Emerging Herbal Bio-actives as Reformed Dipeptidyl Peptidase (DPP-IV) Inhibitors Used for the Management of Diabetes Mellitus: A Brief Review

Review Article

Austin Diabetes Res. 2024; 9(1): 1031.

Emerging Herbal Bio-actives as Reformed Dipeptidyl Peptidase (DPP-IV) Inhibitors Used for the Management of Diabetes Mellitus: A Brief Review

Sakshi Sharma¹*; Sonia Chauhan²

1Swift School of Pharmacy, Ghaggar Sarai, Tehsil Rajpura, District Patiala, Punjab – 140401, India

2Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida, UP, India

*Corresponding author: Sakshi Sharma Swift School of Pharmacy, Ghaggar Sarai, Tehsil Rajpura, District Patiala, Punjab – 140401, India. Email: sakshi.sharma1964@gmail.com

Received: April 06, 2024 Accepted: May 08, 2024 Published: May 15, 2024

Abstract

Background: Diabetes mellitus is a severe metabolic disorder affecting nearly half of the population worldwide and increase patient risk by its other related complication. DPP-IV is a serine aminopeptidase, which plays a crucial part in the glucose metabolic process and causes incretin degradation in GLP-1. It is one of the validated targets for the treatment of Type 2 Diabetes because of its effect of incretin hormone. Nearly seven DPP-4 inhibitors are in the market for treating Type -II diabetes (i.e., Sitagliptin, Vildagliptin, Saxagliptin, Linagliptin, and Alogliptin). They all are synthesized chemically, having good therapeutic efficacy, but their long-term safety use is unknown.

Methods: Moreover, plant-derived products are available in the market and found to be safe and effective, and nearly half of the population consumes these natural or bio-active compounds. Therefore, for developing novel anti-diabetic drugs, these natural products or herbal medicine seems to have good utility.

Result: The present study deals with the progress of new herbal medicine, their crude extract with the mechanism of action having DPP-IV inhibitory activity. Therefore, these could be helpful evidence for developing the next generation of anti-diabetes medicines via inhibiting DPP-4 activity.

Conclusion: The researchers investigating the novel lead for managing diabetes (type II) can also search these natural bioactive for future use. We have summarised the reported herbal Bioactives/Plants for the management of Diabetes mellitus from the year 2001- 2022.

Keywords: Diabetes mellitus; Bioactives; DPP-IV; Extract; Incretin; Medicinal plants

Abbreviation: WHO: World Health Organization; DM: Diabetes Mellitus; GIP: Glucose-dependent insulin-tropic hormone; GLP: Glucogen like peptide; DPP-IV: Dipeptidyl peptidase

Introduction

Diabetes Mellitus (DM) is a common metabolic disorder that is increasing rapidly in the growing era, and according to WHO data, it is considered a primary cause of death worldwide [1]. Amongst all types of diabetes, Type 2 is the most common disorder having 90% of cases. Patient with Type 2 diabetes mellitus shows no apparent symptoms, but still, it is a life-threatening condition. According to the International Diabetes Federation, the cases of diabetes will increase from 415 million (in 2015) and might be increased 642 million (in 2040) [2]. Numerous synthetic drugs are introduced to lower the blood glucose level (i.e., biguanides, incretin mimetics, α glucosidase inhibitor, and DPP-IV inhibitor) [3]. The hormone incretin plays a significant role after ingesting food; GIP and GLP-1 are the two essential enzymes secreted by Incretin that stimulate the insulin release from the β pancreatic cells [4]. Incretin shows the insulinotropic effect; it decreases food intake, inhibits glucagon and gastric emptying time, and slows down glucagon secretion [5]. The action of Incretin (GLP- ad GIP-1) mainly depends on the two N-terminal amino acids that DPP-IV removes. Within 1-2 min, the Incretin is metabolized into inactive form by enzyme DPP-IV and only (10 to 15%) circulating stimulates the pancreas [6]. DPP-IV is an enzyme belonging to the family of serine proteases which involves the degradation of peptide hormones (i.e., glucagon-like peptide and cytokinin) [7]. DPP-IV inhibitors are now widely used in the market. These inhibitors inhibit the enzyme and promote the glucose homestasis [8]. But these synthetic drugs have good therapeutic activity, but they are not safe for the long term, so there is an increase in attention towards plant-derived products; they're bioactive and used to treat type 2 diabetes. Therefore, this review aims to compile the various herbal plants, their extract, mechanism of action, IC50 value, and structure of chemical compounds during 2000-2022, depicted in Table 1 and Table 2.

Table 1: List of synthetic DPP-IV inhibitors available in the market [14].










  


    
Marketed    drugs


    
Vildagliptin


    
Saxagliptin


    
Sitagliptin


    
Linagliptin


    
Alogliptin


  


  


    
DPP-IV    inhibitory potential


    
More    than 95%


    
70-85%


    
More    than 85-95%


    
More    than 75%


    
More    than 85%


  


  


    
Effectivity


    
Highly    effective


    
Moderately    effective


    
Very    highly effective


    
It    shows dose-dependent inhibition and highly effective


    
Shows    high-affinity ad inhibition in a dose-dependent manner


  


  


    
Hypoglycemia    risk


    
No    risk detected


    
No    risk detected


    
No    risk detected


    
No    risk detected


    
No    risk detected


  


  


    
Half-life


    
1.4-1.5hr


    
2.4hr


    
7-14hr


    
11-12hr


    
12.5    to 24hr


  


  


    
Metabolism


    
Metabolized    through kidney


    
Metabolized    through kidney


    
Only    16% metabolised through kidney


    
Primary    exertion through bile and secondary through kidney


    
Metabolized    by cytochrome enzymes.


  


  


    
Approved    countries


    
Europe


    
Europe    and the United States


    
United    States and Europe


    
Europe


    
Under    Investigation


  


  


    
Brand    name


    
Galvus


    
Onglyza


    
Januvia


    
Tradjenta


    
Nesina


  


  


    
Bioavailability


    
±85%


    
±67%


    
±100%


    
±30%


    
±100%


  


  


    
 


      
 


      
Structures


    
 


      


      
 


      
 


    
 


      


    
 


      


    
 


      


    


  


















Table 1: List of synthetic DPP-IV inhibitors available in the market [14].

Table 2: List of reported medicinal plants having DPP-IV inhibitory activity.










  


    
S.No


    
Plant/Family


    
Common    name


    
Dose    mg/kg


      &    ug/ml


    
Part    used


    
Extract


    
Mechanism


  


  


    
1


    
Pueraria    tuberosa


      (Fabaceae)


    
Kudzu


    
50    &100


    
Roots


    
Water


    
Inhibit    DPP-IV enzyme


  


  


    
2


    
Berberi’s    arista


      (Berberidaceae) 


    
Indian    barberry


    
500


    
Bark


    
Methanolic


    
Affect    DPP-IV and endocrine system activity


  


  


    
3


    
Camellia    Sinensis


    
White


      tea


    
200    µM 


    
leaves


    
Ethanolic


    
Increase    insulin secretion


  


  


    
4


    
Castanospermum    australe Cunn. 


    
Blackbean


    
100    &150


    
Seeds


    
-


    
Reduced    blood glucose level, HbA1c, and insulin 


  


  


    
5


    
Fagonia    critica


      (Zygophyllaceae) &


      Hedera nepalensis K.


      (Araliaceae)


    
Dhamasa


      
Albumbar 


    
-


    
Aerial


    
Ethyl    acetate


    
Inhibit    DPP_IV enzyme


  


  


    
6


    
Desmodium    gageticum 


      (Legumioiseae)


    
Sarivan


    
1000μg/ml


    
Aerial


    
Aqueous


    
Decrease    the inactivation of GLP-1 and thereby increase its concentration and its    action


  


  


    
7


    
Mangifera    indica


      (Anacardiaceae)


    
Mango


    
-


    
Leaves


    
Methanolic


    
Increase    the level of GLP-1, improve glucose tolerance, and enhance insulin secretion


  


  


    
8


    
Withania    Somifera


      (Solanaceae)


    
Ashwagandha


    
5,25,125μg/ml


    
Roots,    leaves, Fruit


    
Methanolic


    
It    decreases the blood sugar level by increasing the GLP-1 in the body


  


  


    
9


    
Enicostemma    littorale


      (Gentianceae)


    
-


    
100μl 


    
Whole    plant


    
Ethyl    acetate


    
It    increases insulin secretion by increasing GLP -1 half-life


  


  


    
10


    
Berberis    aristata


      (Berberideaceae)


    
Oregon    grapes


    
500μg/ml


    
Bark


    
Methanolic


    
It    increases insulin secretion


  


  


    
11


    
Corylus avellana L. 


      (Betulaceae) 


    
Hazelnut


    
50μl 


    
nuts


    
Aqueous


    
-


  


  


    
12


    
Commiphora Mukul


      (Burseraceae) 


    
Guggul


    
200mg/kg


    
Gum


    
Hydroalcoholic


    
Decrease    in blood glucose level and HA1c


  


  


    
13


    
Tinospora crispa L. 


      (Menispermaceae) 


    
Guduchi


    
-


    
Stem


    
-


    
Increase    the incretin and GLP-1 levels, which increases the insulin secretion in the    body


  


  


    
14


    
Curculigo latifolia


      (Hypoxideacea) 


    
Lamba


    
30μl 


    
Root,


      
 


      
Fruit


    
Aqueous


    
It    increases insulin secretion and glucose uptake


  


  


    
15


    
Eucalyptus    citriodora


      (Mytraceae)


    
Lemon    scented gum


    
250    mg/5 mL/kg


    
Leaf


    
Ethanolic


    
It    increases insulin secretion and decreases glucose absorption


  


  


    
16


    
Urena Lobata


      (Malvaceae) 


    
Caserweed


    
625, 1 250, 


      2 500, 5 000 and 10 000 mg/mL 


    
Leaf


    
Ethanolic


    
Prevents    GLP degradation and increases insulin secretion


  


  


    
17


    
Abelmoschus    manihot (L.)


      (Malvaceae)


    
Hibiscus


    
312.5;    625; 1250; 2500; 5000; and 10000 μg/mL


    
Leaves


    
Ethanolic


    
-


  


  


    
18


    
Senna    (Cassia) nigricans


      (Fabaceae)


    
Sannai


    
17.3    µU/µl)


    
Whole    plant


    
Methanolic


    
It    breaks the incretin level and increases the GLP level


  


  


    
19


    
Ferula Assafoetida


      (Umbelliferae) 


    
Fennel


    
-


    
Seeds


    
Methanolic


    
It    breaks the incretin level and increases the GLP level


  


















Table 2: List of reported medicinal plants having DPP-IV inhibitory activity.

Table 2 off 1: 










  


    
20


    
Pueraria    tuberosa


      (Fabaceae)


    
Kudzu


    
95µl


    
Roots


    
Aqueous


    
It    decreases glucose production and increases GLP-1 circulation in the body.


    
-


    
[34]


  


  


    
21


    
Lens    culinaris


      (Fabaceae)


    
Lentil


    
-


    
Seeds


    
Ethanolic


    
-


    
51.69    ± 4.83µm 


    
[35]


  


  


    
22


    
Aloe vera


      (Liliaceae) 


    
 


    
30µl


    
Leaves


    
Ethanolic


    
Increase    the plasma insulin ad GLP-1 level


    
8.59    ± 2.61 mM, 


    
[36]


  


  


    
23


    
Trigonella    foenum graecum


    
Fenugreek


    
320µg/ml


    
Seed


    
Methanolic


    
Increase    the plasma insulin ad GLP-1 level


    
80.15%


    
[37]


  


  


    
24


    
Annona squamosa


      (Annonacin)


    
-


    
250mg/5ml


    
Leaves


    
Ethanolic


    
It    suppresses the level of the Dpp-Iv enzyme and increases the incretin level


    
33%


    
[38]


  


  


    
25


    
Spirulina platensis


      (Cyanophycean) 


    
 


    
200µm


    
Whole    plant


    
Butanolic


    
It    suppresses the level of DPP-IV enzyme and increases the incretin level


    
70%


    
[39]


  


  


    
26


    
Boesenbergia    pandurata Roxb


      (Zingiberaceae)


    
Fingerroot


    
-


    
Whole    Plant


    
Ethanolic


    
It    increases the level of GLP-1 and Incretin


    
-


    
[40]


  


  


    
27


    
Pergularia extensa Chiov 


      (Asclepiadaceae) 


    
Daemia    extensa


    
10-30µm


    
Whole    plant


    
Methanolic


    
It    suppresses the level of DPP-IV enzyme and increases the incretin level


    
-


    
[41]


  


  


    
28


    
Ephedra foeminea


      (Ephedraceae) 


    
Jordan


    
0.1ml


    
Aerial


    
Methanolic


    
It    increases insulin release and decreases the glucose uptake


    
50%


    
[42]


  


  


    
29


    
Picrorhiza    kurroa


      (Plantaginaceae)


    
Kutki


    
25µm


    
Whole    plant


    
-


    
Increase    the plasma insulin ad GLP-1 level


    
52.51    ± 5.71 nM 


    
[43]


  


  


    
30


    
Castanospermum    australe


    
-


    
6.4µg/ml


    
Seed


    
Ethanolic


    
It    increases glucose utilization and increases the glycogen stores in the liver.


    
13.96    g/ml 


    
[44]


  


  


    
31


    
Coreopsis    Lanceolate


      (Compositae)


    
lance-leaved    coreopsis 


    
100µg


    
Flower


    
Methanolic


    
It    increases insulin secretion and glucose uptake


    
87.2%


    
[45]


  


  


    
32


    
Nauclea latifolia


      (Rubiaceae) 


    
Pin cushion tree 


    
-


    
Leaf


    
Aqueous


      
Ethanolic


    
-


    
89.6%


    
[46]


  


  


    
33


    
Trillium    govanianum


      (Melanthiaceae)


    
Naag    Chattri


    
181.3 ±    30.2 mg/g


    
Rhizome


    
-


    
It    helps in managing the glucose level in the body.


    
17.68 ±    1.32 μM 


    
[47]


  


  


    
34


    
Angelica keiskei Kodzumi 


      (Apiaceae) 


    
-


    
-


    
Stem


      
Leaves


    
Ethanolic


    
It    helps in reducing the plasma glucose level in the body


    
10.49 μM 


    
[48]


  


  


    
35


    
Phaseolus    vulgaris L.


      (Fabaceae)


    
Black    Bean


    
1mg/ml


    
Bean


    
-


    
It    helps in decreasing glucose uptake and increases the level of Incretin.


    
96.7%


    
[49]


  


  


    
36


    
Quercus variabilis Blume 


      (Fagaceae) 


    
Acorn


    
25µl


    
-


    
Ethanolic


    
It    inhibits the digestive enzymes and glucose transporters.


    
5.25 mg/mL) 


    
[50]


  


  


    
37


    
Prunus    amygdalus


      (Rosaceae)


    
-


    
15ml


    
Seed


    
Methanolic


    
It    inhibits the enzyme Incretin and DPP-IV


    
162.9(lg/mL) 


    
[51]


  


  


    
38


    
Lagerstroemia    speciosa


      (Lythraceae)


    
Banaba


    
-


    
Leaves


    
Methanolic    extract


    
It    inhibits the enzyme Incretin


    
60.22±2.01 


    
[52]


  


  


    
39


    
Rhinacanthus    nasutus (L.)


      (Acanthaceae)


    
Snake    jasmine


    
-


    
Leaves


    
Methanolic


    
It    inhibits the digestive enzymes and glucose transporters


    
34.4 ìg/mL 


    
[53]


  


  


    
40


    
Allium Sativum 


      (Alliaceae) 


    
Garlic


    
10 µL 


    
Bulb


    
Methanolic


    
It    decreases the blood glucose level, increases the Incretin, and increases    insulin secretion.


    
70.88 µg/mL 


    
[54]


  


  


    
41


    
Artemisia Judaica


      (Compositae) 


    
Common    Mugwort


    
-


    
Aerial


    
Hydro-methanolic


    
It    inhibits the enzyme DPP-IV


    
85.89 µg/mL 


    
[55]


  


  


    
42


    
Termialia Arjua 


      (Comitaceae) 


    
Arjun


    
-


    
Bark


    
-


    
It    helps in reducing the plasma glucose level in the body


    
28%


    
[56]


  


  


    
43


    
Eucalyptus citriodora


      (Myrtaceae) 


    
lemon- or    citron-scented gum 


    
8 mU/mL 


    
Leaves


    
Ethanolic


    
It    increases the incretin level and decreases glucagon secretion


    
52%


    
[57]


  


  


    
44


    
Spirulina    platensis


      (Cyanophyceae)


    
-


    
200    μM


    
Leaves


    
Ethanolic


    
It    increases the icreti levele y increasing the GIP-1 ad GLP


    
-


    
[58]


  


  


    
45


    
Melicope Gabra


      (Rutaceae) 


    
Tenggek    burung


    
50µL 


    
Leaves


      
Stem


    
Chloroform


    
It    helps in reducing the plasma glucose level in the body


    
619.31±9.21μg/ml 


    
[59]


  


  


    
46


    
Tenebrio    molitor


    
yellow Mealworms


    
20µL 


    
-


    
Hydroalcoholic


    
It    increases the incretin level in the body


    
(57.56    ± 2.59% 


    
[60]


  


  


    
47


    
Pisum Sativum


      (Fabaceae) 


    
Pea


    
100µm 


    
seed


    
-


    
It    formed the hydrophobic bond with the S1 pocket in DPP-IV and inhibited the    DPP-IV enzyme.


    
11.04μm 


    
[61]


  


  


    
48


    
Brassica oleracea


      (Brassicaceae) 


    
Broccoli 


    
-


    
Stem


      Leaves


    
Hydrolysis


    
It    increases the incretin level in the body


    
99.68μm 


    
[62]


  


  


    
49


    
Chenopodium    quinoa Willd


      (Chenopodiaceae) 


    
Quinoa


    
25μl


    
-


    
N-hexane


    
It    stimulates gastrointestinal digestion and inhibit the DPP-IV enzyme.


    
3.40    ± 0.20 mg/mL 


    
[63]


  


  


    
50


    
Heritiera    fomes


    
Sundari


    
10μl


    
Bark


    
Ethanolic


    
It    increases the insulin release


    
-


    
[64]


  


  


    
51


    
Commiphora Mukul


      (Combiteacea)


      and 


      Phyllanthus emblica


    
Guggul


      
 


      
Amla


    
 


    
Gum


      
 


      
Fruit


    
Hydroalcoholic


    
Increase    the incretin and GLP-1 levels, which increases the insulin secretion in body


    
0.36 µM 


      
0.8 μg/mL 


    
[65]


  


  


    
52


    
Ocimum Sativum


      (Labiateae) 


      
 


      
Momordica Charantia


        (Cucurbitaceae) 


    
Tulsi


      
 


      
 


      
Karela


    
0.1    to 0.5mg/ml


    
Leaves


    
Methanolic


    
It    activates the GLP-1 ad GIP ad increase the incretin level


    
66.81±0.05%


      
 


      
53.25±0.04%


    
[66]


  


  


    
53


    
Palmaria    palmata 


      (Palmariaceae) 


    
Dulse


    
-


    
Species


    
Aqueous


    
It    helps in reducing the plasma glucose level in body


    
1.47 ± 0.09mg/ml


    
[67]


  


  


    
54


    
Lippia    graveolens


      (Verbenaceae) 


    
Wild    oregano


    
50    μL


    
Seeds


    
Methanolic


    
It    inhibits the DPP-IV enzyme and decrease glucose secretion in the body


    
(3.9    ± 0.6 μM 


    
[68]


  


  


    
55


    
Rosa Gallica


      (Rosaceae) 


    
Gallic    source


    
100µM


    
Flower    buds


    
Aqueous


    
It    decreases glucose and increases insulin secretion, and increases the GIP and    GLP-1 levels.


    
25.8    µM and 70% 


    
[69]


  


  


    
56


    
Antidesma    madagascariense Lam.


      (Euphorbiaceae)


    
Bois    bigaignon bâtard 


    
-


    
Leaves


    
Ethyl    acetate


    
Increase    the incretin and GLP-1 levels, which increases the insulin secretion in the    body.


    
79.2    ± 2.8 μg/ml 


    
[70]


  


  


    
57


    
Aronia    arbutifolia (L.)


      (Rosaceae)


    
Red    Chokeberry


    
-


    
Juice


    
Fractioned


    
It    decreases the plasma glucose level in the body and inhibits the DPP-IV enzyme


    
81%


    
[71-72]


  


  


    
58


    
Allophylus Cominia


      (Sapindaceae) 


    
Panigera


    
-


    
Leaves


    
Aqueous


    
It    helps in reducing the plasma glucose level


    
344.3 


    
[73]


  


  


    
59


    
Calocybe Indica


    
Mushroom


    
100μl 


    
-


    
Ethanolic


    
It    controls the glucose level and increases GLP, GIP-1.


    
60.91μg/mL 


    
[74]


  


  


    
60


    
Senna Nigricans


      (Fabaceae) 


    
-


    
1    µg/µl


    
Powder


    
Methanolic


    
It    increases the incretin level


    
56.43%


    
[75]


  


  


    
61


    
Helichrysum arearium


      (Asteraceae) 


    
Dwarf    everlasting


    
-


    
Flower


    
Methanolic


      
Ethanolic


    
It    inhibits the increase in the blood glucose level


    
41.2 μg/ml 


      
16.0μg/ml 


    
[76]


  


  


    
62


    
Mytilus edulis


      (Mytillidae) 


    
Blue    mussel


    
-


    
-


    
Protein


    
It    inhibits the enzyme incretin and increases the half-life of GIP and GLP-1.


    
0.66±0.17 mg/ml 


    
[77]


  


  


    
63


    
Abelmoschus manihot    L. Medic


      (Malvaceae) 


    
Gedi


    
20 μL 


    
Leaves


    
Ethanolic


    
It    inhibits the DPP-IV enzyme and increases the incretin level


    
860.87 μg/mL 


    
[78]


  


















Table 2 off 1:

Mechanism of DPP-IV Action

DPP-IV is an amino peptidase enzyme with 760 amino acids. It contains two subunits having two domains (N terminal domain and C terminal domain). It is already known that GIP (Glucose-dependent insulin-tropic hormone) and GLP-1 (Glucagon l;ike peptide hormone) are incretin hormones that stimulate the release of insulin from pancreatic islets [10]. After food ingestion, these two incretin hormones release and contribute to insulin secretion [11]. DPP-IV enzymes mainly metabolize the Incretin (GLP and GIP-1), which release in response to food ingestion. DPP-IV inhibitors come under the class of oral hypoglycemic drugs, which competitively inhibit the enzyme DPP-IV and prevent the degradation of incretin hormone (GIP and GLP-1), ultimately increasing insulin secretion [12].

Marketed Available Drugs Having DPP-IV Inhibitor Activity

DPP- IV is a new class of oral anti-diabetic drugs. These drugs are active orally, safer, tolerable, and with a low risk of hypoglycemia. Various drugs are available in the market to inhibit the DPP-IV enzyme, out of which three DPP-IV inhibitors are under Investigation. First, reversible drug analogs, including (pyrrolidines and thiazolidines, secondly covalently modifying analogs, including Cyanopyrrolidines and lastly, non-peptidase reversible analogs, including xanthines and aminomethyl pyrimidines [13]. These drugs have specific adverse effects and increase the risk of cardiovascular-related complications and tumor incidence. Table 1 summarises the marketed drugs used in the management of diabetes mellitus which are approved by FDA.

Medicinal Plants Having DPP-IV Inhibitory Activity

In today's era, the use of herbal medicine is increasing very rapidly. This herbal medicine showed a promising effect in managing diabetes and its related complication with a lesser risk of side effects and greater acceptance. In this, we have compiled the data of a list of medicinal plants from natural sources, active parts of plants, their extract, and mechanism of action, along with their IC50 value from 2001-2022, depicted in (Table 2). In this we have summarizes the medicinal plants like Pueraria tuberosa, Berberis arista (14.46 μg/ml), Mangifera indica (182.7μg/ml), Desmodium gageticum (255.5μg/ml), Withania Somifera (8.76μg/ml).

Natural Phytoconstituents Showing DPP-IV Inhibition Activity

The herbal plants, their extracts, and their phytoconstituents have been encouraging throughout the globe since ancient times. Various herbal-based potent leads have been manufactured through integrated methodologies. Most of the herbal leads showed a potent inhibitory effect against DPP-IV. The numerous medicinal plants are recognized and categorized according to their chemical structure, as depicted in Table 3. The various categories of drugs used for DPP-IV, their characteristics, age group of the patient and number of patients involved in the studies, are tabulated in Table 4 and ongoing clinical trials in Table 4.

Table 3: List of herbal phytoconstituents having DPP-IV inhibitory activity.










  


    
S.No


    
Phytoconstituents


    
Biological    plants/ compound


    
Description


    
IC50    value/% inhibition


    
Researchers


    
Reference


  


  


    
1


    
Alkaloids


    
Coptis chinensis


      (Berberine)


    
From    this plant, 9 bioactive    were selected for in vitro bioassay, of which 7 had    DPP-IV activity (IC50<1.00 mM).


    
13.3 µM 


    
Guasch    et al


    
[79]


      
[80]


  


  


    
2


    
Glycosides


    
Lens culinaris


      (kaempferol)


      
 


      
Lens culinaris


        (Robinin)


    
Four    compounds were isolated from the seeds of this plant and tested for their    DPP-IV inhibitory activity.


      Robinin    was isolated from the seeds of this plant and tested their DPP-IV inhibitory    activity.


    
51.9±4.83 µM


      
 


      
37.01    µM 


    
Hyo Young Kim et al.


      
 


      
Kim    et al. 1998


    
[81]


  


  


    
3


    
Flavanoids


    
Lippia graveolens


      &


      Rosmarinus officinalis L


      (Naringeni)


      
Camellia    Sinesis


        (Theaceae)


    
In    this, it was reported that six bioactive from these plants showed potent    DPP-IV inhibitory activity.


      
 


      
Epigallocatechin    gallate 


    
2.5±0.3 μM


      
 


      
 


      
 


      
10.21 µM 


    
Fan J et al.


    
 


      
[82]


  


  


    
4


    
Terpeoids    and Steroids


    
Stevia rebaudiana


      (Rebaudioside A)


      (Stevioside)


    
Molecular    docking identified two main compounds from this plant for DPP-IV inhibitory    activity.


    
-


    
Ayachi    et al.


    
[83]


  


  


    
5


    
Phenols    and Stilbenoid


    
Vitis thunbergii var.


      ((+)-Hopeaphenol, (+)-vitamin A, and


      (−)-vitisin B 


    
The    ethanolic extract from the stems and leaves of plants processes DPP-IV    inhibitory activity.


    
 


      
401


        90.75


      
15.3 μM


    
Lin    et al.


    
[84]


  


















Table 3: List of herbal phytoconstituents having DPP-IV inhibitory activity.

Table 4: List of clinical trial data on DPP-IV inhibitors85.










  


    
NCT    No.


    
Condition


    
Intervention


    
Characteristics


    
Age    group


    
Sex


    
No.    of patient


  


  


    
NCT01588587


    
Diabetes    Mellitus


      (Type    II)


    
1st Drug:    Sitagliptin


      2nd Drug:    Vildagliptin


    
Observational    study type


      Model:    Cohort studies


      Measures    outcomes: Cancer frequency, AGE    concentration


    
25-95years


    
All    type


    
500    patients


  


  


    
NCT00411411


    
Diabetes


      (Type    II)


    
1st    Drug: Januvia


      2nd    Drug: Placebo


    
Interventional    study type


      Model:    Randomized studies, Parallel assessment


    
18-88    years


    
All    type


    
49    patients


  


  


    
NCT01545024


    
Diabetes    Mellitus


      (Type    II)


    
1st    Drug: Sitagliptin (50mg one time per day os)


    
Model:    Observational


    
20-95years


    
All    type


    
60    patients


  


  


    
NCT00111631


    
Diabetes    Mellitus


      (Type    II)


    
1st    Drug: DPP-IV inhibitor


      2nd    Drug: Metformin


      3rd:    Placebo


    
Model:    Interventional


      (phase    2)


    
18-75    years


    
All    type


    
218    patients


  


  


    
NCT03602638


    
Diabetes    Mellitus


      (Type    II)


      DPP-IV    inhibitor GLP-1


    
1st    Drug: Sitagliptin


      2nd    Drug: Acarbose


    
Model:    Interventional


      (Phase    4)


    
18-80    years


    
All    type


    
300    patients


  


  


    
NCT01937598


    
Diabetes    Mellitus


      (Type    II)


    
1st    Drug: Placebo


      2nd    Drug: Sitagliptin


      3rd    Drug: Liraglutide


    
Model:    Interventional


      (Phase    3)


    
25-75years


    
All    type


    
16    patients


  


















Table 4: List of clinical trial data on DPP-IV inhibitors85.

Conclusion

Over the past few decades, the enzyme DPP-IV considers a promising target for the management of Diabetes mellitus. Moreover, some synthetically manufactured compounds are commercially available in the market, but they have been associated with several side effects, and their long-term use is still unknown. DPP-IV inhibitors work by inhibiting the incretin hormone or increasing the GLP-1 and GIP levels via stimulating insulin secretion and inhibiting glucagon secretion. Newer drugs like molecular docking can potentially manage diabetes using some natural products. In- vivo and In- vitro experiments studies are recommended for targeting the DPP-IV enzymes. Traditionally, many natural plants and bioactive extracts are used to treat diabetes. Therefore, the current data gives researchers, the industrial sector, and others a new idea for developing novel formulations but still needs more advanced studies in preclinical and clinical to prove their efficacy and safety in human beings.

Author Statements

Conflict of Interest

The authors declare that there is no conflict of interest.

Acknowledgment

The authors thank NIET (Pharmacy Institute) greater noida for supporting and guiding them.

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Citation: Sharma S, Chauhan S. Emerging Herbal Bio-actives as Reformed Dipeptidyl Peptidase (DPP-IV) Inhibitors Used for the Management of Diabetes Mellitus: A Brief Review. Austin Diabetes Res. 2024; 9(1): 1031.