STUDY OF PLANTS WITH D-CHIRO-INOSITOL AND ITS DERIVATIVES ON DIABETES
HTML Full TextSTUDY OF PLANTS WITH D-CHIRO-INOSITOL AND ITS DERIVATIVES ON DIABETES
Shahdokht Rastegar 1, 2, Shirin Soltani 3, Azade Roohipoor 4 and Esmaeel Ebrahimi * 1, 2
Department of Biochemistry 1, School of Medicine, Research Committee 2, Department of Pharmacology 3, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Department of Biochemistry 4, Taft University of Payame-Noor, Yazd, Iran.
ABSTRACT: Diabetes is an endocrine disorder, and it is due to a deficiency in secretion or action of insulin. The increased prevalence of diabetes in recent decades has made it to severe risk for public health. Human always has great consideration to plants for treatment of illnesses, especially diabetes and it is probably due to common ingredients with mammalian cells such as inositol, especially isomer of D-chiro-inositol, which plays a vital role in the signaling pathway of insulin, and its lack in the structure of inositol phosphoglycan leads to insulin resistance. Therefore, the possession of an inexpensive and available source of this ingredient is essential for patients suffering from diabetes. In the current study, we reviewed the effects of D-chiro-inositol and its derivatives and herbs with them on diabetes.
Keywords: |
Diabetes, Insulin, D-chiro-inositol, Inositol phosphoglycan
INTRODUCTION: Diabetes mellitus is a multi-factorial endocrine disorder with a significant prevalence in worldwide 1, 2. Impairment in insulin secretion and insensitivity of peripheral tissues (skeletal muscle and adipocytes) to insulin are main causes of type 1 and 2 diabetes 3, 4. Study on the prevalence of diabetes mellitus in 219 countries was showed that 382 million people have diabetes; in other words, it has been predicted that the number of people with diabetes about 7% will increase by 2030. 5 Today, diabetes as the fourth main cause of death worldwide is threatening of human health, and according to statistics, every year 6.8% of the world's population die due to complications of diabetes 6.
The increase of blood glucose during diabetes leads to complications such as neuropathy, cardio-myopathy, retinopathy, and nephropathy; however, if this situation gets adjusted, macrovascular and microvascular complications would decrease 7. Improvement of hyperglycemias’ normalizes oxidant-antioxidant imbalance and by reduction of free radicals level modifies any disruptions in diabetes; therefore, blood glucose control is a fundamental strategy for management of diabetes 8. World health organization encourages researches to discover drugs with good efficacy and low side effects to control and treatment of diabetes; and to achieve this goal, plants can be useful due to their rich sources from compounds with biological activity 8.
From nine isomer of inositol, D-chiro-inositol (D-CI) has the most important role in insulin signaling pathway Fig. 1; 9 and given that importance of secondary messengers in insulin resistance, focusing on the metabolism of D-chiro-inositol in diabetes is very pivotal 10.
FIG. 1: ROLE OF D-CHIRO-INOSITOL IN INSULIN SIGNALING PATHWAY
One of the events that occur during digestion of glucose is an increase of activation of inositol phosphoglycan with D-chiro-inositol, but this is an interesting point that there is the possibility of their disorder during diabetes so that their levels severely decrease in patients with non-insulin dependent diabetes mellitus while the level of myoinositol increase 11-13. This is due to the reduction of activity of an enzyme that transforms myoinositol to chiro-inositol in very important areas of development of diabetes such as liver, skeletal muscle and adipocytes 14.
Another reason for the abolishment of D-chiro-inositol effect in diabetes is a reduction of hydrolysis of glycophosphatidylinositol to inositol phosphoglycan after induction of diabetes by streptozotocin howbeit; the increase of the urinary level of D-chiro-inositol in this situation indicates that D-chiro-inositol perturbation is along with defect in glycophosphatidylinositol-dependent insulin signaling 15-17.
Therefore, reduction of D-chiro-inositol embedment in the mediators of insulin signaling pathway due to either transformation increase to myo-inositol by epimerase or hydrolysis decrease of glycophosphatidylinositol has a huge impact on the development of diabetes, and its administration can be a reasonable strategy for control and treatment of diabetes 2, 18. Also, Dchiro-inositol is a presence as methyl form (3-O-methyl-D-chiro-inositol or D-pinitol) in plants that have promising effects on the reducing of diabetes-related disorders 9, 19. Our previous studies have confirmed that plants are a suitable source for remedy of diabetes and management of its complications. We investigated insulin resistance 20, dyslipidemia 21, weight of diabetic rats 22, role of pancreatic duct cell in beta cell neogenesis 23, study of association between beverage consumption pattern and lipid profile 24, cardiac and pancreatic biomarkers 25, induction of insulin secretion 1, hematological factors 26, evaluation of sex cells (gametes) and testicular structure 27 and mechanisms of plant ingredients in the treatment of diabetes mellitus 28 in previous study. Here, we reviewed the effects of D-chiro-inositol and its derivatives and plants with them on diabetes.
Review Method: In the recent study, we reviewed the effects of D-chiro inositol and its derivatives on diabetes in conducted studies on diabetic animal models and patients with type 2 diabetes. We also reviewed plants contain these compounds and their effects on diabetes. For conducting this study, we obtained related articles using keywords such as D-chiro-inositol, D-pinitol, and D-chiro-inositol derivatives, diabetes and herbal medicine since 1980 from to now based on databases such as Wiley, Scopus, Science Direct, Springer and PubMed. Then, the articles were categorized and reviewed.
Effects of Administration of D-chiro-inositol and its Derivatives on Diabetes: In Table 1, the beneficial effects of D-chiro-inositol and its derivatives on diabetes were summarized. According to studies, free D-chiro-inositol or derivatives with methyl such as L-quebrachitol, D-pinitol, pinpollitol and D-ononitol and derivatives containing galactosyl such as ciceritol can be find in plants Fig. 2. 29-32 However, many studies have been done on the effects of free form (D-chiro-inositol) or D-3-O-methyl form (D-pinitol). One of the considered suggestions for improvement of diabetes is the use of nutritional supplements that contain D-chiro-inositol 33.
Insulin is effective on the activity of pyruvate dehydrogenase phosphatase through mediators, and this regulatory role of insulin is abolished during insulin resistance. Given that the vital role of D-chiroinositol in this regulatory pathway, its administration can reduces the effects of insulin resistance, so that treatment with D-chiro-inositol improves complications such as hypertension, obesity, cardiovascular disorders and lactic acidosis 34. However, the use of myo-inositol does not have dramatic effects on the level of blood glucose because two week-treatment with myo-inositol could not reduce the increased blood glucose level followed by streptozotocin injection 35.
TABLE 1: EFFECTS OF ADMINISTRATION OF D-CHIRO-INOSITOL AND ITS DERIVATIVES ON DIABETES
Compound | Subject/animal model | Result(s) | Reference |
D-chiro-inositol | STZ-diabetic rats | Blood glucose reduction by the administration with insulin after 60 min | 36 |
STZ-diabetic rats | 47% blood glucose reduction by the administration with manganese chloride after 120 min | 2 | |
STZ-diabetic rats | Improvement of PPA and CV in sciatic nerves, induction of electrical stimulation in corpus cavernosum and vas deferens | 37 | |
D-pinitol | STZ-diabetic rats | Normalization of blood glucose and lipid
profile in serum, liver, kidney, heart and brain |
8 |
STZ-diabetic rats | Activation increase of SOD ،GPx ،GST, improvement of non-defense antioxidant, Reduction of lipid peroxidation and lipid hydro per oxidation | 40 | |
STZ-diabetic rats | Amelioration of pro-inflammatory factors, insulin serum, and antioxidant-oxidant
a condition in the liver, reduction of lipid peroxidation and lipid hydroperoxidation, protection of the liver structure |
41 | |
Roman-Cowley model of pressure-natriuresis (P-N) in STZ-diabetic rats | Improvement of parameters related to
kidney function such as RVR, FENa, FF, RBF |
42 | |
Type 2 diabetic patients | Reduction of blood glucose (fasting and
post prandial) and HbA1c, lack of significant change on adiponectin, leptin, free fatty acid, CRP, lipid profile and fasting c-peptide |
43 | |
Obese individuals with insulin resistant | Lack of toxic effect by evaluation of whole-body glucose, palmitate and glycerol kinetics under conditions of basal and hyperinsulinemic-euglycemic clamp | 9 | |
STZ/HDF-diabetic rats | Expression increase of PI3Kp85, PI3Kp110, and kinase B/Akt, glycogen storage amelioration by expression inhibition of
GSK-3β and up-regulation of glycogen synthesis |
31 | |
STZ-diabetic rats
Obese-diabetic rats L6 rat muscle cells |
Plasma glucose reduction during oral and intraperitoneal administration in STZ-diabetic rats and not obese-diabetic rats, improvement of glucose transport in L6 rat muscle cells | 44 | |
L-quebrachitol | DB/db Mice | By increase efficacy of pancreas function lead to normalization of serum glucose and insulin | 45 |
Alloxan-diabetic rats | Improvement of blood glucose | 46 |
PPA: peak-to-peak amplitude, CV: conduction velocity, SOD: superoxide dismutase, GPx: glutathione peroxidase, GST: glutathione s-transferase, FENa: fractional excretion of sodium, FF: filtration fraction, RBF: renal blood flow, RVR: renal vascular resistance, CRP: C-reactive protein, PI3K: phosphatidylinositol-3-kinase, GSK-3β: glycogen synthesis kinase-3β.
FIG. 2: D-CHIRO-INOSITOL AND ITS DERIVATIVES IN PLANTS
In one study, it was showed that concurrent administration of insulin and chiro-inositol glycan could significantly reduce blood glucose during 60 min after administration in induced diabetic rats with streptozotocin while administration of insulin without chiro-inositol glycan led to a significant reduction in blood glucose during 120 min 36.
Moreover, it was well confirmed that D-chiro-inositol at a dose of 15 mg/kg and not 5 mg/kg reduces blood glucose in streptozotocin-diabetic rats about 21% during 120 min after administration and this decreasing effect was up to 47% during treatment with D-chiro-inositol (15 mg/kg) along with manganese chloride (8.3 μg/min) in 120 min after administration. It was also determined that 3-O-methyl-D-chiro-inositol in doses of 5 and 15 mg/kg leads to blood glucose reduction about 6% and 22% respectively followed by 120 min administration; and concurrent treatment of 3-O-methyl-D-chiro-inositol (15mg/kg) with manganese chloride (8.3 μg/min) reduces hyperglycemia about 49% at the same time after administration 2.
There is one study in conjunction with the good effects of D-chiro-inositol on neuropathy caused by diabetes. In this study, it was determined that administration of streptozotocin leads to many disturbances in the function of sciatic nerve including, reduction of peak-to-peak amplitude (PPA) and conduction velocity (CV) and also increase of chronaxy. After treatment with 20 mg/kg/12h of D-chiro-inositol, these problems recovered to normal level. Also, D-chiro-inositol improved electrical stimulation of corpus cavernosum and vas deferens and had a protective effect on injuries related to sciatic nerves 37.
D-pinitol is one of the rich sources of inositol in the herbs, and it has been determined that mimics the effects of insulin 38, 39. D-pinitol can consider as an anti-hyperlipidemic compound because it has been examined that treatment of diabetic rats with D-pinitol leads to the reduction of glucose, total cholesterol, triglyceride, free fatty acids, and phospholipids in serum, liver, kidney, heart and brain. Additionally, reduction in low-density lipoprotein (LDL) and very low -density lipoprotein (VLDL) and an increase of high-density lipoprotein (HDL) level by D-pinitol administration has been seen 8.
In a study, the effects of treatment with 50 mg/kg of D-pinitol on antioxidant status in plasma and pancreas of diabetic rats during one month were examined. According to this study, this dose of D-pinitol resulted in the balance of antioxidant status through its effect on antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and glutathione s-transferase) and non-enzymatic antioxidant compounds (Vitamin E, vitamin C, ceruloplasmin and reduced glutathione). Therefore, to keep antioxidant defense by D-pinitol reduces induced damage on pancreas because lipid peroxidation and hydroperoxidation in the pancreas were significantly decreased after treatment with D-pinitol 40.
In a study, Sivakumar et al., 2010 have shown that hypoglycemic effect of D-pinitol (50 mg/kg b.w.) is parallel to the improvement of inflammatory markers (TNF-α, IL-1β, IL-6, NF-κB p65 unit and nitric oxide) and an increase of insulin level in diabetic rat’s serum. Also, there was a reasonable relationship between oxidant-antioxidant balance (by measurement of enzymatic and non-enzymatic antioxidant defense biomarkers) and reduction of lipid peroxide and hydroperoxide level in liver. Moreover, these results were confirmed after liver histopathologic evaluation 41.
A research group was determined that impairment of kidney function under diabetes condition and treatment with D-pinitol can prevent it. In this study, in order to induction of renal dysfunction, the Roman-Cowley model of pressure-natriuresis (PN) was used and measurement of factors such as fractional excretion of sodium (FENA), filtration fraction (FF), renal blood flow (RBF), renal vascular resistance (RVR) and glomerular filtration rate (GFR) confirmed improvement of kidney function after two month examination in diabetic rats 42. The observation of useful effects in improvement of diabetes during a study on treatment with D-pinitol in animal models encourages researchers to examine its effects on diabetic patients.
On this basis, Kim et al., 2007 conducted a study on the effects of treatment with 20 mg/kg per day of D-pinitol on diabetic patients with poor response to sulfonylurea, metformin and insulin during twelve weeks. According to this study, D-pinitol caused a significant reduction in blood glucose (fasting and after a meal) and HBA1c. Albeit, any significant changes have not seen in adiponectin, leptin, free fatty acids, and c-reactive protein and lipid profile (total cholesterol, triglyceride, and HDL- and LDL-cholesterol) and fasting c-peptide in serum 43. Moreover, determination of whole-body glucose, palmitate, and glycerol kinetics under both basic and hyperinsulinemic-euglycemic clamp conditions was confirmed sensitivity of glucose and lipid metabolism to insulin after daily treatment with 20 mg/kg D-pinitol within 4 weeks in obese patients with type 2 diabetes 9.
Although, D-pinitol is anti-hyperglycemic compound, but has been recently understood its molecular effect mechanism so that in the conducted study by Gao et al., 2015 on streptozotocin-induced type 2 diabetes rats with high-fat diet showed that D-pinitol has effects similar to insulin in liver. It could actives signaling pathway of PI3K/AKT by an increase of expression of phosphatidylinositol-3-kinase (PI3K) P85, PI3KP110 and kinase B/AKT (at ser473). It was also increased glycogen content in the liver by inhibition of expression of glycogen synthesis kinase-3β (GSK-3β) protein and up-regulation of glycogen synthesis 31.
Also, according to a study conducted by Bates et al., 2000 oral and intraperitoneal administration of D-pinitol (100 mg/kg) results in plasma glucose reduction in streptozotocin-diabetic mice while there was not hypoglycemia in obese-diabetic mice. Moreover, this study indicated that D-pinitol improves glucose transport in L6 rat muscle cells 44. In association with other derivatives of D-chiro-inositol, it has been reported that ten-week treatment with sea buckthorn juice enriched with L-quebrachitol (2-0-methyl-chiro-inositol) improves resistance to induced diabetes in db/db mice.
Indeed, L-quebrachitol had an important role in the normalization of glucose and insulin level through improvement of pancreas performance 45. It has also reported by Musalmah et al., 2001 that treatment with L-quebrachitol and L-chiro-inositol recover the level of blood glucose in diabetic rats 46.
Effects of Plants with D-chiro-inositol and its Derivatives on Diabetes: In Table 2, the effects of D-chiro-inositol and its derivatives on diabetes was showed; these plants including:
TABLE 2: EFFECTS OF PLANTS WITH D-CHIRO INOSITOL AND ITS DERIVATIVES ON DIABETES
Plant | Subject/animal model/cell line/method | Result(s) | Reference |
Soybean (Glycine max) |
Type 2 diabetic patients | Reduction of glucose, fructose, HbA1c, insulin, HOMA-IR and lipid profile in blood | 39 |
Korean type 2 diabetic
patients |
Inhibition of postprandial
hyperglycemia, lack of good effect on blood insulin |
19 | |
Buckwheat
(Fagopyrum esculentum) |
STZ-diabetic rats | 12 and 19% reduction of hyperglycemia after 90 and 120 min respectively | 16 |
Tartary buckwheat (Fagopyrum tataricum) |
KK-Ay mice | Amelioration of serum level of glucose, total cholesterol, TG, C-peptide, glucagon and BUN, reduction of immunologic
reaction in pancreas |
52 |
Carob tree (Ceratonia siliqua) |
STZ-diabetic rats | Normalization of serum level
of glucose and lipid profile |
53 |
STZ-diabetic rats | The protective effect on kidney
Function |
54 | |
Column chromatography with ion exchange | Confirmation of D-pinitol
Isolation |
55 | |
Dragon fruit (Hylocereus polyrhizus) |
STZ-diabetic rats | Improvement of cardiac function and oxidative condition | 56 |
Fructose-diabetic rats | Amelioration of insulin resistant, hypertriglyceridemia, and atherosclerotic changes | 57 | |
X-ray crystallography,
HPLC, LC-MS/MS, and NMR |
Confirmation of myo-inositol in
plant |
58 | |
Fig leaf gourd (Cucurbita ficifolia) |
STZ-diabetic rats | Improvement of polydipsia and
hyperphagia, hyperglycemia and plasma lipid peroxidation, positive effect on glutathione cycle in liver, pancreas, and kidney |
59 |
STZ-diabetic rats | Normalization of the level of
hyperglycemia, GTT, total hemoglobin, insulin and liver glycogen |
60 | |
STZ-diabetic rats | Anti-inflammatory and
antioxidant effects |
61 | |
3T3-L1 cell line | Anti-inflammatory and antioxidant effects | 62 | |
STZ-diabetic rats | Anti-diabetic property except
effect on ATP-sensitive potassium channel |
63 | |
Mung Bean (vigna radiata ) |
KK-Ay mice | Level improvement of glucose,
C-peptide, glucagon, total cholesterol, TG and BUN in plasma, reduction of immunologic reaction in the pancreas |
65 |
HOMA-IR: homeostatic model assessment for insulin resistant, STZ: streptozotocin, TG: triglyceride, BUN: blood urea nitrogen, GTT: glucose tolerance test.
Soybean (Glycine max): It has been determined that D-chiro-inositol and its methylated form (D- pinitol) are great part of cyclitols of soybean 47. In a study, it was found that D-pinitol is one of the main ingredients in soybean. According to this study, if soybean leaf (its ethanol extract) place in an aqueous fraction and fully remove lipids through ion exchange resins, ultimately obtain a crystalline product with 85.5% D-pinitol 48. Treatment of thirty patients with type 2 diabetes by isolated D-pinitol from soybean (600 mg twice a day for 13 weeks) resulted in the reduction of blood glucose, fructose, HbA1c, insulin and HOMA-IR (an assessment index of insulin resistance). Also, this study confirms good effects of D-pinitol on lipid profile 39. Remarkable effects of D-pinitol obtained from soybean persuade researchers to use it as a dietary supplement. In one study, fifteen Korean diabetic patients were treated with cooked white rice with 50 g of carbohydrates (with or without soybean D-pinitol). This study was showed that D-pinitol prevents the increase of blood glucose 90 to 120 min after a meal; however, an acceptable effect on insulin level was not observed 19.
Buckwheat (Fagopyrum esculentum): Studies show that Fagopyrum esculentum (buckwheat) is rich in D-chiro-inositol derivatives. Based on a study conducted by Horbowicz et al., 1998 O-α-D-galactopyranosyl- (1→2)- D-chiro-inositol (fagopyritol B1) is the most important carbohydrate in buckwheat seeds 49. It has been reported that seeds of buckwheat have 40% of fagopyritols (mano, dio tri galactosyl derivatives related to D-chiro inositol) in each 6.4 g of total soluble carbohydrates per 100 g of dry weight 50. Also, the extract with D-chiro-inositol can be isolated from buckwheat by thin layer chromatography, sodium periodate and blue benzidine 51. In one study, it has been showed that administration of concentrated buckwheat (including 10 and 20 mg of D-chiro-inositol per kg of body weight) has a significant effect on reduction of blood glucose level in streptozotocin-induced diabetic rats so that a reduction of 12-19% in serum glucose observed after 90 and 120 min administration. Therefore, its administrations as a dietary supplement can seem reasonable for diabetic’s patients 16.
Tartary Buckwheat (Fagopyrum tataricum): Fagopyrum tataricum (tartary buckwheat) is another type of buckwheat. The examination of tartary buckwheat extract rich of D-chiro-inositol on KK-Ay mice was showed that treatment with 20 g/kg its extract had no toxic effects. Additionally, this extract resulted in the reduction of blood glucose, total cholesterol, triglycerides, C-peptide, glucagon, and blood urea nitrogen and also improvement of the induced immune response in the pancreas at the end of period study 52.
Carob Tree (Ceratonia siliqua): Using 600 mg/kg of ethanol extract prepared from carob seeds was obtained promising effects on improvement of glucose and lipid profile in diabetic rats 53. Also, ethanol extracts of carob seeds (600 mg/kg) reduce induced-damages to kidney caused by streptozotocin injection after 16 days of treatment because it could perfectly balance the level of renal biomarkers (creatinine, uric acid, blood urea nitrogen, Na+, K+, and Ca+2) in serum 54. It has also been reported that through chromatography along with ion exchange resin, D-pinitol was separated from this plant 55. According to these studies, it considered that D-pinitol is effective in anti-diabetic features of carob.
Dragon Fruit (Hylocereus polyrhizus): In one study, it was well found that five-week treatment of aqueous extract obtained from fruit pulp of Hylocereus polyrhizus (250 and 500 mg/kg) is very affective in blood glucose normalization. This study was also showed that it has a pivotal effect on kidney function because of improvement of parameters such as pulse wave velocity (leading to a decrease in aortic stiffness), systolic blood pressure, and pulse pressure at the end of the study. Also decrease in plasma level of malondialdehyde, an increase of enzyme activity of superoxide dismutase and total antioxidant capacity reflected a recuperation of oxidative condition in diabetic rats 56. The anti-diabetic effects of Hylocereus polyrhizus can be attributed to the presence of antioxidants and fiber because six-week treatment with its fresh fruit juice rather than use of processed fruits under heat of 95 °C and 105 °C (containing low level of antioxidants and fiber) significantly improved insulin resistance, hypertriglyceridemia and atherosclerotic changes in rats received fructose 57. On the other hand, by use of X-ray crystallography, HPLC, LC-MS/MS and NMR the presence of myo-inositol crystals in H. polyrhizus has been reported 58.
Fig Leaf Gourd (Cucurbita ficifolia): Administration of 200 mg/kg of Cucurbita ficifolia as an aqueous extract for one month reduces symptoms such as polydipsia, and hyperphagia in streptozotocin-induced diabetic rats. It also significantly reduces blood glucose and lipid peroxidation in plasma. The aqueous extract of Cucurbita ficifolia has a positive effect on glutathione cycle in liver, pancreas, and kidney so that levels of reduced and oxidized glutathione, the activity of glutathione peroxidase and glutathione reductase were completely normalized followed by treatment 59. Also, administration of Cucurbita ficifolia (containing 10-20 mg/kg D-chiro-inositol) in terms of normalization of factors such as blood glucose, glucose tolerance test, liver glycogen, total hemoglobin, and plasma insulin is similar to the effects of administration of 20 mg/kg D-chiro-inositol. Thus, this herb as a rich source of D-chiro-inositol can use by diabetic patients 60.
According to a study performed by Ramos et al., 2012 the anti-diabetic characteristic of Cucurbita ficifolia is related to the existence of D-ciro-inositol. AP fraction (fraction containing D-chiro-inosito) obtained from the fruit of Cucurbita ficifolia has 3.31 mg/g of D-chiro-inositol. In this study treatment design was contain first preventive treatment for two weeks and then treatment continued after induction of diabetes with streptozotocin for the 33-day course. In final, it was confirmed that AP fraction has an anti-inflammatory effect and leads to a reduction of TNF-α and also increase of IFN-γ and IL-6 in serum but it increases the anti-inflammatory cytokine level of IL-10. AP fraction was also effective in the increase of glutathione level and reduction of malondialdehyde in liver 61.
Comparing the effects of aqueous extract of Cucurbita ficifolia and synthetic D-chiro-inositol on the oxidative state and level of pre-inflammatory factors in adipocytes (3T3-L1) was showed that both lead to a reduction of hydrogen peroxide and GSH/GSSG ratio and activity increase of glutathione peroxidase. The synthetic D-chiroinositol reduced mRNA level and amount secretion of TNFα, IL-6, and resistin while reduction effects of Cucurbita ficifolia extract was only on resistin level and even increased the level of IL-6 62.
Although, aqueous extract of Cucurbita ficifolia along with high degree of D-chiro-inositol significantly reduced blood sugar and triglyceride level in streptozotocin -induced diabetic rats during a one-month study, but it not inhibited diazoxide-induced relaxation of rat aortic ring precontracted with phenylephrine. Indeed, the glucose-lowering effect of its extract was not through its effect on ATP-dependent potassium channels 63.
Mung Bean (Vigna radiate): Examination of D-chiro-Inositol content in 110 species of mung bean was showed that it is valuable in terms of containing D-chiro-Inositol and can use as a food grain in the diet of individuals with diabetes 64. Besides, it considered as an anti-diabetic herb. The administration 2 and 3 g/kg mung bean sprouts extract, and mung bean seed coat extract have an entirely good effect on the normalization of factors such as blood glucose, plasma C-peptide, glucagon, total cholesterol, triglycerides, and blood urea nitrogen, respectively during five-week treatment in KK-Ay mice and it also balances the immune response in their pancreas 65.
Prospects: It has been suggested that imperfection in D-chiro-inositol metabolism has a vital role in the development of insulin resistance forasmuch as the presence of D-chiro inositol is essential in the building of inositol phosphoglycans in insulin signaling pathway 9, 16. Here, we examined the effects of D-chiro-inositol and its derivatives on diabetes. We also categorized the plants, which contained such compounds. We mention that to possess an available and inexpensive source of D-chiro-inositol is necessary for patients with diabetes and herbs can help us to achieve this goal.
FIG. 3: STRUCTURE OF GALACTOSAMINE-CHIRO-INOSITOL PSEUDO-DISACCHARIDE Mn2+ CHELATE
Thus, world health organization (WHO) persuade researchers in the field of diabetes to more focus on plants and their compounds for remedy of diabetes because by use of plants can obtain impressive treatment with fewer side effects 8. One way to obtain D-chiro-inositol is the use of aqueous solution of kasugamycin fungal by ion exchange resins 66. Additionally, beef liver is another non-plant source of D-chiro-inositol and a compound called galactosamine chiro-inositol pseudo-disaccharide Mn+2 chelate (INS-2, 1) was isolated from it which has like insulin effect and leads to hypoglycemia in an animal model of diabetes Fig. 3. 67
CONCLUSION: Based on our review, D-chiro-inositol is the presence in plants spatially in Fabaceae family. Also, in Cucurbitaceae, D-chiro-inositol was only found in Cucurbita ficifolia; thus, examination of content D-chiro-inositol of both families is valuable owing to their most are comestible.
Finally, we suggest that investigate the effects of herbs such as Lens culinaris (lentil), Cicer arietinum (chickpea), Phaseolus vulgaris (pinto bean), Vicia sativa (vetch) and Vigna unguiculata (black-eyed pea or cowpea) on diabetes. Our suggestion is a comparison between effects of other derivatives of D-chiro inositol such as ciceritol (pinitol digalactoside), D-ononitol (4-O methyl-myo-inositol), pinpollitol(di-O-methyl – (+) - chiro-inositol) to D-chiro-inositol on diabetes.
ACKNOWLEDGEMENT: Nil
CONFLICT OF INTEREST: The authors declare that there is not any conflict of interest in this study.
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How to cite this article:
Rastegar S, Soltani S, Roohipoor A and Ebrahimi E: Study of plants with D-chiro-inositol and its derivatives on diabetes. Int J Pharmacognosy 2017; 4(2): 43-53. doi link: http://dx.doi.org/10.13040/IJPSR.0975-8232.IJP.4(2).43-53.
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Article Information
1
43-53
699
1149
English
IJP
S. Rastegar, S. Soltani, A. Roohipoor and E. Ebrahimi *
Department of Biochemistry, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
E.Ebrahimi92@yahoo.com
30 November 2016
22 December 2016
26 December 2016
10.13040/IJPSR.0975-8232.IJP.4(2).43-53
01 February 2017