess hypoglycaemic properties when injected subcutaneously (Baldwa et al., 1977). We have previously reported (Karunanayake et al., 1984) significant oral hypoglycaemic activity of M. charactiu (that is locally cultivated and used in 0378~8741/86/$02.45 0 1986 Elsevier Scientific Publishers Ireland Ltd. Published and Printed in Ireland
218
the treatment of diabetes) available in Sri Lanka in laboratory animals. The present studies were undertaken to further evaluate the oral hypoglycaemic activity of Sri Lankan variety of ikf. charantia in non-insulin dependent maturity onset diabetics.
Materials and methods Diabetic patients
Eighteen newly diagnosed maturity onset diabetic patients (average age 38.2 years) free from ketoacidosis, cerebrovascular disease, acute myocardial infarction and renal complications were selected. These patients were not on any anti-diabetic drugs. Preparation
of juice
Fresh unripe fruits of M. charantia were obtained from the market, washed well and the seeds removed. The fleshy part was then cut into thin slices and macerated in a mechanical grinder. The pulp was then squeezed in a thick cloth and the juice obtained immediately frozen. Before using, the frozen juice was thawed and centrifuged at 10,000 rev./mm in a Damon I.E.C. B-20A centrifuge at 4°C for 10 min. The supematant was decanted and lOO-ml aliquots of the clear juice was given orally to patients. Oral glucose
tolerance
test
Following an overnight fast, standard glucose tolerance test (50 g glucose) was performed with all patients receiving 100 ml distilled water instead of M. charuntia 30 min before the glucose load. The oral glucose tolerance test was repeated on a subsequent day with all patients receiving 100 ml M. charantia juice 30 min before the oral glucose load. Blood sugar estimation
Blood samples (0.05 ml) were obtained by finger tip puncture using microcaps (Drummond Scientific Company, U.S.A.) and the blood glucose levels were estimated by the glucose-oxidase method of Hugget and Nixon (1957). Results and discussion
The glucose tolerance curves of all 18 patients are illustrated in Fig. 1 with a normal glucose tolerance curve of a healthy adult for comparison. It is apparent that all 18 patients were clearly diabetic. Comparative analysis of the percentage increase of blood sugar of each of these curves with the corresponding ones obtained with the administration of M. charantiu juice 30 min prior to glucose loading revealed that the patients could be divided into two groups. The first group, consisting of 13 patients, showed a significant improvement in glucose tolerance following
279
*
i
I
1
I
t
,
1;
2
2;
TIME
J
(h)
Fig. 1. Glucose tolerance curves of the diabetic patients and that of a normal healthy adult. All individuals were given 100 ml distilled water 30 min before the glucose load. s--.---* glucose tolerance curves of diabetics; *-, glucose tolerance of noTa human. ’
the prior administration of M. charantia juice. The second group, consisting of 5 patients, showed no significant improvement in their glucose tolerance. In Fig. 2, the mean (mean of the percentage increase of blood glucose + S.E.M.) glucose tolerance curve of the responding group is compared with that obtained with prior administration of M. c~u~u~~~ujuice. Statistical analysis by Student t-test revealed a si~ific~t difference between the two
Fig. 2. The pooled glucose tolerance curves of diabetic patients responding to M. charantia. During test all patients received 100 ml M. charantia 30 min before the glucose load and in the control all patients received 100 ml distilled water instead of M. charantio. The results are given as percentage increase of blood glucose. The S.E.M. values are given controls; Aby bars. l-, A, tests.
curves from the 1.5 h time point (0.5 > P > 0.1, 0.5 > P > 0.1, 0.02 > P > 0.01, P < 0.001, P < 0.001 at 0.5,1,1.5, 2 and 2.5 h, respectively). Similar curves for the group showing no improvement in the glucose tolerance are given in Fig. 3. There was no statistical difference between the two curves. However, the analysis of the total data, irrespective of the apparent difference in response to treatment, still confirmed the oral hypoglycaemic activity of M. charuntia. The mean total area under the test (AI. churuntiu treated) glucose tolerance curves (187.0 cm2) was significantly lower (0.01 > P > 0.001)than the area (243.6 cm2) under the control glucose tolerance curves (Table 1). The difference in response observed with the five patients in this study could also have been due to intra-individual variation usually seen in biological systems. The present study while confirming the oral hypoglycaemic activity of M. churuntia grown in Sri Lanka, gives scientific validity for the use of M. churuntiu as an oral hypoglycaemic agent by the traditional medical practitioners of Sri Lanka.
281
1
:
TIME
1’
2
2'
b
(h)
Fig. 3. The pooled glucose tolerance curves of diabetic patients not responding to M. charantia. The test received 100 ml of M. charantia juice 30 min before the glucose load while the control received 100 ml distilled water instead. The results are given as percentage increase of blood glucose. S.E.M. values are given as bars. l -0, controls; A----A , tests .
Acknowledgements This work was supported by grant No. 531 from the International Foundation for Science, Sweden, and by the grant No. RG 83/29 from the Natural Resources, Science and Energy Authority of Sri Lanka. TABLE 1 COMPARISON OF MEAN TOTAL AREAS OF GLUCOSE TOLERANCE UNDER DIFFERENT TREATMENTS The results are given as mean + S.E.M. Total area k S.E.M. (cm2 ) (n = 18) Control
Test
243.6 k 14.5
187.0 + 13.82 0.01 > P > 0.001
CURVES
282
References Akhtar, M.S., Athar, M.A. and Yaqub, M. (1981) Effect of Momordica charuntia on blood glucose levels of normal and Alloxan diabetic rabbits. Planta Medicu 42, (3), 205-212. Akhtar, M.S. (1982) Trial of Momordicu churuntiu Linn. (karela) powder in patients with maturity onset diabetes. Journal of the Pakistan Medical Association 32, 106-107. Aslam, M. and Stockley, J.H. (1979) Interaction between curry ingredients and drug (Chlorpropamide). Lancet i, 607. Baldwa, VS., Bhandari, CM., Pangaria, A. and Goyal, R.K. (1977) Clinical trial with patients with Diabetes mellitus of an insulin like compound obtained from a plant source. Uppsulu Journal of Medical Science 82, 39-41. Hugget, A. St. G. and Nixon, D.A. (1957) Use of glucose oxidase, peroxidase and dianisidine in the determination of blood and urinary glucose. Luncet ii, 368-370. Karunanayake, E.H., Welihinda, J., Sirimanne, S.R. and Sinnadorai, G. (1984) Oral hypoglycaemic activity of some medicinal plants of Sri Lanka. Journal of Ethnopharmacology 11, 223-231. Khanna, P., Jain, S.C., Pangaria, A. and Dixit, V.P. (1981) Hypoglycaemic activity of polypeptide p from plant source. Journal of Natural Products 44, 648-655. Leatherdale, B.A., Panesar, R.K., Singh, G., Atkins, T.W., Bailey, C.J. and Bignell, A.H.C. (1981) Improvement in glucose tolerance due to Momordica churantiu (Karela). British Medical Journal 282, 1823-1824. Rivera, G. (1942) Preliminary chemical and pharmacological studies on “Cundeamor” Momordicu charuntia L. Part 2. American Journal of Phurmucology 1114, 72-87. Sharma, V.N., Sogani, R.K. and Arora, R.B. (1960) Some observations on the hypoglycaemic activity of Momordicu churuntiu. Indian Journal of Medical Research 48, (4), 471-477.