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  • Phytochemicals in The Management of Diabetes Mellitus: A Comprehensive Review

  • Photo Rutuja Pangavhane * Photo Mukund Pache

  • Department of pharmacognosy, K. V. N. Naik SP Sanstha’s, Institute of pharmaceutical Education and Research, Canada Corner, Nashik, 422002, Maharashtra, India

Abstract

Diabetes mellitus is a complex metabolic disorder resulting from inadequate insulin secretion or compromised insulin function. Hyperglycaemia and glucose intolerance resulting from insulin resistance are defining characteristics of diabetes, a metabolic and endocrine disorder. Hyperglycaemia is a prevalent condition linked to diabetes mellitus, potentially leading to many problems such as peripheral vascular diseases, diabetic nephropathy, retinal impairment, neuropathy, delayed wound healing, myocardial infarctions, and ketoacidosis. Synthetic pharmaceuticals are costly and have a significant risk of unwanted effects when employed in the treatment of diabetes. Herbal products provide a substantial focus for medicinal research owing to their extensive diversity and few adverse effects. In developing nations with few resources, medicinal plants and phytoconstituents are essential for treating diabetes mellitus. Integrating plant-based foods into the daily diet offers several health benefits, such as weight management in obese individuals and mitigating elevated blood sugar levels (hyperglycaemia) observed in diabetes mellitus. The identification of phytochemicals in medicinal plants is a great opportunity for the development of innovative diabetes therapies. Medicinal plants can aid in preventing and treating diabetes due to their phytochemicals, including phenolics, alkaloids, polysaccharides, and glycosides. Phenolics encompass terpenoids, steroids, and flavonoids. Multiple epidemiological studies have evidenced the efficacy of a plant-based diet (vegetables, fruits, herbs, and spices) in preventing and managing diabetes. This article aims to provide a comprehensive overview of phytochemicals exhibiting hypoglycaemic action.

Keywords

Diabetes mellitus DM, Insulin, Hyperglycaemia, Medicinal plants, Natural treatment, Phytochemicals

Introduction

Diabetes mellitus, a metabolic disorder with several causes, is defined by sustained hyperglycaemia and metabolic disturbances in lipids, carbs, and proteins resulting from inadequate insulin synthesis and activity.1 Diabetes is a disorder that impacts the metabolism of proteins, lipids, and carbohydrates, resulting from either diminished insulin production or heightened resistance to its effects.2 Diabetes mellitus (DM), a metabolic disorder with potential environmental or genetic causes, increases a patient's risk of getting many other diseases.3 Diabetes mellitus is the most common endocrine disorder worldwide, marked by insulin resistance, impaired insulin signalling, beta-cell dysfunction, and aberrant metabolism of glucose, proteins, and lipids.4 One of the most common outcomes of untreated diabetes is hyperglycaemia. The condition is referred to as hyperglycaemia or increased blood glucose levels.5 Insulin is a hormone that regulates blood sugar levels. Diabetes increases the likelihood of stroke and cardiovascular disease. Cardiovascular disease is responsible for 50% of fatalities among individuals with diabetes. Diabetes is a primary cause of renal failure.6

The four principal types of diabetes are:

1. Type 1 diabetes (T1DM)

2. Type 2 diabetes (T2DM)

3. gestational diabetes (GDM)

4. Monogenic diabetes, particularly maturity-onset diabetes of the young (MOD), is widely acknowledged.

These four principal types of diabetes are widely acknowledged and are broadly recognised. Because they affect a considerably larger number of patients than other types.7 T1DM and T2DM are the most recognised forms of diabetes. Type 1 Diabetes Mellitus (T1DM), formerly referred to as insulin-dependent diabetes, predominantly impacts adolescents and young adults.8 The demise of β-cells in the pancreas complicates insulin production. Type 2 diabetes constitutes almost 90% of all instances. Type 2 diabetes predominantly impacts individuals over 40; nevertheless, the escalating rates of juvenile obesity are leading to a growing incidence among younger populations. This condition is characterised by insufficient organ resistance and the dysfunction of pancreatic beta cells, leading to insulin depletion.9 Chronic insulin resistance and pancreatic beta cell dysfunction, which may occur during pregnancy, are associated with gestational diabetes mellitus (GDM). MODY is a rare genetic variant of diabetes mellitus that usually presents during adolescence or early adulthood.10

Common Symptoms of Type 2 Diabetes: Dehydration, emesis, polyphagia, myalgia, anorexia, peripheral neuropathy, foot infections, polydipsia, delayed wound healing, renal failure, cardiovascular disorders, polyuria, coma, and, in severe cases, mortality.11 Individuals with type 2 diabetes frequently utilise various categories of oral hypoglycaemic agents. The list includes α-glucosidase inhibitors, meglitinides, sulfonylureas, thiazolidinediones, amylin analogues, SGLT-2 inhibitors, metformin, GLP-1 mimetics, DPP-4 inhibitors, and incretin receptor dual agonists. Insulin is solely utilised for the treatment of type 1 diabetes. Should alternative drugs be ineffectual, we subsequently give insulin.12 Hypoglycaemia is a significant side effect of antidiabetic medicines, as reported. Frequently reported adverse effects encompass gastrointestinal disturbances, gas production, bloating, nausea, and infections of the respiratory and urinary tracts.13

The role of natural treatments in diabetes management: Botanical sources produce diverse pharmaceuticals. Plant-based medications are regarded as the principal method for maintaining human health by averting diseases and their related effects or responses.14 Incorporating edible plants with established antihyperglycemic qualities, such as clove, bitter melon, neem, moringa, black seeds, turmeric, or cinnamon, into daily meals may be less detrimental than conventional drugs.15 Pharmaceuticals derived from flora have historically served as a valuable alternative. Ethnobotanical findings indicate that over 800 plants may possess preventative capabilities against diabetes.16 The World Health Organisation WHO has recommended the investigation of traditional plant remedies for diabetes, as they can be efficiently treated, exhibit minimal toxicity and adverse effects, and are considered promising candidates for oral medication.17 The scientific validation of several plant species has proven the efficacy of botanicals in reducing blood glucose levels. Plant-based compounds are believed to have a key role in the treatment of diabetes, according to reports of their potential efficacy against the illness. This requires further investigation to develop suitable pharmaceuticals and nutraceuticals from natural sources. Herbal medicines have been utilised to treat diabetic retinopathy, diabetic peripheral neuropathy, insulin-dependent diabetes, non-insulin-dependent diabetes, and other related disorders.18 Researchers have recently identified many phytochemicals having antidiabetic effects in plants. Polysaccharides, alkaloids, amino acids, flavonoids, saponins, glycosides, dietary fibres, glycolipids, peptidoglycans, and other phytoconstituents obtained from diverse plants are potent hypoglycaemic agents.19 Plants synthesise alkaloids, flavonoids, tannins, terpenoids, ferulic acid, and many secondary metabolites, all of which have hypoglycaemic effects. Alkaloids reduce blood sugar levels by inhibiting alpha-glucosidase activity and decreasing the absorption of glucose across the intestinal epithelium. They likely achieve this by stimulating insulin secretion from the pancreatic islets. Flavonoids reduce blood sugar levels and enhance glucose metabolism in the liver. Steroid glycosides, triterpenoids, and saponins enhance insulin secretion and inhibit the formation of blood glucose in circulation. Polysaccharides reduce blood glucose levels, improve glucose tolerance, and increase serum insulin levels. Compounds such as ferulic acid enhance insulin secretion. 20 Additionally, unlike conventional medicine, which addresses a singular, isolated active compound, herbal therapy encompasses the entire plant or particular portions of the plant. The utilisation of the entire plant is believed to yield a superior synergistic effect due to the collaborative action of all its compounds, resulting in a more potent and integrated influence. 21

Phytochemicals for the treatment of diabetes mellitus:

Alkaloids:

Alkaloids are secondary metabolites in plants characterised by the presence of basic nitrogen atoms.22 Various therapeutic plants contain distinct types of alkaloids. Bacteria, fungi, and various other organisms also possess alkaloids.23

Alkaloid classification:

1. True alkaloids: Atropine, nicotine, morphine.

2. Protoalkaloids: Ephedrine, Adrenaline, Mescaline.

3. Pseudoalkaloids—Theophylline, Theobromine, Caffeine

4. Polyamine alkaloids—putrescine, spermidine, and spermine

5. Peptide and Cyclopeptide Alkaloids

Alkaloids employ several mechanisms to elicit a wide range of antidiabetic benefits. Species such as Tinospora cordifolia and Berberis spp. possess berberine in their root and stem bark. The foliage and stems of Catharanthus roseus contain catharanthine, vindoline, and vindolinine, which aid in the treatment of diabetes mellitus.24

Table 1. A list of significant alkaloids that are used to treat diabetes.

Plant name

Phytoconstituents

Plant parts

References

Berberis spp. Tinospora cordifolia

Berberine

Roots, stem-bark

25

Catharanthus roseus

Catharanthine, vindoline and vindolinine

Leaves, stems

26

Syzygium malaccense

Casuarine 6-o—glucoside

Bark

27

Nicandra physalodes

Calystegine B2

Fruits

28

Tribulus terrestris

Harmane, norharmane,

-

29

Cryptolepis sanguinolenta

Cryptolepine

-

30

Syzygium cumini

Jambosine

Seeds, fruits, bark

31

Trigonella- foenum-graecum

Trigonelline

Seeds

32

Swertia chirayita

Swerchirin

-

33

Morus alba

1-deoxynojirimycin

Morus alba

34

Glycosides:

A glycoside is a chemical that consists of a sugar moiety linked to a non-sugar moiety. Plants possess glycosides, which are vital for living organisms. The glycoside Jamboline, present in the seeds of Eugenia jambolana, may assist in reducing blood sugar levels. Before the availability of insulin, individuals commonly utilised Vaccinium myrtillus L. (Ericaceae) leaves as a remedy for diabetes. 35

Table 2. A list of significant Glycosides that are used to treat diabetes.

Plant name

Phytoconstituents

Plant parts

References

Kalopanax pictus

Kalopanax

Stem bark

36

Syzygium cumini

Jamboline or antimellin

Seeds

37

Myrcia multiflora

Myrciacitrins I and II and myrciaphenones A and B

Leaves

38

Vaccinium myrtillus

Neomyrtillin

Leaves

39

Ficus bengalensis

Perlargonidin 3-o—l rhamnoside

Bark

40

Anemarrhena asphodeloides

Pseudoprototinosaponin AIII & prototinosaponin AIII

Rizomes

41

Microcos paniculata

Vitexin, isovitexin and isorhamnetin 3-O—D-rutinoside Microcos paniculata Leaves

Leaves

42

Flavonoids:

Plants possess polyphenolic compounds known as flavonoids, which have numerous medical applications and are abundantly present in seeds, nuts, flowers, stems, fruits, vegetables, and green tea.43 Flavonoids are a beneficial category of naturally occurring compounds having hypoglycaemic properties.44

There are six distinct classes of flavonoids:

1. Anthocyanins

2. Catechins

3. Flavanols

4. Flavones

5. Flavanones

6. Isoflavones

The antioxidant properties of flavonoids and their capacity to alter particular cellular signals enhance their antidiabetic effects.

The Function of Flavonoids in Diabetes Management:

1.Aldose Reductase Inhibition:

Flavonoids inhibit aldose reductase, reducing glucose conversion to sorbitol. This prevents sorbitol accumulation, hence reducing oxidative stress and diabetes-related complications such as retinopathy and neuropathy.

2. Pancreatic β-Cell Regeneration:

Flavonoids reduce oxidative stress and apoptosis, facilitating the regeneration of pancreatic β-cells. They enhance antioxidant defences and activate Nrf2 (nuclear factor erythroid 2-related factor 2).

3. Insulin Release Enhancement:

Flavonoids enhance insulin secretion by modulating the GLP-1 and PKA pathways. Moreover, they enhance β-cell functionality by mitigating inflammation.

4. Augmentation of Calcium Ion Uptake:

An increase in the absorption of calcium ions. Flavonoids enhance the exocytosis of insulin granules by augmenting Ca²? influx in pancreatic β-cells. Increased calcium levels also enhance glucose regulation by promoting insulin secretion. 45

Table 3. A list of significant flavonoids that are used to treat diabetes.

Plant name

Phytoconstituents

Plant parts

References

Ficus benghalensis

Bengalenoside

Stem bark

46

Camellia sinensis

Epigallocatechin gallate

Leaves

47

Bergenia ciliata

--3-O-galloylepicatechin, --3- O-galloylcatechin

-

48

Glycine spp.

Genistein

Soya beans

49

Citrus spp.

Hesperidin, naringin

 

50

Amygdalus davidiana var. Davidiana

Prunin

Stems

51

Bauhinia forficate

Kaempferitrin

Leaves

52

Jindai soybean

Kaempferol

Leaves

53

Garc inia kola

Kolaviron

-

54

Ficus bengalensis

Leucodelphinidin

Bark

55

Anemarrhena asphodeloides

Mangiferin

Rhizomes

56

Pterocarpus marsupium

Marsupsin, pterostilbene

Heartwood

57

Chamaecostus cuspidatus

Quercetin

-

58

Bombax ceiba

Shamimin

Leaves

59

Polysaccharides:

Polysaccharides are bioactive macromolecules originating from plants, fungi, and microbes. Polysaccharides function in multiple capacities, such as elevating serum insulin levels, reducing blood glucose levels, and improving glucose tolerance.

Hypoglycaemia has been observed to respond favourably to natural polysaccharides. Cinnamomum zeylanicum separates L-arabino-D-xylan, cinnzeylanin, cinnzeylanol, and D-glucan. These chemicals regulate the breakdown and absorption of carbohydrates. 60

Table 4. A list of significant polysaccharides that are used to treat diabetes.

Plant name

Phytoconstituents

Plant parts

References

Aconitum carmichaeli

Aconitans A-D

Roots

61

Atractylodes japonica

Atractans A

Rhizomes

62

Ganoderma lucidum

Ganoderans A and B.

Fruit bodies

63

Cyamopsis tetragonolobus Amorphophallus konjac

Galactomannan gum

Seeds tubers

64

Terpenoids and Steroids:

Triterpenes serve as steroids' fundamental components in plants and animals 65. Terpenoids and steroids are bioactive compounds present in numerous plants. They exhibit potential in the treatment of diabetes mellitus due to their distinct pharmacological features. Their primary roles in diabetes management encompass antioxidant, anti-inflammatory, and antihyperglycemic effects.

1. Terpenoids in diabetes mellitus:

Terpenoids, or isoprenoids, constitute a diverse category of naturally occurring chemical substances derived from isoprene units. Their capacity to modulate blood glucose levels has been examined. Terpenoids with antidiabetic properties, such as olive leaves containing oleanolic acid, enhance insulin sensitivity. Apples and basil possess Ursolic acid, which enhances glucose uptake in skeletal muscles. Ginsenosides, derived from ginseng, augment glucose metabolism and stimulate insulin secretion. Turmeric curcumin reduces blood glucose levels via modifying insulin signalling.

2. Steroids in diabetes mellitus:

Individuals are utilising steroids to regulate their diabetes. Steroids, particularly phytosterols and steroidal saponins, modulate glucose metabolism. Examples of antidiabetic medications and consequences of steroids: Diosgenin in fenugreek enhances insulin secretion and reduces hyperglycaemia. Phytosterol beta-sitosterol from plants improves glucose regulation and lipid metabolism. Ashwagandha, scientifically known as Withania somnifera, comprises withanolides that reduce blood glucose levels and enhance insulin sensitivity.

Table 5. A list of significant terpenoids and Steroids that are used to treat diabetes.

Plant name

Phytoconstituents

Plant parts

References

Ficus racemosa

Alpha-amyrin acetate

Fruits

66

Andrographis paniculata

Andrographolide

Leaves

67

Zanthoxylum gilletii

3 -acetoxy-16 -hydroxybetulinic acid

Stem bark

68

Bumelia sartorum

Bassic acid

Root bark

69

Momordica charantia

Charantin

Seeds, fruits

70

Zizyphus spina-christi

Christinin A

Leaves

71

Lagerstroemia speciosa

Colosolic acid, maslinic acid

Leaves

72

Vitex spp.

Corosolic acid

Leaves

73

Aralia elata

Elatosides E

Root cortex

74

Aesculus hippocastanum

Escins-IIA and IIB

Seeds

75

Coleus forskohlii

Forskolin

-

76

Panax species

Ginsenosides

Rhizomes

77

Gymnema sylvestre

Gymnemic acid IV

Leaves

78

Kochia scoparia

Momordin ic

Fruits

79

Azadirachta indica

Beta-sitosterol

-

80

Polygala senega

Senegin derivatives

-

81

CONCLUSION:

Diabetes may be the most rapidly proliferating metabolic disorder globally, and as our comprehension of its complexities expands, so does the necessity for more efficacious therapies. This condition pertains to the metabolism of carbohydrates, lipids, and proteins, resulting from either insulin resistance or diminished insulin synthesis. Globally, individuals utilise traditional herbal remedies to manage diabetes owing to their availability and cost-effectiveness. This review article presents information on various phytoconstituents employed in the treatment of diabetes mellitus. Notwithstanding its therapeutic potential, additional research is required to resolve challenges related to standards, bioavailability, and safety concerns. Comprehensive research, including pharmacokinetic analysis and clinical trials, is required to establish the safety and efficacy of phytoconstituents. The integration of these natural compounds into conventional diabetes treatment regimens may yield novel, cost-effective, and safer alternatives for diabetic individuals. To enhance the medicinal utility of phytoconstituents, further research is necessary to refine extraction techniques, investigate their synergistic interactions, and develop novel combinations. Biotechnology and ethnopharmacology could collaborate to enhance the efficacy of phytomedicine-based treatments for diabetes

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  57. Manickam, M.; Ramanathan, M.; Jahromi, M.A.; Chansouria, J.P.; Ray, A.B. Antihyperglycaemic activity of phenolics from Pterocarpus marsupium. J. Nat. Prod., 1997, 60, 609-610.
  58. Hii, C.S.; Howell, S.L. Effects of flavonoids on insulin secretion and 45 Ca2+ handling in rat islets of Langerhans. J. Endocrinol., 1985, 107, 1-8.
  59. Saleem, R.; Ahmad, M.; Hussain, S.A.; Qazi, A.M.; Ahmad, S.I.; Qazi, M.H.; Ali, M.; Faizi, S.; Akhtar, S.; Husnain, S.N. Hypotensive, hypoglycaemic and toxicological studies on the flavonol C-glycoside shamimin from Bombax ceiba. Planta Med., 1999, 65, 331-334.
  60. Solomon TP, Blannin AK. Effects of short term cinnamon ingestion on in vivo glucose tolerance. Diabetes Obes Metab. 2007;  9: 895–901.
  61. Konno, C.; Morayana, M.; Sugiyama, K.; Arai, M.; Murakami. M.; Takahashi, M.; Hikino, H. Isolation and hypoglycaemic activity of aconitans A, B, C and D, glycans of Aconitum carmichaeli roots. Planta Med., 1985, 51, 160-161.
  62. Konno, C.; Suzuki, Y.; Oishi, K.; Munakata, E.; Hikino, H. Isolation and hypoglycemic activity of atractans A, B and C, glycans of Atractylodes japonica rhizomes. Planta Med., 1985, 2, 102-103.
  63. Hikino, H.; Konno, C.; Mirin, Y.; Hayashi, T. Isolation and hypoglycemic activity of ganoderans A and B, glycans of Ganoderma lucidum fruit bodies1. Planta Med., 1985, 514, 339-340.
  64. Jenkins, D.J.A.; Goff, D.V.; Leeds, A.R.; Alberti, K.G.M.M.; Wolever, T.M.S.; Gassull, M.A.; Hockaday, T.D.R. Unabsorbable carbohydrates and diabetes: decreased postprandial hyperglycaemia. Lancet, 1976, 2, 172-174.
  65. Rao, A.V.; Gurfinkel, D.M. The bioactivity of saponins: triterpenoid and steroidal glycosides. Drug Metabol. Drug Interact., 2000, 17, 211-235.
  66. Narender, T.; Khaliq, T.; Singh, A.B.; Joshi, M.D.; Mishra, P.; Chaturvedi, J.P.; Srivastava, A.K.; Maurya, R.; Agarwal, S.C. Synthesis of alpha-amyrin derivatives and their in vivo antihyperglycemic activity. Eur. J. Med. Chem., 2009, 44(3), 1215-1222.
  67. Yu, B.C.; Chang, C.K.; Su, C.F.; Cheng, J.T. Mediation of betaendorphin in andrographolide-induced plasma glucose-lowering action in type I diabetes-like animals. Naunyn Schmiedebergs Arch. Pharmacol., 2008, 77(4-6), 529-540. 
  68. Mbaze, L.M.; Poumale, H.M.; Wansi, J.D.; Lado, J.A.; Khan, S.N.; Iqbal, M.C.; Ngadjui, B.T.; Laatsch, H. -Glucosidase inhibitory pentacyclic triterpenes from the stem bark of Fagara tessmannii (Rutaceae). Phytochemistry, 2007, 68(5), 591-595.
  69. Naik, S.R.; Barbosa, F.J.M.; Dhuley, J.N.; Deshmukh, V. Probable mechanism of hypoglycemic activity of bassic acid, a natural product isolated from Bumelia sartorum. J. Ethnopharmacol., 1991, 33(1-2), 37-44.
  70. Ng, T.B.; Wong, C.M.; Li, W.W.; Yeung, H.W. Insulin-like molecules in Momordica charantia seeds. J. Ethnopharmacol., 1986, 15, 107-117.
  71. Glombitza, K.W.; Mahran, G.H.; Mirhom, Y.W.; Michel, K.G.; Motawi, T.K. Hypoglycaemic and antihyperglycaemic effects of Zizyphus spina-christi in rats. Planta Med., 1994, 60(3), 244-247.
  72. Kakuda, T.; Sakane, I.; Takihara, T.; Ozaki, Y.; Takeuchi, H.; Kuroyanagi, M. Hypoglycaemic effect of extracts from Lagerstroemia speciosa L. Leaves in genetically KK-AY mice. Biosci. Biotechnol. Biochem., 1996, 60, 204-208.
  73. Sundaram, R.; Naresh, R.; Shanthi, P.; Sachdanandam, P. Antihyperglycemic effect of iridoid glucoside, isolated from the leaves of Vitex negundo in streptozotocin-induced diabetic rats with special reference to glycoprotein components. Phytomedicine, 2012, 19 (3-4), 211-216.
  74. Yoshikawa, M.; Yoshizumi, S.; Ueno, T.; Matsuda, H.; Murakami, T.; Yamahara, J.; Murakami, N. Medicinal foodstuffs. I. Hypoglycaemic constituents from a garnish foodstuff “taranome,” the young shoot of Aralia elata Seem: elatosides G, H, I, J, and K. Chem. Pharm. Bull., 1995, 43, 1878-1882.
  75. Yoshikawa, M.; Harada, E.; Murakami, T.; Matsuda, H.; Wariishi, N.; Yamahara, J.; Murakami, N.; Kitagawa, I. Escins-Ia, Ib, IIa, IIb and IIIa bioactive triterpene oligoglycosides from the seeds of Aesculus hippocastanum L: Their inhibitory effects on ethanol absorption, and hypoglycaemic activity on glucose tolerance test. Chem. Pharm. Bull., 1994, 42, 1357-1359. 
  76. Wiedenkeller, D.E.; Sharp, G.W.G. Effects of forskolin on insulin release and cyclic AMP content in rat pancreatic islets. Endocrinology, 1983,113, 2311-2313.
  77. Attele, A.S.; Wu, J.A.; Yuan, C.S. Ginseng pharmacology: multiple constituents and multiple actions. Biochem. Pharmacol., 1999, 58, 1685-1693. 
  78. Sugihara, Y.; Nojima, H.; Matsuda, H.; Murakami, T.; Yoshikawa, M.; Kimura, I. Antihyperglycemic effects of gymnemic acid IV, a compound derived from Gymnema sylvestre leaves in streptozoto cindiabetic streptozotocin diabetic mice. J. Asian Nat. Prod. Res., 2000, 2, 321-327. 
  79. Yoshikawa, M.; Shimada, H.; Morikawa, T.; Yoshizumi, S.; Matsumura, N.; Murakami, T.; Matsuda, H.; Hori, K.; Yamahara, J. Medicinal foodstuffs. VII. On the saponin constituents with glucose and alcohol absorption-inhibitory activity from a food garnish “Tonburi”, the fruit of Japanese Kochia scoparia  Schard: structures of scoparianosides A, B, and. C. Chem. Pharm. Bull., 1997, 45, 1300-1305.
  80. Available at: (Accessed July 16, 2011)
  81. Yoshikawa, M.; Murakami, T.; Matsuda, H.; Ueno, T.; Kadoya, M.; Yamahara, J.; Murakami, N. Bioactive saponins and glycosides. II. Senegae radix. (2): Chemical structures, hypoglycemic activity, and ethanol absorption-inhibitory effect of Esenegasaponin c, Z-senegasaponin c, and Z-senegins II, III, and IV. Chem. Pharm. Bull., 1996, 44(7), 1305-1313.

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  56. Toshihiro, M.; Naoki, I.; Motoshi, K.; Hiroyuki, I.; Masayoshi, K.; Yasuhiro, K.; Torao, I.; Minoru, O.; Keiichiro, T. The Suppressive effect of mangiferin with exercise on blood lipids in type 2 diabetes. Biol. Pharm. Bull., 2001, 24(9), 1091-1092.
  57. Manickam, M.; Ramanathan, M.; Jahromi, M.A.; Chansouria, J.P.; Ray, A.B. Antihyperglycaemic activity of phenolics from Pterocarpus marsupium. J. Nat. Prod., 1997, 60, 609-610.
  58. Hii, C.S.; Howell, S.L. Effects of flavonoids on insulin secretion and 45 Ca2+ handling in rat islets of Langerhans. J. Endocrinol., 1985, 107, 1-8.
  59. Saleem, R.; Ahmad, M.; Hussain, S.A.; Qazi, A.M.; Ahmad, S.I.; Qazi, M.H.; Ali, M.; Faizi, S.; Akhtar, S.; Husnain, S.N. Hypotensive, hypoglycaemic and toxicological studies on the flavonol C-glycoside shamimin from Bombax ceiba. Planta Med., 1999, 65, 331-334.
  60. Solomon TP, Blannin AK. Effects of short term cinnamon ingestion on in vivo glucose tolerance. Diabetes Obes Metab. 2007;  9: 895–901.
  61. Konno, C.; Morayana, M.; Sugiyama, K.; Arai, M.; Murakami. M.; Takahashi, M.; Hikino, H. Isolation and hypoglycaemic activity of aconitans A, B, C and D, glycans of Aconitum carmichaeli roots. Planta Med., 1985, 51, 160-161.
  62. Konno, C.; Suzuki, Y.; Oishi, K.; Munakata, E.; Hikino, H. Isolation and hypoglycemic activity of atractans A, B and C, glycans of Atractylodes japonica rhizomes. Planta Med., 1985, 2, 102-103.
  63. Hikino, H.; Konno, C.; Mirin, Y.; Hayashi, T. Isolation and hypoglycemic activity of ganoderans A and B, glycans of Ganoderma lucidum fruit bodies1. Planta Med., 1985, 514, 339-340.
  64. Jenkins, D.J.A.; Goff, D.V.; Leeds, A.R.; Alberti, K.G.M.M.; Wolever, T.M.S.; Gassull, M.A.; Hockaday, T.D.R. Unabsorbable carbohydrates and diabetes: decreased postprandial hyperglycaemia. Lancet, 1976, 2, 172-174.
  65. Rao, A.V.; Gurfinkel, D.M. The bioactivity of saponins: triterpenoid and steroidal glycosides. Drug Metabol. Drug Interact., 2000, 17, 211-235.
  66. Narender, T.; Khaliq, T.; Singh, A.B.; Joshi, M.D.; Mishra, P.; Chaturvedi, J.P.; Srivastava, A.K.; Maurya, R.; Agarwal, S.C. Synthesis of alpha-amyrin derivatives and their in vivo antihyperglycemic activity. Eur. J. Med. Chem., 2009, 44(3), 1215-1222.
  67. Yu, B.C.; Chang, C.K.; Su, C.F.; Cheng, J.T. Mediation of betaendorphin in andrographolide-induced plasma glucose-lowering action in type I diabetes-like animals. Naunyn Schmiedebergs Arch. Pharmacol., 2008, 77(4-6), 529-540. 
  68. Mbaze, L.M.; Poumale, H.M.; Wansi, J.D.; Lado, J.A.; Khan, S.N.; Iqbal, M.C.; Ngadjui, B.T.; Laatsch, H. -Glucosidase inhibitory pentacyclic triterpenes from the stem bark of Fagara tessmannii (Rutaceae). Phytochemistry, 2007, 68(5), 591-595.
  69. Naik, S.R.; Barbosa, F.J.M.; Dhuley, J.N.; Deshmukh, V. Probable mechanism of hypoglycemic activity of bassic acid, a natural product isolated from Bumelia sartorum. J. Ethnopharmacol., 1991, 33(1-2), 37-44.
  70. Ng, T.B.; Wong, C.M.; Li, W.W.; Yeung, H.W. Insulin-like molecules in Momordica charantia seeds. J. Ethnopharmacol., 1986, 15, 107-117.
  71. Glombitza, K.W.; Mahran, G.H.; Mirhom, Y.W.; Michel, K.G.; Motawi, T.K. Hypoglycaemic and antihyperglycaemic effects of Zizyphus spina-christi in rats. Planta Med., 1994, 60(3), 244-247.
  72. Kakuda, T.; Sakane, I.; Takihara, T.; Ozaki, Y.; Takeuchi, H.; Kuroyanagi, M. Hypoglycaemic effect of extracts from Lagerstroemia speciosa L. Leaves in genetically KK-AY mice. Biosci. Biotechnol. Biochem., 1996, 60, 204-208.
  73. Sundaram, R.; Naresh, R.; Shanthi, P.; Sachdanandam, P. Antihyperglycemic effect of iridoid glucoside, isolated from the leaves of Vitex negundo in streptozotocin-induced diabetic rats with special reference to glycoprotein components. Phytomedicine, 2012, 19 (3-4), 211-216.
  74. Yoshikawa, M.; Yoshizumi, S.; Ueno, T.; Matsuda, H.; Murakami, T.; Yamahara, J.; Murakami, N. Medicinal foodstuffs. I. Hypoglycaemic constituents from a garnish foodstuff “taranome,” the young shoot of Aralia elata Seem: elatosides G, H, I, J, and K. Chem. Pharm. Bull., 1995, 43, 1878-1882.
  75. Yoshikawa, M.; Harada, E.; Murakami, T.; Matsuda, H.; Wariishi, N.; Yamahara, J.; Murakami, N.; Kitagawa, I. Escins-Ia, Ib, IIa, IIb and IIIa bioactive triterpene oligoglycosides from the seeds of Aesculus hippocastanum L: Their inhibitory effects on ethanol absorption, and hypoglycaemic activity on glucose tolerance test. Chem. Pharm. Bull., 1994, 42, 1357-1359. 
  76. Wiedenkeller, D.E.; Sharp, G.W.G. Effects of forskolin on insulin release and cyclic AMP content in rat pancreatic islets. Endocrinology, 1983,113, 2311-2313.
  77. Attele, A.S.; Wu, J.A.; Yuan, C.S. Ginseng pharmacology: multiple constituents and multiple actions. Biochem. Pharmacol., 1999, 58, 1685-1693. 
  78. Sugihara, Y.; Nojima, H.; Matsuda, H.; Murakami, T.; Yoshikawa, M.; Kimura, I. Antihyperglycemic effects of gymnemic acid IV, a compound derived from Gymnema sylvestre leaves in streptozoto cindiabetic streptozotocin diabetic mice. J. Asian Nat. Prod. Res., 2000, 2, 321-327. 
  79. Yoshikawa, M.; Shimada, H.; Morikawa, T.; Yoshizumi, S.; Matsumura, N.; Murakami, T.; Matsuda, H.; Hori, K.; Yamahara, J. Medicinal foodstuffs. VII. On the saponin constituents with glucose and alcohol absorption-inhibitory activity from a food garnish “Tonburi”, the fruit of Japanese Kochia scoparia  Schard: structures of scoparianosides A, B, and. C. Chem. Pharm. Bull., 1997, 45, 1300-1305.
  80. Available at: (Accessed July 16, 2011)
  81. Yoshikawa, M.; Murakami, T.; Matsuda, H.; Ueno, T.; Kadoya, M.; Yamahara, J.; Murakami, N. Bioactive saponins and glycosides. II. Senegae radix. (2): Chemical structures, hypoglycemic activity, and ethanol absorption-inhibitory effect of Esenegasaponin c, Z-senegasaponin c, and Z-senegins II, III, and IV. Chem. Pharm. Bull., 1996, 44(7), 1305-1313.

Photo
Rutuja Pangavhane
Corresponding author

Department of pharmacognosy, K. V. N. Naik SP Sanstha’s, Institute of pharmaceutical Education and Research, Canada Corner, Nashik, 422002, Maharashtra, India

Photo
Mukund Pache
Co-author

Department of pharmacognosy, K. V. N. Naik SP Sanstha’s, Institute of pharmaceutical Education and Research, Canada Corner, Nashik, 422002, Maharashtra, India

Rutuja Pangavhane*, Mukund Pache, Phytochemicals in The Management of Diabetes Mellitus: A Comprehensive Review, Int. J. Sci. R. Tech., 2025, 2 (4), 06-14. https://doi.org/10.5281/zenodo.15122232

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